Culture

SMART breakthrough in detection of SARS-CoV-2 variant in wastewater

image: SMART AMR researchers Wei Lin Lee (left), Xiaoqiong Gu (centre) and Federica Armas (right) evaluate a 384-well plate set up for variant detection assays

Image: 
Zhan Yi Lee

Researchers from the Antimicrobial Resistance (AMR) Interdisciplinary Research Group (IRG) at Singapore-MIT Alliance for Research and Technology (SMART), MIT's research enterprise in Singapore, alongside collaborators from Biobot Analytics, Nanyang Technological University (NTU) and Massachusetts Institute of Technology (MIT), have successfully developed an innovative, open-source molecular detection method that is able to detect and quantify the B.1.1.7 (Alpha) variant of SARS-CoV-2. The breakthrough paves the way for rapid, inexpensive surveillance of other SARS-CoV-2 variants in wastewater.

As the world continues to battle and contain COVID-19, the recent identification of SARS-CoV-2 variants with higher transmissibility and increased severity has made the development of convenient variant tracking methods essential. Currently, identified variants include the B.1.17 (Alpha) variant first identified in the United Kingdom and the B.1.617.2 (Delta) variant first detected in India.

Wastewater surveillance has emerged as a critical public health tool to safely and efficiently track the SARS-CoV-2 epidemic in a non-intrusive manner, providing complementary information that enables health authorities to acquire actionable community-level information. Most recently, viral fragments of SARS-CoV-2 were detected in housing estates in Singapore through a proactive wastewater surveillance programme. This information, alongside surveillance testing, allowed Singapore's Ministry of Health (MOH) to swiftly respond, isolate and conduct swab tests as part of precautionary measures.

However, detecting variants through wastewater surveillance is less commonplace due to challenges in existing technology. Next-generation sequencing (NGS) for wastewater surveillance is time-consuming and expensive. They also lack the sensitivity required to detect low variant abundances in dilute and mixed wastewater samples due to inconsistent and/or low sequencing coverage.

The method developed by the researchers is uniquely tailored to address these challenges and expands the utility of wastewater surveillance beyond testing for SARS-CoV-2, towards tracking the spread of SARS-CoV-2 variants of concern. Dr Wei Lin Lee, Research Scientist at SMART AMR and first author on the paper added, "This is especially important in countries battling SARS-CoV-2 variants. Wastewater surveillance will help find out the true proportion and spread of the variants in the local communities. Our method is sensitive enough to detect variants in highly diluted SARS-CoV-2 concentrations typically seen in wastewater samples, and produces reliable results even for samples which contain multiple SARS-CoV-2 lineages."

Led by Associate Professor Janelle Thompson of NTU, and MIT Professor and SMART AMR Principal Investigator Eric Alm, the team's research "Quantitative SARS-CoV-2 Alpha variant B.1.1.7 Tracking in Wastewater by Allele-Specific RT-qPCR" has been published in prestigious journal, Environmental Science & Technology Letters. The research explains the innovative, open-source molecular detection method based on allele-specific RT-qPCR that detects and quantifies the B.1.1.7 (Alpha) variant. The developed assay, tested and validated in wastewater samples across 19 communities in the US, is able to reliably detect and quantify low levels of the B.1.1.7 (Alpha) variant with low cross-reactivity, and at variant proportions down to 1% in a background of mixed SARS-CoV-2 viruses.

Targeting spike protein mutations that are highly predictive of the B.1.1.7 (Alpha) variant, the method can be implemented using commercially available RT-qPCR protocols. Unlike commercially available products that use proprietary primers and probes for wastewater surveillance, the paper details the open-source method and its development that can be freely used by other organisations and research institutes for their work on wastewater surveillance of SARS-CoV-2 and its variants.

The breakthrough by the research team in Singapore is currently utilised by Biobot Analytics, a global leader in wastewater epidemiology headquartered in Cambridge, Massachusetts, in the US, serving states and localities throughout the country. Using the method, Biobot Analytics is able to accept and analyse wastewater samples for the B.1.1.7 (Alpha) variant and plans to add additional variants to its analysis as methods are developed.

"Using the team's innovative method, we have been able to monitor the B.1.1.7 (Alpha) variant in local populations in the US - empowering leaders with information about COVID-19 trends in their communities and allowing them to make considered recommendations and changes to control measures," said Dr Mariana Matus, Biobot Analytics CEO and Cofounder.

The SMART AMR team is also currently developing specific assays that will be able to detect and quantify the B.1.617.2 (Delta) variant, which has recently been identified as a variant of concern by the World Health Organisation.

"This method can be rapidly adapted to detect new variants of concern beyond B.1.1.7," said co-corresponding author Professor Eric Alm of MIT and Principal Investigator at SMART AMR. "Our partnership with Biobot Analytics has translated our research into real-world impact beyond the shores of Singapore and aid in the detection of COVID-19 and its variants, serving as an early warning system and guidance for policymakers as they trace infection clusters and consider suitable public health measures."

Credit: 
Singapore-MIT Alliance for Research and Technology (SMART)

Astrophysicist outlines plans for the gravitational wave observatory on the moon

image: Conceptual design of Gravitational-wave Lunar Observatory for Cosmology on the surface of the moon.

Image: 
Karan Jani

THE IDEA

Vanderbilt astrophysicist Karan Jani has led a series of studies that make the first case for a gravitational wave infrastructure on the surface of the moon. The experiment, dubbed Gravitational-Wave Lunar Observatory for Cosmology, uses the moon's environment and geocentric orbit to analyze mergers of black holes, neuron stars and dark matter candidates within almost 70 percent of the entire observable volume of the universe, he said.

"By tapping into the natural conditions on the moon, we showed that one of the most challenging spectrum of gravitational waves can be measured better from the lunar surface, which so far seems impossible from Earth or space," Jani said.

WHY IT MATTERS

"The moon offers an ideal backdrop for the ultimate gravitational wave observatory, since it lacks an atmosphere and noticeable seismic noise, which we must mitigate at great cost for laser interferometers on Earth," said Avi Loeb, professor of science at Harvard University and bestselling author of books about black holes, the first stars, the search for extraterrestrial life and the future of the universe. "A lunar observatory would provide unprecedented sensitivity for discovering sources that we do not anticipate and that could inform us of new physics. GLOC could be the jewel in the crown of science on the surface of the moon."

This work comes as NASA revives its Artemis program, which aims to send the first woman and the next man to the moon as early as 2024. Ongoing commercial work by aerospace companies, including SpaceX and BlueOrigin, also has added to the momentum behind planning for ambitious scientific infrastructure on the surface of the moon.

WHAT'S NEXT

"In the coming years, we hope to develop a pathfinder mission on the moon to test the technologies of GLOC," Jani said. "Unlike space missions that last only a few years, the great investment benefit of GLOC is it establishes a permanent base on the moon from where we can study the universe for generations, quite literally the entirety of this century." Currently the observatory is theoretical, with Jani and Loeb receiving a strong endorsement from the international gravitational-wave community.

"It was a great privilege to collaborate with an innovative young thinker like Karan Jani," Loeb said. "He may live long enough to witness the project come to fruition."

Credit: 
Vanderbilt University

SARS-CoV-2 variant B.1.617 gives the immune system a hard time

image: The spike protein on the surface of SARS-CoV-2 virions mediates entry into target cells. It Is the main target for neutralizing antibodies that are produced following infection or vaccination. In case of the B.1.617 variant, the spike protein has acquired mutations that increase efficiency of virus entry into cells and reduce sensitivity to antibody-mediated neutralization.

Image: 
Markus Hoffmann

SARS-CoV-2 still poses major challenges to mankind. The frequent emergence of mutant forms makes the threat posed by the virus difficult to predict. The SARS-CoV-2 variant B.1.617 circulated in India and gave rise to the Delta variant, B.1.617.2, which is now becoming dominant in many countries. Infection researchers from the German Primate Center (DPZ) - Leibniz Institute for Primate Research in Göttingen have investigated the B.1.617 variant in detail. In cell culture studies, they found that this variant can infect certain lung and intestinal cell lines more efficiently than the original virus. The researchers also demonstrated that B.1.617 is less sensitive to inhibition by antibodies present in the blood of convalescent or vaccinated individuals and resistant to a therapeutic antibody used for COVID-19 treatment. These properties may enable B.1.617 and its subtypes to rapidly spread in the human population, thereby increasing the risk of incompletely vaccinated individuals and individuals with declining immune protection to become infected (Cell Reports).

The spike protein is embedded in the viral envelope and facilitates SARS-CoV-2 entry into host cells. Without the activity of the spike protein the virus cannot replicate in the human body. The currently known virus variants harbor different mutations in the spike protein, some of which make it easier for them to infect host cells and evade the immune system of infected individuals. The B.1.617 variant carries eight different mutations in the spike protein, including two within the receptor binding domain, which is essential for viral attachment to cells and represents the main target for neutralizing antibodies.

A team led by Markus Hoffmann and Stefan Pöhlmann, infection researchers at the German Primate Center, and including scientists from the University Hospital of Göttingen, the University of Erlangen and the Hannover Medical School, investigated how the mutations impact the ability of the B.1.617 variant to enter host cells and how efficiently the antibody response in vaccinated and recovered individuals inhibits this variant.

First, the researchers analyzed entry of the B.1.617 variant into different human cell lines. In two cell lines derived from lung and colon, respectively, they detected a 50 percent increase in the virus' entry efficiency.

The researchers also investigated the efficacy of four different therapeutic antibodies that have been approved for the treatment of COVID-19 patients. They found that the B.1.617 variant was completely resistant against one of these antibodies and slightly less inhibited by another antibody.

In a third step, the scientists tested the efficacy of antibodies from the blood of recovered and vaccinated individuals. Here, they found a two- to threefold reduction in protection against the B.1.617 variant.

"Our study shows that this virus variant can infect lung and intestinal cells more efficiently, suggesting increased viral fitness," Markus Hoffmann, lead author of the study, summarizes the results. "In addition, the protective effect of antibodies is limited because they block the cell entry of B.1.617 less efficiently than that of the original virus. As a result, individuals who are not fully vaccinated or were infected a long time ago and thus produce low amounts of antibodies, may be poorly protected against infection with the B.1.617 variant.

Stefan Pöhlmann, Head of the Infection Biology Unit at the DPZ adds: "In order to prevent further spread of the B.1.617 variant, especially its subtype Delta, and to prevent the emergence of new virus variants it is advisable to quickly achieve full immunization of all people that are willing to be vaccinated. It is also necessary to investigate whether booster vaccinations with existing vaccines or vaccines optimized to target variants provide long-lasting and broad protection."

Credit: 
Deutsches Primatenzentrum (DPZ)/German Primate Center

Many ICU staff have experienced mental health conditions in COVID-19 pandemic

A high proportion of staff working in intensive care units during the COVID-19 pandemic have experienced mental health conditions, according to a new study.

In a study of 515 healthcare staff working in intensive care units (ICUs) across seven countries, the researchers found that on average 48 percent of participants showed signs of mental health conditions - depression, insomnia and post-traumatic stress disorder (PTSD). Their mental health was assessed using a detailed questionnaire and a clinical scoring system.

The team also found a 40 per cent increase in the conditions for those who spent more than six hours in personal protective equipment (PPE) over a course of a day, compared to those who didn't.

The study, led by researchers at Imperial College London, is published in the British Journal of Nursing and is the first to evaluate ICU workers' mental health during the COVID-19 pandemic. In line with the UK Government's report on burnout in NHS staff published in June 2021, the researchers suggest that the high level of mental health conditions found among the ICU staff surveyed should inform local and national wellbeing policies.

Dr Ahmed Ezzat, lead author of the study and Honorary Clinical Fellow at Imperial College London, said:

"This is a timely study which acts as a stark reminder of the personal challenges healthcare staff are facing as a result of COVID-19. As within wider society, mental illness of healthcare staff still remains a taboo subject for some.

"Recent public campaigns have started the conversation, but we have a long way to go. COVID-19 has acutely exacerbated the issue, and our concern is how staff resilience has been exhausted and what national medium or long term resources are set in place by policy makers to safeguard this workforce from severe mental illness.

"We have an opportunity to hold a national dialogue of healthcare leaders, stakeholders and governments around the world to address mental health within healthcare."

Dr Matthieu Komorowski, senior author of the study and Clinical Senior Lecturer in the Department of Surgery and Cancer at Imperial College London, said:

"The COVID-19 pandemic has impacted the physical and mental health of healthcare workers around the world. The large number of patients admitted to hospital at the height of the pandemic has put considerable demand and pressure on ICUs and staff. Although there has been much reporting on the mental health of frontline workers there has been little done to assess the impact of the pandemic on those who were treating the sickest patients in ICU.

"This study shows the impact of working in ICU on staff's mental health. We saw high levels of depression, insomnia and PTSD. Factors such as individual isolation, loss of social support during lockdown, combined with a change in work pattern may have exacerbated these conditions.

"Work related stress is well documented in healthcare workers and this has been worsened by the COVID-19 crisis. The results of this study suggest that all ICU staff should have access to early and effective mental health assistance as part of a wider staff health and wellbeing strategy. This is especially pressing as hospitals and governments prepare their workforce for potential further surges of COVID-19 patients."

During the height of the COVID-19 pandemic there were large intakes of patients admitted to ICUs, exceeding capacity. To manage demand, many hospitals have had to increase the ICU workforce via staff redeployment, with staff required to undertake duties that require different skills from their normal roles.

Although the mental health burden in healthcare workers caused by COVID-19 has gained increasing attention, there has been a lack of data, especially relating to healthcare workers in ICU.

The researchers wanted to examine whether critical care staff experienced adverse mental health in a similar way to frontline healthcare workers, during the height of the COVID-19 pandemic.

The team recruited 515 healthcare workers working in ICUs in May 2020. They covered a range of roles such as nurses, junior and senior doctors, healthcare assistants and physiotherapists. Participants were from the UK (73), France (309), Italy (31), Taiwan (29), Belgium (2), Egypt (3) and China (68). They were recruited by word of mouth, emails and social media platforms.

Using a detailed questionnaire, the team asked participants questions on their wellbeing and anxieties. They then scored their responses using three different grading systems used in clinical settings to identify depression, PTSD and insomnia. The team found that across the various countries explored, 37 percent of respondents exceeded the threshold for signs of depression, 78 for insomnia and 28 percent for PTSD.

The team also identified an increase in the scores in those who spent more than six hours in PPE over a course of a day. On average, there was a 40 percent increase in the depression score for those spending over six hours in PPE compared to those who didn't and a 23 per cent increase in the insomnia and PTSD scores, suggesting that mental health conditions amplify with longer time spent in PPE.

The authors also found that 57 percent of respondents declared feeling very or extremely worried about getting infected, while 21 percent were very or extremely worried about dying after catching the virus. Overall, 78 percent of respondents reported feeling at least a little numb about the loss of human lives, and most (89 percent) thought about these difficult experiences outside of work.

Finally, 88 percent agreed that healthcare staff should be offered dedicated time off work once it was clinically safe to do so, and 85 percent were in favour of offering individual counselling sessions to healthcare workers.

The authors acknowledge there are some limitations to the study as respondents were self-selecting rather than randomly chosen, which could affect how representative this group was of ICU workers as a whole. Of those who responded, 11 said they had pre-existing mental health conditions. Despite this, the researchers suggest the data provides a useful indicator of mental wellbeing across ICU staff and the findings can be used to devise local and national policies to address this.

Credit: 
Imperial College London

Unravelling the knotty problem of the Sun's activity

image: Simulation of twisted magnetic field lines emerging through the photosphere, the visible surface of the Sun.

Image: 
MacTaggart et al.

A new approach to analysing the development of magnetic tangles on the Sun has led to a breakthrough in a longstanding debate about how solar energy is injected into the solar atmosphere before being released into space, causing space weather events. The first direct evidence that field lines become knotted before they emerge at the visible surface of the Sun has implications for our ability to predict the behaviour of active regions and the nature of the solar interior. Dr Christopher Prior of the Department of Mathematical Sciences, Durham University, will present the work today at the virtual National Astronomy Meeting (NAM 2021).

Researchers are generally in agreement that solar activity is caused by instabilities in giant twists of magnetic ropes threading the visible surface of the Sun, known as the photosphere. However, there has been an ongoing debate about how these tangles form. The two dominant theories have suggested either that coils of field lines emerge through the photosphere from the convection zone below, or that the feet of arching field lines wrap around each other on the surface itself and create braids. Both mechanisms could theoretically produce effects like sunspot rotation and dramatic solar flares but, to date, no direct observational evidence had conclusively supported either scenario.

Prior and colleagues from the University of Glasgow and INAF-Osservatorio Astrofisico di Catania in Italy came up with a new direct measure of the entanglement of the magnetic field by tracking the rotation of field lines at the points where they intersect with the photosphere. This 'magnetic winding' should manifest in different ways for each of the two theories. Thus, applying magnetic winding to observations of the photosphere and examining the resulting patterns could enable a definitive answer to be reached for which theory was correct.

The researchers studied the magnetic winding for 10 active regions on the Sun in observations by solar missions. In every case, the results matched the emergence theory of pre-twisted magnetic field lines rising up from the convection zone.

Prior explains: "The pattern for pre-twisted field lines exactly matched the observational data we considered initially, and this has since been found to be true for all data sets of active regions we have looked at so far. We anticipate that magnetic winding will become a staple quantity in the interpretation of magnetic field structure from observational data."

Credit: 
Royal Astronomical Society

Cell couriers deliver clue to cancer metastasis

image: Integrins being moved inside a migrating cell. Integrins appear as dark spots, cell nucleus is blue.

Image: 
Méghane Sittewelle, University of Warwick

A protein involved in making cells move offers a clue to how certain types of cancer metastasize and develop into secondary tumours, according to new research from the University of Warwick.

Scientists from Warwick Medical School have demonstrated for the first time that levels of this protein can increase and decrease the movement of a cell, including cancer cells - suggesting that they could play a role in the spread of tumours.

The study is published today (21 July) in the Journal of Cell Biology and was funded by the Medical Research Council, part of UK Research and Innovation.

The researchers are investigating a tiny cell component called an Intracellular nanovesicle (INV) which acts like a courier within a cell by transporting cargo to where it is needed. When a cell moves, the INV moves a particle called an integrin from the cell's surface to 'unstick it' from the surface it is attached to. It then recycles and replaces the integrin to stick it to a new surface.

INVs have a protein called Tumour Protein D54, increased levels of which have been associated with certain types of breast cancer and often a poor prognosis for the patient. These patients tend to have more metastases, where tumour cells spread to other parts of the body.

To investigate TPD54's role in cell movement, the Warwick team observed cells migrating on a surface coated with fibronectin, a type of extra-cellular matrix, using a live cell microscope. They then reduced or increased the expression of the protein TPD54 to mimic the expression in a cancer cell, observing how the cell migrates more or less depending upon the levels of TPD54.

They also conducted the same experiment using ovarian cancer cells inside a 3D mesh rich in fibronectin, a more accurate representation of how a cell would behave inside a tumour. When they depleted the levels of the TPD54 protein, the scientists could see that the cells migrated less.

Lead author Professor Stephen Royle, of Warwick Medical School at the University of Warwick, said: "There are circumstances where you don't want cells to move around, such as in cancer. We show in this paper that if you decrease the levels of the TPD54 protein then cells move less, and if you increase the levels they move more. It offers an explanation for why cancer cells that have overexpression of this protein tend to be more metastatic and spread.

"The name Tumour Protein D54 comes from the fact that it is overexpressed in cancer but not a lot is known about it at the molecular level. We have found how this protein attaches to INVs inside cells and controls what cells normally do."

Despite its name, Tumour Protein D54 is involved in a number of normal processes of a cell, and is also involved in the immune response, wound healing, and other functions. The research suggests that TDP54 would not be an ideal target for a cancer intervention due to its role in these normal functions of the cell, but it does give scientists a better understanding of how integrin trafficking is altered in cancer.

Professor Royle adds: "This protein is actually a healthy protein. It's needed for these INVs to move around, to move other cargoes, and perform other functions besides migration. It's one of the most highly expressed proteins in normal cells which indicates that it's probably doing something important. We think it has something to do with this army of INV couriers working within a cell.

"But in cancer, we've suddenly got lots of couriers trafficking lots of integrins, and so we get more movement of cells and that's not good. If you've got cancer cells, you don't want them to migrate."

The Warwick group discovered INVs in 2019, having previously been overlooked. At around 30 nanometres across, they were so small that the team had to use a combination of electron microscopy and the Warwick Open Source Microscope, a super-resolution light microscope built at the University of Warwick, to observe them.

Professor Royle adds: "They were hiding in plain sight - you can go back to micrographs from the fifties and can see that they were there, it's just we didn't have the tools to find them.

"The bigger question for us is how these vesicles behave and what they carry. They carry a whole range of other proteins and they are likely involved in lots of other cell functions. The thinking within the field is that cargoes like integrins are trafficked in very large tubules, but we're showing that it's actually happening in these smaller vesicles."

Credit: 
University of Warwick

A large tidal stream observed in the Sombrero galaxy

video: An image of the galaxy is shown on the left and a simulation movie that matches the current location of the flow is shown on the right.

Image: 
Denis Erkal (University of Surrey, UK), David Martínez-Delgado (IAA-CSIC).

According to the latest cosmological models, large spiral galaxies such as the Milky Way grew by absorbing smaller galaxies, by a sort of galactic cannibalism. Evidence for this is given by very large structures, the tidal stellar streams, which are observed around them, which are the remains of these satellite galaxies. But the full histories of the majority of these cases are hard to study, because these flows of stars are very faint, and only the remains of the most recent mergers have been detected.

A study led by the Instituto de Astrofísica de Andalucía (IAA-CSIC), with the participation of the Instituto de Astrofísica de Canarias (IAC), has made detailed observations of a large tidal flow around the Sombrero galaxy, whose strange morphology has still not been definitively explained. The results are published today in the journal Monthly Notices of the Royal Astronomical Society (MNRAS).

The Sombrero galaxy (Messier 104) is a galaxy some thirty million light years away, which is part of the Local Supercluster (a group of galaxies which includes the Virgo cluster and the Local Group containing the Milky Way). It has roughly one third of the diameter of the Milky Way, and shows characteristics of both of the dominant types of galaxies in the Universe, the spirals and the ellipticals. It has spiral arms, and a very large bright central bulge, which makes it look like a hybrid of the two types.

"Our motive for obtaining these very deep images of the Sombrero galaxy (Messier 104) was to look for the remains of its merger with a very massive galaxy. This possible collision was recently suggested on the basis of studies of the stellar population of its strange halo obtained with the Hubble Space Telescope", says David Martínez-Delgado, a researcher at the IAA-CSIC and first author of the paper reporting the work.

The observations with the Hubble, in 2020, showed that the halo, an extensive and faint region surrounding the Sombrero galaxy, shows many stars rich in metals, elements heavier than hydrogen and helium. This is a feature to typical of new generations of stars, which are normally found in the discs of galaxies, and are quite unusual in galactic halos, which are populated by old stars. To explain their presence astronomers suggested what is known as "a wet merger", a scenario in which a large elliptical galaxy is rejuvenated by large quantities of gas and dust from another massive galaxy, which went into the formation of the disc which we now observe.

"In our images we have not found any evidence to support this hypothesis, although we cannot rule out that it could have happened several thousand million years ago, and the debris is completely dissipated by now -explains David Martínez-Delgado-. In our search we have in fact been able to trace for the first time the complete tidal stream which surrounds the disc of this galaxy, and our theoretical simulations have let us reconstruct its formation in the last three thousand million years, by cannibalism of a satellite dwarf galaxy".

"Observational techniques in present day Astrophysics need advanced image processing. Our modelling of the bright stars around the Sombrero galaxy, and at the same time of the halo light of the galaxy itself has enabled us to unveil the nature of this tidal stream. It is remarkable that thanks to these advanced photometric techniques we have been able to do front line science with a Messier object using only an 18 cm (diameter) telescope", explains Javier Román, a postdoctoral researcher at the IAC and a co-author of the study.

The research team rejects the idea that the large stellar tidal stream, known for more than three decades, could be related to the event which produced the strange morphology of the Sombrero galaxy which, if it was caused by a wet merger, would need the interaction of two galaxies with large masses.

The work has been possible thanks to the collaboration between professional and amateur astronomers. "We have collaborated with the Spanish astrophotographer Manuel Jiménez, who took the images with a robotic telescope of 18 centimetre diameter, and the well-known australian astrophotographer David Malin, who discovered this tidal stream on photographic plates taken in the 90's of the last century. This collaboration shows the potential of amateur telescopes to take deep images of nearby galaxies which give important clues about the process of their assembly which is continuing until the present epoch", concludes Martínez-Delgado.

Credit: 
Instituto de Astrofísica de Canarias (IAC)

UM researchers publish study on genomics of pregnancy-induced diabetes

Pregnancy-induced diabetes, also known as gestational diabetes, is a common metabolic complication of pregnancy. The disorder carries a significant risk of adverse obstetric outcome. Additionally, it is associated with a high risk of recurrence, progression to maternal type 2 diabetes as well as an elevated risk of obesity in foetuses exposed to hyperglycaemia during gestation.

The mechanisms causing gestational diabetes are complex and incompletely understood. The disorder has a strong underlying genetic element that interacts with lifestyle factors and the physiologic changes accompanying pregnancy to alter maternal glucose regulation.

A team of researchers from the Faculty of Medicine and Surgery have applied high-throughput genomics to identify rare highly-penetrant genetic variants that drive the development of gestational diabetes.

The study, entitled 'Screening for monogenic subtypes of gestational diabetes in a high prevalence island population - a whole exome sequencing study' provides the first description of atypical diabetes presenting in pregnancy in the Maltese population.

This research integrates clinical medicine, genomics and protein modelling with longitudinal follow-up data. The paper highlights the genetic heterogeneity underlying disorders of glucose regulation and reinforces the role of precision medicine research in unravelling the aetiology of complex traits.

Credit: 
University of Malta

Awareness without a sense of self

In the context of meditation practice, meditators can experience a state of "pure awareness" or "pure consciousness", in which they perceive consciousness itself. This state can be experienced in various ways, but evidently incorporates specific sensations as well as non-specific accompanying perceptions, feelings, and thoughts. These are just some of the findings of the most extensive survey of meditators ever conducted on the experience of pure consciousness. The findings of the survey recently have been published in PLOS ONE. The study was conducted by Professor Thomas Metzinger from the Department of Philosophy at Johannes Gutenberg University Mainz (JGU) and Dr. Alex Gamma from the Psychiatric Hospital of the University of Zurich. They designed an online questionnaire comprising more than a hundred questions and asked thousands of meditators worldwide to answer it. "The goal of our research was not to learn more about meditation. We are interested in human consciousness," said Metzinger. "Our working hypothesis was that pure consciousness is the simplest form of conscious experience. And our goal was to develop a minimal model explanation of human consciousness experience on the basis of this hypothesis." The study is part of the international Minimal Phenomenal Experience (MPE) project led by Metzinger.

The online questionnaire was made available in five languages - German, English, French, Spanish, and Italian - and was completed by approximately 3,600 meditators in 2020. In addition to questions about the participants themselves, such as gender, age, and meditation techniques used, the questionnaire consisted of 92 questions about their experience of pure awareness. Instructing the meditators to select and focus on one particular experience of pure awareness, the questionnaire included questions like: "Did you experience sensations of temperature?", "Were you in a positive mood?", or "Did you experience thoughts?". Each of these could be answered on a scale from "no" to "yes, very intensely" via a slider bar. Of the questionnaires Metzinger and Gamma received back, 1,400 were filled out in full and so could be used for a so-called factor analysis. They employed this type of statistical evaluation to identify groups of questions that were frequently answered in a similar manner. "This led us to identify twelve groups, which in turn allowed us to name twelve factors that characterize pure consciousness," Metzinger explained. "According to this scheme, typical characteristics of pure consciousness seem to be, for example, the perception of silence, clarity, and an alert awareness without egoic self-consciousness. Time, effort, and desire, which can certainly transpire in parallel, are experienced somewhat less explicitly."

"Based on these twelve factors, we can now develop a prototypical minimal model of human consciousness," said Metzinger. In addition, the study opens up numerous avenues for further research. Neuroscientists from the USA, Australia, and Switzerland, for instance, have already inquired whether they can use the questionnaire for their own research. For his own part, Metzinger hopes to discover whether pure consciousness - that is, the quality of consciousness in itself - is also experienced in situations other than meditation: "The responses we received also included personal reports suggesting that pure consciousness is also experienced in other situations, such as during accidents and serious illness, at the threshold between sleep and wakefulness, or when immersed in play as a child."

Credit: 
Johannes Gutenberg Universitaet Mainz

Researchers develop tool that may help in understanding inaccuracy in eyewitness testimony

video: University of Toronto Department of Psychology researchers have developed a new tool called a "scene wheel" to help understand how we perceive and remember visual experiences such as witnessing crimes or accidents.

Image: 
Faculty of Arts & Science/University of Toronto

TORONTO, ON - Researchers at the University of Toronto have developed an innovative tool to aid in the investigation of how we perceive and remember visual experiences.

The new tool, referred to as a "scene wheel," will help researchers study how accurately we construct mental representations of visual experiences for later retrieval -- for example, how well an eyewitness recalls details of a crime or accident.

"We know that eyewitness testimony is not reliable," says Gaeun Son. "With the new scene wheel, we can start to characterize the specific nature of those memory failures."

Son is a PhD student in the Faculty of Arts & Science's Department of Psychology and lead author of a paper published in Behavior Research Methods that describes the scene wheel methodology.

"Studying how people perceive and remember the world requires careful control of the physical stimuli presented in experiments," says Michael Mack. "This kind of control isn't difficult in experiments using simple stimuli like colour. But it's very challenging for more complex, realistic scenes."

Mack and Dirk Bernhardt-Walther are both professors of psychology in the department and co-authors of the study.

Traditional experiments in this field involve test subjects performing tasks such as identifying which colour or which arrangement of graphic symbols most resembles a previously viewed colour or graphic. While these methods provide some insight, their simplicity imposes a fundamental limit to what they can reveal.

The scene wheel moves into a whole new experimental realm by using highly realistic images that more closely simulate our day-to-day visual experiences -- while still providing the rigorous control needed.

The wheel is a continuous, looping series of gradually changing images depicting typical domestic spaces: dining rooms, living rooms and bedrooms. The images are detailed and realistic, and vary continuously in subtle ways: tables subtly transform into desks, mirrors become framed pictures, walls become windows, etc.

The collaborators used deep-learning methods in computer vision -- specifically, generative adversarial networks (GAN) -- to create the images and arrange them in a continuous "spectrum" analogous to a 360-degree colour wheel.

"The success of this project is all thanks to the recent revolution in deep-learning fields," says Son. "Especially in GANs which is the same sort of approach used in creating so-called 'deep fake' videos in which one person's face is very realistically replaced with someone else's."

To test whether their approach worked, the researchers had subjects view a still image of a scene from the wheel for one second, followed by a blank screen. Next, the subjects were presented with a scene similar to the one they just viewed.

The subjects then altered the second image by moving their cursor in a circle around it. As they moved their cursor, the scene changed. Subjects were asked to stop their cursor when the image matched their memory of the original image.

"With the scene wheel, we've provided a new experimental bridge that brings more of the richness of everyday experience into a controlled experimental setting," says Son. "We anticipate that our method will allow researchers to test the validity of classic findings in the field that are based on experiments using simple stimuli."

What's more, the approach could lead to different applications. For example, it could potentially lead to a wheel that uses faces instead of rooms. Such a "face wheel" could take the place of police lineups which are not particularly reliable in identifying individuals.

Says Mack, "Our method will allow for a better understanding of how precise that identification of individuals actually is."

Credit: 
University of Toronto

Traditional Japanese food may hold building blocks of COVID-19 treatments

image: Researchers from the Tokyo University of Agriculture and Technology found that an extract made from natto appears to digest the binding site of SARS-CoV-2, inhibiting the virus's ability to infect cells. More research is needed to identify the molecular mechanism of this inhibition.

Image: 
Part of Figure is adopted from Biochemical and Biophysical Research Communications Volume 570, 17 September 2021, Pages 21-25. © 2021 The Authors. Published by Elsevier Inc.

Natto, a fermented soybean dish often served for breakfast in Japan, originated at the turn of the last millennium but may hold an answer to a modern problem: COVID-19, according to a new study based on cell cultures.

Long thought to contribute to longer, healthier lives across Japan -- the country with the longest life expectancy on Earth and home to more than a quarter of the world's population aged 65 years or older -- natto was previously found to be a diet staple in those who were least likely to die from stroke or cardiac disease. Now, researchers have found that extract made from the sticky, strong smelling natto may inhibit the ability of the virus that causes COVID-19 to infect cells.

The team published its results on July 13th in Biochemical and Biophysical Research Communications.

"Traditionally, Japanese people have assumed that natto is beneficial for their health," said paper author Tetsuya Mizutani, director of the Center for Infectious Disease Epidemiology and Prevention Research at the Tokyo University of Agriculture and Technology (CEPiR-TUAT). "In recent years, research studies have revealed scientific evidence for this belief. In this study, we investigated natto's antiviral effects on SARS-CoV-2, the virus that causes COVID-19, and bovine herpesvirus 1 (BHV-1), which causes respiratory disease in cattle."

Natto is made by fermenting soybeans with Bacillus subtilis, a bacteria found in plant and in soil. The researchers prepared two natto extracts from the food, one with heat and one without. They applied the extracts to sets of lab-cultured cells from cattle and from humans. One set was infected with SARS-CoV-2, while the other set was infected with BHV-1.

When treated with the natto extract made without heat, both SARS-CoV-2 and BHV-1 lost the ability to infect cells. However, neither virus appeared to be affected by the heat-treated natto extract.

"We found what appears to be a protease or proteases -- proteins that metabolize other proteins -- in the natto extract directly digests the receptor binding domain on the spike protein in SARS-CoV-2," Mizutani said, noting that the protease appears to break down in heat, losing the ability to digest proteins and letting the virus remain infectious.

The spike protein sits on the virus's surface and binds to a receptor on host cells. With an inactive spike protein, SARS-CoV-2 cannot infect healthy cells. The researchers found a similar effect on BHV-1.

"We also confirmed that the natto extract has the same digestive effects on the receptor binding domain proteins of the SARS-CoV-2 mutated strains, such as the Alpha variant," Mizutani said.

While the results are promising, Mizutani said, he also cautioned that further studies are needed to identify the exact molecular mechanisms at work. He also stressed that the research does not provide any evidence of reduced viral infection simply by eating natto. Once the components are identified and their functions verified, the researchers plan to advance their work to clinical studies in animal models.

"Although there are vaccines for COVID-19, we do not know how they effective they may be against every variant," Mizutani said. "It will also take time to vaccinate everyone, and there are still reports of breakthrough cases, so we need to make treatments for those who develop COVID-19. This work may offer a big hint for such pharmaceutical design."

Credit: 
Tokyo University of Agriculture and Technology

Researchers discover nucleotide sequence responsible for effectively fighting pathologies

image: The pattern discovered by the researchers. Letters that grow upwards represent error-free microRNA processing, while those growing downwards represent a processing pattern with errors. The bigger the letter, the stronger the correlation.

Image: 
Nersisyan S. et al.

Researchers from HSE University have discovered nucleotide sequences characteristic of microRNA isoforms (microRNAs with errors). The discovery will help predict errors in microRNA behaviour and create drugs that can detect targets (such as viruses) more effectively. The results of the study have been published in the RNA Biology journal.

MicroRNAs (miRNAs) are very small molecules that regulate all the processes in a cell, including the transformation of inherited information in RNA or proteins (gene expression). Each microRNA has its own unique set of targets--genes whose activity it can suppress. Recent studies show that even slight changes in microRNA nucleotide sequences (so-called microRNA isoforms or isomiRs) can completely rebuild numerous targets. This can drastically alter the biological function of the molecule. However, until recently, researchers did not know why some microRNAs have isoforms, while others do not.

HSE Faculty of Biology and Biotechnology researchers Anton Zhiyanov, Stepan Nersisyan, and Alexander Tonevitsky applied bioinformatics methods to find the answer to this question. The team managed to create an algorithm that characterizes the fundamental differences between microRNAs that have isoforms and those that do not.

Their study also has important applications for the creation of artificial molecules similar to microRNAs. Dozens of research teams across the globe are currently working to solve this problem. Researchers artificially synthetize molecules that are similar to microRNAs (so-called short hairpin RNAs or shRNAs) in order to 'knock down' the gene they are interested in. In addition to having academic applications, this technology is also used in therapy to suppress 'bad' genes that cause diseases.

The authors of the study demonstrated that such artificially synthetized molecules can also have isoforms.

'Some combinations of nucleotides (AGCU, AGUU) are most often found in microRNAs where no errors occur. Combinations such as CCAG and some of its variations can predict changes and target failure with up to 70% precision. Sequencing short hairpin RNAs from our own experiments revealed that they also have isoforms. This means that it is possible to have a situation where we invent a molecule with a specific list of targets, but in practice, isoforms appear with unintended targets of their own. Our algorithm helps predict such events at the computer analysis stage without having to carry out costly experiments,' said Stepan Nersisyan, Junior Research Fellow at the HSE International Laboratory of Microphysiological Systems.

Credit: 
National Research University Higher School of Economics

Toxic facility relocation depends on community pressure

URBANA, Ill. - No one wants to live near a toxic plant. Toxic-releasing facilities such as paper, pulp, and other manufacturing plants negatively affect human health, environmental quality, and property values. And communities with lower income and educational attainment are more likely to house such facilities.

Since mandatory reporting about toxic facilities became publicly available in 1990, affected communities have increasingly expressed concern through the media, and engaged in targeted collective action and "toxic torts" lawsuits for health and environmental damages.

New research from the University of Illinois explores the effects of community pressure on the relocation of toxic-releasing facilities.

"Current studies usually focus on the question of where new plants choose to locate. Our research looks at whether facilities make relocation decisions based on the socioeconomic characteristics of the community," explains Xiao Wang, graduate student alum from the Department of Agricultural and Consumer Economics (ACE) at U of I and lead author on the paper. Co-authors include Madhu Khanna, ACES distinguished professor in ACE; George Deltas, Department of Economics at U of I; and Xiang Bi, University of Florida.

Using the Toxics Release Inventory (TRI), an environmental disclosure program that makes information about these facilities publicly available, the study looks at how much community pressure can "push and pull" facilities to relocate, thus adding to environmental injustice when they move into disadvantaged communities. This effect results in a "redistribution of pollution," the researchers note.

Information disclosure programs like the TRI help to empower communities and the public to impose pressure on facilities to improve environmental performance. However, even with the TRI available to the general public, there are imbalances across communities, due to unintended consequences of the TRI as well as more ingrained socioeconomic inequities.

"Our study finds the extent to which communities can push out toxic plants differs based on their socioeconomic characteristics. After the disclosure of toxic release information, socially disadvantaged communities were less able to do so, and this resulted in facilities moving out of communities with higher educational status and income to those with lower," Wang explains.

The researchers found that toxic-releasing facilities are more likely to move from communities with high population density, income, and education level. On the flipside, a plant is more likely to migrate into communities with lower population density, income, and education level. Furthermore, the move is often associated with the plant's growth in both size and emissions. A facility will even plan to move in anticipation of the public disclosure of the TRI and the expected community backlash.

The authors conclude that policymakers need to consider the side effects of public disclosure programs like the TRI.

"Our study shows that TRI has the effect of redistributing pollution across locations. Policy makers need to consider the potential side effect of such a regulatory tool on distributional justice and strengthen the channels for vulnerable populations to voice their concerns about facility location in addition to strengthening zoning laws and regulations," Khanna states.

Credit: 
University of Illinois College of Agricultural, Consumer and Environmental Sciences

Sandia designs better batteries for grid-scale energy storage

image: Postdoctoral researcher Martha Gross works in an argon glove box with a test battery cell illustrating a lab-scale sodium iodide battery. The Sandia National Laboratories research team developed a new sodium iodide catholyte solution (purple liquid) and a special ceramic separator to allow the molten sodium battery to operate at 230 degrees Fahrenheit (110 degrees Celsius).

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Photo by Randy Montoya/Sandia National Laboratories

ALBUQUERQUE, N.M. -- Researchers at Sandia National Laboratories have designed a new class of molten sodium batteries for grid-scale energy storage. The new battery design was shared in a paper published today in the scientific journal Cell Reports Physical Science.

Molten sodium batteries have been used for many years to store energy from renewable sources, such as solar panels and wind turbines. However, commercially available molten sodium batteries, called sodium-sulfur batteries, typically operate at 520-660 degrees Fahrenheit. Sandia's new molten sodium-iodide battery operates at a much cooler 230 degrees Fahrenheit instead.

"We've been working to bring the operating temperature of molten sodium batteries down as low as physically possible," said Leo Small, the lead researcher on the project. "There's a whole cascading cost savings that comes along with lowering the battery temperature. You can use less expensive materials. The batteries need less insulation and the wiring that connects all the batteries can be a lot thinner."

However, the battery chemistry that works at 550 degrees doesn't work at 230 degrees, he added. Among the major innovations that allowed this lower operating temperature was the development of what he calls a catholyte. A catholyte is a liquid mixture of two salts, in this case, sodium iodide and gallium chloride.

Basics of building better batteries

A basic lead-acid battery, commonly used as a car ignition battery, has a lead plate and a lead dioxide plate with a sulfuric acid electrolyte in the middle. As energy is discharged from the battery, the lead plate reacts with sulfuric acid to form lead sulfate and electrons. These electrons start the car and return to the other side of the battery, where the lead dioxide plate uses the electrons and sulfuric acid to form lead sulfate and water. For the new molten sodium battery, the lead plate is replaced by liquid sodium metal, and the lead dioxide plate is replaced by a liquid mixture of sodium iodide and a small amount of gallium chloride, said Erik Spoerke, a materials scientist who has been working on molten sodium batteries for more than a decade.

When energy is discharged from the new battery, the sodium metal produces sodium ions and electrons. On the other side, the electrons turn iodine into iodide ions. The sodium ions move across a separator to the other side where they react with the iodide ions to form molten sodium iodide salt. Instead of a sulfuric acid electrolyte, the middle of the battery is a special ceramic separator that allows only sodium ions to move from side to side, nothing else.

"In our system, unlike a lithium ion battery, everything is liquid on the two sides," Spoerke said. "That means we don't have to deal with issues like the material undergoing complex phase changes or falling apart; it's all liquid. Basically, these liquid-based batteries don't have as limited a lifetime as many other batteries."

In fact, commercial molten sodium batteries have lifetimes of 10-15 years, significantly longer than standard lead-acid batteries or lithium ion batteries.

Long-lasting batteries that are safer

Sandia's small, lab-scale sodium-iodide battery was tested for eight months inside an oven. Martha Gross, a postdoctoral researcher who has worked on the laboratory tests for the past two years, conducted experiments charging and discharging the battery more than 400 times over those eight months.

Because of the COVID-19 pandemic, they had to pause the experiment for a month and let the molten sodium and the catholyte cool down to room temperature and freeze, she said. Gross was pleased that after warming the battery up, it still worked.

This means that if a large-scale energy disruption were to occur, like what occurred in Texas in February, the sodium-iodide batteries could be used, and then allowed to cool until frozen. Once the disruption was over, they could be warmed up, recharged and returned to normal operation without a lengthy or costly start-up process, and without degradation of the battery's internal chemistry, Spoerke added.

Sodium-iodide batteries are also safer. Spoerke said, "A lithium ion battery catches on fire when there is a failure inside the battery, leading to runaway overheating of the battery. We've proven that cannot happen with our battery chemistry. Our battery, if you were to take the ceramic separator out, and allow the sodium metal to mix with the salts, nothing happens. Certainly, the battery stops working, but there's no violent chemical reaction or fire."

If an outside fire engulfs a sodium-iodide battery, it is likely the battery will crack and fail, but it shouldn't add fuel to the fire or cause a sodium fire, Small added.

Additionally, at 3.6 volts, the new sodium-iodide battery has a 40% higher operating voltage than a commercial molten sodium battery. This voltage leads to higher energy density, and that means that potential future batteries made with this chemistry would need fewer cells, fewer connections between cells and an overall lower unit cost to store the same amount of electricity, Small said.

"We were really excited about how much energy we could potentially cram into the system because of the new catholyte we're reporting in this paper," Gross added. "Molten sodium batteries have existed for decades, and they're all over the globe, but no one ever talks about them. So, being able to lower the temperature and come back with some numbers and say, 'this is a really, really viable system' is pretty neat."

The future of sodium-iodide batteries

The next step for the sodium-iodide battery project is to continue to tune and refine the catholyte chemistry to replace the gallium chloride component, Small said. Gallium chloride is very expensive, more than 100 times as expensive as table salt.

The team is also working on various engineering tweaks to get the battery to charge and discharge faster and more fully, Spoerke added. One previously identified modification to speed up the battery charging was to coat the molten sodium side of the ceramic separator with a thin layer of tin.

Spoerke added that it would likely take five to 10 years to get sodium-iodide batteries to market, with most of the remaining challenges being commercialization challenges, rather than technical challenges.

"This is the first demonstration of long-term, stable cycling of a low-temperature molten-sodium battery," Spoerke said. "The magic of what we've put together is that we've identified salt chemistry and electrochemistry that allow us to operate effectively at 230 degrees Fahrenheit. This low-temperature sodium-iodide configuration is sort of a reinvention of what it means to have a molten sodium battery."

The development of the new sodium battery was supported by the Department of Energy's Office of Electricity Energy Storage Program.

Credit: 
DOE/Sandia National Laboratories

A new model of coral reef health

image: The Global Reef Expedition provided the data needed to model and map coral reef health and resiliency across the South Pacific.

Image: 
© Keith A. Ellenbogen/iLCP

Scientists have developed a new way to model and map the health of coral reef ecosystems using data collected on the Khaled bin Sultan Living Oceans Foundation's Global Reef Expedition. This innovative method, presented today at the International Coral Reef Symposium (ICRS), can determine which natural and anthropogenic factors are most likely to lead to persistently vibrant coral and fish communities. Their findings can help scientists identify the reefs most likely to survive in a changing world.

The new models are a first step in being able to produce maps of global coral reef resilience.

To create these models, scientist Anna Bakker needed a lot of data on coral reefs from many countries across the South Pacific. She found what she needed in the data collected on the Khaled bin Sultan Living Oceans Foundation's (KSLOF's) Global Reef Expedition--a 10-year research mission that circumnavigated the globe to study the health and resiliency of coral reefs in an attempt to address the coral reef crisis. This expedition was an ambitious undertaking, involving more than 200 scientists from around the world who worked together with local experts to survey more than 1,000 reefs in 16 countries. In addition to a treasure-trove of standardized and geo-referenced data on coral cover, fish biomass, and algae, the expedition produced over 65,000 square kilometers of high-resolution marine habitat maps that KSLOF verified with data collected in the field.

"This research would not have been possible without the massive amount of field data collected on the Global Reef Expedition," said Anna Bakker, a Ph.D. student at the University of Miami's Rosenstiel School of Marine and Atmospheric Science and the lead author of the study. "The sheer amount of benthic and fish observations collected in the field from around the world enabled us to take a holistic look at indicators of coral reef health--such as coral cover or fish biomass--and figure out what drives one coral reef to be healthier than another."

Bakker pooled all of the data collected in the South Pacific--from Palau, the Solomon Islands, New Caledonia, Fiji, Tonga, the Cook Islands, and French Polynesia--into her models. She correlated fish biomass as well as coral and algal cover with dozens of natural and anthropogenic factors such as wave energy, degree heating weeks, human density, and protected areas to determine which factors were driving differences observed in the marine environment.

She found that there were only a few major factors that drove variations in the health of the coral reef community. Fish biomass was primarily driven by biophysical drivers such as water temperature. In contrast, the algal cover was driven mainly by anthropogenic factors, with significantly less macroalgae in places with more terrestrial and marine protected areas. Coral cover was more complicated and correlated with many natural and anthropogenic factors, chiefly human population, development, and water temperature.

This short list of the most important drivers can help conservationists prioritize what factors need to be addressed to protect coral reefs and identify which reefs are more likely to thrive in a rapidly changing world.

"Anna's work is an important step in the scaling of local measures of reef resilience to a global appraisal," said Sam Purkis, KSLOF's Chief Scientist as well as Professor and Chair of the Department of Marine Geosciences at the University of Miami's Rosenstiel School of Marine and Atmospheric Science.

The model results presented today covered coral reefs in the South Pacific, but future research Bakker intends to conduct will use the same modeling approach to identify the primary drivers of the health of coral reef ecosystems and the status of their fish and coral communities, and model and map the potential resilience of coral reefs in the Indian and Pacific Oceans and their associated seas.

These coral reef resiliency maps will provide marine managers with critical information on where to focus their limited time and resources to protect coral reefs. At the same time, the analysis of the primary socio-environmental factors that influence the health of coral and reef fish communities will provide conservationists with insight into what measures they can use to preserve these reefs before it is too late.

"When we embarked on the Global Reef Expedition in 2006, we had no idea our data could be used in this way. The technology to develop and run these kinds of models did not exist yet. But we knew we were collecting valuable data that needed to stand the test of time," said Alexandra Dempsey, the Director of Science Management at KSLOF and one of the authors of today's research presentation. "The Global Reef Expedition mission gave us the chance to study some of the most remote and pristine coral reefs in the world. Now, it is providing the conservation community with the information we need to identify the reefs that can be saved before it is too late to save them. Let's not waste this opportunity."

Credit: 
Khaled bin Sultan Living Oceans Foundation