Culture

EU imports of certain products contribute significantly to deforestation in other parts of the world.

In a new study, researchers from Chalmers University of Technology, Sweden, and University of Louvain, Belgium, evaluated thousands of policy proposals for how the EU could reduce this impact, to assess which would have the largest potential to reduce deforestation - while also being politically feasible.

"Unsurprisingly, there is weaker support for tougher regulations, such as import restrictions on certain goods. But our study shows that there is broad support in general, including for certain policies that have real potential to reduce imported deforestation," says Martin Persson, Associate Professor of Physical Resource Theory at Chalmers University of Technology.

Previous research has already shown the EU's great impact in this area. More than half of tropical deforestation is linked to production of food and animal feed, such as palm oil, soybeans, wood products, cocoa and coffee - goods which the EU imports in vast quantities. The question is, what can the EU do to reduce its contribution to deforestation?

"This issue is particularly interesting now, as this year the EU is planning to present legislative proposals for reducing deforestation caused by European consumption. The question has been discussed by the EU since 2008, but now something political is actually happening," says Simon Bager, a doctoral student at the University of Louvain (UCLouvain), and lead author of the study.

The authors of the article mapped 1 141 different proposals, originating from open consultations and workshops, where the EU has collected ideas from companies, interest groups and think tanks. The researchers also compiled proposals from a large number of research reports, policy briefs and other publications, where different stakeholders have put forward various policy proposals. After grouping together similar proposals, they arrived at 86 unique suggestions.

Two suggestions stand out from the crowd

Finding proposals for measures that would have the desired effect but are also possible to implement in practice, and enjoy the necessary political support, is no easy task. But after their extensive survey, the researchers identify two policy options in particular which show particular promise:

- The first is to make importers of produce responsible for any deforestation in their supply chains, by requiring them to carry out the requisite due diligence."If the importing companies' suppliers have products that contribute to deforestation, the company may be held responsible for this. We consider such a system to be credible and possible to implement both politically and practically - there are already examples from France and England where similar systems have been implemented or are in the process thereof," says Simon Bager. "Due diligence is also the measure which is most common in our survey, put forward by many different types of actors, and there is broad support for this proposal. However, it is important to emphasise that for such a system to have an impact on deforestation, it must be carefully designed, including which companies are affected by the requirements, and which sanctions and liability options exist."

- The other possibility is to support multi-stakeholder forums, where companies, civil society organisations, and politicians come together to agree on possible measures for ridding a supply-chain, commodity, or area, of deforestation. There are positive examples here too, the most notable being the Amazon Soy Moratorium from 2006, when actors including Greenpeace and the World Wide Fund for Nature gathered with soy producers and exporters and agreed to end soy exports from deforested areas in the Amazon rainforest. "Examples such as these demonstrate the effect that multi-stakeholder forums can have. And in our opinion, it is a measure that is easier to get acceptance for, because it is an opportunity for the affected parties to be directly involved in helping design the measures themselves," says Martin.

A delicate balance

The researchers also investigated how to deal with the trade-off between policy impacts and feasibility. An important part of this is combining different complementary measures. Trade regulations on their own, for example, risk hitting poorer producing countries harder, and should therefore be combined with targeted aid to help introduce more sustainable production methods, increasing yields without having to resort to deforestation. This would also reduce the risk of goods that are produced on deforested land simply being sold in markets other than the EU.

"If the EU now focuses on its contribution to deforestation, the effect may be that what is produced on newly deforested land is sold to other countries, while the EU gets the 'good' products. Therefore, our assessment is that the EU should ensure that the measures introduced are combined with those which contribute to an overall transition to sustainable land use in producing countries," says Simon Bager.

In conclusion, the researchers summarise three essential principles needed for new measures, if the EU is serious about reducing its impact on tropical deforestation. "First, enact measures that actually are able to bring about change. Second, use a range of measures, combining different tools and instruments to contribute to reduced deforestation. Finally, ensure the direct involvement of supply chain actors within particularly important regions, expanding and broadening the measures over time," concludes Simon Bager.

The authors hope that the research and identified policy options can serve as inspiration for policy makers, NGOs, industries, and other stakeholders working to address the EU's deforestation footprint. With at least 86 different unique alternatives, there is a wide range of opportunities to focus on the problem - very few of these are political 'non-starters' or proposals which would have no effect on the issue.

Air pollution from the burning of fossil fuels impacts human health but predicting pollution levels at a given time and place remains challenging, according to a team of scientists who are turning to deep learning to improve air quality estimates. Results of the team's study could be helpful for modelers examining how economic factors like industrial productivity and health factors like hospitalizations change with pollution levels.

"Air quality is one of the major issues within an urban area that affects people's lives," said Manzhu Yu, assistant professor of geography at Penn State. "Yet existing observations are not adequate to provide comprehensive information that may help vulnerable populations to plan ahead."

Satellite and ground-based observations each measure air pollution, but they are limited, the scientists said. Satellites, for instance, may pass a given location at the same time each day and miss how emissions vary at different hours. Ground-based weather stations continuously collect data but only in a limited number of locations.

To address this, the scientists used deep learning, a type of machine learning, to analyze the relationship between satellite and ground-based observations of nitrogen dioxide in the greater Los Angeles area. Nitrogen dioxide is largely associated with emissions from traffic and power plants, the scientists said.

"The problem right now is nitrogen dioxide varies a lot during the day," Yu said. "But we haven't had an hourly, sub-urban scale product available to track air pollution. By comparing surface level and satellite observations, we can actually produce estimates with higher spatial and temporal resolution."

The learned relationship allowed the researchers to take daily satellite observations and create hourly estimates of atmospheric nitrogen dioxide in roughly 3-mile grids, the scientists said. They recently reported their findings in the journal Science of the Total Environment.

"The challenge here is whether we can find a linkage between measurements from earth's surface and satellite observations of the troposphere, which are actually far away from each other. That's where deep learning comes in."

Deep learning algorithms operate much like the human brain and feature multiple layers of artificial neurons for processing data and creating patterns. The system learns and trains itself based on connections it finds within large amounts of data, the scientists said.

The scientists tested two deep-learning algorithms and found the one that compared the ground-based observations directly to the satellite observations more accurately predicted nitrogen dioxide levels. Adding information like meteorological data, elevation and the locations of the ground-based stations and major roads and power plants improved the prediction accuracy further.

Yu said the study could be repeated for other greenhouse gases and applied to different cities or on regional and continental scales, the scientists said. In addition, the model could be updated when new, higher-resolution satellites are launched.

"With a high spatiotemporal resolution, our results will facilitate the study between air quality and health issues and improve the understanding of the dynamic evolution of airborne pollutants," Yu said.

Scientists from Nagoya University, Yokohama City University and Chubu University have developed a system which enables the live imaging of the formation of the female gamete in plants.

In flowering plants, the sperm cell and egg cell meet and fertilization takes place in the flower. While sperm cells are made in the pollen, egg cells are made in the ovule, the structure that becomes the seed. However, as the ovule is buried deep within the pistil, it has thus far been impossible to observe the formation of the egg cell in living plants.

The team, led by Dr Daisuke Kurihara and Dr Tetsuya Higashiyama of Nagoya University Institute of Transformative Bio-Molecules (WPI-ITbM), Dr Daichi Susaki of Yokohama City University Kihara Institute for Biological Research and Dr Takamasa Suzuki of Chubu University College of Bioscience and Biotechnology, using the ovule culturing technology that they had developed previously, succeeded in capturing images of the egg cell being formed inside the ovule. On top of that, they were able to isolate the egg cell and its neighboring cells, and by analyzing the genes expressed in these few cells, identify how the cells adjoining the egg cell determine its fate.

Living things which carry out sexual reproduction produce offspring via a fertilization process involving male and female gametes. In animals, the female gamete (the egg) is produced by meiosis, a type of cell division that halves the number of chromosomes present in the cell. However, the process in flowering plants is rather more lengthy. Following meiosis, karyomitosis (nuclear division) takes place three times within the cell, resulting in the production of a single cell with eight nuclei. This cell then divides, producing cells with a variety of different roles including two gametes, the egg cell and central cell, and the synergid cells. However, it was not yet understood precisely how the two female gametes were produced among the seven new cells that result from this process of division.

Using an ovule culturing method that they had developed previously, the research team attempted the observation in real time of the formation of the female gamete in Arabidopsis thaliana. They saw that when the first nuclear division takes place, the resulting two nuclei go to the opposite ends of the cell. Dividing again into four, the nuclei then line up along the edge of the cell. Finally, dividing again into eight, the plasma membranes are constructed around the nuclei, forming the cells which are attached to the two gametes (the egg cell and central cell). Having observed 157 cases of this division, they found that the nuclei close to where the pollen tube penetrates would become the nuclei of the synergid, egg and central cells, demonstrating that the position of the nuclei within the cell has a strong correlation with cell fate.

Continuing, in order to find out when the various cells' fates are determined, they analyzed the time at which expression of the specific transcription factor myb98, important for the differentiation and function of the synergid cells, commenced. They found that myb98 begins to be expressed very shortly after the nuclei divide into 8 and are enclosed by the plasma membranes. Given that the specific transcription factor for the egg cell can also be found in the egg cell at the same early stage, it can be considered that cell fate is determined immediately after the formation of the plasma membranes, or possibly even earlier.

The time at which cell fate is determined is significant because it gives us an insight into how plants remain adaptable to environmental conditions by flexibly changing cell fate and thus ensuring the survival of crucial cells such as gametes.

Looking to the future, the research team's focus will be on discovering how the cell fate change is accomplished, and explaining its molecular mechanism. Once the molecular mechanism has been analyzed, it is expected that this field of research will contribute to the development of methods to increase plant fertilization rates and environmental resistance, offering the prospect of solving key issues in food supply that affect millions of people around the world.

A team of researchers has identified several candidates for drugs against the coronavirus SARS-CoV-2 at DESY´s high-brilliance X-ray lightsource PETRA III. They bind to an important protein of the virus and could thus be the basis for a drug against Covid-19. In a so-called X-ray screening, the researchers, under the leadership of DESY, tested almost 6000 known active substances that already exist for the treatment of other diseases in a short amount of time. After measuring about 7000 samples, the team was able to identify a total of 37 substances that bind to the main protease (Mpro) of the SARS-CoV-2 virus, as the scientists report online today in the journal Science. Seven of these substances inhibit the activity of the protein and thus slow down the multiplication of the virus. Two of them do this so promisingly that they are currently under further investigation in preclinical studies. This drug screening - probably the largest of its kind - also revealed a new binding site on the main protease of the virus to which drugs can bind.

In contrast to vaccines, which help healthy people to defend themselves against the virus, drug research is looking for drugs that slow down or stop the reproduction of the virus in the body of people who are already infected. Viruses cannot reproduce on their own. Instead, they introduce their own genetic material into the cells of their host and make them produce new viruses. Proteins such as the main protease of the virus play an important role in this process. Protease cuts protein chains produced by the host cell according to the blueprint of the virus genetic material into smaller parts that are necessary for the reproduction of the virus. If the main protease can be blocked, the cycle can possibly be interrupted; the virus can no longer reproduce and the infection is defeated.

Beamline P11 of DESY´s PETRA III research lightsource specialises in structural biology studies. Here, the three-dimensional structure of proteins can be imaged with atomic precision. The research team led by DESY physicist Alke Meents used this special capability to examine several thousand active substances from a library of the Fraunhofer Institute for Translational Medicine and Pharmacology and another library from the Italian company Dompé Farmaceutici SpA to see whether and how they "dock" to the main protease - the first important step in blocking it. Like a key in a lock, the drug molecule fits into a binding centre of the protease. The advantage of the drug library is that it contains active substances that have already been approved for the treatment of humans or those that are currently in various testing phases. Suitable candidates to combat SARS-CoV-2 could therefore be used in clinical trials considerably faster, saving months or years of drug development.

The special technical equipment at the PETRA III station P11 includes fully automated sample changes with a robotic arm, so that each of the more than 7000 measurements took only about three minutes. With the help of automated data analysis, the team was able to quickly separate the wheat from the chaff. "Using a high-throughput method, we were able to find a total of 37 active substances that bind with the main protease," says Meents, who initiated the experiments.

In a next step, the researchers at the Bernhard Nocht Institute for Tropical Medicine investigated whether these active substances inhibit or even prevent virus replication in cell cultures and how compatible they are for the host cells. This reduced the number of suitable active substances to seven, two of which stood out in particular. "The active substances Calpeptin and Pelitinib clearly showed the highest antivirality with good cell compatibility. Our cooperation partners have therefore already started preclinical investigations with these two substances," explains DESY researcher Sebastian Günther, first author of the Science publication.

In their drug screening using protein crystallography, the researchers did not examine fragments of potential drugs as is usually the case, but complete molecules of the drug. In the process, however, the team of more than 100 scientists also discovered something completely unexpected: they found a binding site on the main protease that had been completely unknown until then. "It was not only a nice surprise that we were able to discover a new drug binding site on the main protease - a result that can really only be achieved at a synchrotron light source like PETRA III - but that even one of the two promising drug candidates binds precisely to this site," says Christian Betzel from the excellence cluster CUI of the University of Hamburg, co-initiator of the study.

"A particular strength of our method of X-ray screening compared to other screening methods is that we obtain the three-dimensional structure of the protein-drug complexes as a result and can thus identify the binding of the drugs to the protein at the atomic level. Even if the two most promising candidates do not make it into clinical trials, the 37 substances that bind to the main protease form a valuable database for drug developments based on them," explains Patrick Reinke, DESY researcher and co-author of the publication.

"The investigations at PETRA III impressively show how relevant high-brilliance synchrotron lightsources are for the development of future medicines and for health research as a whole," stresses Helmut Dosch, Chairman of the DESY Directorate. "We must and want to expand our infrastructures even more in the future to cope with health crises like the current one."

April 2, 2021 - For patients undergoing spinal surgery, the diagnosis of cannabis use disorder is associated with higher complication rates, including substantially increased risks of stroke and respiratory complications, reports a study in Spine. The journal is published in the Lippincott portfolio by Wolters Kluwer.

"Chronic cannabis use among patients undergoing spine surgery is associated with higher rates of inpatient neurovascular, thromboembolic, and pulmonary complications, and less favorable overall discharge disposition," according to the new research by Ankit Indravadan Mehta, MD, FAANS and colleagues of the University of Illinois at Chicago. "The treatment of these patients is also associated with increased length of stay and cost of hospitalization."

For chronic cannabis users, surgical care may be 'extremely complex and difficult'

Using a national hospital database (Nationwide Inpatient Sample), the researchers identified nearly 433,000 patients who underwent common elective spinal surgery procedures between 2012 and 2015. About 2,400 patients had a diagnosis of cannabis use disorder, defined as continued use of cannabis despite significant distress or impairment.

On initial analysis, there were some important differences between patients with and without cannabis use disorder. Patients diagnosed with problematic cannabis use were younger, more likely to be male, and had lower rates of accompanying medical disorders (comorbidity). They were also much more likely to use tobacco: about 71 versus 31 percent.

Using a technique called propensity score matching, Dr. Mehta and colleagues created matched groups of 2,184 chronic cannabis users versus non-users with similar characteristics and comorbidities. A wide range of complications and other hospital outcomes of spinal surgery were compared between groups.

Patients with cannabis use disorder were at increased risk for several types of complications after spinal surgery. The cannabis users were about twice as likely to develop respiratory and blood clot-related (thromboembolism) complications. They also had nearly a threefold increase in the risk of stroke and other neurologic complications. Risk of bloodstream infection (septicemia or sepsis) was increased by 50 percent.

There were also more myocardial infarctions (heart attacks) among patients with cannabis use disorder. However, on further analysis, this was related to their much higher rate of tobacco use.

Patients with cannabis use disorder also spent nearly two more days in the hospital (about seven versus five days) and had hospital costs nearly $15,000 higher. They were also more likely to be discharged to a nursing or rehabilitation facility and less likely to receive home health care.

The results are of special concern as cannabis use becomes increasingly legalized and accepted in the United States. Estimates suggest that more than 15 percent of Americans use cannabis. Rates of cannabis use and cannabis use disorder have "increased drastically" in recent years, according to the authors.

The findings have important implications for anesthesia and surgical management in patients with cannabis use disorder, Dr. Mehta and colleagues believe. For example, such patients may need higher doses of opioid medications to achieve adequate pain management after spinal surgery. That may lead to slower recovery, requiring longer hospital stays and more intensive rehabilitation that cannot be done at home. The researchers also note previous studies outlining the mechanisms by which cannabis use may lead to increased risk of respiratory, thromboembolic, and neurologic complications.

"This study reveals multiple aspects of perioperative care that are extremely complex and difficult in patients with cannabis use disorder," Dr. Mehta and coauthors write. "Their high-risk cardiorespiratory profiles combined with specialized anesthetic considerations [before, during, and after surgery] necessitate very unique perioperative management. We hope this research will lead to future prospective trials for specific interventions that could improve outcomes in this specific population."

Obesity rates have increased dramatically in developed countries over the past 40 years -- and many people have assumed that food marketing is at least in part to blame. But are people with obesity really more susceptible to food marketing? And if they are, is that a permanent predisposition, or can it change over time?

According to a new study by UBC Sauder School of Business Assistant Professor Dr. Yann Cornil (he/him/his) and French researchers, people with obesity do tend to be more responsive to food marketing -- but when their weight drops significantly, so does their responsiveness to marketing.

For the study, which was published in the Journal of Consumer Psychology, the researchers followed three groups: patients with severe obesity before they had gastric bypass or other weight-loss surgeries (collectively known as bariatric surgery), as well as three and 12 months after; people with obesity who were not undergoing bariatric surgery; and people who were not obese.

To measure their responsiveness to food marketing, the researchers evaluated what's called framing effects -- that is, how branding, advertising, and labeling "frame," and thus influence food evaluations and choices. In one study, participants were asked to estimate the calorie content in well-known snacks and drinks including some, which marketers typically framed as healthy (i.e. apple juice, granola bars), and others, which are not framed as healthy (i.e. soft drinks, chocolate bars).

The researchers found that everyone underestimated the calorie content of snacks that were framed as healthy but the effect was more pronounced in people with obesity.

To further test the framing effect, the researchers had participants hypothetically choose a portion of french fries from a fast food restaurant, and gave them the nutritional information they would need to make an informed decision. The three options were always the same in quantity -- 71g, 117g, and 154g -- but in one instance they were labeled small, medium and large, and in another instance the same portions were labeled mini, small and medium: a marketing tactic aimed at making larger portions seem more reasonable.

"We measured how likely people were sensitive to that framing, and whether it would change their choice of fries quantity depending on how the portions are labeled," explains Dr. Cornil, who says the people with obesity were more likely to follow the labeling and not the actual information about quantity -- so they would choose the portion labeled "medium" even though that's quite large.

Overall the researchers, who worked closely with the Pitié-Salpêtrière Hospital in Paris, found that the people with obesity tended to be more responsive to food marketing -- but when they lost a significant amount of weight because of bariatric surgery, their level of responsiveness to food marketing dropped substantially.

"People with obesity going through bariatric surgery will become less responsive to marketing over time," says Dr. Cornil. "And after 12 months, their responsiveness to marketing reaches the level of people with more medically-recommended weight."

Dr. Cornil says it's not clear whether people with obesity become less responsive to marketing because of physiological changes following the surgery -- hormonal, neurological shifts or changes to the gut microbiota -- or because of people's desire to change their lifestyles and habits. Another possible reason, he adds, is that people's tastes tend to shift following bariatric surgery.

"The results clearly suggest a bidirectional influence between people's weight status, psychology and responsiveness to the environment -- including marketing," says Dr. Cornil. "So, it's a complex relationship."

However, had the researchers found the responsiveness to marketing remained high even after weight loss, it would have pointed to a deeper-rooted predisposition.

"That would mean people are endowed with unchangeable psychological characteristics that would always make them more responsive to marketing -- which would make it very difficult to sustain a medically-recommended weight," he explains. "But one of the positive things is that after significant weight loss, people become less responsive to marketing, such that it is more sustainable to remain at a lower body mass index."

Dr. Cornil says the findings are especially important because for years, researchers have assumed that marketing messages -- especially for foods that are high-calorie and low in nutrition -- are at least partly responsible for the obesity epidemic, but there wasn't clear empirical evidence.

"Our results provide important insights for policy-makers in charge of regulating food marketing in order to curb obesity," says Dr. Cornil.

Oak Brook, IL - The April edition of SLAS Technology features the cover article "Therapeutic Potential of Reactive Oxygen Species: State of the Art and Recent Advances" by Valeria Graceffa, Ph.D. (Institute of Technology Sligo, Sligo, Ireland).

The cover article explores the therapeutic potential of reactive oxygen species (ROS) including applications ranging from wound healing and hair growth enhancement, to cancer treatment, stem cell differentiation and tissue engineering. At low concentrations, ROS can be utilized as inexpensive and convenient inducers of tissue regeneration, triggering stem cell differentiation and enhancing collagen synthesis. Recent cancer studies have represented ROS as the 'Achilles Heels' of cancers given their high basal levels, leaving tumoral cells unable to sufficiently handle the additional source of oxidative stress. Because of this, higher doses of ROS are used for targeted killing of tumor cells. Lack of understanding of the technicalities between anabolic and cytotoxic effects means limited ROS clinical translation opportunities. While there is ample potential for the use of ROS, new strategies to control temporal pattern of ROS release have yet to be developed.

The April issue of SLAS Technology includes six articles of original research including:

Highly Versatile Cloud-Based Automation Solution for the Remote Design and Execution of Experiment Protocols during the COVID-19 Pandemic

Metabolomic Signatures in Pediatric Crohn's Disease Patients with Mild or Quiescent Disease Treated with Partial Enteral Nutrition: A Feasibility Study

Acoustic Ejection/Full-Scan Mass Spectrometry Analysis for High-Throughput Compound Plate Quality Control

An Emerging Fluorescence-Based Technique for Quantification and Protein Profiling of Extracellular Vesicles

Development of an Enhanced Throughput Radial Cell Migration Device

A Variable Scheduling Maintenance Culture Platform for Mammalian Cells

Other articles include:

Application of Artificial Intelligence to Address Issues Related to the COVID-19 Virus

Therapeutic Potential of Reactive Oxygen Species: State of the Art and Recent Advances

Recent Developments in Bacterial Chemotaxis Analysis Based on the Microfluidic System

Development of a Gold Nanoparticle-Based Colorimetric Sensor for Water for Injection At-Line Impurity Testing

Integrating Mobile Robots into Automated Laboratory Processes: A Suitable Workflow Management System

Genome sequencing of thousands of SARS-CoV-2 samples shows that surges of COVID-19 cases are driven by the appearance of new coronavirus variants, according to new research from the School of Veterinary Medicine at the University of California, Davis published April 1 in Scientific Reports.

"As variants emerge, you're going to get new outbreaks," said Bart Weimer, professor of population health and reproduction at the UC Davis School of Veterinary Medicine. The merger of classical epidemiology with genomics provides a tool public health authorities could use to predict the course of pandemics, whether of coronavirus, influenza or some new pathogen.

Although it has just 15 genes, SARS-CoV-2 is constantly mutating. Most of these changes make very little difference but sometimes the virus becomes more or less transmissible.

Weimer and graduate student DJ Darwin R. Bandoy initially analyzed the genomes of 150 SARS-CoV-2 strains, mostly from outbreaks in Asia prior to March 1, 2020, as well as epidemiology and transmission information for those outbreaks. They classified outbreaks by stage: index (no outbreak), takeoff, exponential growth and decline. The ease of transmission of a virus is set by the value R, or reproductive number, where R is the average number of new infections caused by each infected person.

They combined all this information into a metric called GENI, for pathogen genome identity. Comparing GENI scores with the phase of an epidemic showed that an increase in genetic variation immediately preceded exponential growth in cases, for example in South Korea in late February. In Singapore, however, bursts of variation were associated with smaller outbreaks that public health authorities were able to quickly bring under control.

20,000 virus samples

Weimer and Bandoy then looked at 20,000 sequences of SARS-CoV-2 viruses collected and from February to April 2020 in the United Kingdom and compared them with data on cases.

They found that the GENI variation score rose steadily with the number of cases. When the British government imposed a national lockdown in late March, the number of new cases stabilized but the GENI score continued to rise. This shows that measures such as banning gatherings, mask mandates and social distancing are effective in controlling spread of disease in the face of rapid virus evolution.

It could also help explain "superspreader" events when large numbers of people get infected in a single incident where precautions are relaxed.

Weimer said he hopes that public health authorities will take up the approach of measuring virus variation and linking it to the local transmission rate, R.

"In this way you can get a very early warning of when a new outbreak is coming," he said. "Here's a recipe for how to go about it."

In some cancers, including leukemia in children and adolescents, obesity can negatively affect survival outcomes. Obese young people with leukemia are 50% more likely to relapse after treatment than their lean counterparts.

Now, a study led by researchers at UCLA and Children's Hospital Los Angeles has shown that a combination of modest dietary changes and exercise can dramatically improve survival outcomes for those with acute lymphoblastic leukemia, the most common childhood cancer.

The researchers found that patients who reduced their calorie intake by 10% or more and adopted a moderate exercise program immediately after their diagnosis had, on average, 70% less chance of having lingering leukemia cells after a month of chemotherapy than those not on the diet-and-exercise regimen.

Lingering cancer cells in the bone marrow, which are more likely to be found in overweight individuals, are associated with worse survival and a higher risk of relapse, often leading to more intense treatments like bone marrow transplants and immunotherapy.

"We tested a very mild diet because this was our first time trying it, and the first month of treatment is already so difficult for patients and families," said senior author Dr. Steven Mittelman, chief of pediatric endocrinology at UCLA Mattel Children's Hospital and a member of the UCLA Jonsson Comprehensive Cancer Center. "But even with these mild changes in diet and exercise, the intervention was extremely effective in reducing the chance of having detectable leukemia in the bone marrow."

As part of the clinical trial, which took place at Children's Hospital Los Angeles, researchers worked with registered dieticians and physical therapists to create personalized 28-day interventions for 40 young people between the ages of 10 and 21 who were newly diagnosed with acute lymphoblastic leukemia.

The intervention was designed to cut participants' calorie intake by a minimum of 10% in order to reduce both fat gain and lean muscle loss. The physical activity component included a target level of 200 minutes per week of moderate exercise.

The results, published in the American Society of Hematology's journal Blood Advances, showed a decrease in fat gain among those who were overweight and obese, as well as an improved insulin sensitivity and an increase in the beneficial hormone adiponectin, which is involved in regulating glucose and breaking down fatty acids. Most importantly, the researchers found a 70% decrease in the chance of having lingering leukemia cells in the bone marrow -- known medically as minimal residual disease -- when compared with a historical control group.

"We hoped the intervention would improve outcomes, but we had no idea it would be so effective," Mittelman said. "We can't really add more toxic chemotherapies to the intense initial treatment phase, but this is an intervention that likely has no negative side effects. In fact, we hope it may even reduce toxicities caused by chemotherapy."

"This is the first trial to test a diet-and-exercise intervention to improve treatment outcomes from a childhood cancer," said principal investigator and lead author Dr. Etan Orgel, Director of the Medical Supportive Care Service in the Cancer and Blood Disease Institute at Children's Hospital Los Angeles. "This is an exciting proof-of-concept, which may have great implications for other cancers as well."

Next steps include further testing of the approach in a multicenter randomized trial, which will be launched later this year, the researchers said.

Hamilton, ON (April 1, 2021) - People living with the often-debilitating effects of Crohn's disease may finally gain some relief, thanks to ground-breaking research led by McMaster University.

McMaster investigator Brian Coombes said his team identified a strain of adherent-invasive E-coli (AIEC) that is strongly implicated in the condition and is often found in the intestines of people with Crohn's disease.

"If you examine the gut lining of patients with Crohn's disease, you will find that around 70 to 80 per cent of them test positive for AIEC bacteria, but one of the things we don't understand is why," said Coombes, professor and chair of the Department of Biochemistry and Biomedical Sciences, and the Canada Research Chair in Infectious Disease Pathogenesis.

"We believe that AIEC is a potential trigger of Crohn's disease."

By mutating every gene in a particular strain of AIEC and testing how those mutants grow in mice, the researchers were able to pinpoint which genes allowed the bacteria to freely colonize the gut linings of people with Crohn's disease.

AIEC bacteria grow in a biofilm that coats cells lining the intestinal wall, protecting them from both the immune system and antibiotics. In this research, the team identified a critical protein structure on the surface of the bacteria that allow them to grow in biofilms.

Coombes said Crohn's disease is caused by the immune system's inability to "switch off" its inflammatory response to gut bacteria. Symptoms include severe diarrhoea, fatigue, weight loss and malnutrition.

Current treatments focus on easing the inflammation, but do not address the root cause of the condition.

"New therapies are on the way - we are one step closer to figuring out how this Crohn's disease-associated bacteria lives in the gut and when we do that, we can develop new treatments," said Coombes.

The team's findings were led by postdoctoral fellow, Wael Elhenawy and published in Nature Communications.

LA JOLLA--(April 1, 2021) Neurons lack the ability to replicate their DNA, so they're constantly working to repair damage to their genome. Now, a new study by Salk scientists finds that these repairs are not random, but instead focus on protecting certain genetic "hot spots" that appear to play a critical role in neural identity and function.

The findings, published in the April 2, 2021, issue of Science, give novel insights into the genetic structures involved in aging and neurodegeneration, and could point to the development of potential new therapies for diseases such Alzheimer's, Parkinson's and other age-related dementia disorders.

"This research shows for the first time that there are sections of genome that neurons prioritize when it comes to repair," says Professor and Salk President Rusty Gage, the paper's co-corresponding author. "We're excited about the potential of these findings to change the way we view many age-related diseases of the nervous system and potentially explore DNA repair as a therapeutic approach."

Unlike other cells, neurons generally don't replace themselves over time, making them among the longest-living cells in the human body. Their longevity makes it even more important that they repair lesions in their DNA as they age, in order to maintain their function over the decades of a human life span. As they get older, neurons' ability to make these genetic repairs declines, which could explain why people develop age-related neurodegenerative diseases like Alzheimer's and Parkinson's.

To investigate how neurons maintain genome health, the study authors developed a new technique they term Repair-seq. The team produced neurons from stem cells and fed them synthetic nucleosides--molecules that serve as building blocks for DNA. These artificial nucleosides could be found via DNA sequencing and imaged, showing where the neurons used them to make repairs to DNA that was damaged by normal cellular processes. While the scientists expected to see some prioritization, they were surprised by just how focused the neurons were on protecting certain sections of the genome.

"What we saw was incredibly sharp, well-defined regions of repair; very focused areas that were substantially higher than background levels," says co-first and co-corresponding author Dylan Reid, a former Salk postdoctoral scholar and now a fellow at Vertex Pharmaceutics. "The proteins that sit on these 'hot spots' are implicated in neurodegenerative disease, and the sites are also linked to aging."

The authors found approximately 65,000 hot spots that covered around 2 percent of the neuronal genome. They then used proteomics approaches to detect what proteins were found at these hot spots, implicating many splicing-related proteins. (These are involved in the eventual production of other proteins.) Many of these sites appeared to be quite stable when the cells were treated with DNA-damaging agents, and the most stable DNA repair hot spots were found to be strongly associated with sites where chemical tags attach ("methylation") that are best at predicting neuronal age.

Previous research has focused on identifying the sections of DNA that suffer genetic damage, but this is the first time researchers have looked for where the genome is being heavily repaired.

"We flipped the paradigm from looking for damage to looking for repair, and that's why we were able to find these hot spots," Reid says. "This is really new biology that might eventually change how we understand neurons in the nervous system, and the more we understand that, the more we can look to develop therapies addressing age-related diseases."

Gage, who holds the Vi and John Adler Chair for Research on Age-Related Neurodegenerative Disease, adds, "Understanding which areas within the genome are vulnerable to damage is a very exciting topic for our lab. We think Repair-seq will be a powerful tool for research, and we continue to explore additional new methods to study genome integrity, particularly in relation to aging and disease."

Chestnut Hill, MA (4/1/2021) - A gender gap in negotiation emerges as early as age eight, a finding that sheds new light on the wage gap women face in the workforce, according to new research from Boston College's Cooperation Lab, lead by Associate Professor of Psychology and Neuroscience Katherine McAuliffe.

The study of 240 boys and girls between ages four and nine, published recently in the journal Psychological Science, found the gap appears when girls who participated in the study were asked to negotiate with a male evaluator, a finding that mirrors the dynamics of the negotiation gap that persists between men and women in the workforce.

The researchers say this study is the first to identify a gender gap in negotiation among children.

"We found that--consistent with adult work--girls asked for less than boys when negotiating with a man," said McAuliffe. "We did not see this gender gap when children were negotiating with a woman. There is still much more work to be done, but one thing this tells us is that we should be teaching young girls to advocate for themselves in the context of negotiation from as early elementary school."

The results point to a disparity that takes root in childhood which may help explain the well-documented gender gap in pay that separates women and men, said McAuliffe, who co-authored the study with New York University graduate student Sophie Arnold, who spent two summers working in McAuliffe's Cooperation Lab, which studies how attributes like fairness develop in children.

McAuliffe and Arnold say the findings reveal a need to determine if cultural signals sent to girls are to blame and whether there should be interventions in childhood to ensure that both girls and boys feel comfortable advocating for themselves, regardless of the gender of the person they are talking with.

"Boys and girls performed equally between the ages of four and seven," said Arnold, whose work on the project became her undergraduate honors thesis at the University of Chicago. "But by age eight, we see girls are requesting less than boys when they are negotiating with a man. It's not that girls are negotiating less overall - it's only when children are negotiating with a man that we see these gender differences emerge."

Prior studies of adults have found gender differences in negotiation, but could not explain their origins, said the authors. The researchers tested 240 children between the ages of 4 and 9 to determine whether girls in the age range would negotiate differently than boys and whether girls, like women, would ask for less from a man than a woman.

"Although adult research supports the existence of gender differences in negotiation, it cannot reveal their origins. Learning when these gender differences emerge is imperative for understanding what individual and societal factors lead to these gender differences in adulthood," write Arnold and McAuliffe.

The experiments were modeled on real-world scenarios, the authors said. In phase one, children completed a task and then were allowed to ask for as many stickers as they liked as a reward. Unbeknownst to them, the evaluator would always accept requests for two stickers or less, and always reject requests above that threshold. If a request was rejected, negotiations would progress to the next phase.

In the second phase, the evaluator explained the rules of negotiation to the children and spelled out how their next sticker requests could be handled in a way that highlighted the risk and reward inherent to negotiations.

The results revealed a significant interaction between age, participant gender, and evaluator gender. For girls, the number of stickers initially requested decreased with age when the evaluator was a male. When the evaluator was female, girls requested more stickers with age.

Boys, on the other hand, made requests that did not change with age or the gender of the evaluator.

In measuring persistence, a proxy for negotiation length, the study found that girls' persistence decreased with age when the evaluator was male, but remained the same with age when the evaluator was female. For boys, persistence did not change with age or depending on the gender of the evaluator.

"Our study is the first to show that gender differences in negotiation emerge in childhood," the co-authors write. "Older girls in our paradigm differed from boys in how much they were willing to ask for from a male evaluator, showing a striking resemblance to findings in adults. Girls are not asking for less from both evaluators but instead are negotiating less only with the male evaluator."

"Our findings add negotiation to the list of early-developing gendered behaviors that may lead to and magnify the wage gap in adulthood," the researchers report.

McAuliffe said the next steps in this area of study include trying to determine why these differences emerge.

She and Arnold highlighted two potential avenues for future research: status and gender stereotypes. It could be the case that the gender differences observed in this study are not unique to gender but reflect a more general dynamic due to perceived status of social groups. Namely, that individuals perceived to be a part of a lower status group (in the US, with respect to gender, this would be girls or women) request less from individuals who are perceived to be part of a higher status group (men).

With respect to gender stereotypes, it could be the case that girls are adopting gender stereotypes about communality or modesty that in turn shape their behavior with men. More research is needed to understand how these avenues contribute to the development of gender differences in negotiation.

The challenge of the next steps in this research are clarifying exactly what explains the development of this behavior and trying to develop interventions that could help remedy the imbalance, said McAuliffe.

Children and young adults who receive CAR T-cell therapy for the most common childhood cancer - acute lymphoblastic leukemia - suffer remarkably fewer relapses and are far more likely to survive when the treatment is paired with a subsequent stem cell transplant, a new study finds.

The research, with an average follow up of nearly five years, suggests that stem cell transplants offer long-term benefits for young patients who receive the cutting-edge immunotherapy. CAR T-cell therapy results in complete remission in 60%-100% of patients initially, but the relapse rate is high. However, among those who received a stem cell transplant after CARs, the relapse rate was less than 10% two years later.

"More than 50% of kids in other studies with a different CAR relapse, with the majority of them losing the target the CAR goes after," said researcher Daniel "Trey" Lee, MD, a pediatric oncologist and Director of Pediatric Stem Cell Transplant and Immunotherapy at UVA Children's and the UVA Cancer Center. "Most of these kids have a single shot at this life-saving and paradigm-changing therapy called CAR T-cells. We should do all we can to maximize the chance for a cure, and right now that means a transplant after CAR therapy for most."

About CAR T-Cell Therapy

Chimeric antigen receptor (CAR) T-cell therapy takes a person's own immune cells and genetically modifies them to make them more effective cancer killers.

The approach has shown high remission rates - up to 100% - 28 days after it is given to children and young adults with B-cell acute lymphoblastic leukemia. But a significant number relapse, the limited data available suggests. One study found that more than 40% had relapsed 13.1 months later.

To determine if stem cell transplants could help, the new study looked at outcomes in 50 children and young adults, ages 4 to 30. The median age was 13.5 years.

Among the 21 who received an allogenic stem cell transplant after CARs, only 9.5% had relapsed 24 months later. In comparison, all of those who did not receive a stem-cell transplant had relapsed.

"Even as impactful as CAR T-cell therapy is for children with relapsed leukemia, we now know that the best outcomes happen when the child undergoes a stem cell transplant afterwards," Lee said. "Many parents turn to CAR T-cells to possibly avoid a stem cell transplant, and that is entirely understandable. But there is a window of opportunity after CARs to cure more of these incurable kids with a transplant; our study demonstrates this." His hope for the future is for the field to be able to distinguish up front those who need a transplant and those who do not.

A series of studies led by researchers from Hong Kong Baptist University (HKBU) have revealed that hyocholic acid and its derivatives (collectively known as HCAs), a component of bile acids that facilitate fat digestion, are a promising risk indicator of type 2 diabetes. The strong efficacy of HCAs in regulating blood glucose levels and protecting against diabetes has also been uncovered. The findings open a window for the development of HCA-based predictive markers as well as anti-diabetic drugs.

The research results have been published in the international scientific journals Cell Metabolism and Nature Communications.

High concentration of HCAs protects pigs from diabetes

Inspired by the traditional Chinese medical book Compendium of Materia Medica, which recorded the use of pig bile to treat excessive thirst, a condition known today as diabetes, Professor Jia Wei, Chair Professor of the School of Chinese Medicine at HKBU, led research teams to conduct a series of studies on the role of HCAs in glucose homeostasis and diabetes prevention.

Diabetes is characterised by high blood glucose levels. Through a series of tests conducted on 55 humans, 32 mice and 12 pigs, Professor Jia's team confirmed that fasting blood glucose levels in pigs are significantly lower than that of humans and mice. As HCAs constitute nearly 80% of bile acids in pigs, while the proportions in humans and mice are only about 2% and 3% respectively, a negative correlation between HCAs and blood glucose levels was observed.

The result indicates the potential role of HCAs in the maintenance of stable glucose levels. This may explain why pigs, unlike humans, seldom suffer from diabetes despite their low physical activity levels and consumption of a calorie-rich diet.

HCAs correlate with diabetes and metabolic health

To analyse the correlation between the levels of HCAs and the occurrence of diabetes in humans, data was collected from two large-scale cohort studies, namely the Shanghai Obesity Study and the Shanghai Diabetes Study. The researchers examined the serum bile acid profiles of 1,107 participants of the Shanghai Obesity Study, which was published in 2013. The participants were divided into three groups: healthy lean, healthy obese and obese with type 2 diabetes. It was discovered that the levels of serum HCAs were significantly lower in the healthy obese and obese with type 2 diabetes groups.

In another study, the serum bile acids of 132 participants of the Shanghai Diabetes Study were investigated. They were all healthy (at baseline) when they were enrolled in the study between 1998 and 2001. Ten years later, 86 of them had become metabolically unhealthy, while 46 remained healthy. Analysis showed that, compared with those who remained healthy ten years later, those who had become metabolically unhealthy had significantly lower baseline levels of serum HCAs, illustrating that levels of HCAs are a strong predictor of metabolic syndromes such as diabetes.

HCAs regulate blood glucose levels in animal models

Through a series of laboratory experiments, the researchers looked further into the mechanisms that underpin the key role that HCAs play in regulating blood glucose levels. In an animal model experiment, the researchers suppressed the synthesis of HCAs in the livers of a group of pigs by around 30%, and they found that their blood glucose levels increased by 30% when compared with the control group. HCAs were then given to the pigs, after which their blood glucose levels eased off.

Another experiment conducted by the researchers focused on the effect of HCAs on glucagon-like peptide-1 (GLP-1). GLP-1 is a hormone produced by L-cells, a type of enteroendocrine cell that enhances insulin secretion and decreases blood glucose. In a laboratory setting, different kinds of bile acids, including HCAs, were applied to L-cells, at varying levels of concentration. Results showed that at a high concentration of 50 micromolar, HCAs were the most effective at stimulating GLP-1 secretion when compared with other types of bile acids. The findings also revealed that HCAs regulate blood glucose levels by stimulating the secretion of GLP-1 and thus insulin production.

Potential for diabetes prediction and treatment

"The results of our studies provide evidence of how HCAs help to regulate blood glucose levels, and they have revealed the mechanism of how it is achieved at a cellular level. HCAs demonstrate promising potential, and they could be developed into an agent for the prediction and treatment of type 2 diabetes," said Professor Jia.

"As gut microbiota can regulate the metabolism of HCAs, targeting the intestines instead of the pancreas could be a prospective novel strategy for treating diabetes. We will further investigate how to increase the secretion levels of HCAs in diabetic patients by regulating the intestinal bacteria," he added.

Autistic adults can be wrongly perceived as deceptive and lacking credibility, Flinders University researchers say, with this working against many caught in the legal system.

Ahead of World Autism Awareness Day (2 April 2021), a new paper in the Journal of Autism and Developmental Disorders asked 1,410 civilians to respond to video recordings with 30 adults with Autism Spectrum Disorder (ASD) and 29 non-ASD individuals to examine whether stereotypical behaviors associated with autism influenced people's perceptions of the individual.

Common behaviors include gaze aversion, repetitive body movements, literal interpretations of figurative language and poor reciprocity.

Co-author Flinders Professor Robyn Young, author of Crime and Autism Spectrum Disorder: Myths and Mechanisms (2015) with Emeritus Professor Neil Brewer, says "it's unfortunate that many of the behaviors that are believed to be portrayed by people who are being deceptive, often erroneously, are also commonly seen among people on the autism spectrum".

These behaviors can therefore disadvantage a person who has autism when they interact with the criminal judicial system, the Flinders University professors argue.

Professor Young regularly consults with the legal system to educate judges and juries about ASD so that an autistic person's presentation will not be misinterpreted by people who do not understand their condition. "We have now extracted recent statistics suggesting that sentences of autistic people are on average higher than their non-autistic peers who have committed similar offences," she says.

"If you ask most people how they determine if someone is not telling the truth, they will often refer to lack of eye contact or fidgety behavior," says lead author Dr Alliyza Lim.

"Even though our study actually showed that none of these behaviors individually were directly linked to a person being considered as less credible and more deceptive, overall autistic people are considered less reliable than their non-ASD peers."

Autistic individuals may be erroneously perceived as deceptive and lacking credibility (2021) by A Lim, RL Young and N Brewer has been published in the Journal of Autism and Developmental Disorders (Springer Nature) DOI 10.1007/s10803-021-04963-4.

Autism, or ASD, refers to a broad range of conditions characterised by challenges with social skills, repetitive behaviours, speech and non-verbal communication. Autism affects an estimated 1 in 160 children and the WHO is calling for more intervention services and broader actions for making physical, social and attitudinal environments more accessible, inclusive and supportive for people with ASD.

An Autism Awareness Australia report (2020) revealed 60.5% of adults with ASD surveyed had communication issues and 48% behaviour issues which led them to seek help.