Earth

At least 26 per cent of our oceans need urgent conservation attention to preserve Earth’s marine biodiversity, a University of Queensland-led international study has found.

Dr Kendall Jones said the international community needed to rapidly increase marine conservation efforts to maintain the health of the world’s oceans.

“Preserving a portion of habitat for all marine species would require 8.5 million square kilometres of new conservation areas,” Dr Jones said.

“Currently one-third of all marine species have less than 10 per cent of their range covered by protected areas.

“Conserving the areas we’ve identified in our study would give all marine species a reasonable amount of space to live free from human impacts like fishing, commercial shipping or pesticide runoff.”

The authors mapped more than 22,000 marine species habitats and applied a mathematical approach to identify the minimum area required to capture a portion of each species range.

They also included areas of international importance for biodiversity (known as Key Biodiversity Areas), and areas where human impacts on the ocean are extremely low (known as marine wildernesses).

They found that the total ocean area required for conservation varied from 26-41 per cent, depending on the proportion of each species range conserved.

Key regions for conservation included the Northern Pacific Ocean near China and Japan, and the Atlantic between West Africa and the Americas.

Director of Science at the Wildlife Conservation Society and UQ scientist Professor James Watson said the findings demonstrated the need for greater worldwide conservation efforts.

“The world’s nations will be coming together in China this year to sign an agreement that will guide global conservation for the next ten years,” Professor Watson said.

“This science shows that governments must act boldly, as they did for the Paris Agreement on climate change, if we are to stop the extinction crisis facing many marine species.”

Professor Watson said it was crucial that global conservation strategies involved rapid action to protect endangered species and ecosystems, combined with approaches to sustainably manage the ocean in its entirety.

“This isn’t just about strict marine protected areas,” he said.

“We need to use a broad range of strategies such as no-fishing zones, community marine reserves and broad-scale policies to put an end to illegal and unsustainable commercial fishing operations.”

The authors stress that ocean conservation was essential for people and biodiversity.

“Millions of people around the world depend on marine biodiversity as a crucial source of food and income,” Professor Watson said.

“A well-designed global conservation agreement will help preserve these livelihoods into the future.”

Macrocycles are molecules made of large rings of atoms. Despite being relatively big and flexible, the molecules don't always stay "floppy" -- they can actually lock themselves into specific shapes and geometries.

In manufacturing, controlling the three-dimensional shapes of macrocycles is critical. It helps decide, for example, whether the aroma in a perfume is unique or whether a prescription drug will work on a particular disease.

But for synthetic chemists, those who study the construction of molecules, controlling the topology of the large rings has not been a straightforward process - until now, that is, thanks to research done at Université de Montréal.

In a study published today in Science, a team led by chemistry professor Shawn Collins reports they have succeeded in using a natural process called biocatalysis to control the shapes of macrocycles.

And that could be a boon for the making of pharmaceuticals and electronics, they say.

"The shapes of the macrocycles we have made is what makes them special -- they are what we call planar chiral," said Collins. "And the planar chiral topology controls how the molecules interact with nature. In general, macrocycles with planar chirality are underexplored, because chemists usually have a lot of trouble making them."

Until now, they had two choices: perform multi-step syntheses that are tedious and wasteful, or they could exploit methods that employ catalysts based on elements that are toxic, expensive and non-abundant in the Earth's crust, such as ruthenium and rhodium.

Both approaches have long frustrated chemists, and Collins' team looked for an alternative. They found it in biocatalysis, a process that uses enzymes, biological and typically non-toxic catalysts, as a solution to preparing planar chiral macrocycles.

Remarkably, even though chemists had never before explored biocatalysis for the synthesis of planar chiral macrocycles, it turned out there was a commercially available product that could prepare the macrocycle: a lipase enzyme called CALB.

Using it, the biocatalysts were able to shape the macrocycles in often near-perfect selectivity, even though the enzyme had not evolved for that purpose.

Importantly, Collins and his team came up with a synthetic plan that involved using simple molecular building blocks to "decorate" macrocycles with functionality. "Functionality are handles, or simple groups of atoms that be easily transformed into arrangements that are more complex," Collins explained.

"Our hope is that the macrocycles can now be tailored to impact industry. Planar chiral macrocycles have already been known to act as antibiotics and anticancer agents. Applications in electronic materials -- in lasers and display devices, for example -- could be possible using the approach."

DNA is the hereditary material in humans, a unique cookbook of who we are. This is where you'll find the answer as to why you have your specific eye and hair colour, or perhaps why you sunburn easily.

Imagine your DNA as a giant cookbook with thousands of recipes. These recipes are genes that have to be read every single day.

You may think that a skin cell only contains the recipes it needs to work as a skin cell, and that a muscle cell only contains the recipes that make it a muscle cell. While this might seem logical, this is not how information in cells is stored.

The skin cell contains the recipes for all the other cell types as well. All cells of our body have the same "cookbook" with the same "recipes" - even though only a specific set of recipes is read in each cell. The process of reading the recipes is known as transcription.

How do skin cells know which recipes they need? And how can they know which recipes they shouldn't use? Or that one or more recipes contain mistakes that will completely spoil the dish?

What determines which recipe should be used in which cell are the little "notes" that "helpers" place on each of the recipes: "Cook this one!" "Don't use this recipe!" "Watch out for the mistake on page 237!"

These helpers are called enzymes. The notes are called epigenetic marks.

While there are many recipes that need to be used in each cell, every recipe needs to result in a five-star dish, every time. However sometimes the food is cooked too fast, resulting in certain dishes being imperfect, a bit too salty, or too spicy. When the "food" is cooked in a hurry, with small mistakes being made in certain dishes, the cells can become cancer cells. The cancer cells are thus like a super-stressed chef.

Similarly, mistakes in some of the "recipes" can lead to other diseases, like ALS or intellectual disabilities.

Is it possible to correct the recipes, or prevent cooking of the bad dishes? In other words, how can we stop cancer cell growth?

The traditional way to treat cancer is to use drugs that remove cancer cells, which contain multiple incorrect "recipes" and divide too fast.

"Drugs currently used in clinics target specific cancer cells properties, with the aim to eradicate cancer," says Barbara van Loon.

Barbara van Loon came to the Norwegian University of Science and Technology (NTNU) from Switzerland a few years ago as an Onsager and Outstanding Academic Fellow. She worked as research fellow previously at MIT and the University of Zurich.

Very recently she and her research team made a novel discovery about the repair of genetic information, which was published in the renowned journal Nature Communications.

Van Loon's research team discovered that the "helpers" which read the recipes, and the "helpers" that correct them, work together.

Van Loon says that through cross-talk with transcription machinery repair enzymes both maintain the integrity of genetic information, as well as influence how this information is being used.

The communication between various "helpers" is required, both to correct the mistakes in the recipes, as well as to determine how final dishes will be made.

The findings of Van Loon group provide new insights into maintenance of genetic information, stored within the "cookbook of life", and have long-term potential to serve as basis for development of drugs to treat diseases, like cancer.

As we all know, during our life, we make good choices as well as certain bad ones. Perhaps we eat too much unhealthy food, or have a bad life style. We may live in a city with high air pollution. Maybe we smoke.

All of these choices can cause changes in the cookbook recipes. Although the recipes were correct to begin with, the life we ??live can lead to mistakes, which can pile up and consequently lead to onset of diseases, like cancer.

"Detailed understanding of basic cellular processes is the key to development of better treatments," says Van Loon.

Van Loon works in basic scientific research, and studies fundamental processes in human body. Her research focuses on discovering new cellular relationships.

Basic research provides the important knowledge that is the foundation for major breakthroughs in medical treatments.

These new findings are an important piece of a large puzzle that may result in breakthroughs such as development of novel therapies.

Lightning - one, two, three - and thunder. For centuries, people have estimated the distance of a thunderstorm from the time between lightning and thunder. The greater the time gap between the two signals, the further away the observer is from the location of the lightning. This is because lightning propagates at the speed of light with almost no time delay, while thunder propagates at the much slower speed of sound of around 340 metres per second.

Earthquakes also send out signals that propagate at the speed of light (300,000 kilometers per second) and can be recorded long before the relatively slow seismic waves (about 8 kilometers per second). However, the signals that travel at the speed of light are not lightning bolts, but sudden changes in gravity caused by a shift in the earth's internal mass. Only recently, these so-called PEGS signals (PEGS = Prompt elasto-gravity signals) were detected by seismic measurements. With the help of these signals, it might be possible to detect an earthquake very early before the arrival of the destructive earthquake or tsunami waves.

However, the gravitational effect of this phenomenon is very small. It amounts to less than one billionth of the earth's gravity. Therefore, PEGS signals could only be recorded for the strongest earthquakes. In addition, the process of their generation is complex: they are not only generated directly at the source of the earthquake, but also continuously as the earthquake waves propagate through the earth's interior.

Until now, there has been no direct and exact method to reliably simulate the generation of PEGS signals in the computer. The algorithm now proposed by the GFZ researchers around Rongjiang Wang can calculate PEGS signals with high accuracy and without much effort for the first time. The researchers were also able to show that the signals allow conclusions to be drawn about the strength, duration and mechanism of very large earthquakes. The study was published in the journal Earth and Planetary Science Letters.

An earthquake shifts the rock slabs in the earth's interior abruptly, and thus changes the mass distribution in the earth. In strong earthquakes, this displacement can amount to several meters. "Since the gravity that can be measured locally depends on the mass distribution in the vicinity of the measuring point, every earthquake generates a small but immediate change in gravity," says Rongjiang Wang, scientific coordinator of the new study.

However, every earthquake also generates waves in the earth itself, which in turn change the density of the rocks and thus the gravitation a little bit for a short time - the earth's gravity oscillates to some extent in sync with the earthquake. Furthermore, this oscillating gravity produces a short-term force effect on the rock, which in turn triggers secondary seismic waves. Some of these gravitationally triggered secondary seismic waves can be observed even before the arrival of the primary seismic waves.

"We faced the problem of integrating these multiple interactions to make more accurate estimates and predictions about the strength of the signals," says Torsten Dahm, head of the section Physics of Earthquakes and Volcanoes at GFZ. "Rongjiang Wang had the ingenious idea of adapting an algorithm we had developed earlier to the PEGS problem - and succeeded."

"We first applied our new algorithm to the Tohoku quake off Japan in 2011, which was also the cause of the Fukushima tsunami," says Sebastian Heimann, program developer and data analyst at GFZ. "There, measurements on the strength of the PEGS signal were already available. The consistency was perfect. This gave us certainty for the prediction of other earthquakes and the potential of the signals for new applications."

In the future, by evaluating the changes in gravity many hundreds of kilometres away from the epicentre of an earthquake off the coast, this method could be used to determine, even during the earthquake itself, whether a strong earthquake is involved that could trigger a tsunami, according to the researchers. "However, there is still a long way to go," says Rongjiang Wang. "Today's measuring instruments are not yet sensitive enough, and the environmentally induced interference signals are too great for the PEGS signals to be directly integrated into a functioning tsunami early warning system."

HAMILTON, ON - New research from McMaster Children's Hospital shows that two out of three young mothers have at least one mental health problem.

Researchers found that teen mothers have a much higher prevalence of mental health challenges than mothers aged 21 and older and teens who aren't parents. Almost 40% of young moms have more than one mental health issue,
including depression, a range of anxiety disorders and hyperactivity. This is up to four times higher than in mothers aged 21 years or older and teens without children.

"Now that we understand that young mothers can struggle with problems other than just postpartum depression, our findings can be used to develop better screening processes, more effectively detect mental health problems in teenaged mothers, and direct treatment," says Dr. Ryan Van Lieshout, a psychiatrist and Canada Research Chair in the Perinatal Programming of Mental Disorders. He is also an associate professor of psychiatry and behavioural neurosciences at McMaster University.

"We hope that this sparks partnerships between healthcare, educational, and social service organizations so that we can meet the needs of this vulnerable population."

The study, recently published in the Journal of Adolescent Health, says identifying and treating mental health issues in young mothers is especially important as their health also affects the wellbeing of their children. The research recommends "further efforts should be directed at engaging and treating this high-risk group."

"Young mothers can face a great deal of adversity both before and after becoming a parent, yet next-to-nothing has been known about the rates and types of significant mental health problems among these women in our community," says Dr. Van Lieshout. "We did this study to better understand these problems so that we can help to improve outcomes for young mothers and their families."

Between 2012 and 2015, the Young Mothers Health Study recruited 450 mothers aged younger than 21 years old and 100 comparison mothers aged older than 20 years old at the time of their first delivery. The moms were from Hamilton, Niagara, Haldimand-Norfolk, and Brant counties. Funded by Hamilton Health Sciences, this study is the first in Canada and one of the first in the world to use diagnostic interviews to examine a range of mental health problems beyond postpartum depression.

"Because Canadian teen mothers are a difficult group to study, most previous research was based on very small samples and used mailed questionnaires rather than doing direct interviews," says Dr. Van Lieshout, who was lead author on the research paper. "Structured diagnostic interviews are the gold standard for this kind of research. We're glad to have used this method to talk to hundreds of young mothers about their experiences."

Age-matched young mothers were also compared with 15- to 17-year-old women without children from the 2014 Ontario Child Health Study who were assessed for mental disorders.

The low-pressure area that has been lingering west-northwest of American Samoa for several days has organized into a tropical depression. NASA's Terra satellite passed over the Southern Pacific Ocean and provided forecasters with a visible image of Tropical Depression 18P.

On Feb.21, the Moderate Resolution Imaging Spectroradiometer or MODIS instrument that flies aboard NASA's Terra satellite provided a visible image of 18P that showed an improved cyclonic circulation along the southern end of a line of deep convection and thunderstorms that extends north-to-south.

At 10 a.m. EST (1500 UTC) on Feb. 21, the Joint Typhoon Warning Center said Tropical Cyclone 18P had maximum sustained winds near 30 knots (34.5 mph/55.5 kph). It was located near latitude 12.9 degrees south and longitude 174.8 degrees west, about 280 nautical miles west-northwest of Pago Pago, American Samoa. 18P is moving to the east-southeast.

The tropical cyclone is forecast to intensify to a tropical storm reaching maximum sustained winds to 45 knots as it passes near American Samoa on Feb. 22. In three days, vertical wind shear is expected to kick in which will cause the storm to dissipate quickly.

In addition to Tropical Cyclone 18P, Tropical Storm Vicky has developed to the southeast of American Samoa. Together, these systems have generated several warnings and watches. On Feb. 21, the National Weather Service (NWS) in Pago Pago has continued the Flash Flood Watch for all of American Samoa through Saturday, Feb. 22. The NWS forecast page stated, "The active monsoon trough remains across the area with several hybrid lows developing northwest and moving swiftly across the islands through the week. A flash flood watch means that conditions may develop that lead to flash flooding. Flash flooding is a very dangerous situation."

NASA's Terra satellite is one in a fleet of NASA satellites that provide data for hurricane research.

Tropical cyclones/hurricanes are the most powerful weather events on Earth. NASA's expertise in space and scientific exploration contributes to essential services provided to the American people by other federal agencies, such as hurricane weather forecasting.

Researchers at CHU Sainte-Justine and Université de Montréal have discovered a new mechanism involved in the expression of Down syndrome, one of the main causes of intellectual disability and congenital heart defects in children. The study's findings were published today in Current Biology.

Down syndrome (SD), also called trisomy 21 syndrome, is a genetic condition that affects approximately one in every 800 children born in Canada. In these individuals, many genes are expressed abnormally at the same time, making it difficult to determine which genes contribute to which differences.

Professor Jannic Boehm's research team focused on RCAN1, a gene that is overexpressed in the brains of fetuses with Down syndrome. The team's work provides insights into how the gene influences the way the condition manifests itself.

Synaptic plasticity, memory and learning

The human brain is made up of hundreds of billions of cells known as neurons. They communicate with each other through synapses, which are small gaps between neurons. The ability of synapses to strengthen or weaken over time is known as "synaptic plasticity." It's an important biological phenomenon because it's essential for memory and learning.

"There are two kinds of synaptic plasticity: long-term potentiation, which strengthens synapses and improves interaction between neurons, and long-term depression, which weakens synapses," said Boehm, a professor at Université de Montréal and researcher at CHU Sainte-Justine.

"We already knew that synaptic plasticity is influenced by certain proteins," added Anthony Dudilot, one of the study's first authors. "For example, calcineurin is inhibited when long-term potentiation is induced, but it's activated when long-term depression begins. But the molecular mechanism underlying calcineurin regulation was less clear."

The research team found that the various signalling pathways that trigger synaptic potentiation or depression converge on RCAN1. They also determined that the gene regulates calcineurin activity by inhibiting or facilitating it.

Given its dual role as an inhibitor/facilitator, the researchers deduced that RCAN1 works as a "switch" that regulates synaptic plasticity, thereby affecting learning and memory.

A better future for all patients

"This is the first time that the molecular mechanism for calcineurin regulation in bidirectional synaptic plasticity has been determined," said Boehm. "This breakthrough explains how overexpression of the RCAN1 gene could cause intellectual disabilities in individuals with Down syndrome. It also opens up the possibility of developing innovative treatments for affected patients."

A research team at the VIB-KU Leuven Center for Microbiology and the KU Leuven Department of Biology showed that, contrary to generally held belief, most components of essential oils could meet the criteria set for drug candidates. Essential oil components are the constituents of essential oils, which are complex mixtures of plant metabolites obtained by dry or steam distillation, or by citrus peel pressing.

Revisiting essential oils

The research project, supervised by prof. Patrick Van Dijck (VIB-KU Leuven Center for Microbiology) and prof. Walter Luyten (KU Leuven Department of Biology), is rooted in the observation that in the past decades, drug discovery has mainly shifted to high-throughput screening of large, synthetically produced chemical libraries, while natural product drug research has diminished.

Prof. Van Dijck: "Natural products such as essential oils and their components are often avoided in drug discovery, for example, because they are relatively hydrophobic and volatile. This can cause interference during (high throughput) screening."

However, recent technical developments combined with restrictions on the use of chemicals led to a renewed interest in natural product drug discovery. Some of the new methods to study essential oils and their components were developed in the laboratory of prof. Van Dijck under the coordination of Dr. Adam Feyaerts, mainly with the aim of finding new antimicrobials, for example antifungal drugs.

Dr. Adam Feyaerts: "Nowadays, a relatively large number of essential oils and their components are already available as dietary supplements, but only a few have made the transition to drugs. As most technical barriers were removed, I wondered whether avoiding essential oils and their components in drug discovery was still justified. So, we evaluated certain parameters used in conventional drug discovery for more than 600 essential oil components to assess their potential as drug candidates."

Prof. Walter Luyten: "The discovery and development of a new drug takes a long time and is very expensive, not in the least because so many initial candidates turn out not to be suitable. In other words, the earlier in the drug discovery process non-promising molecules can be eliminated, the better. Many candidate drug molecules fail when they are tested in animals."

A treasure trove of potential drugs?
Fortunately, in silico drug discovery filters have been developed that can predict drug disposition based on combinations of specific calculated parameters, which reduced the rate at which potential drugs failed later in the drug development pipeline. This study shows that essential oil components can be assessed using the filters implemented by the pharmaceutical industry.

Dr. Adam Feyaerts: "Our findings suggest that essential oil components can be promising sources of new drugs and deserve more attention, especially if they originate from essential oils that have already shown clinical benefits. Essential oil components also have unique properties that might be useful for some therapeutic applications, such as for lung or airway diseases, for transdermal administration, and for diseases of the central nervous system."

Utrecht, The Netherlands, 20th of February 2020. While the genome editing tool CRISPR/Cas9, developed in 2012, cuts a mutation out of a gene and replaces it with a gene-piece, a newer type of CRISPR, called base-editing, can repair a mutation without cutting the DNA. Therefore, genome editing using base-editor is considered safer. Scientists from the research groups of Hans Clevers (Hubrecht Institute) and Jeffrey Beekman (UMC Utrecht) show for the first time that this base-editing can safely cure cystic fibrosis in stem cells derived from patients. The results of this study were published in Cell Stem Cell on the 20th of February.

In 2018 a new CRISPR-enzyme was developed that makes the CRISPR technique more precise and less error-prone, according to biologists Maarten Geurts (Hubrecht Institute) and Eyleen de Poel (UMC Utrecht). Maarten: "In traditional CRISPR/Cas9 genome editing a specific piece of the DNA is cut out resulting in DNA damage. This is done with the aim that the cell repairs this cut using a lab-made piece of 'healthy' DNA. However, in the new CRISPR-technique, called base editing, the Cas-part is altered in such a way that it no longer creates a cut, but still detects the mutation. So, instead of creating a cut and replacing the faulty DNA, the mutation is directly repaired on site, making this a more effective genome editing tool." The current research shows that this new version of CRISPR/Cas9 can be safely and effectively applied in human stem cells.

Miniguts

The Hubrecht Organoid Technology foundation and the UMC Utrecht have generated a biobank consisting of intestinal organoids. These are tiny versions of the gut, that are established in the lab using the stem cells of cystic fibrosis (CF) patients. The miniguts are used for disease modeling and the development of new therapies. The biobank was set up together with many CF centers across Europe and the Dutch CF Foundation (NCFS). In this study, the miniguts were used to test whether the new base-editing technique can be applied in human stem cells. Maarten explains how this exactly works: "CF is caused by a mistake, a mutation, in the CFTR-gene leading to malfunctioning of the gene. As a consequence, the mucus in many organs, including the lungs, is less hydrated, resulting in mucus build-up and organ failure. With the new base-editing technique the mutation in the CFTR-gene can be detected and repaired without creating further damage in the genome."

Even though this research shows that this novel CRISPR tool is effective in the lab, this does not mean that patients can already benefit from it. Eyleen: "This research represents a big step towards genetic repair of diseases in patients. However, a big question that remains is how to deliver the CRISPR-enzyme to the appropriate organs in the patient. Cystic fibrosis might also not be the most suitable disease to treat with CRISPR, as many organs are affected by the disease. Currently, the first medical applications with CRISPR gene editing are showing impressive clinical effects in diseases that affect a single organ or tissue such as sickle cell anemia. Further research is needed before the base-editor can be used for clinical application. However, in part due to this study, the first clinical applications may already happen in the coming five years.

BOSTON - Deep within the lining of the human intestine lies the source of the organ's ability to renew itself and recover from damage: intestinal stem cells (ISCs), lodged in pockets of tissue called crypts, generate the cells that continuously repopulate the intestinal lining. Even the stem cells themselves have a safety net: when they're damaged, healthy replacements appear in less than a week.

For years, scientists have debated how the ISCs' re-emergence occurs. Some have held that the intestine keeps a pool of ISCs on reserve - a kind of backup-backup supply - to replenish the cache of front-line ISCs that have been lost. Others have maintained that something more involuted is as work: The ISCs, like queen bees, give rise to more specialized, or "differentiated," progeny - in this case, daughter cells that form the inner lining of the intestine. When the ISCs are damaged, this school of thought held, the daughter cells reverse course and "de-differentiate" - reverting into the ISCs from which they arose.

A new study by Dana-Farber Cancer Institute scientists comes down solidly on the latter option. Published online today by the journal Cell Stem Cell, the researchers found that ISCs and their daughter cells have a strikingly reciprocal relationship: under normal conditions, ISCs differentiate into daughter cells, and, if the ISCs are lost, the daughter cells simply reverse course and become ISCs.

"Our findings suggest that the restoration of intestinal stem cells occurs entirely by the process of de-differentiation," says the study's senior author, Ramesh Shivdasani, MD, PhD, of Dana-Farber, Brigham and Women's Hospital (BWH), and the Harvard Stem Cell Institute. "We showed there's no need for a reserve set of ISCs."

Bolstering their findings, the researchers were also able to capture the de-differentiation process in real time. When cells begin to de-differentiate, they switch on a gene that that allows them to be isolated and collected with laboratory techniques, Shivdasani explains. Through this process, researchers were able to capture the cells along a continuum of de-differentiation. Shivdasani likens it to a baseball play in which a runner is tagged out between first and second base.

Heavy turnover

The intestine is one of just three tissues in the body, along with the skin and blood, in which cells are constantly turning over - dying and being replaced by freshly made cells. They share this quality because they are the tissues most intimately in contact with material from the environment, and therefore with potentially harmful substances. The constant turnover, it's thought, is a way to prevent toxic substances from having lasting effects on cells and their offspring.

The crypts that hold ISCs are, in a sense, misnamed. Far from being enclosures where dead cells are entombed, they are the sites where ISCs daily generate the billions of daughter cells that take the place of defunct intestinal cells.

One of the chief characteristics of ISCs is that they are extremely radiosensitive, or vulnerable to radiation. People exposed to high levels of radioactivity, in the form of nuclear fallout, for example, can suffer severe intestinal damage because the loss of ISCs halts production of cells to regenerate the damaged tissue. But if ISCs succumb easily to radiation, they also make a rapid return. Patients with radiation-induced intestinal damage who can be kept alive for a week often recover as their ISC levels bounce back.

To determine whether this rebound is due to a reserve stockpile of ISCs or to de-differentiation of daughter cells, Shivdasani and his collaborators performed a kind of time-lapse experiment. They treated a collection of ISC cells with the drug tamoxifen, which caused the cells and their offspring to become fluorescent. They waited 48 hours for the label to take hold, then killed the ISC cells. If the daughter cells were indeed de-differentiating, any ISC cells produced after that point would be fluorescent. That's exactly what researchers found.

While scientists have been able to convert many kinds of differentiated cells into stem cells using laboratory techniques, Shivdasani and his colleagues' discovery demonstrates that de-differentiation ismore than a curious act of nature; it is the principal means to restore damaged stem cell in the intestine. It's not known whether cells in other organs and tissues have this capability, but it remains an open avenue of investigation.

"It also isn't clear how the crypt knows that stem cells have died and need to be replaced," Shivdasani remarks, "or how the daughter cells receive the signal to de-differentiate. This is a subject we're currently exploring."

What The Study Did: Data from 82 prison inmates treated in a glaucoma clinic at an academic hospital were used in this observational study to report on how treatment and follow-up, including medication adherence, were are managed.

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

Authors: Levi N. Kanu, M.D., of the University of Illinois at Chicago, is the corresponding author.

(doi:10.1001/jamaophthalmol.2020.0001)

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

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Image-based sexual abuse in Australia is increasing, according to new research.

A survey of more than 2000 Australians found 1 in 3 had been victims of image-based abuse, compared with 1 in 5 in 2016.

The survey also found the perpetration of image-based abuse had increased, with 1 in 6 people surveyed reporting they had taken, shared or made threats to share a nude or sexual image of a person without that person's consent, compared with 1 in 10 of those surveyed in 2016.

The findings are detailed in a new report Image-Based Sexual Abuse: An International Study of Victims and Perpetrators, which presents the results of the first cross-national survey on image-based sexual abuse, conducted in Australia, New Zealand and the United Kingdom in 2019.

The Australian survey follows a similar study conducted in 2016 - the first of its kind - allowing the researchers to compare results for the first time.

Image-based sexual abuse is the non-consensual taking, sharing or threatening to share nude or sexual images of a person, including the use of digitally-altered imagery.

Lead author Associate Professor Anastasia Powell said although it's commonly referred to as "revenge porn", the study shows the perpetration of image-based abuse is not limited to jilted ex-lovers out for vengeance.

"We found that image-based sexual abuse is used by perpetrators of domestic violence and sexual assault, in stalking and sexual harassment, as well as in threats and bullying by peers and other known people," Powell said.

"Not only this, but we found high numbers of victims had never consented to having their image taken.

"Our interviews with victims uncovered cases of people being photographed or filmed without their knowledge in the shower, while sleeping, over Skype and during sex.

"We also found no increase in people sending consensual sexy selfies. All this suggests it's not victim behaviour driving the rise in abuse, but rather the actions of perpetrators."

The survey of 2,054 Australians aged 16-64 also found that:

Young people were twice as likely as those aged over 40 to be victims of image-based sexual abuse, with those aged between 20 and 29 years the most likely group to be victims.

Men and women reported a similar frequency of victimisation, but women experienced higher levels of harm from the abuse, including being more than twice as likely as men to report being fearful for their safety from the perpetrator.

Men were more likely than women to be perpetrators.

Perpetrators reported that their reasons for the abuse included for fun, to flirt or be sexy, to impress friends or trade images, to control, embarrass, and/or get back at the person in the image.

The most common sites for distribution were social media, email and mobile messages.

Rates of image-based sexual abuse victimisation were similar across Australia (35.2%), UK (39%) and New Zealand (39%).

Notably, while results showed strong support among survey respondents for image-based sexual abuse to be made a criminal offence (at more than 80%), less than half knew that it that it actually was a crime to take, distribute or threaten to share nude or sexual images of a person without consent.

Co-author Associate Professor Asher Flynn from Monash University said these findings highlighted the need for greater awareness-raising and legal education.

"Though most states and territories in Australia now have specific laws criminalising image-based sexual abuse, we need to make sure that those laws are enforced - that victims are supported, and perpetrators are held to account," Flynn said.

"There is also a need to build information about the seriousness and harmfulness of image-based sexual abuse into respectful relationships education.

"But most of all, we need community attitudes to change so that whether it is our friend, a family member, a fellow student or co-worker whose image is shared without consent - we place the blame and shame on the perpetrator of the image-based sexual abuse and not on the victim."

New scientific findings released today in the peer-reviewed journal Nature Communications, show that expansion Aof the Pacific Remote Islands and Papahanaumokuakea marine national monuments did not cause overall economic harm to the Hawaii-based longline tuna fishing fleet.

The results of this study, which was supported by the Pew Bertarelli Ocean Legacy Project, represent the first economic analysis of two of the largest protected areas on Earth. The monuments protect an area larger than the land mass of Alaska, Texas and California combined. The study co-authors, led by John Lynham, professor in the Department of Economics at the University of Hawai'i at Manoa, analyzed observer records of individual fishing events, logbook summary reports, and detailed satellite data on vessel movements.

"By analyzing independently collected data, we found that catch per unit effort has increased overall for the Hawaii-based longline industry following each expansion," says Lynham. "The bottom line is that these monuments are not causing substantial economic losses to the fishery."

In 2014 and 2016, President Barack Obama significantly expanded the monuments, collectively protecting a little more than 1 million square miles (2.78 million square kilometers) of healthy coral reefs, undocumented deep-sea creatures, and large predatory species such as sharks, tuna, and marine mammals. This built upon actions taken by President George W. Bush--who designated both the Pacific Remote Islands and Papahanaumokuakea marine national monuments in 2006 and 2009, respectively.

"The effect of a marine protected area on a fishery is often difficult to assess because of the many factors that affect catch such as ocean conditions, prices, and changing regulations. A strength of this study is that by comparing the longline tuna fishery to two other fisheries unaffected by the monument designation we've controlled for factors that could be biasing the results. Our conclusion from this is clear: Papahanaumokuakea and the Pacific Remote Islands marine national monuments have not hurt the fishing industry overall. This is not too surprising when you consider that, in 2015, when Papahanaumokuakea was still open to fishing, 97% of tuna fishing was taking place outside the monument in waters that are still open to fishing today."

Prior to the expansion of the Papahanaumokuakea Marine National Monument, representatives of the longline fishing industry in Hawaii argued that the expansion would result in direct losses as high as $10 million annually, and that total indirect losses to the fishing-dependent economy could reach $30 million. The new analysis shows that after the expansions, the Hawaii-based longline industry has been catching more fish, while the distance fleet the travels has remained unchanged. Moreover, the total catch and total revenue in the fishery have increased since the expansions began. Specifically, the average revenue from 2014 to 2017 was 13.7 percent higher than from 2010 to 2013.

A recent study of indigenous people in southern Chile challenges some Western assumptions about children's emotional capabilities and highlights the potential value of spending time outdoors to help children regulate their emotions.

"I think many people, particularly in Western cultures, think children are less capable than they actually are," says Amy Halberstadt, a professor of psychology at North Carolina State University and corresponding author of a paper on the work. "Our study shows that this is not universal.

"For example, our work with the Mapuche people makes clear that they have different expectations about their children's ability to manage fear. And the role they feel nature plays in helping children maintain their emotional equilibrium is also distinct."

For the study, researchers conducted a survey of 271 parents and teachers in southern Chile. One hundred six of the study participants were Mapuche, an indigenous people of the region. The remaining 165 were non-Mapuche.

Survey questions were developed based on interviews and focus groups. The questions were aimed at gaining a better understanding of cultural differences regarding the beliefs that adults have about children and children's emotions.

One finding was that Mapuche parents and teachers were significantly more likely than non-Mapuche to expect their children to be able to control fear.

"To be clear, we're not talking about children being stoic about their fear," Halberstadt says. "We're talking about an expectation that children understand a situation and either take action or accept the situation without becoming afraid."

"The Mapuche believe that part of growing up is learning not to be afraid, and this is something that is actively fostered," says Dejah Oertwig, co-author of the paper and a Ph.D. student at NC State. "Mapuche parents support the development of emotional skills like this one through the way they help children interpret the world around them."

The study found that Mapuche also place a great deal of value on a child's relationship with nature.

"The Mapuche believe children should respect, but not fear, nature," Halberstadt says. "They also believe nature can help children become calm, cope with sadness in a positive way and otherwise regulate negative emotions.

"Parents here in the U.S. may want to view these approaches as possible strategies they can use at home," Halberstadt says. "I don't think there are necessarily prescriptions for success in any one approach, but broadening our appreciation of what's possible for kids could yield positive outcomes for young people. It might be a good idea to see if spending more time outside, and respecting and appreciating nature, do help us regulate our own emotions or help our children find balance."

Two research teams from the Max Delbrück Center for Molecular Medicine and their collaborators have produced a detailed cell atlas of an entire salivary gland tumor in a mouse model, mapping individual cells throughout the tumor and its surrounding tissue. The "single cell" approach, recently described in Nature Communications, has provided key insights about cellular composition changes through the earliest stages of cancer development.

A solid tumor is not, as many might assume, a lump of cells that are all the same. Rather it is mix of many different cell types, including a variety of stromal and immune cells besides the actual tumor cells.

"Conventional methods in molecular biology often consider a sample as a whole, which fails to recognize the complexity within it," said Dr. Samantha Praktiknjo, senior scientist and first author from MDC's Systems Biology of Gene Regulatory Elements Lab headed by Professor Nikolaus Rajewsky at the Berlin Institute for Medical Systems Biology (BIMSB). Developing a detailed understanding of the different cells within a tumor and how they interact could help identify more effective treatment strategies.

Strength in numbers

The team used single-cell RNA sequencing technologies developed in the Rajewsky lab and novel epitope profiling to produce the cell atlas, and identified the cells that were specific to the tumor by leveraging the reproducibility and the large sample size of their data.

The latter was possible by using a mouse model, developed in MDC's Signal Transduction in Development and Cancer Lab headed by Professor Walter Birchmeier, which harbors designed mutations that induce a salivary gland squamous cell carcinoma. This system provides a consistent supply of genetically similar tumors to sequence from the earliest stages of development, which is nearly impossible with human patients.

"In a patient, the tumor is already developed and you cannot go back and rewind time and look at how it started," said Dr. Benedikt Obermayer, a co-first author now at the Berlin Institute of Health (BIH). "Here, we have a model that is so controlled, we can watch it happen." And Dr. Qionghua Zhu, the third first author and a former postdoc at the Birchmeier Lab, added: "To fight cancer effectively, we need to find the driver mutations. This method gives us clues about the evolution trajectories of a tumor."

Sequencing technologies have advanced so that it is now possible to quickly and affordably sequence the RNA inside single cells, one at a time, as well as the proteins on the surfaces of cells in the tissues. While other methods grind up the tissue and identify what genes and molecules are present in the mix, the single cell approach precisely identifies how many of each type of cell is present, and which genes and molecules are associated with which cell.

For this study, the researchers sequenced more than 26,000 individual salivary gland cells from mice with tumors and healthy mice. They used computational models to analyze the huge amount of data and identify each individual cell and sort them into groups - such as stromal cells, immune cells, saliva producing cells, cancer cells - based on the hundreds of genes expressed and molecules present.

A surprise

The single cell approach revealed something that surprised the researchers: "When I saw the data, I thought, where is the tumor?" Obermayer said. The population of cancer stem cells in the tumor was extremely small - less than one percent of all profiled cells in the tissue. Due to their low abundance, investigation of these cells still heavily depends on assumptions about surface markers and is often performed in cell culture-based systems. Here, the authors were able to identify the cancer stem cells directly from the solid tumor samples with their single cell approach.

Furthermore, the team was able to predict the progression of the different cell types through different stages of tumor development. Their model suggests that the cancer stem cells emerge from cancerous basal cells, then develop into another subtype before ultimately becoming a population of cells similar to luminal cells, a cell type present in normal, healthy salivary glands.

This progression supports the idea that when something goes awry in the basal cells of this solid tumor model, they are triggered to turn into cancer stem cells, which can then become a different type of cell. "What I found fascinating was clearly seeing the order of signals and events, transitioning from the progenitor to the progeny populations of the cancer stem cells," Praktiknjo said.

Next steps

Further research is required to verify that individual cells are transforming through these stages, and explore the cellular and molecular interactions driving tumor growth. The team anticipates the approach they've demonstrated here can be applied to other cancer types as well.

"To me the main conceptual insight is that we can apply ideas from single-cell based developmental biology to reconstruct molecular progression of tumorigenesis ," said Professor Nikolaus Rajewsky, who heads MDC's Systems Biology of Gene Regulatory Elements Lab and is the scientific director of the BIMSB.