Culture

Corals, like all animals, must eat to live. The problem is that most corals grow in tropical waters that are poor in nutrients, sort of like ocean deserts; it's this lack of nutrients that makes the water around coral reefs so crystal clear. Because food is not readily available, corals have developed a remarkable feeding mechanism that involves a symbiotic relationship with single-celled algae. These algae grow inside the corals, using the coral tissue as shelter and absorbing the CO2 that the corals produce. In exchange, the algae provide corals with nutrients they produce through photosynthesis. These algae contain a variety of pigments, which give the coral reefs the colors they're known for.

Over the past 35 years, tropical oceans have experienced multiple major heat waves. Scientists have observed that during these episodes, the algae - stressed by the warmer temperatures - release compounds that are toxic to the coral, prompting the coral to expel the algae from their tissue. That means the corals lose their color and their primary food source, and then begin to starve. This is the process of coral bleaching. And it has been occurring more and more frequently, threatening the survival of many reefs, including Australia's Great Barrier Reef. Bleached corals do not necessarily die; their symbiotic algae population can be reestablished if the conditions around a reef return to normal. But if the heat persists, or is aggravated by other factors like pollution, the coral becomes too weak to survive.

In a paper published in the prestigious PNAS on 25 January, an international team of scientists that includes Nils Rädecker at EPFL's Laboratory for Biological Geochemistry (LGB), reveals a major discovery related to how the symbiotic relationship ends between the coral and algae. "We showed for the first time that the coral starts to suffer from hunger long before the algae are expelled. The algae apparently stop providing sufficient nutrients while they are still inside the coral tissue," he says.

When symbiosis no longer works

Scientists already knew that ocean warming is the main factor causing the symbiotic relationship to break down. But what Rädecker's team discovered was that the coral is already in a stressed state and lacking nutrients even before the algae begin releasing toxic compounds. "The roots of the problem are much deeper than we thought, and they involve an early breakdown of the metabolic exchanges in these fascinating organisms," says Anders Meibom, the head of LGB and a world-renowned coral expert.

Rädecker spent more than a year studying a coral reef just off the coast of Thuwal, Saudi Arabia - the city where the Red Sea Research Center, part of the King Abdullah University of Science and Technology, is located. He then replicated these environmental conditions in the aquaria at the Center so that he could investigate the corals under controlled conditions. The data were then analyzed at several laboratories, including EPFL and the Biology Department at the University of Konstanz in Germany.

Calling known facts into question

"Based on what we found, we can determine which environmental conditions other than temperature (such as water quality) stress the corals in a reef, and use this information to predict whether the reef will bleach. Our findings can also be used to identify corals that are particularly resistant to bleaching, like those in the Gulf of Aqaba and elsewhere in the Red Sea. That will tell scientists which reefs should be protected because they have a better chance of survival," says Rädecker.

According to Meibom, this study makes a major contribution to coral research and sheds new light on earlier observations. "Nils' research has uncovered metabolic mechanisms that play a fundamental role in the coral bleaching process - and that we didn't understand the importance of until now. I believe he found the key to what's actually going on inside corals when they're stressed by global warming," he says.

A team from the Computer Vision Center (CVC) and the University of Barcelona has published the results of a study that evaluates the accuracy and bias in gender and skin colour of automatic face recognition algorithms tested with real world data. Although the top solutions exceed the 99.9% of accuracy, researchers have detected some groups that show higher false positive or false negative rates.

Face recognition has been routinely used by both private and governmental organizations worldwide. Automatic face recognition can be used for legitimate and beneficial purposes (e.g. to improve security) but at the same time its power and ubiquity increases a potential negative impact that unfair methods can have on society (e.g. discrimination against ethnic minorities). A necessary, albeit not sufficient, condition for a legitimate deployment of face recognition algorithms is the equal accuracy for all demographic groups.

With this purpose in mind, researchers from the Human Pose Recovery and Behavior Analysis Group at the Computer Vision Center (CVC) - University of Barcelona (UB), led by Sergio Escalera, organized a challenge within the European Conference of Computer Vision (ECCV) 2020. The results, recently published in the journal Computer Vision - ECCV 2020 Workshops, evaluated the accuracy of the submitted algorithms by the participants on the face verification task in the presence of other confounding attributes.

The challenge was a success, since "it attracted 151 participants, who made more than 1,800 submissions in total, exceeding our expectations regarding the number of participants and submissions" explained Sergio Escalera, also member of the Institute of Mathematics of the UB.

The participants used a not balanced image dataset, which simulates a real world scenario where AI based models are supposed to be trained and evaluated on imbalanced data (considerably more white males than dark females). In total, they worked with 152,917 images from 6,139 identities.

The images were annotated for two protected attributes: gender and skin colour; and five legitimate attributes: age group (0-34, 35-64, 65+), head pose (frontal, other), image source (still image, video frame), wearing glasses and a bounding box size.

The obtained results were very promising. Top winning solutions exceeded 99.9% of accuracy while achieving very low scores in the proposed bias metrics, "which can be considered a step toward the development of fairer face recognition methods" expounded Julio C. S. Jacques Jr., researcher at the CVC and at the Open University of Catalonia. The analysis of top 10 teams showed higher false positive rates for females with dark skin tone and for samples where both individuals wear glasses. In contrast, there were higher false negative rates for males with light skin tone and for samples where both individuals were aged 35 and below. Also, it was found that in the dataset individuals younger than 35 wear glasses less often than older individuals, resulting in a combination of effects of these attributes.

"This was not a surprise, since the adopted dataset was not balanced regarding the different demographic attributes. However, it shows that overall accuracy is not enough when the goal is to build fair face recognition methods, and that future works on the topic must take into account accuracy and bias mitigation together", concluded Julio C. S. Jacques Jr.

A lot is known about galaxies. We know, for instance, that the stars within them are shaped from a blend of old star dust and molecules suspended in gas. What remains a mystery, however, is the process that leads to these simple elements being pulled together to form a new star.

But now an international team of scientists, including astrophysicists from the University of Bath in the UK and the National Astronomical Observatory (OAN) in Madrid, Spain have taken a significant step towards understanding how a galaxy's gaseous content becomes organised into a new generation of stars.

Their findings have important implications for our understanding of how stars formed during the early days of the universe, when galaxy collisions were frequent and dramatic, and star and galaxy formation occurred more actively than it does now.

For this study, the researchers used the Chile-based Atacama Large Millimeter Array (ALMA) - a network of radio telescopes combined to form one, mega telescope - to observe a type of galaxy called a tidal dwarf galaxy (TDG). TDGs emerge from the debris of two older galaxies colliding with great force. They are actively star-forming systems and pristine environments for scientists trying to piece together the early days of other galaxies, including our own - the Milky Way (thought to be 13.6-billion years old).

"The little galaxy we've been studying was born in a violent, gas-rich galactic collision and offers us a unique laboratory to study the physics of star formation in extreme environments," said co-author Professor Carole Mundell, head of Astrophysics at the University of Bath.

From their observations, the researchers learnt that a TDG's molecular clouds are similar to those found in the Milky Way, both in terms of size and content. This suggests there is a universal star-formation process at play throughout the universe.

Unexpectedly, however, the TDG in the study (labelled TDG J1023+1952) also displayed a profusion of dispersed gas. In the Milky Way, clouds of gas are by far the most prominent star-forming factories.

"The fact that molecular gas appears in both cloud form and as diffuse gas was a surprise," said Professor Mundell.

Dr Miguel Querejeta from the OAN in Spain and lead author of the study added: "ALMA's observations were made with great precision so we can say with confidence that the contribution of diffuse gas is much higher in the tidal dwarf galaxy we studied than typically found in normal galaxies."

He added: "This most likely means most of the molecular gas in this tidal dwarf galaxy is not involved in forming stars, which questions popular assumptions about star formation."

Because of the vast distance that separates Earth from TDG J1023+1952 (around 50 million light years), individual clouds of molecular gas appear as tiny regions in the sky when viewed through the naked eye. However, ALMA has the power to distinguish the smallest details.

"We have managed to identify clouds with an apparent size as small as observing a coin placed several kilometres away from us," said Professor Mundell, adding: "It's remarkable that we can now study stars and the gas clouds from which they are formed in a violent extragalactic collision with the same detail that we can study those forming in the calm environment of our own Milky Way."

Children of mothers experiencing depressive symptoms are more at risk, as adolescents, of experiencing suicidal thoughts and attempting suicide.

New research suggests that this link may be explained by loneliness, potentially opening new ways for youth suicide prevention.

The study - by the universities of Exeter, Montréal, Laval and McGill - used data from more than 1,600 families from the Québec Longitudinal Study of Child Development, a representative sample of new-borns in Quebec followed from birth to 20 years of age.

Mothers were asked about depressive symptoms (such as sadness and losing interest in formerly pleasurable activities) at regular intervals while their children were aged five months to seven years.

The resulting information gave a measure of depressive symptoms - not a clinical diagnosis of depression.

Adolescents completed self-reports about suicidal thoughts and attempts at age 13-20 years.

Children of mothers with higher levels of depressive symptoms were approximately 15% more likely to have suicidal thoughts and/or attempt suicide as adolescents compared to children of mothers with lower levels of depressive symptoms.

"We cannot say to what extent this association is due to childhood experiences, genetics or other factors," said lead author Dr Lamprini Psychogiou, of the University of Exeter.

"But identifying some of the mechanisms explaining why those children are at increased suicide risk later in life is essential to understand how to prevent suicide among children of mothers with depression."

To this aim, the authors investigated whether feeling of loneliness and social withdrawal reported by the adolescents at age 10-13 years may account for this association.

"We found that maternal depressive symptoms in the early years of a child's life are associated with those children self-reporting elevated levels of loneliness as adolescents, which, in turn, is associated with suicidality," said Dr Psychogiou.

"We do know that social relationships in general, and peer relationships in particular, are really important for adolescents. Feeling lonely in early adolescence may influence how one perceives life as being worth living.

"Our findings are important because they suggest that interventions targeting loneliness in young adolescence for children of mothers with depression, may potentially help reduce their risk of suicidal thoughts or suicide attempts later in life.

"It's important to note that our study did not examine cause and effect."

Further studies are needed to quantify to what extent reducing feeling of loneliness translates into a decrease in suicide risk for those adolescents.

Cisplatin has been used to treat cancer since the 1970s. Since then, many other platinum-containing cytostatic drugs have been developed, such as triplatinNC, a highly charged complex that contains three ligand-bridged platinum atoms. Unlike cisplatin, this drug also directly inhibits metastasis. The reason for this seems to be modulation of the geometry of a sugar component of heparan sulfate, an important component of the extracellular matrix, reports a research team in the journal Angewandte Chemie.

Heparan sulfate, a glycosaminoglycan, is a chain of ring-shaped sugar molecules. It is involved in many regulatory processes, as well as in the growth and metastasis of tumors. In order for a tumor to grow and form metastases, the extracellular matrix must be broken up in certain locations to allow cells to migrate. The splitting of heparan sulfate by the enzyme heparanase and the release of certain growth factors that bind to heparan sulfate play an important role in this process.

In order to shed light on the interaction of heparan sulfate with triplatinNC, a team led by Anil K. Gorle, Susan J. Berners-Price, and Nicholas P. Farrell at Griffith University (Brisbane, Australia), and Virginia Commonwealth University and Massey Cancer Center (Richmond, Virginia, USA), used fondaparinux (FPX), a molecule made of five sugar units, as a model for heparan sulfate. A combination of computer calculations and experimental data showed that triplatinNC changes the geometry of a specific sugar component of heparan sulfate (a sulfated iduronic acid). The six-membered ring of the iduronic acid can adopt two different spatial conformations: a chair form or a twist-boat form. In free FPX, the chair and twist-boat forms are in a 35:65 ratio. In the presence of triplatinNC, this shifts to 75:25. In the now preferred chair form, there is a pocket into which the platinum drug fits very well, allowing it to bind strongly. In actual heparan sulfate, the result of the strong bonding by triplatinNC is to effectively block it from being split by heparanase.

A tumor cell line in a synthetic extracellular matrix served as a model for triple-negative breast cancer, which is an aggressive form of cancer that is especially hard to treat. Treatment with heparinase initiated significant cell migration in the model. Prior treatment with triplatinNC significantly reduced cell migration--an effect not seen with cisplatin. The team was also able to confirm the anti-metastatic activity of triplatinNC in tests with mice.

TriplatinNC thus demonstrates dual activity. In addition to a cytotoxic effect caused by its action on DNA, it has an anti-metastatic effect caused by interference with the functionality of heparan sulfate. This opens new possibilities for the design of anti-metastatic platinum complexes.

It is clear that COVID-19 has drastically changed our world, but how can we use the lessons learnt to build a more resilient and sustainable future? The International Institute for Applied Systems Analysis (IIASA) and the International Science Council (ISC) have drawn on the combined strengths and expertise of the two organizations to help find a way forward.

The COVID-19 pandemic, which has impacted almost every aspect of our lives over the past year, is a warning: We need to step back from business-as-usual onto new transformative pathways to reach the Sustainable Development Goals and the commitments of the Paris Agreement. Systems science is ideally positioned to address global impacts and harness opportunities brought about by COVID-19, as only systemic thinking and approaches can ensure that investment in post-COVID-19 recovery efforts is leveraged to embed the structural changes required for long-term sustainability and resilience with the multiple dividends that these will confer.

To address emerging issues and provide science based insights to make this possible, IIASA and the ISC brought together experts from all over the world through the IIASA-ISC Consultative Science Platform "Bouncing Forward Sustainably: Pathways to a post-COVID world". The platform serves as a global hub for consultation, deliberation, and collaboration among scientists, policymakers, and representatives from civil society around four key interconnected themes: Governance for Sustainability, Strengthening Science Systems, Resilient Food Systems, and Sustainable Energy. The outputs of the initiative, which are informed and supported by an advisory board under the patronage of the former Secretary-General of the United Nations, H.E. Ban Ki-moon, includes a series of reports with key messages and recommendations for policymakers, which will be launched at an event on Tuesday, 26 January:

Synthesis Report: This report is a synthesis of the four thematic reports produced as part of the IIASA-ISC Consultative Science Platform and presents eight recommendations that have the potential to enable systemic transformations and structural changes. Operationalizing these recommendations would facilitate a more sustainable and resilient future for humanity, as we recover from COVID-19. The authors, being conscious of the need for greater equity and resilience in a new sustainable future, have also sought to be practical by prioritizing the transformative changes that seem most feasible, can be applied early, and that could make a significant contribution to a sustainable recovery.

Enhancing Governance for Sustainability: The authors suggest that global cooperation is enhanced in mission-oriented ways to drive governance reform at all levels. This crisis may constitute an opportunity to enable higher levels of change in international governance arrangements, particularly with a view to mainstreaming a risk perspective and advocating for more reflexive, transformative governance, thus adding new dynamics to ongoing global governance reform initiatives. The report's recommendations include increasing awareness and understanding of compound and systemic risks across governance arrangements at multiple scales to be better prepared for similar crises in the future; moving systemic resilience center-stage; and devising and implementing a science-based tracking mechanism to assess the degree of alignment of COVID-19 recovery packages with the ambitions of the Sustainable Development Goals while focusing on generating systemic resilience.

Strengthening Science Systems: This report contains a number of recommendations grouped under five interrelated transformative changes aimed at ensuring a more effective response of the science system to future global crises. These changes address the need to strengthen transdisciplinary research on critical risks; enhance the diffusion of knowledge within the science system; increase the capacity of the science system to respond rapidly with high-quality research; improve the science-policy interface; and enhance public understanding and trust in science. The report also identifies three axes of simultaneous improvement to move science systems to a new frontier: reacting more rapidly through increased agility; enhancing the quality of output for greater reliability; and linking more effectively to policy and to the public for increased relevance.

Rethinking Energy Solutions: Three areas were identified for immediate action. All three are designed to address the drivers of demand and consumption through measures like remote working, digitalization, and the reshaping of urban spaces and their use; maximizing sustainable energy independence at local and individual levels through, for instance, decentralized renewable energy solutions and efficiency enhancing measures; and influencing behavior towards responsible consumption such as encouraging new trends in mobility, less material consumption, and sharing vs. ownership models.

Resilient Food Systems: The report argues that the emphasis on efficiency, which has to a large extent been driving the evolution of food systems, needs to be counter-balanced by a greater systemic emphasis on resilience and equity concerns. As illustrated by the pandemic, this entails expanding the scope and reach of social safety nets and protection schemes. It also includes assessing, and where necessary adjusting supply chains and trade in their capacity to absorb and adapt to a multitude of risks. Human and planetary health perspectives should be integral aspects of food system policies, regulations, and incentive structures going forward. Innovation capacities need be secured during the recovery to meet rising demands placed on the food system and enhance preparedness for future risks and sustainability challenges, supported by an emphasis on collaboration and strengthening of the science-policy interface for contextual solutions.

For those who are diagnosed and have begun treatment for HIV, it is standard practice to regularly monitor viral load in the blood to assess response to treatment. A study of people living with HIV in Ethiopia shows that poverty and labour mobility are linked to high viral load despite treatment, indicating treatment failure. The researchers behind the study recommend that socioeconomic conditions should be taken into account to a greater extent in low-income countries to ensure that HIV treatment can achieve the best possible results.

Treatment using antiretroviral therapy (ART) is the same across the globe. For people living with HIV in low-income countries, however, it still remains difficult to get continuous clinical follow-up after a confirmed diagnosis, as access to laboratory testing and/or advanced care is often limited.

"HIV in Ethiopia is a socioeconomic challenge with several factors determining how well the individual responds to HIV treatment. Lack of adherence to daily medication and irregular virus monitoring of those living with HIV pose a threat to both individuals and communities, as drug-resistant viruses can be transmitted to other people", says Martin Plymoth, physician and first author.

According to the researchers, there is a lack of previous research into how socioeconomic conditions affect antiretroviral treatment in people living with HIV in sub-Saharan Africa.

"We saw that having a high viral load in the blood during treatment was clearly connected to belonging tolower-income categories and to work mobility, meaning people who need to travel to several different places for work, sometimes far from home. In particular, we were able to identify truck drivers as belonging to this group, which suggests that these types of work could pose a risk to successful HIV treatment. The study cannot determine whether there is a causal connection or simply a correlation, however", adds Plymoth.

A total of 307 individuals living with HIV took part and were divided into two equal groups in a case-control study; people with high viral loads in the blood and virally suppressed patients (virus levels that were not measurable). The participants were adults aged 15 years and over who were receiving antiretroviral treatment at Ethiopian health centres and whose viral loads had been measured within three months before start of the study. The researchers interviewed all participants to obtain detailed information about their socioeconomic conditions, medical history and social behaviours.

The surveys were conducted in Adama and in two smaller towns located along the main road from central Ethiopia to the port of Djibouti. There are more individuals belonging to risk groups such as lorry drivers and sex workers in this area, and the prevalence of HIV is higher than it is among the general Ethiopian population; it is also one of the major transportation routes in the country.

"The majority of the participants came from major urban areas, so we cannot say for sure if the same connections exist in people living with HIV in rural areas", explains Per Björkman, Professor of clinical infection medicine at Lund University and senior consultant at Skåne University Hospital in Malmö, who has been leading the study.

Nevertheless, the researchers believe that the results clearly show how important it is to take into account the socioeconomic conditions of individuals in low-income countries to ensure well-adjusted HIV treatment.

Olive trees are some of the most important woody crops in the world and Verticillium wilt, caused by the Verticillium dahliae fungus, is the most concerning disease for farmers in the olive sector.

In Spain, the leader in olive oil and table olive production, the increase in Verticillium wilt is primarily due to taking over infested soils formerly used for cotton (one of the main hosts for this pathogen) and the spread of a defoliating variant of the pathogen, which is more ferocious and ends up killing the olive tree.

This is why agronomy research efforts are focused on the search for the most resistant crops and the implementation of practices that reduce disease rates. In this vein, UCOLIVO Group researcher Juan Moral at the María de Maeztu Excellence Unit, Agronomy Department, has been able to reduce disease occurrence using an Integrated Disease Management approach at a commercial olive grove with the Picual variety, affected by the pathogen.

Since 1998, in the Grañon olive grove, a strategy integrating different practices has been used: replacing dead olive trees with crops that are more resistant to Verticillium wilt such as Frantoio trees after soil solarization (disinfestation using translucent plastic), chemical weed control, refraining from tilling, burning the waste from pruning and increasing the plantation density with more Frantoio olive trees.

Upon comparing the Verticillium wilt epidemic at the Grañón grove with that at the Ancla grove, located in the same area, but using traditional management techniques, tilling and substituting sick olive trees with trees from the same Picual variety in soil without solarization, it was verified how the intensity and severity of the epidemic at the second olive grove was greater than at the Grañón grove. In addition, the comparison between the varieties Picual and Frantoio at the Grañón farm allowed researchers to observe how "the impact of the variety in the decrease in Verticillium wilt is even greater than the rest of the control practices that were used" as pointed out by Moral, since Frantoio trees suffered less from the disease. While the yearly mortality rate of the trees was 5.6% for Picual trees on the farm using traditional techniques, at the Grañón olive farm Picual trees suffered at a mortality rate of 3.1% and Frantoio trees only 0.6%.

This study signifies, for the first time, the integration of an Integrated Disease Management approach at a olive farm in field conditions. In addition, it is the first time the Frantoio variety, which is more resistant to Verticillium wilt, was commercially planted in Spain.

With these results, farmers in the olive sector now have an efficient new tool that can keep their farms safe.

ISIS, Al Qaeda, and the Taliban use their English-language magazines to encourage women to support jihad in different ways, according to new research.

Experts hope highlighting these varying recruitment strategies will be of use for those trying to stop radicalisation and terrorism.

The Taliban-produced magazines encourage women to carry out a traditional role in the home and support men rather than to be violent and commit jihad themselves. Tahrik-e Taliban Pakistan (TTP) and ISIS encourage women to be violent - to pick up arms and fight. The magazines encourage women to leave their husbands if they don't support jihad, even without permission.

Researchers from the University of Exeter analysed sixty-eight English language jihadi magazines by Islamic State (ISIS), TTP - the Pakistani Taliban group which operates on the border of Pakistan and Afghanistan which pledge allegiance to ISIS, Al Qaeda, and the Taliban, coding data about the themes and messages they found manually to see how frequently they were found in the publication. Their research is published in the journal Small Wars & Insurgencies

Researchers examined at 68 magazines produced between 2013 and 2020. The Taliban haven't produced magazines in English since 2015. ISIS stopped producing magazines in 2017, but one was produced in 2020. Al Qaeda also stopped producing magazines in 2017, but started again in 2019 and 2020.

The magazines are made for Muslims living in the West, they are put online but are often taken down quickly by security services around the world.

Dr Weeda Mehran, who led the study, said: "Our research show the magazines are designed to recruit women by tapping into their role in the community and within their family. The Taliban magazines make women feel as if they have been victimised, and men should join jihad to protect them. ISIS depicts, women either as ideal role models who should be followed, or as the enemy. These strategies are tailored towards attracting women to join the group

"Both ISIS and TTP are more likely than the Taliban and Al Qaeda to encourage women to join jihad. ISIS even went to the extent to encourage married women to leave their husbands and join the Caliphate, if the husband refused to join jihad.

"These different strategies are explained by the fact that ISIS aim to bring women from abroad to establish the caliphate, so their focus is less on local values. This means they break with traditional values to encourage women to leave their homes, communities and families. The Taliban are more bound to local areas, so don't encourage women from abroad to join them. This needs to be built into de-radicalisation work, which must be as targeted as possible to be effective."

All the magazines pit jihadi women against 'othered' Muslim women and 'enemy' women - those who believe in gender equality, assume jobs within the security sector of governments, do not wear Islamic hijab and reject polygamy.

Over the past decade, there has been an increase in suicide bombings by women acting on behalf of violent jihadi organisations, notably the Chechen rebels, the al-Aqsa Martyrs Brigade, the Palestinian Islamic Jihad, HAMAS, Al Qaeda, and ISIS.

Dr Mehran said: "These groups use a wide variety of themes to persuade women to undertake jihad. Sometimes this is injustice, where women are depicted as victims and in need of protection. This is less common in ISIS and TTP magazines than in those published by Al Qaeda and the Taliban.

"The Taliban and Al Qaeda less likely than ISIS and TTP to vilify women or depict them as role models. ISIS is less likely than Al Qaeda, the Taliban and TTP to portray women as victims. Al Qaeda, the Taliban and TTP show a higher tendency to portray women as in need of protection."

TTP magazines attacked gender equality policies of Pakistani states and Malala Yousafzai, while ISIS and Al Qaeda attacked women who do not adhere to sharia laws, while pious, modest, religious women were depicted as role models.

All the cells in the human body share the same genes. But how our genes are expressed determines whether a cell becomes a brain cell or a liver cell. In addition, changes in gene expression often play a significant role in development of diseases.

One mechanism that contributes to the changes in gene expression is the interaction between the proteins called histones and enzymes known as HDACs. These enzymes help the cell divide and develop, which is the reason why they serve as targets for anti-cancer medicine: When you inhibit the enzymes, the cancer cells will stop dividing and growing further.

Despite being targets for clinically approved medicines, researchers do not know all the details of how they work in the cell. Now, researchers from the University of Copenhagen have developed a method that will help change that.

"We have shown details of how these enzymes interact with proteins around our DNA, and our method provides a new means for identifying possible anti-cancer drugs very quickly. In the study, we show that the method works: We synthesized a peptide that affected just the right parts of living human cells, using the same target as anti-cancer medicine uses today," says Carlos Moreno-Yruela, postdoc at the Department of Drug Design and Pharmacology.

Unmodified peptide had effect

HDACs are a group of eleven different enzymes, which means that targeting them all at once with a non-selective medicine will result in affecting many essential processes in the body. This may also explain some of the side effects in the clinically approved HDAC-inhibiting anti-cancer medicine.

"Our detailed insight into the enzymes' interactions gained with the new method provide hope for the development of more specific HDAC inhibitors with potential as drug candidates. This could bode well for the development of more sophisticated compounds for cancer therapy with fewer side effects," says Professor Christian Adam Olsen.

In the study, the researchers used the new method for identifying peptides, which they resynthesized in larger amounts and subjected to human cells. The results were exactly what they hoped: The expected HDACs were also inhibited in living cells.

"We were surprised to see such a prominent effect of an unoptimized peptide in cells. Normally, one would need to introduce a variety of modifications to optimize its properties. But this, almost fully natural, peptide had a really potent effect, which emphasizes the potential of our findings," says Christian Adam Olsen.

The researchers now hope to use the method for identifying promising drug candidates which could go on to pre-clinical testing.

Nonalcoholic fatty liver disease (NAFLD) is a widespread condition in the Western World. Around 30% of the population have lipid droplets stored in their liver which diminish its function in the long term. Main causes for NAFLD are our high-caloric diet in combination with a sedentary lifestyle. Hitherto, researchers have not fully understood the cause of this disease and despite the high number of affected individuals, there is no approved therapy.

In order to improve our understanding of the basic mechanisms underlying the etiology of NAFLD, Dr. Nina Graffmann, Prof. James Adjaye and the team of the Institute for Stem Cell research and Regenerative Medicine from the University Hospital Duesseldorf differentiated induced pluripotent stem cells (iPSCs) derived from healthy donors and NAFLD patients into hepatocyte-like cells (HLCs). The HLCs were stimulated with fatty acids to mimic a scenario where an individual consumes excess fat in their diet. The lipid droplets produced in HLCs are akin to lipid droplets seen in the livers of NAFLD patients.

The analysis of fat incorporation was carried out in collaboration with Prof. Beller of the Systems Biology of Lipid Metabolism group - Heinrich-Heine-University Duesseldorf, Germany.

The recent publication in Biology Open (Publisher-Company of Biologists) demonstrates a strong heterogeneity between cell lines, regarding gene expression and lipid droplet morphology. The scientists think that this is due to the plethora of metabolic networks involved in the development of the disease. It also mirrors the multifaceted, patient-dependent phenotypes which make NAFLD a highly complex disease as the group has shown in an earlier study (Wruck et al, 2015). Nonetheless, the scientists could identify gene expression patterns that correlate with disease severity.

Adiponectin is a molecule synthesized by human fat cells, which has been shown to positively influence hepatocyte metabolism. In the institute for Organic Chemistry and Macromolecular Chemistrymof Heinrich-Heine-University Duesseldorf, Prof. Constantin Czekelius and his team produced a synthetic analogue called AdipoRon for this study. AdipoRon has been first used in mice, were it had a significant anti-diabetic effect (Okada-Iwabu et al, 2013).

Treating HLCs with AdipoRon again resulted in cell line / genetic background specific effects. In addition, AdipoRon affected transcription of genes associated with metabolism, transport, immune system, cell stress and signalling.

"We could recapitulate important aspects of NAFLD with our stem cell based cell culture model. We are going to use it for further studies, because established animal models cannot reproduce the complex human metabolic pathways involved in the development of the disease," explains Dr. Graffmann.

"Once again we have shown that although iPSC- derived hepatocyte-like cells are immature in nature, i.e. fetal, these cells still have immense usefulness in their application in drug discovery and for dissecting disease mechanisms such as NAFLD" says Prof. James Adjaye.

COLUMBUS, Ohio - Older minority cancer patients with poor social determinants of health are significantly more likely to experience negative surgical outcomes compared to white patients with similar risk factors, according to a new study published by researchers at The Ohio State University Comprehensive Cancer Center - Arthur G. James Cancer Hospital and Richard J. Solove Research Institute (OSUCCC - James).

A new retrospective analysis of more than 200,000 patients conducted by researchers with the OSUCCC - James suggests that minority patients living in high socially vulnerable neighborhoods had a 40% increased risk of a complication and 23% increased risk of 90-day mortality compared with white patients for neighborhoods with low social vulnerability. The U.S. Centers for Disease Control (CDC) defines social vulnerability as "potential negative effects on communities caused by external stresses on human health."

Study results were published online ahead of print in the Journal of the American College of Surgeons Jan. 25, 2021, and were highlighted in the 2020 Southern Surgical Association Program.

"This study speaks to how health care and health outcomes extend beyond the doors of the hospital and even beyond the specifics of the disease the patient may have. Ultimately, the resources in the patient's community may be as important to a patient's health as what goes on in the hospital," said Timothy Pawlik, MD, senior author of the study and holder of the Urban Meyer III and Shelley Meyer Chair for Cancer Research at the OSUCCC - James. Pawlik serves as surgeon-in-chief at the Ohio State Wexner Medical Center and as chair of the Department of Surgery in the Ohio State College of Medicine.

"This issue is not new, but the data strongly suggests we could significantly improve surgical outcomes by intentionally integrating vulnerability assessments into our national standard of care models. By doing so, we could help identify the most vulnerable among us - upfront - and provide additional supports as patients move through treatment and recovery," Pawlik added. "The data emphasize how efforts to improve outcomes for cancer patients need to extend beyond the hospital and address systemic health-related disparities within the communities in which patients live."

Study Method and Results

For this retrospective study, researchers used a novel risk stratification tool called the social vulnerability index (SVI), a composite measure of 15 social and economic factors. Although the CDC created the SVI using census data to identify communities needing greater support during disasters, researchers recently have applied it to medical studies.

Researchers identified 203,800 patients age 65 or older from the 2016-2017 Medicare inpatient claims files who underwent an operation for one of three common cancers--lung, colon and rectal--or for cancer of the esophagus between 2013-2017. The investigators merged the Medicare information with the CDC's SVI for each patient's county of residence. The SVI includes county-level data such as unemployment rates, racial distribution, prevalence of people with disabilities, vehicle access and overcrowded community living. A high SVI score indicates greater social vulnerability.

Researchers found that minority patients with high SVI scores had a 47% increased chance of an extended length-of-stay, 40% increased odds of a surgical complication and 23% increased odds of 90-day mortality. When comparing white to non-white patients with a similar social vulnerability risk factor score, non-white patients fared worse in overall recovery.

Additionally, researchers noted that older patients who underwent a cancer operation and resided in areas with high social vulnerability were less likely to achieve a "textbook outcome" as a result of their procedures. A "textbook outcome" means that these patients did not have in-hospital complications, an extended hospitalization or a readmission within three months, and that they were alive 90 days after surgery.

Differences Noted by Race

As social vulnerability increased, the outcomes differences by race became more pronounced, Pawlik said.

"Especially for Black and Hispanic individuals, the impact of residing in a socially vulnerable community was much more pronounced," he added. "They had much greater risk of having adverse outcomes than white patients."

Even when the researchers matched patients' characteristics, such as age and cancer type, they found that Blacks and Hispanic patients from high-SVI counties had 26% lower odds of receiving a textbook outcome compared to whites from a low-SVI county.

In general, the differences in textbook outcomes were driven by complications and prolonged hospitalization, according to Pawlik.

"Patients from socially vulnerable communities had the most difficulty achieving a postoperative course without a complication, and they were the most likely to have an extended length of stay. These patients are in double and triple jeopardy," Pawlik said. "Our data clearly showed a disparity in health, as defined by textbook outcome, with poorer outcomes if a patient was a minority, or from a highly socially vulnerable community or, in particular, both."

Recommendations Based on Findings

Pawlik cautioned that, because the SVI is population-based, it is not a useful tool to calculate risk at the individual level. Instead, he says, health care providers should ask about patients' home situations and address their potential lack of resources/support as a routine step in standard of care across all health care systems.

"Make sure patients have the necessary support in the community they are going back into, with access to such things as food, basic services, transportation, home health care and wound care," Pawlik said. "Strong, individualized discharge planning and partnering with community leaders to ensure a smoother transition from the hospital back into the community are key."

CHAMPAIGN, Ill. -- Absent a widely available vaccine, mitigation measures such as stay-at-home mandates, lockdowns or shelter-in-place orders have been the major public health policies deployed by state governments to curb the spread of COVID-19.

But given the uncertain duration of such policies, questions have been raised about the potential negative mental health consequences of extended lockdowns with indefinite end dates. But according to new research co-written by a team of University of Illinois Urbana-Champaign experts who study the intersection of health care and public policy, the negative mental health effects of such lockdowns are temporary and gradually decrease over time as people adjust to their "new normal."

Research co-written by Dolores Albarracín, a professor of psychology and of business administration at Illinois, and Bita Fayaz Farkhad, an economist and a postdoctoral researcher in psychology at Illinois, found that social distancing policies correlated with immediate increases in interest in obtaining information about "isolation" and "worry" - but those effects tapered off two to four weeks after their respective peaks.

"Previous studies of the psychological impact of lockdowns during other disease outbreaks have indicated that quarantines are associated with increased mental health symptoms," Farkhad said. "We wanted to study how serious the mental health impact of the mitigation phase was during the initial COVID-19 outbreak last spring. Did it go beyond people feeling anxious or disheartened? Was it long lasting, and did it increase suicide ideation and the need for medical treatment for depression?

"These questions are, quite obviously, important from a mental and public health perspective."

Albarracín and Farkhad measured mental health trends from January 2020 through the end of June by analyzing daily, state-located search data via Google Trends, which afforded the researchers a large-scale search overview and the ability to parse information about searches for a given period in a search locale. The researchers first used a set of terms related to mitigation policies, and then obtained data on searches about mental health. The search data set also included terms for in-home activities.

The researchers found that the negative effects of stay-at-home orders weren't as dire as initially thought.

"At the outset of the pandemic, consistent with prior research, social distancing policies correlated with a spike in searches about how to deal with isolation and worry, which shouldn't be surprising," said Albarracín, also the director of the Social Action Lab at Illinois. "Generally speaking, if you have a pandemic or an economic shock, that's going to produce its own level of anxiety, depression and negative feelings, and we had both with COVID-19."

But the effects on searches for isolation and worry due to the mitigation policies were temporary and decreased gradually after peaking, the researchers said.

"Our findings showed that even though the mitigation measures increased negative feelings of isolation or worry, the effects were mostly transient," Farkhad said. "A potential explanation of this finding is that even though social isolation increased risk factors for mental health, the stay-at-home order also increased within-home hours that might promote new routines and greater social support within the family. Searches for activities such as 'exercise,' 'Netflix' and 'cooking' were positively associated with the stay-at-home policy, suggesting that individuals enjoyed spending more time at home."

Moreover, the policies correlated with a reduction in searches for "antidepressants" and "suicide," thus revealing no evidence of increases in severe symptomatology, according to the paper.

"It is possible that people who were able to work from home liked working from home, liked being able to set their own schedule and liked being able to exercise more, all of which has positive mental and physical health benefits," Farkhad said. "Although they might not be able to go out to a restaurant or bar, they have a little bit more control over other aspects of their life, which enhances well-being."

"That suggests that people adjusted to their new situation and that the negative mental health effects dissipated."

The public health policy implications are that if states need to go through an extended lockdown period again with COVID-19, health professionals ought to pay extra attention to people with acute cases of depression and anxiety, and target them for extra help via telemedicine, Farkhad said.

"However, the psychological distress following the lockdown orders is likely to be low compared with the overall health benefits of mitigating the COVID-19 pandemic," she said. "Implementing interventions aimed at increasing social connection and social support might be an important mechanism for addressing the potential negative psychological consequences if sheltering-in-place becomes necessary once again to tame the COVID-19 pandemic."

ITHACA, N.Y. - Researchers from Cornell University and the National Park Service have pinpointed and confirmed the location of the remnants of a wooden fort in Alaska - the Tlingit people's last physical bulwark against Russian colonization forces in 1804 - by using geophysical imaging techniques and ground-penetrating radar.

The fort was the last physical barrier to fall before Russia's six-decade occupation of Alaska, which ended when the United States purchased Alaska in 1867 for $7 million.

The Tlingit built what they called Shiskinoow - the "sapling fort" - on a peninsula in modern-day Sitka, Alaska, where the mouth of Kasda Heen (Indian River) meets Sitka Sound at the Sitka National Historical Park.

"The fort's definitive physical location had eluded investigators for a century," said co-author Thomas Urban, research scientist at Cornell. "Previous archaeological digs had found some suggestive clues, but they never really found conclusive evidence that tied these clues together."

To find Shiskinoow, Urban created a grid to see if the electromagnetic induction methods could spot the potential outline of the fort and then created a small grid for dragging the ground-penetrating radar. Urban's modern tools picked up the fort's unusual perimeter shape.

"We believe this survey has yielded the only convincing, multi-method evidence to date for the location of the sapling fort, which is a significant locus in New World colonial history and an important cultural symbol of Tlingit resistance to colonization," Urban said.

In 1799, Russia sent a small army to take over Alaska in order to develop the fur trade, but the Tlingit successfully expelled them in 1802. Expecting the Russians to return, the Tlingit built a wooden fort over two years - the trapezoidal-shaped Shiskinoow. The Tlingit armed it with guns, cannons and gunpowder obtained from British American traders.

When the Russians returned in 1804, the Tlingit held them off for five days, but suffered a setback when a gunpowder supply being carried to the fort from storage across Sitka Sound blew up in a canoe. The Tlingit clans escaped Shiskinoow by night across Shee (Baranov Island) to Cháatl ?áa Noow (Halibut Man Fort) and the Russians then established a trading post at what is now Sitka.

"A large-scale survey was necessary to convincingly rule out alternative locations for this historically and culturally significant structure," said co-author Brinnen Carter of the National Parks Service.

Findings of a new study published by researchers from Trinity College Dublin and St James's Hospital outline the health impacts faced by older people while cocooning during the Covid-19 pandemic. The findings are published in the Quarterly Journal of Medicine here: https://bit.ly/3qGKJoI.

Cocooning involves staying at home and reducing face-to-face interaction with other people and is an important part of the response to the COVID-19 pandemic, with an overall aim to prevent transmission to vulnerable older people. However, concerns exist regarding the long-term adverse effects it may have on their physical and mental health.

The research examines trends in physical and mental health, access to healthcare services and attitudes to Covid-19 while cocooning amongst people aged 70 years or more who did not contract Covid-19.

KEY FINDINGS

Almost 40% of participants reported that their mental health was worse or much worse since the start of cocooning.

Over 57% of participants reported loneliness at least some of the time while cocooning with 1 in 8 reporting that they were lonely 'very often'. Participants were almost twice as likely to report loneliness if they lived alone.

Over 40% of participants reported a decline in their physical health since cocooning and 1 in 5 reported not leaving their house at all since being advised to cocoon

Despite this, over 60% of participants reported that they agreed with the government advice regarding cocooning while one quarter of participants reported that they did not agree with the advice.

Over 40% of participants reported that they disliked the term 'cocooning' however, while almost 10% reported that they liked the term.

Almost 1 in 6 participants reported that while cocooning they did not seek medical attention for an illness, when they otherwise would have done so. Half of those who did not seek medical attention said this was because they were afraid of catching COVID-19.

Dr Robert Briggs, Medical Gerontology, Trinity College and Consultant Geriatrician, St James's Hospital, Dublin and senior author of the study said:

"These findings highlight the potential secondary impact of the COVID-19 pandemic on older people. While cocooning is important and reduces the likelihood of older people becoming unwell with COVID-19, there may be important adverse impacts on the health of those who cocoon that also need to be addressed. Given the possibility of further waves of COVID-19, with the likelihood of ongoing restrictions despite the rollout of vaccines, clear policies and advice for older people around strategies to maintain social engagement, manage loneliness and continue physical activity should be a priority.''

Dr Laura Bailey, Specialist Registrar in Geriatric Medicine, St James's Hospital, Dublin and first author of the study said:

"It is a particular worry that 1 in 6 older people who were acutely unwell did not seek medical attention, often for fear of contracting Covid-19. We must give a clear message to older people that when you are unwell that you should seek medical attention and that hospitals and general practices have appropriate infection control practices in place and continue to deal with non-Covid-19 related medical issues.''