Brain

Women, newborns, young children and adolescents are losing 20 percent of their health and social services due to the COVID-19 pandemic says a Panel of senior global health experts.

"Health systems in both rich and poor nations are massively struggling and the services for mothers, newborns, young children and adolescents are crumbling," says Elizabeth Mason, M.D, co-chair of the UN Secretary-General's Independent Accountability Panel (IAP) for Every Woman, Every Child, Every Adolescent reviewing the impact of COVID-19 on these groups.

"Especially worrisome are declines in access to life-saving vaccines for children and maternal health services due to closures and movement restrictions. Immunization campaigns are being halted and health workers are being diverted from maternity to COVID-19 units," Dr. Mason adds.

The Panel provides an overview of estimated impacts from COVID-19 pandemic on women, newborns, young children and adolescents since its start in January.

5.3 million deaths in children under 5 by pre-pandemic estimates, and over 400,000 additional deaths due to COVID-19-related disruptions in services.

2.5 million newborn deaths pre-pandemic, with a minimum of 168,000 additional deaths estimated.

295,000 maternal deaths pre-pandemic, with an additional 24,400 additional deaths estimated.

13.5 million children missed vaccinations against life-threatening diseases.

More than 20 countries reported vaccine shortages caused by the pandemic.

Disruption to contraceptive supplies leading to 15 million unintended pregnancies among women and adolescent girls in low- and middle-income countries.

‘Backdoor’ legislation being pushed through that adversely affects the sexual and reproductive health and rights of women and adolescents

Around 42-66 million children risk falling into extreme poverty.

Some 370 million children are missing school meals.

Adolescents facing increasing social isolation and mental health challenges

Women disproportionally suffering increased depression, anxiety and uncertainty.

15 million additional acts of violence against women and girls every three months of lockdown. In some countries, emergency calls increased by 30 percent.

"These new findings show how weak our health systems are at protecting mothers, newborns, young children and adolescents," says Joy Phumaphi, co-chair of the Panel and former WHO Assistant Director-General. "We are at a point where decades of progress for this group could be easily reversed."

The COVID-19 pandemic has interrupted steady progress and has led to increased poverty and unemployment. Early data finds women experience not only loss of various categories of support and social safety nets, but also an inability to access increased support, compared to men.

"COVID-19 is making a bad situation worse," says Ms. Phumaphi, reflecting the conclusion of the Panel's report (at https://bit.ly/2ZPuTfH).

“The lives’ of every mother, newborn, child and adolescent matter,” says Giorgi Pkhakadze, a professor of Epidemiology and Public Health, David Tvildiani Medical University, Georgia. “Quality healthcare is not a luxury, but a life-saving resource.”

Since 2000, maternal and children under 5 deaths have been cut by 40 percent, because of focused leadership and investment, even in the poorest nations. Also, in the last decade, more than $50 billion has been raised through the Every Woman Every Child movement to meet the health and medical needs of this vulnerable group. Even the poorest countries have shown progress, especially in reducing under 5 mortality.

The Scorecard

To understand and analyze the basic needs and gaps for mothers, newborns, young children and adolescents by country, the Panel has created a Scorecard for 193 nations, by income category, of seven key indicators (see the full Scorecard at https://bit.ly/38xi4KJ):

Maternal mortality ratio (per 100,000 live births)

Stillbirth rate (per 1,000 total births)

Neonatal mortality rate (per 1,000 live births)

Under-5 mortality rate (per 1,000 live births)

Adolescent mortality rate (per 100, 000 population)

Birth registration (proportion of children under 5 years with civil authority registered births)

Death registration (completeness of cause-of-death data)

Each indicator for the 193 countries is colour-coded to depict a country's current status relative to global/country targets: dark green for surpassed, light green for advanced, yellow for intermediate, and red for catching-up countries.

"The colour-coding makes it easy to pick out the countries where mothers, newborns, young children and adolescents are thriving and countries where they need help," says Dr. Nicholas Alipui, M.D., a visiting scholar at Yale University and former UNICEF Director of Programmes.

Countries with all dark green surpassed in all seven categories are Finland, Iceland, Slovenia, Luxembourg, Japan, Norway, Estonia Sweden, Italy, Spain, Czechia, Austria, Belgium, Ireland, Germany, Australia, Israel, Portugal, Netherlands, France, Switzerland, Denmark, United Kingdom, Hungary, Poland, Greece, Croatia, Canada, Slovakia, Malta, Bahrain, Belarus, Cuba, Republic of North Macedonia.

Countries that are all dark green, surpassed global targets - except for a light green, advanced ranking for adolescent deaths are: Latvia, Lithuania, New Zealand, United States, Uruguay, Seychelles, Bulgaria, Russian Federation, Romania, Costa Rica, Georgia, Kazakhstan

Countries that are mainly red, catching up are Mauritania, Cameroon, Angola, Lesotho, Côte d'Ivoire, Nigeria, Guinea Bissau, the Democratic Republic of the Congo, South Sudan, Sierra Leone, Central African Republic, Chad, Somalia.

The gap between rich and poor countries is huge. For example: Under 5 mortality rate (per 1,000 live births): Finland -1.7, Iceland and San Marino -2, Slovenia 2.1, Cyprus and Luxembourg -2.4, and Japan -2.5. That compares to the Central African Republic -116.5, Chad -119, Nigeria -119.9, and Somalia -121.5.

On maternal mortality ratio (per 100,000 live births): Norway, Italy, Poland and Belarus - 2, Finland, Czechia, Greece and United Arab Emirates -3. That compares to Nigeria - 917, Sierra Leone -1,120, Chad -1,140 and South Sudan -1,150.

Ethnic minority communities even in the wealthiest countries have large disparities of both morbidity and mortality. A number of factors create disparities: racism, low wages, limited opportunities, and poor education. This exacerbates poor health, lack of access to health, water and sanitation.

Women, children and adolescents in countries with access to similar economic resources sometimes experience different health outcomes. For example, the United States spends more than twice as much on health than either Japan or France, yet children in the US are more likely to die before their 5th birthday and women are more than twice as likely to die in childbirth.

Another example: Nigeria spends around 74 USD per capita on health, compared to 34 USD in Tanzania. However, Nigeria has more than double the child mortality rate compared to Tanzania, 120 and 53 deaths per 1,000 live births, respectively. This reflects significant inequalities and other disparities.

"Critical gaps in quality health service delivery and financial protection require urgent remedy and action," says Dr. Alipui. "These gaps are found between countries and within countries."

Losing ground

Besides the loss of services due to the pandemic, IAP has found that globally implementation is 20 percent behind on the UN's 2030 goals (Every Woman Every Child - the Global Strategy for Women's, Children's and Adolescent's Health 2016-2030) to reduce preventable deaths for mothers, newborns, young children and adolescents.

The UN goals include:

  Maternal deaths- a global decline to less than 70 deaths per 100,000 live births.

Newborn deaths- each country reduces to at least as low as 12 deaths per 1000 live births.

Children under 5 deaths - each country reduces to at least as low as 25 deaths per 1000 births.

More than 190 countries have agreed to these targets.

The IAP's 2020 report, published this week, calls for leaders to fulfill their commitments and lays out the action needed to get back on track. Commitments to universal health coverage, primary health care, International Health Regulations and sustainable development, were urgently needed before the pandemic. Now with COVID-19, they are even more important.

About 2 USD trillion a year lost due to inefficiencies, corruption and waste

Besides the 20 percent deficit, the Panel found that 2 trillion USD a year is lost to health expenditures, due to inefficiencies, corruption and waste.

"How money is spent is every bit as important as how much is spent to improve health and socioeconomic benefits," points out Ms. Phumaphi. "The key is full accountability which connects commitment to progress."

"A key element to sustainable progress is strong citizen voices which advocate for full accountability at all levels, community, state and national," says Dr. Alipui.

"Mass protests clamouring for racial justice in both health and policing in the United States and around the globe have laid bare how central accountability is to achieving justice and a fairer world," explains Alicia Ely Yamin, LLD and a senior fellow in global health and rights at Harvard Law School. 

The seven big "Lacks"

There are still a host of basic problems blocking advancement of the health of mothers, newborns, young children and adolescents. These "lacks" relate to commitments that world leaders have made at the highest level. The UN's Sustainable Development Goals, High-level Political Declaration on Universal Health Coverage and the Every Woman Every Child Global Strategy are examples of commitments at the highest level, and yet these gaps persist.

1. Health workers. The world needs an additional 18 million health workers.

2. Health Data. Data emerging from countries on COVID-19 has been incomplete.

Estimates and projections based on modeling to assess country risks and progress on COVID-19 and the health of mothers, newborns, young children and adolescents vary widely. Thus, outcomes end up patchy. The lack of relevant and accurate data constrains governments' abilities to make informed decisions to ensure people's health and wellbeing of this vulnerable group.

Often, simple information has not been collected. Globally, one in 4 births of children under five are not registered with a civil authority; only 93 out of 193 countries are currently able to register more than 80 percent of adult deaths.

3. Accountability. Accountability is a must-have, not a nice-to-have. It must be permanently embedded so that every leader and every government is obliged to do what they have committed to do. Private sector and development partners should 'do no harm' and provide assistance and technical cooperation to help countries make progress on health targets. Citizens need to participate fully and voice their experiences.

"Accountability connects commitments to progress in a justifiable and constructive way," says Shyama Kuruvilla, Ph.D. who directs the Panel's secretariat. "As the Panel's report shows, accountability is critical to accelerate improvement."

For the accountability cycle to work, a formal, institutionalized relationship is needed between the monitoring, review and recommendations, and the remedy and action that follows.

By investing in institutionalizing accountability processes, countries can increase their capacity to apply lessons rapidly and effectively during and after events such as the COVID-19 pandemic and to rectify and remedy problems.

4. Underinvestment in common goods for health. Common goods for health (such as for legislation and regulation, health surveillance and information, population services, and communication) form the foundation for strong health systems that are resilient and responsive, not only to population health needs but also to emergencies. The lack of these critical investments in public goods for health, both national and international, have shown up in the fault lines of the COVID-19 response with millions of people's lives, health and livelihoods put at risk, especially mothers, newborns, young child and adolescents.

5. Universal Health Coverage and Primary Health Care. On the path to universal health coverage (quality health services and financial protection), only between one-third and one-half of the world's population were covered by the essential health services they need, including interventions for women, children and adolescents. More than 900 million people experienced catastrophic health expenditure last year. One of the smartest investments that countries can make is in primary health care. Investing an additional 200 billion USD a year on scaling up primary health care across low- and middle-income countries could save 60 million lives and increase average life expectancy by 3.7 years by 2030 and contribute significantly to socio-economic development.

6. Progress across other sectors, e.g. water, sanitation and hygiene. From 2000 to 2017, the population using safely managed sanitation services increased from 28 percent to 45 percent. Though 60 percent of the global population has basic hand-washing facilities with soap and water available at home, 3 billion people still lack such facilities and 1.4 billion had no facilities at all. The United Nations warns that the risk of disruption to these services from lockdowns endangers health, especially from waterborne diseases, and the containment of COVID-19.

7. Inequities are a critical concern. There are gaping gaps between rich and poor, and racial discrimination, geographical and other factors limit access to services. Capital regions often have higher coverage of basic health and multisectoral services than other sub-regions demonstrating sub-national inequalities. Inequities will worsen from the COVID-19 pandemic, compounded by lack of financial and social protection, and the most vulnerable, including women, children and adolescents would be hardest hit.

Osaka, Japan - Mesenchymal stem cells (MSCs) have the potential to differentiate into a range of different cell types, including bone, fat, and muscle cells. But it's their ability to stimulate the repair of damaged tissue that has captured the interest of researchers worldwide, with MSCs demonstrating therapeutic effects in the treatment of conditions such as heart disease, liver cirrhosis, and diabetes.

However, despite the success of several clinical trials, researchers have struggled to explain the sometimes variable results of MSC therapy.

In a recent study published in Molecular Therapy, a research team led by Osaka University investigated possible reasons for the inconsistent outcomes of MSC therapy, showing that host factors and not just the MSCs themselves may be to blame.

"We recently reported that adiponectin, a beneficial hormone secreted by fat cells that plays a role in muscle regeneration, binds to receptor protein T-cadherin on cell surfaces," explains lead author Yuto Nakamura. "Given that T-cadherin is abundant on the surfaces of MSCs, we investigated whether adiponectin is involved in the regenerative activity of MSCs in a model of heart failure."

Adiponectin is found in high concentrations in blood and has been shown to stimulate the production of exosomes, small membrane-bound vesicles that carry proteins, lipids, and DNA between cells. Interestingly, exosomes secreted by stem cells carry signals that stimulate the repair of recipient cells.

By first measuring exosome production in a cell culture-based system, the researchers confirmed that increasing amounts of adiponectin led to a corresponding increase in the abundance of MSC-derived exosomes, which was reliant on the expression of T-cadherin.

Injection of the MSCs into mice suffering from heart failure resulted in a significant improvement in left ventricular cardiac function, which was associated with the increased number of exosomes in circulation. Most importantly though, cardiac function following MSC therapy could be further strengthened by the increases of adiponectin level in blood.

"Together, our assays showed that MSCs exert their therapeutic effects on cardiac function through the production of exosomes, which is influenced by host plasma adiponectin levels and is reliant on MSC T-cadherin expression," says study corresponding author Shunbun Kita.

"Given these results, drugs such as a PPARγ agonists, which increase adiponectin production, could be administered in combination with MSC therapy to significantly enhance the therapeutic potential—not only for severe heart failure, but also for a variety of diseases involving tissue damage, including COVID-19-associated acute respiratory distress syndrome."

And in case you were wondering, it turns out that too much fat is actually detrimental to adiponectin production, so doctors won't be prescribing a high fat diet any time soon!

Due to border closures in the wake of the corona crisis, the arrival of refugees in Europe has temporarily dipped. However, worldwide numbers of refugees have surged, again, within a year, driven by violence, war, persecution, economic hardship, or climate change. In the foreseeable future, many refugees will not be able to return to their homes. The integration of refugees in receiving countries is the most promising and decent response to this situation. Yet, how such integration can be achieved remains an open issue and ongoing challenge. What are the potential barriers to integration among refugees and residents in receiving countries? How can the different needs, feelings, and concerns of these groups be balanced and conflicts be resolved?

Psychologists at the University of Münster (Germany) have developed a model of the psychological factors that are critical for successful integration of refugees. The model, running under the acronym PARI (Psychological Antecedents of Refugee Integration), takes into account the perspectives of both refugees and members of the receiving society. The researchers have published their model in the journal "Perspectives on Psychological Science".

About the model

The PARI model was developed by Gerald Echterhoff, Jens Hellmann, Mitja Back, Joscha Kärtner, Nexhmedin Morina and Guido Hertel from the Institute of Psychology at Münster University. The authors consider distinctive features of refugee migration: being forced to leave one's home country, associated with various perils and risks to one's safety and wellbeing. What matters from a psychological perspective is the subjective perception of being forced to migrate rather than the "objective" circumstances of migration or the legal conditions of being granted refugee status. "From a psychological point of view, refugees experience external pressures that force them to migrate. As a result, they see migration as being imposed on them, leaving no alternative," explains Dr. Jens Hellmann.

According to the PARI model, the characteristics of forced migration trigger predictable responses in both refugees and members of the receiving society, revealing a specific psychological signature of reactions to refugeehood. For instance, the stress and perils of migration can strengthen refugees' need for integration in a safe receiving country. However, the feeling of losing control, the role of being a needy victim, or coping with traumatic memories can restrict mental resources needed for adaptation and integration.

Residents' responses to the distinctive characteristics of refugee immigration can also tilt towards the positive or negative side: "On the one hand, the perception of forced migration and its associated perils can strengthen residents' empathy for immigrants who come as refugees. On the other hand, these perceptions can also induce residents to experience increased feelings of threat and lack of control," says lead author Prof. Gerald Echterhoff.

Tsukuba, Japan - Researchers at the University of Tsukuba used advanced metrics from information theory to describe the collective behavior of small schools of ayu fish. They found that the overall dynamics were noticeably different for groups of three or more, compared with smaller groups, even over very short timescales. This work may help shed light on fundamental problems in complexity theory and assist in the development of cooperative biomimetic swarming robots.

Some of the most difficult questions in science today deal with the same fundamental question: How can complex dynamics arise from simple, local interactions? For example, schools of fish and flocks of birds can move and turn in near perfect synchrony without any top-down control from a leader. To try to make progress on this question, integrated information theory (IIT) has been used to provide a mathematical framework for measuring how information passes back and forth from individuals to the group as a whole.

A team including Professor Takayuki Niizato at the University of Tsukuba studied the swimming of Ayu, which are small fish related to smelts. Ayu were randomly chosen and placed in a tank in groups of 2, 3, 4, or 5 fish.

Explains Professor Niizato, "The trajectory of each fish was tracked, and a computer calculated three binary parameters for every fish at each time step. These parameters were as follows: if the subject fish was close to another fish, if the fish was turning, and if another fish was in its field of view. We found that, over times ranging from 40 milliseconds to one second, a grouping of three fish acted very differently than a pair."

In this study, "integrated information" quantified the extent to which the cause and effect in a system can be explained by the repertoires of its components. And "integrated conceptual information" was used as an expression of the fish school's group collective action, roughly how much the behavior of individual members is dependent on the behavior of the group.

"The aim of IIT is to try to shift the paradigm from 'what a system does' to 'what a system is.' The former tries to analyze the system on the basis of observable behavior, while the latter tries to determine its intrinsic causal structure," says Professor Niizato.

This work may help make inroads in some truly difficult questions surrounding group dynamics that emerge naturally when simple components join to form a complex group. This may also aid in the development of "swarming" robots that, like schools of fish or ant colonies, make use of this principle to achieve complicated goals.

The science community should withdraw from involvement in international tests such as PISA because they have forced schools to adopt "narrow" curricula and pedagogies, a study says.

Researchers examining the future of science lessons post-covid have also urged teachers and educators to develop a new focus on the environment and health. They have argued children need to learn more about the complexities of research in lessons to improve scientific literacy.

The study, by Professor Justin Dillon from the University of Exeter and Dr Lucy Avraamidou from the University of Groningen, says international tests, and PISA, in particular, have "failed to provide adequate information about scientific literacy in any useful shape or form". The researchers argue their influence has forced many school systems to adopt "reductionist curricula and a narrow range of pedagogies".

Professor Dillon said: "We want to stimulate the development of science education in the post-pandemic era, to invite our community to engage with pressing issues with the curriculum and assessment. It is of paramount importance that social justice is used to shape a vision for science education in the post-pandemic era. Failure to do this will only serve as a way of perpetuating existing inequalities.

"During the pandemic science and scientists find themselves in the spotlight as both potential saviours or as untrustworthy puppets in ways that would have been unthinkable a year ago. Yet science education and science educators are invisible."

The researchers argue in the Journal for Activist Science & Technology Education that science lessons currently emphase facts, while the processes of science is more similar to a "black box". They say students are rarely taught about the key processes of scientific research which go on to save lives.

Professor Dillon said: "At school pupils earn science is logical, empirical, and a reliable enterprise carried out by highly trained and trustworthy people. This is not always the case, but children do not question it. The result is, although the public has high trust and confidence in science and believes that science provides great benefits to the world, many people continue to deny the conclusions of science in areas such as evolution, climate change and vaccination. Too many people are not functionally scientifically literate. What scientists do, what kinds of data they collect and how they analyze those data to form conclusions, remain a mystery for most young people."

The study says teachers need to be in a position to switch quickly to an "accessible, inclusive, equitable, and engaging" science education online with support for parents and carers, because currently teachers do not seem to be learning anything systematically about what works in terms of taking schools online. Researchers say being forced to explore the potential of various technologies and digital tools for teaching and learning might serve as an awakening to the possibilities of the private sector and industry in sponsoring educational research and forming of industry-university coalitions.

With the advent of super-resolution microscopy, scientists can study close protein associations better than ever before. In the latest edition of eLife, the team of Wim Annaert (VIB-KU Leuven) combines state-of-the-art imaging techniques to investigate the distribution of γ-secretase, a protein complex associated with both Alzheimer's disease and cancer.

γ-Secretase is a transmembrane enzyme complex consisting of four different protein subunits. It has received a lot of research attention because of its link to Alzheimer's disease and cancer but because of a lack of resolution, it has for long been difficult to directly visualize protein associations within and between these complexes.

"While enormous progress has been made in the past years to unveil γ-secretase protein structure at atomic resolution, we were still lacking direct visual evidence on its distribution in membranes of living cells," says prof. Wim Annaert from the VIB-KU Leuven Center for Brain & Disease Research.

His team studies the molecular biology of membrane transport in health and disease, and took advantage of advances in super-resolution microscopy to analyze the distribution of γ-secretase complexes.

Visualizing single γ-secretase complexes

"Given the diffraction limit of light, conventional microscopy is limited to ~200 nm lateral resolution, which means that proteins that are closer together cannot be distinguished from one another," explains Abril Escamilla-Ayala, PhD student in the lab of Annaert. "This dramatically changed with the introduction of super-resolution and quantitative microscopy. Now we can really look at subcellular structures in close up, and study the nano-scale distribution of single proteins and complexes in their native context."

The team used complementary imaging strategies to show--for the first time-- the stoichiometry of the γ-secretase complex while embedded in its natural environment. They found that the majority of the complexes present at the cell surface are either monomers or dimers, whereas higher order assemblies are rare.

Hotspots

Secretases--such as γ-secretase--trim pieces off other proteins embedded in the cell membrane. Annaert and his team looked at associations between γ-secretase and two of its substrates (the amyloid precursor protein and N-cadherin) and between γ-secretase and two other secretases (ADAM10 and BACE1). They detected associations within 100 nm distance between γ-secretase and its substrates, but not other secretases--although there were dynamic hotspots for secretase recruitment.

"In contrast to earlier studies, our findings do not support the notion of so-called mega-associations of γ-secretase with other secretases. Rather, our findings suggest that 'hotspots' are frequented transiently by different secretases," says Annaert. Interestingly, treatment with γ-secretase inhibitors resulted in a decrease in hotspots.

The findings highlight the power of super-resolution microscopy for the study of γ-secretase distribution and dynamics in the membrane in real-time. When it comes to its role in Alzheimer's disease, Annaert believes that nanoscale resolution studies will be the way forward: "Characterizing the distribution, associations and dynamics of the enzyme complex at neuronal contact sites will give a much more detailed insight on the molecular mechanisms driving the disease.

Publication

Super-resolution microscopy reveals majorly mono- and dimeric presenilin1/γ-secretase at the cell surface, Escamilla-Ayala et al. eLife 2020

Questions from patients

A breakthrough in research is not the same as a breakthrough in medicine. The realizations of VIB researchers can form the basis of new therapies, but the development path still takes years. This can raise a lot of questions. That is why we ask you to please refer questions in your report or article to the email address that VIB makes available for this purpose: patienteninfo@vib.be. Everyone can submit questions concerning this and other medically-oriented research directly to VIB via this address.

KAIST researchers have used an X-ray method to track how proteins fold, which could improve computer simulations of this process, with implications for understanding diseases and improving drug discovery. Their findings were reported in the Proceedings of the National Academy of Sciences of the United States of America (PNAS) on June 30.

When proteins are translated from their DNA codes, they quickly transform from a non-functional, unfolded state into their folded, functional state. Problems in folding can lead to diseases like Alzheimer's and Parkinson's.

"Protein folding is one of the most important biological processes, as it forms the functioning 3D protein structure," explained the physical chemist Hyotcherl Ihee of the Department of Chemistry at KAIST. Dr. Tae Wu Kim, the lead author of this research from Ihee's group, added, "Understanding the mechanisms of protein folding is important, and could pave the way for disease study and drug development."

Ihee's team developed an approach using an X-ray scattering technique to uncover how the protein cytochrome c folds from its initial unfolded state. This protein is composed of a chain of 104 amino acids with an iron-containing heme molecule. It is often used for protein folding studies.

The researchers placed the protein in a solution and shined ultraviolet light on it. This process provides electrons to cytochrome c, reducing the iron within it from the ferric to the ferrous form, which initiates folding. As this was happening, the researchers beamed X-rays at very short intervals onto the sample. The X-rays scattered off all the atomic pairs in the sample and a detector continuously recorded the X-ray scattering patterns. The X-ray scattering patterns provided direct information regarding the 3D protein structure and the changes made in these patterns over time showed real-time motion of the protein during the folding process.

The team found cytochrome c proteins initially exist in a wide variety of unfolded states. Once the folding process is triggered, they stop by a group of intermediates within 31.6 microseconds, and then those intermediates follow different pathways with different folding times to reach an energetically stable folded state.

"We don't know if this diversity in folding paths can be generalized to other proteins," Ihee confessed. He continued, "However, we believe that our approach can be used to study other protein folding systems."

Ihee hopes this approach can improve the accuracy of models that simulate protein interactions by including information on their unstructured states. These simulations are important as they can help identify barriers to proper folding and predict a protein's folded state given its amino acid sequence. Ultimately, the models could help clarify how some diseases develop and how drugs interact with various protein structures.

Populations around the world are living longer lives than was the norm just a few decades ago, presenting governments with significant challenges in terms of caring for their growing elderly populations. According to a new study published in PLOS ONE, understanding how to assess who is elderly is a crucial first step for our understanding of population aging.

The UN's Profiles of Ageing 2019 provides people who study population aging with a choice of perspectives, namely a conventional potential support ratio (PSR) and a prospective potential support ratio (PPSR). The difference between the two is based on different threshold ages at which people are first seen as "old". In the PSR the threshold age is 65 years and is fixed independently of time or place, while in the PPSR, the threshold age is the age where remaining life expectancy is 15 years. The first is commonly known as the conventional old age threshold and the second as the prospective old age threshold. The conventional old age threshold is the most commonly used, but it has the disadvantage that it does not change over time and is the same for all countries regardless of their trajectories of aging. This is of course not the case, as today's 65 year-olds are very different from their counterparts half a century ago, and are also likely to be very different from what they will be like half a century in the future. People also age differently depending on where they live and across population subgroups.

In their study, the authors propose that the old age threshold should be determined using an equivalency criterion - in other words, people at the old age threshold should be roughly similar to one another in terms of relevant characteristics regardless of when and where they lived. Using historical data on five-year death rates (the proportion of people dying between ages x and x+5) at the old age threshold as an indicator of one aspect of health, the researchers assessed the extent to which the two approaches used by the UN are consistent with the equivalency criterion. The results indicate that the old age threshold based on a fixed remaining life expectancy is consistent with the equivalency criterion, while the old age threshold based on a fixed chronological age is not. Specifically, five-year death rates at the old age threshold based on a fixed chronological age strongly decline over time, while the one based on a fixed remaining life expectancy is almost constant.

This implies that if the equivalency criterion were not at least approximately adhered to, people with a particular five-year death rate in one country would be categorized as old, while people in another country with the same five-year death rate would not be. The study is based on previous research by the authors in which they developed measures of population aging adjusted for changes in remaining life expectancy - a so-called dynamic old age threshold - and provides additional arguments around why it would be beneficial to use such measures of aging. They highlight that when this dynamic old age threshold is used to study people in many countries over long periods of time, at that threshold, people have roughly the same health.

"We wanted to provide researchers with a solid argument around why measures of aging based on a fixed remaining life expectancy should be used and how similar groups of older people should be defined. We want people to understand that the use of an old age threshold based on a fixed chronological age does not produce groups of adults whose relevant characteristics are comparable across time and space. The equivalency criterion is effective in making that decision because it defines who is elderly in a consistent way based on characteristics relevant to the study of population aging," explains IIASA researcher and study author Warren Sanderson.

"The picture of population aging that emerges when measures consistent with the equivalency criterion are used are markedly different from those that result when the equivalency criterion is not adhered to. We recommend that measures of aging that do not adhere to the equivalency criterion should only be used in special circumstances where it is inconsequential," concludes study author Sergei Scherbov, a researcher in the IIASA World Population Program.

Coral death is impacting oceans worldwide as a consequence of climate change. The concern is that corals cannot keep pace with the rate of ocean warming. In particular, because a temperature increase of only one degree Celsius can make the difference between healthy and dying coral reefs. Some corals, however, are more resistant to increasing temperatures. In order to effectively protect coral reef habitats, it is important to identify which corals and reef sites are more resistant and thus have a greater chance of survival.

For this purpose, the research team led by Konstanz biologist Professor Christian Voolstra developed a rapid stress test to assess coral thermotolerance. The "Coral Bleaching Automated Stress System" (CBASS) makes it possible to assess coral thermotolerance on site and within a single day - much faster than current experimental procedures that typically take several weeks to months in a laboratory. A description of the test and a demonstration of its utility to resolve thermotolerance differences between close-by reef sites was published as an online early article on 21 June 2020 in the journal Global Change Biology.

The test system is highly mobile, can be deployed on boats, and is straightforward to use: Corals are placed in test boxes at the location where they were collected and then subjected to thermal exposures at different temperatures - a type of stress test for the corals. Using a standardized procedure, researchers can then record the results and compare how different corals react to the same set of temperature exposures.

"We focused on building the test boxes with materials that are available in almost any hardware store or shop selling aquarium equipment. We want these test boxes to be used widely and this is why we made all instructions for setting up the tests as well as our results and evaluation methods freely available", Professor Christian Voolstra states in reference to the online archive: https://github.com/reefgenomics/CBASSvsCLASSIC

Read the full article in campus.kn, the online magazine of the University of Konstanz: https://campus.uni-konstanz.de/en/science/stress-testing-coral-in-a-box

The key components of electrical connections between light receptors in the eye and the impact of these connections on the early steps of visual signal processing have been identified for the first time, according to research published today in Science Advances by The University of Texas Health Science Center at Houston (UTHealth).

To understand fully how the light receptors, called photoreceptors, impact the early stages of the process of vision, researchers have traditionally focused their attention on how two key sensory cells - rods and cones - convert elementary particles of light into electrical signals and how these signals are relayed to the brain through devoted circuits. Rods are used for night vision and cones are used for daytime and color vision. While it has been known for some time that electrical signals can spread between photoreceptors through cell connectors called gap junctions, the nature and function have remained poorly understood.

"This research will lead to a better understanding of how the retina processes signals from the rods and the cones in the eyes, in particular under ambient lighting conditions when both photoreceptor types are active, such as at dawn and dusk. This knowledge is currently missing and may have to be taken into consideration when designing photoreceptor or retinal implants to restore vision," said Christophe P. Ribelayga, PhD, co-lead author of the study and associate professor and Bernice Weingarten Chair in the Ruiz Department of Ophthalmology & Visual Science at McGovern Medical School at UTHealth.

Co-lead author Steve Massey, PhD, is professor, Elizabeth Morford Chair, and research director in the Ruiz Department of Ophthalmology & Visual Science at McGovern Medical School at UTHealth.

The coupling - or communication - between rods and cones in the retina is critical for understanding how the visual signaling process works.

What the researchers discovered, to their surprise, is that rods do not directly communicate with other rods and cones seldom communicate directly with other cones. Instead, the majority of signaling happens through communication between rods and cones. Researchers identified a specific protein called connexin36 (Cx36) as the main component of rod/cone gap junctions.

"We noted that every single rod has electrical access to a cone and that cone/cone gap junctions are very rare," Massey said. "We estimated that more than 95% of all gap junctions between photoreceptors are rod/cone gap junctions; they have the largest volume and the largest conductance. So, rod/cone gap junctions dominate the network of photoreceptors both in size and number."

To help researchers better understand how the photoreceptor network is organized, they developed genetic mouse strains for the work that were bred to eliminate gap junctions in either rods or cones.

"Our study has important implications," said Ribelayga. "Our data position rod/cone gap junctions as the keystone of the photoreceptor network. The rod/cone gap junction is the entry of a rod pathway through which signals of rod origin can travel across the retina. We have thus generated mice that are essentially deficient for the entry of this pathway. In future experiments, we will use these animals to determine the functional importance of the rod/cone pathway in the retinal processing of rod signals and for vision."

In 2018, researchers in the Ruiz Department of Ophthalmology & Visual Science received more than $4 million in grants from the National Institutes of Health's National Eye Institute to study photoreceptor development, function, and electrical interactions. Ribelayga and Massey led the effort to lay out the architecture of the network of electrically coupled receptors, a critical step toward a better understanding of how photoreceptors encode light signals and how the retina processes these signals.

Planar cell polarity (PCP), a process in which the epithelial tissues are polarized within the plane of the epithelium, plays an important role in development and organ function. Defects in PCP are associated with a variety of human diseases including cancer metastasis, neurological disorders, skeletal dysplasias and congenital heart disease. The establishment of PCP is regulated by an evolutionarily conserved set of signaling proteins. After their synthesis, many of these PCP proteins are delivered along the secretory transport pathway to the cell surface, where they perform their physiological functions. However, the molecular mechanisms that regulate PCP protein transport remain largely unclear.

In the secretory transport pathway, newly synthesized transmembrane PCP proteins are firstly translocated into an intracellular organelle called the endoplasmic reticulum (ER), where they are folded and modified. These proteins are then packaged into transport vesicles mediated by the COPII machinery. These transport vesicles function as vehicles to deliver their cargo proteins to the next station, the Golgi apparatus, en route to the cell surface. Movie 1 demonstrates surface delivery of newly synthesized epidermal growth factors receptor (EGFR) in this pathway1.

Prof Guo and his collaborators discovered that a polybasic motif located on Frizzled-6 directly interacts with the E62 and E63 residues on an important component in the COPII machinery, Sar1A. This novel protein interaction is critical for exporting Frizzled-6 out of the ER, the first step in the secretory transport pathway. In addition, the study indicates that association of another PCP protein, CELSR1, with Frizzled-6 is important, enabling efficient Frizzled-6 delivery to the cell surface, providing a quality-control mechanism that ensures appropriate stoichiometry of these two PCP proteins at cell surface.

These studies uncover novel insight into the molecular machinery that regulates ER export of Frizzled-6. Activation of PCP pathway plays important roles in cancer metastasis. Currently, there is no effective therapeutic strategy to specifically downregulate PCP pathway. PCP proteins need to be located on cell surface to regulate PCP. Prof Guo's study provides important information to guide the rational design of inhibitors to block SAR1A/Frizzled6 interaction to inhibit the surface delivery process, offering a novel therapeutic strategy to downregulate PCP signaling for cancer treatment.

Older adults with both hearing and visual impairments--or dual sensory impairment--had a significantly higher risk for dementia in a recent study published in Alzheimer's & Dementia: Diagnosis, Assessment & Disease Monitoring.

In the study of 2,051 older adults (22.8% with hearing or visual impairment and 5.1% with both impairments) who were followed over eight years, dual sensory impairment was associated with an 86% higher risk for dementia compared with having no sensory impairments. During follow-up, dementia developed in 14.3% in those with no sensory impairments, 16.9% in those with one sensory impairment, and 28.8% in those with dual sensory impairment.

Participants with dual sensory impairment were also twice as likely to develop Alzheimer's disease (the most common form of dementia) than those without sensory impairments.

"Evaluation of vision and hearing in older adults may predict who will develop dementia and Alzheimer's. This has important implications on identifying potential participants in prevention trials for Alzheimer's disease, as well as whether treatments for vision and hearing loss can modify risk for dementia," said lead author Phillip H. Hwang, of the University of Washington.

Increasing the levels of a chemical found in all human cells could boost a woman's fertility and help select the best eggs for IVF, according to University of Queensland research.

In the world's most in-depth study of the final steps of egg maturation, the quality of a woman's eggs was found to be significantly dependent on the important metabolic coenzyme called nicotinamide adenine dinucleotide (NAD+).

UQ Centre for Clinical Research scientist Professor Hayden Homer said NAD+ helps to ensure that eggs retain the bulk of their cellular building blocks as they mature.

"NAD+ is a critical coenzyme found in every cell in your body, and it's involved in hundreds of metabolic processes, but levels decline with age," Professor Homer said.

"Egg quality declines relatively early, from the age of 30 years onwards, making it increasingly difficult to get pregnant.

"If we can maintain steady levels of NAD+ we may improve a woman's chances of getting pregnant both naturally and through IVF."

Professor Homer said an increasing number of women have to resort to IVF to have children due to delays in childbearing.

Around four per cent of all children born in Australia are the result of IVF - that's the equivalent one child in every average sized classroom.

The success rates of IVF significantly drops from 35 per cent in patients under 30 years old to just eight per cent for women over 40 years of age.

However, a quarter of Australian women undergoing IVF are over the age of 40.

Professor Homer's research team made the discovery by studying the motion of spindles, the structure that pulls chromosomes apart, in living eggs undergoing maturation.

The four-year project consisted of undertaking high-resolution time-lapse imaging of live eggs lacking the NAD+ biosynthetic enzyme - Nampt.

They tracked the speed of spindles during the final stages of egg maturation and found that a "burst" of speed dependent upon NAD+ is required to prevent the egg from losing too much of its building blocks.

"With technological advances, this work will bring us closer to being able to select the best eggs for IVF treatment and to improving egg quality," Professor Homer said.

Researchers at CRANN and the School of Physics at Trinity College Dublin have created an innovative new device that will emit single particles of light, or photons, from quantum dots that are the key to practical quantum computers, quantum communications, and other quantum devices.

The team has made a significant improvement on previous designs in photonic systems via their device, which allows for controllable, directional emission of single photons and which produces entangled states of pairs of quantum dots.

Qubits and the promise of quantum computing

The promise of quantum computers leverages the properties of quantum bits - "qubits" - to execute computations. Current computers process and store information in bits of either 0s or 1s whereas qubits can be 0 and 1 simultaneously. That means quantum computers will have much greater computational powers over and above classical computers.

Scientists are exploring different options and designs to make quantum computing a viable reality. One proposed idea utilises photonic systems, making use of quantum properties of light at the nanoscale, as qubits. The Trinity team explores such a system in their recently published paper in the high-profile journal Nano Letters.

Their system utilises single photons of light emitted in a controlled fashion in time and space from quantum emitters (nanoscale materials known as quantum dots). For applications such as quantum computing, it is necessary to control emissions from these dots and to produce quantum entanglement of emission from pairs of these dots.

Quantum entanglement is a fundamental property of quantum mechanics and occurs when a pair or group of particles are quantum-mechanically linked in a way such that the quantum state of each particle of the pair cannot be described independently of the state of the others. Essentially, two entangled quantum dots can emit entangled photons.

Professor John Donegan, CRANN and Trinity's School of Physics, said:

"The device works by placing a metal tip within a few nanometers of a surface containing the quantum dots. The tip is excited by light and produces an electric field of such enormous intensity that it can greatly increase the number of single photons emitted by the dots. This strong field can also couple emission from pairs of quantum dots, entangling their states in a way that is unique to quantum emitters of light."

The other significant advantage is the mechanism by which the device works over current state-of-art photonic devices for quantum computing applications.

Professor Ortwin Hess, Professor of Quantum Nanophotonics in Trinity's School of Physics and CRANN, added: "By scanning the metal tip over the surface containing the quantum dots, we can generate the single photon emission as required. Such a device is much simpler than current systems that attempt to fix a metal tip, or a cavity, in close proximity to a quantum dot. We now expect that this device and its operation will have a striking effect on research in quantum emitters for quantum technologies."

National and regional policies aimed at addressing pollution fueled by nitrogen lag behind scientific knowledge of the problem, finds a new analysis by an international team of researchers. Its work, which appears in the journal Nature Sustainability, reveals how governmental regulations favor nitrogen use for commercial enterprise over curbing its environmental impacts.

"There is a large gap between what scientists understand about nitrogen pollution and how policymakers address it," says David Kanter, an assistant professor in New York University's Department of Environmental Studies and one of the paper's co-authors. "By favoring the use of fertilizers and other nitrogen-rich materials for agricultural purposes over scientifically informed controls, governments around the globe are coming up short in addressing environmental concerns."

The analysis, conducted with Wilfried Winiwarter of the International Institute for Applied Systems Analysis in Austria and Poland's University of Zielona Góra, examined more than 2,700 nitrogen policies in 186 countries. It is the first to study nitrogen policy on a global scale.

Specifically, it examined both national and regional policies by continent, then considered the policy category they fell under (e.g., regulatory, economic, etc.), which sectors these policies applied to (e.g., agriculture, waste, transportation, etc.), and where resulting nitrogen-fueled pollution ended up--also known as "environmental sink" (e.g., air, water, soil, etc.)--as a result of these policies.

Overall, the analysis revealed a nearly complete lack of policies that address nitrogen impacts across multiple destinations, or sinks.

"This reveals how environmental policy around the world is currently not equipped to address such a cross-cutting pollutant," explains Kanter.

Notably, there were significantly more policies in the agricultural sector--the dominant source of nitrogen pollution--that incentivize nitrogen use or manage its commerce (640 policies) than aim to reduce nitrogen pollution (190 policies).