Culture

Healthy lung cells support the survival of breast cancer cells, allowing them to hibernate in the lung before forming secondary tumours, according to new research from the Crick. The findings could help the development of new treatments that interfere with this behaviour, reducing the number of secondary cancers.

The study, published in Nature Cell Biology, used a mouse model to show that, after cancer cells from a breast tumour arrive in the lungs, a signal sent out from the lung cells causes cancer cells to change shape and grow protrusions that latch onto the lung tissue. The lung cells then protect them within the lung tissue.

By using a treatment that interferes with the growth of these protrusions on the breast cancer cells, the researchers found that mice who received the treatment grew fewer secondary tumours than the control mice.

The researchers then analysed the genes that are turned on in the hibernating cells. This enabled them to find a key gene, sFRP2, that regulates the formation of cell protrusions and the survival of breast cancer cells in the lung.

"Cancer can survive, hibernating in different parts of the body, for many years. By showing how the microenvironment around the cancer cell can support its survival, in our case how the lung cells help the breast cancer cells, opens the door to potential new treatments which target this relationship," says Erik Sahai, co-lead author and group leader of the Crick's Tumour Cell Biology Laboratory.

The cancer cells were tested over the course of up to four weeks, during which they remained inactive. In comparison, other cell types continued to remain active, showing that the hibernation of these cells is due to a special relationship they have with the lung environment around them.

"The mechanism behind how cancer cells survive in tissues they have travelled to is not yet well understood. But with many cancers spreading around the body and consequently many patients suffering from relapses, a deeper understanding of the process is vital and something we'll continue to explore," says Marco Montagner, co-lead author and former postdoc in the Crick's Tumour Cell Biology Laboratory, who is now based at the University of Padua.

Around 55,000 people in the UK are diagnosed with breast cancer each year. This cancer can spread through the blood or lymphatic system to another part of the body, commonly the lungs, liver, brain or bones. Where breast cancer spreads to the lungs, there can be a long time between the cells arriving in the lungs and the formation of a secondary tumour. This gap is one factor that explains why people may relapse a long time after the initial disease.

The researchers are continuing to explore the relationship between cancer and non-cancerous cells in a secondary location in the body. At the Crick, researchers are now studying what happens when cells from colorectal cancer and melanomas form secondary tumours in the liver. While at the University of Padua, studies are ongoing into the genes which are over-expressed in hibernating breast cancer cells.

Taking a cat to the vets can be a stressful experience, both for cat and owner. However, a study published in this month's issue of the Journal of Feline Medicine and Surgery (JFMS)1 has shown that playing cat-specific music during the visit can help.

The use of music has become increasingly popular in human medicine, with studies showing a range of benefits, from improving motor and cognitive function in stroke patients to reducing anxiety associated with medical examinations, diagnostic procedures and surgery. The benefits of music are also being investigated in cats and other animals. Research published previously in JFMS has indicated that cats that are under general anaesthesia remain physiologically responsive to music;2 furthermore, they appear to be in a more relaxed state when played classical music, compared with pop and heavy metal.3

In this latest study, researchers at Louisiana State University (LSU), USA, have taken the analysis of the impact of different types of music a step further by exploring the calming effects of music composed specifically for cats. Musical pieces that are considered pleasing to the human ear often have a beat similar to the human resting pulse rate and contain frequencies from the human vocal range. This principle has been extended to cat-specific music, which is composed of lines based on affiliative cat vocalisations, such as purring and suckling sounds, as well as frequencies similar to the feline vocal range, which is two octaves higher than for humans.

In order to assess the effects of cat-specific music, 20 pet cats enrolled in the LSU study were played 20 minutes of cat-specific music ('Scooter Bere's Aria' by David Teie - http://www.youtube.com/watch?v=vGyElqvALbY), classical music ('Élégie' by Fauré) or no music (silence) in a random order at each of three physical examinations at the veterinary clinic, 2 weeks apart. Cat stress scores, based on the behaviour and body posture of the cats, and handling scale scores, based on the cats' reactions to the handler, were assigned for each of the cats from video recordings of the examinations; neutrophil:lymphocyte ratios from blood samples were also measured to look for a physiological stress response.

The study found that the cats appeared to be less stressed during the examination - as indicated by lower cat stress scores and handling scale scores - when played the cat-specific music, compared with both classical music and no music. This effect was not reflected in the neutrophil:lymphocyte ratio, but the researchers suggest that 20 minutes may not have been long enough to allow music to affect this measure.

By decreasing stress levels, the researchers conclude that cat-specific music may not only have benefits in terms of the welfare of the cat, but owners can feel reassured that their cat will have a more comfortable visit, and the veterinary team will be able to assess their feline patients more accurately.

In search of new ways to sequence human genomes and read critical alterations in DNA, researchers at Johns Hopkins Medicine say they have successfully used the gene cutting tool CRISPR to make cuts in DNA around lengthy tumor genes, which can be used to collect sequence information.

A report on the proof-of-principle experiments using genomes from human breast cancer cells and tissue appears in the Feb. 10 issue of Nature Biotechnology.

The researchers say that pairing CRISPR with tools that sequence the DNA components of human cancer tissue is a technique that could, one day, enable fast, relatively cheap sequencing of patients' tumors, streamlining the selection and use of treatments that target highly specific and personal genetic alterations.

"For tumor sequencing in cancer patients, you don't necessarily need to sequence the whole cancer genome," says Winston Timp, Ph.D., assistant professor of biomedical engineering and molecular biology and genetics at the Johns Hopkins University School of Medicine. "Deep sequencing of particular areas of genetic interest can be very informative."

In conventional genome sequencing, scientists have to make many copies of the DNA at issue, randomly break the DNA into segments, and feed the broken segments through a computerized machine that reads the string of chemical compounds called nucleic acids, made up of the four "bases" that form DNA, and are lettered A, C, G and T. Then, scientists look for overlapping regions of the broken segments and fit them together like tiles on a roof to form long regions of DNA that make up a gene.

In their experiments, Timp and M.D./Ph.D. student Timothy Gilpatrick were able to skip the DNA-copying part of conventional sequencing by using CRISPR to make targeted cuts in DNA isolated from a sliver of tissue taken from a patient's breast cancer tumor.

Then, the scientists glued so-called "sequencing adaptors" to the CRISPR-snipped ends of the DNA sections. The adaptors serve as a kind of handle that guide DNA to tiny holes or "nanopores" which read the sequence.

By passing DNA through the narrow hole, a sequencer can build a read-out of DNA letters based on the unique electrical current that occurs when each chemical code "letter" slides through the hole.

Among 10 breast cancer genes the team focused on, the Johns Hopkins scientists were able to use nanopore sequencing on breast cancer cell lines and tissue samples to detect a type of DNA alteration called methylation, where chemicals called methyl groups are added to DNA around genes that affect how genes are read.

The researchers found a location of decreased DNA methylation in a gene called keratin 19 (KRT19), which is important in cell structure and scaffolding. Previous studies have shown that a decrease in DNA methylation in KRT19 is associated with tumor spread.

In the breast cancer cell lines they studied, the Johns Hopkins team was able to generate an average of 400 "reads" per basepair, a reading "depth" hundreds of times better than some conventional sequencing tools.

Among their samples of human breast cancer tumor tissue taken at biopsies, the team was able to produce an average of 100 reads per region. "This is certainly less than what we can do with cell lines, but we have to be more gentle with DNA from human tissue samples because it's been frozen and thawed several times," says Timp.

In addition to their studies of DNA methylation and small mutations, Timp and Gilpatrick sequenced the gene commonly associated with breast cancer: BRCA1, which spans a region on the genome more than 80,000 bases long. "This gene is really long, and we were able to collect sequencing reads which went all the way through this large and complex region," says Gilpatrick.

"Because we can use this technique to sequence really long genes, we may be able to catch big missing blocks of DNA we wouldn't be able to find with more conventional sequencing tools," says Timp.

In addition to its potential to guide treatment for patients, Timp says the combination of CRISPR technology and nanopore sequencing provides such depth that it may help scientists find new disease-linked gene alterations specific to one allele (inherited from one parent) and not another.

Timp and Gilpatrick plan to continue refining the CRISPR/nanopore sequencing technique and testing its capabilities in other tumor types.

For the first time, researchers at the Paul Scherrer Institute PSI have recorded a "3D film" of magnetic processes on the nanometer scale. This reveals a variety of dynamics inside the material, including the motion of swirling boundaries between different magnetic domains. The insights were gained with a method newly developed at the Swiss Light Source SLS. It could help to make magnetic data storage devices more compact and efficient. The researchers are publishing the results of their investigations today in the journal Nature Nanotechnology.

A magnetic sticker staying attached to a refrigerator door is hardly surprising. However, when one approaches the nanometre range (where one nanometer is one millionth of a millimeter), physicists still find magnets, and their behaviour, puzzling. At the same time, the effects occurring on this small scale are highly relevant for future technologies. Now, for the first time, PSI researchers were able to record a short "film" of the three-dimensional magnetic structure inside a material with nanoscale resolution.

"Magnetism plays a role in many ways in our everyday lives; but at this very small, fundamental level, the phenomena are not yet fully understood", explains Claire Donnelly, lead author of the study. Donnelly was a researcher at PSI at the time of the experiment and now works at the University of Cambridge in the UK.

The researchers used X-ray light from the Swiss Light Source SLS at PSI and a special tomographic method they recently developed there, which they call "time-resolved ptychographic laminography". Their team consisted of scientists at PSI and ETH Zurich, as well as in the UK. The sample they examined consisted of a gadolinium-cobalt compound patterned into a circular disc.

More than four days for seven images

"With our method we can non-destructively scan the material and from the data reconstruct several successive 3D images of the inner magnetic structure", says PSI researcher Manuel Guizar-Sicairos. "We can visualise the orientation of the magnetic moment at every measured point in the material and represent them as tiny magnetic compass needles."

Just like magnetic filings, these compass needles react to an external magnetic field and to each other, forming intricate patterns throughout the entire object. The patterns contain areas - so-called domains - in which the magnetisation points predominantly in one direction. The transitions between two such areas, i.e., the domain walls, are of particular interest to researchers: "People have proposed using them as memory bits, which could possibly be used to pack data even more tightly than when using the domains", says Donnelly. The details of these domain walls have only recently been made visible in 3D at PSI, among other places, using state-of-the-art imaging methods.

In the present study, the researchers went one step further by mapping the motion of both the domains and the domain boundaries. "We have taken seven snapshots showing points in time that are only a quarter of a billionth of a second apart. In these we can see how a domain boundary moves back and forth." It took the scientists a little more than four days of constant measuring to collect the data, which later yielded this sequence of seven images.

Like stroboscopic light

The observed movement of the domain boundary was repeatedly and specifically induced by the researchers themselves through an externally applied magnetic field. Their images were therefore not actually recorded within a quarter of a billionth of a second. Instead, the scientists created a time loop of the changing magnetic field and took images at different points in time within it- similar to stroboscopic light seemingly slowing down a repetitive movement.

The recording of the 3D images from inside the sample in turn draws on a basic principle from computed tomography (CT). Similar to medical CT scans, the X-rays were used to take many radioscopic images of the sample one after the other, each from a slightly different angle. From the data collected, the researchers were able to recover their 3D maps of the magnetisation using software they had developed for this purpose.

"With this method, we have not just achieved time-resolved 3D movies of the interior of an object", says Donnelly happily. "We also have been able to map the nanoscale dynamics in a magnet. In other words, we have shown that our new technique is really relevant to the development of new technology." And Guizar-Sicairos adds: "Our new method is also suitable for other materials and could therefore have many more useful applications in the future."

Researchers have developed a new, inexpensive technology that could save lives and money by routinely screening women for breast cancer without exposure to radiation.

The system, developed by researchers at the University of Waterloo, uses harmless microwaves and artificial intelligence (AI) software to detect even small, early-stage tumors within minutes.

"Our top priorities were to make this detection-based modality fast and inexpensive," said Omar Ramahi, a professor of electrical and computer engineering at Waterloo. "We have incredibly encouraging results and we believe that is because of its simplicity."

A prototype device - the culmination of 15 years of work on the use of microwaves for tumor detection, not imaging - cost less than $5,000 to build.

It consists of a small sensor in an adjustable box about 15 centimetres square that is situated under an opening in a padded examination table.

Patients lie face-down on the table so that one breast at a time is positioned in the box. The sensor emits microwaves that bounce back and are then processed by AI software on a laptop computer.

By comparing the tissue composition of one breast with the other, the system is sensitive enough to detect anomalies less than one centimeter in diameter.

Ramahi said a negative result could quickly rule out cancer, while a positive result would trigger referral for more expensive tests using mammography or magnetic resonance imaging (MRI).

"If women were screened regularly with this, potential problems would be caught much sooner - in the early stages of cancer," he said. "Our system can complement existing technology, reserving much more expensive options for when they're really needed.

"We need a mixture, a combination of technologies. When our device sent up a red flag, it would mean more investigation was warranted."

In addition to reducing patient wait times and enabling earlier diagnosis, Ramahi said, the device would eliminate radiation exposure, improve patient comfort and work on particularly dense breasts, a problem with mammograms.

It would also save health-care systems enormous amounts of money and, because of its low cost and ease of use, dramatically increase access to screening in the developing world.

Researchers have applied for a patent and started a company, Wave Intelligence Inc. of Waterloo, to commercialize the system and hope to begin trials on patients within six months. Three rounds of preliminary testing included the use of artificial human torsos known as phantoms.

CHAMPAIGN, Ill. -- Scientists deployed motion-sensitive camera traps across a 50-square-mile swath of Bukit Barisan Selatan National Park in southern Sumatra and, over the course of eight years, recorded the haunts and habits of dozens of species, including the Sumatran tiger and other rare and endangered wildlife. Their observations offer insight into how abundant these species are and show how smaller creatures avoid being eaten by tigers and other carnivores.

They report their findings in the journal Animal Biodiversity and Conservation.

"A lot of my research focuses on natural history, where I'm trying to understand behaviors and aspects of ecology that no one has been able to record before," said Max Allen, a wildlife ecologist at the Illinois Natural History Survey who led the research. "And camera traps are a good way to document a community of terrestrial animals." The INHS is a division of the Prairie Research Institute at the University of Illinois at Urbana-Champaign.

The cameras captured a total of 39 animal species, including critically endangered Sumatran tigers, Sumatran elephants and Sunda pangolins, as well as carnivores including Asian golden cats, marbled cats, Sunda clouded leopards, Malayan sun bears and masked palm civets.

The frequency and time of sightings revealed that the tigers were most active during the day, with the majority of sightings in midday. The species that compete with tigers as top carnivores appeared to be doing their best to avoid going out during the tigers' peak activity times.

For example, camera sightings of Sumatran clouded leopards - which are not strictly nocturnal - dropped off precipitously in the hours before noon and picked up a bit in late evening, when tigers were rarely seen. Sumatran tigers and Sunda clouded leopards compete for larger prey, and tigers are likely to attack them on sight, Allen said.

The behavior of smaller cats, however, suggests that they do not fear or actively avoid tigers.

"The daytime activity of the marbled cat, for example, actually overlaps highly with that of the tigers," Allen said. It's likely the marbled cats are small enough to be eating prey - like rodents - that are of no consequence to tigers.

The camera traps recorded 28 species not seen in earlier surveys, including the critically endangered Sunda pangolin, and the endangered dhole and otter civet. Surveys from previous studies captured eight species that the camera traps missed, however. These include the critically endangered Sumatran rhinocerous, the endangered dark-handed gibbon and the endangered hairy-nosed otter.

Despite their limitations, camera traps often capture things that people surveying in the wild will miss, Allen said.

"There are a lot of interesting behaviors that we just can't capture through classic field methods that camera trapping allows us to document," he said. For example, in an earlier camera-trap study of Sunda clouded leopards in Borneo, Allen and his colleagues discovered that the male clouded leopards would scent mark, scratching and urinating to establish their territory and to attract mates - something other researchers had never observed before.

"There are gaps in our knowledge that camera traps can fill," Allen said. "It would be difficult to document these behaviors and interactions by other means."

The structure of a transport complex used by bacteria to import aspartate has been mapped in unique detail by University of Groningen scientists. The proteins were imaged using cryo-electron microscopy. The results reveal that the transporter works very efficiently. This is especially interesting as a similar transporter is vital for signal transduction between human brain cells. The study results were published in Nature Communications on 21 February.

Cells use a myriad of transport proteins to shuttle substances across their membranes: food and building blocks are imported, toxins and other waste is exported. One example is the aspartate transporter, which bacteria use to import this amino acid. The Membrane Enzymology research group led by Professor Dirk Slotboom and the Structural Biology group led by Dr Albert Guskov at the Groningen Institute for Biomolecular Sciences & Biotechnology have studied this transporter for several years, partly because it is a good model for the human transporter that removes the neurotransmitter glutamate from the synaptic cleft, a vital step in the working of our brain cells.

Goods lift

The aspartate transporter in bacterial membranes is a trimer, which means that three identical units are held together tightly to form one complex. Aspartate is picked up from the environment, transported through the cell membrane and released on the inside of the cell. Three sodium ions per unit power this transition, which can be compared to a goods lift: the aspartate and sodium ions bind to part of the transport protein, which then enters the cell. After delivering the aspartate, it exits again.

'We previously mapped the structure of the complex with aspartate using x-ray crystallography,' explains Slotboom. These studies showed that the three lifts in the complex were always in the same position. 'However, biochemical evidence suggested they might work independently of one another.' That is why he decided to study the transport complex in a more native environment, inside a membrane. This was done using cryo-electron microscopy, a method for creating images of protein complexes.

Questions

The proteins were inserted into small patches of lipid bilayers, kept together by a protein belt. These lipid nanodiscs were quickly frozen and studied in a cryo-electron microscope. By combining a large number of images, the transport complex was imaged at a resolution of 3.2-3.5 angstroms.

'What we saw was very different from the structures obtained with X-ray crystallography: in most complexes, the lifts were in different positions, consistent with independent movements,' says Valentina Arkhipova, a postdoctoral researcher in the Slotboom group and first author of the paper. This raises the question of why the protein would form a trimeric complex. Arkhipova: 'The lift part of each unit requires support to move through the membrane. A single lift anchored inside the membrane might start to wobble. But three lifts with connected anchors form a stable structure.'

Leakage

Another possibility is that the anchor part of the trimer makes the membrane around it a little thinner and less rigid, which makes it easier for the lift to pass through. 'A monomer would only have this effect on one side, which is energetically less advantageous,' explains Slotboom. Indeed, studies of lipid nanodiscs containing the transport complex show bending of the bilayer.

The structures also provide an indication of how the transport system prevents leakage of sodium. Slotboom: 'The lift has a kind of door that, when open, protrudes and prevents the lift from moving.' The transport process first requires that two sodium ions enter the lift. The negatively charged aspartate can then bind inside, which enables a third sodium ion to enter and bind to the door, closing it. It is therefore impossible for the lift to transport only sodium, which would dissipate the sodium gradient across the membrane driving the transport.

Brains

'It makes the system very efficient', says Slotboom. For bacteria, this efficiency may be only a small selective evolutionary advantage. However, for the analogous glutamate transporter in our brains, it is vital. Glutamate is excreted by nerve cells into the synaptic cleft, where it excites the adjacent neuron. After excitation, it has to be removed very quickly and efficiently to reduce noise in signal transmission. Slotboom: 'For this system, it is vital that there be no leakage.'

Researchers at McGill University have discovered that a protein found in the membrane of our sensory neurons are involved in our capacity to feel mechanical pain, laying the foundation for the development of powerful new analgesic drugs.

The study, published in Cell, is the first to show that TACAN, a highly conserved protein among vertebrates whose function remained unclear, is in fact involved in detecting mechanical pain by converting mechanical pressures into electric signals.

Using molecular and cellular approaches with electrophysiology, Reza Sharif-Naeini, a professor in McGill's Department of Physiology, and his team were able to establish that TACAN is found on the membrane of pain sensing cells where it forms tunnel like pores, a structure known as an ion channel.

The researchers also created a mouse model where TACAN could be "turned off," making the animals significantly less sensitive to painful mechanical stimuli.

"This demonstrates that TACAN contributes to sensing mechanical pain," says Sharif-Naeini, who is also the study's senior author.

A decade-long search

About 70 years ago, scientists imagined that tiny sensors might be responsible for providing our brain with useful information about our environment, explaining our sense of touch or our capacity to feel pain when pinched.

These sensors have since been discovered to be ion channels - pore like structures capable of translating mechanical pressures exerted on a cell into electrical signals that travel to the brain to be processed - a phenomenon known as mechanotransduction.

This phenomenon has been shown to be central in several physiological processes such as hearing, touch and the sensation of thirst. But the identity of the sensor responsible for mechanical pain remained elusive.

Because "most of the pain we feel - a pinch or a stubbed toe - is mechanical in nature," Sharif-Naeini said that competition to find the newly discovered sensor was fierce.

With the rampant problem of opioid overuse, the finding has practical implications for people who suffer from chronic pain. Patients with conditions such as osteoarthritis, rheumatoid arthritis or neuropathic pain often develop mechanical allodynia, a condition where mechanical pain receptors become overly sensitive. Trivial things such as walking or a light touch thus become extremely painful, leading to a significant reduction in the quality of their lives.

"Now that we have identified the sensor associated with mechanical pain, we can start designing new powerful analgesic drugs that can block its action. This discovery is really exciting and brings new hope for novel pain treatment," adds Sharif-Naeini.

As ocean warming causes fish stocks to migrate toward cooler waters to maintain their preferred thermal environment, many of the nations that rely on commercial fish species as an integral part of their economy could suffer.

A new study published in Nature Sustainability from the University of Delaware, the University of California, Santa Barbara and Hokkaido University, shows that nations in the tropics -- especially Northwest African nations -- are especially vulnerable to this potential species loss due to climate change. Not only are tropical countries at risk for the loss of fish stocks, the study found there are not currently any adequate policy interventions to help mitigate affected countries' potential losses.

Kimberly Oremus, assistant professor in the School of Marine Science and Policy in UD's College of Earth, Ocean and Environment, explained that when the researchers looked at international agreements, including the United Nations Convention on the Law of the Sea, they found no specific text for what happens when fish leave a country's Exclusive Economic Zone (EEZ), a zone established to give a country national jurisdiction over a fishery resource.

That means countries could be vulnerable to economic losses, and those potential losses could make the fish populations themselves vulnerable as well.

"We realized there was an incentive for countries when they lose a fish or anticipate that loss to go ahead and overfish before it leaves because otherwise, they don't get the monetary benefits of the resource," said Oremus.

Mapping Species Loss

The researchers used previously projected changes in the distribution range of 779 commercial fish species to estimate the number of species exiting national jurisdiction under contrasting emissions scenarios up to 2100.

Tropical nations in particular stand to lose the most species because there are few if any stocks to replace those leaving. Under a moderate emissions scenario, the research showed that by the year 2100, the average tropical nation could lose 7 percent of the species that were present in 2012.

"The tropics are predicted to lose more fish species than other regions because fish usually have a temperature range that they're comfortable living in and if it gets too hot, and they have nowhere else to go, they're going to migrate towards the poles," said Oremus.

Northwestern African EEZs could lose the highest percentage of species, with a 6-25% reduction predicted by 2050 and a 30-58% reduction predicted by 2100 under the moderate and most severe scenarios, respectively.

Readiness to Address the Problem

While the exit of stocks from national fisheries is inevitable, carefully designed international cooperation could ease the impact on individual nations while preserving the resource for others.

In addition to looking at the species loss, the researchers examined 127 international fisheries agreements, looking at the large, regional ones as well as smaller bi-lateral agreements. They found that none of the agreements have language that prepares countries for the exits of stock, climate change or range shifts.

"We found that there is no fisheries agreement that is explicitly focused on this issue. None," said co-author James Salzman, a distinguished professor of environmental law at UC Santa Barbara's Bren School of Environmental Science and Management. "There's a gap in international law."

Traditional fisheries management assumes that fish are a renewable natural resource and that so long as their geographic range is static, they will remain plentiful in the absence of overfishing.

But the long-term migration of a species out of a country due to climate change means that fish stocks may not always be renewable on the level of a given jurisdiction, even if they remain renewable on an international scale. For the jurisdiction losing the stock, this creates an incentive to overfish before it exits.

Oremus said that policy makers need to think about how those countries could be compensated for the loss of fish stocks due to climate change, which might help prevent countries from overfishing stocks before they exit their EEZs. International agreements regarding climate change have mechanisms to consider compensation for losses, and that policy avenue may work better than the scores of fisheries agreements that Oremus' team found were not set up to wrestle with the question at all.

How to handle liability for loss and damages from climate change -- including whether countries that are more developed and have emitted more carbon dioxide should be compensating countries that are less developed -- has been an ongoing discussion throughout the annual United Nations' Conference of the Parties (COP) meetings during which countries work to address climate change.

In the most recent COP 25 meeting in Madrid in December, compensation was again discussed, and the meeting highlighted the interplay between climate change and the ocean, but fisheries were not addressed.

"Policy in the tropics really needs to focus on this now," said Salzman. "I think this could shift some of the way the loss and damage debate happens in the climate arena, because fisheries really have been overlooked."

While the Small Island Developing States have so far concentrated on concerns about becoming climate migrants as their land is overtaken by the ocean, Oremus said the study should encourage them and other tropical nations to bring fisheries into the conversation.

"For many nations where fish are one of the main economic resources driving their gross domestic product, this is something that they'll want to take into account when they join together to try and negotiate climate agreements," said Oremus.

If the immune system attacks its own body, it can often have devastating consequences: autoantibodies bind to the body's structures, triggering functional disorders. The receptors for glutamate, a neurotransmitter, can also become the target of autoantibodies. Researchers at the Max Planck Institute of Experimental Medicine in Göttingen have been investigating the circumstances under which autoantibodies for a particular glutamate receptor - known as the NMDA receptor - are formed, and their effects in the brain. The researchers have discovered that the level of these autoantibodies in the blood can fluctuate considerably over a person's lifetime - independent of health conditions - and increases with age. Chronic stress can, however, drive up the concentration of these autoantibodies in the blood even in early life. According to the researchers, when the antibodies are able to enter the brain to act on NMDA receptors, people suffer less depression and anxiety. These autoantibodies are clearly acting as the body's own antidepressants.

Glutamate receptors sit in the nerve cell membrane and bind to glutamate, a neurotransmitter. The NMDA receptor is a receptor type essential for learning and memory. Up to 20 percent of the population have antibodies against this receptor in their blood.

Usually, the blood-brain barrier prevents these antibodies crossing from the blood into the brain. Only if this barrier is damaged can the antibodies have any greater effect. If the antibodies bind to NMDA receptors in the brain, these are then removed from the nerve cell membrane ('internalized'). This disrupts the signalling to neighbouring cells. If an inflammation is present in the brain, for example, due to a viral infection, the presence of these autoantibodies can lead to a so-called 'anti-NMDAR-encephalitis': an illness brought to the public's attention by the 2016 film 'Brain on Fire'. The effect of these NMDA receptor autoantibodies can typically influence the symptoms of the underlying encephalitis, contributing to epileptic seizures, impaired movement, psychosis and loss of cognitive function.

Autoantibody levels increase with age

In a new study, Hannelore Ehrenreich and her colleagues from the Max Planck Institute of Experimental Medicine in Göttingen have discovered that the concentration of these autoantibodies in the blood of mice and humans can fluctuate considerably over time. However, the level rises with age, as the body is continually exposed to factors which stimulate the immune system, and with it, autoantibody production. One of these factors is stress. According to the researchers, chronically stressed mice show a higher level of NMDA receptor autoantibodies in their blood compared to their non-stressed conspecifics.

Ehrenreich and her team also analysed the concentration of antibodies in the blood of young migrants. "People who are subjected to high stress in their lives have a greater probability of carrying NMDA receptor autoantibodies in their blood, even at a young age," says Ehrenreich. These are like a ticking time bomb in the body. "If an infection or some other factor appears which weakens the blood-brain barrier, the autoantibodies enter the brain and can cause epileptic seizures or other neurological disorders," says Ehrenreich. A good example would be Knut, the famous Berlin polar bear.

Positive effect of antibodies

However, the researchers' recent study has for the first time indicated that the autoantibodies can also play a positive role in the brain. Mice with a more permeable blood-brain barrier and NMDA receptor autoantibodies in the brain were significantly more mobile and less depressed during times of chronic stress than their conspecifics with an intact blood-brain barrier. An analysis of a large patient database revealed that people with NMDA autoantibodies and a permeable blood-brain barrier also suffered significantly less depression and anxiety.

The NMDA autoantibody obviously plays a role in the brain similar to ketamine, an antidepressant that also acts on NMDA receptors. "The effect of these autoantibodies - whether they contribute to the symptoms of an encephalitis or inhibit depression - is evidently determined not only by their level in the brain, but also by any underlying condition, in particular the presence or absence of inflammation," explains Ehrenreich.

The success of life on earth is based on the amazing ability of living cells to divide themselves into two daughter cells. During such a division process, the outer cell membrane has to undergo a series of morphological transformations that ultimately lead to membrane fission. Scientists at the Max Planck Institute of Colloids and Interfaces, Potsdam, and at the Max Planck Institute for Polymer Research, Mainz, have now achieved unprecedented control over these shape transformations and the resulting division process by anchoring low densities of proteins to the artificial cell membranes.

All living organisms on earth are built up from individual cells. Furthermore, the proliferation and growth of these organisms is based on the ability of each cell to divide into two daughter cells. During the division process, the cell membrane, which provides the outer boundary of the cell, has to undergo a series of morphological transformations that ultimately lead to the fission of the cell membrane. To control this process, today's cells rely on highly specialized protein complexes, which are driven by ATP hydrolysis. It turns out, however, that controlled division can be achieved in a much simpler way, as researchers at the Max Planck Institute of Colloids and Interfaces, Potsdam, and at the Max Planck Institute for Polymer Research, Mainz, have recently demonstrated for artificial cells. These cells are provided by giant lipid vesicles, which have the size of a typical animal cell and are bounded by a single lipid membrane, which provides a robust and stable barrier between the interior and exterior aqueous solution. This compartmentalization is a crucial feature of cell membranes as well.

In addition, vesicle and cell membranes have essentially the same molecular architecture and consist of molecular bilayers with two molecular leaflets that define the two sides of the membranes: the inner leaflet is exposed to the interior, the outer leaflet to the exterior solution. On the one hand, artificial cells with a wide membrane neck remain stable for days and weeks. On the other hand, as soon as the neck has closed down the membrane generates a constriction force onto this neck that cleaves the neck and divides the artificial cell into two daughter cells.

Constriction forces generated by membrane asymmetry

In addition to demonstrating the division of artificial cells, the researchers around Reinhard Lipowsky also identified the novel mechanism, by which this constriction force can be controlled in a systematic manner. To do this, they designed membranes whose inner and outer leaflets differ in their molecular composition by exposing the outer leaflets to a variable concentration of protein. This asymmetry between the two leaflets generates a preferred or spontaneous curvature that determines the shape of the artificial cells. Furthermore, once a closed membrane neck has been formed, the spontaneous curvature generates a local constriction force that leads to the division of these cells. Thus, quite surprisingly, the complete division of the artificial cells is driven by the mechanical properties of the membranes: the force that divides the membrane neck arises directly from the asymmetry of the bilayer membranes.

Versatile module for synthetic biology

In this way, a simple and generic mechanism for the division of artificial cells has been identified. This mechanism does not depend on the precise nature of the molecular interactions that generate the bilayer asymmetry and the associated spontaneous curvature, as has been explicitly demonstrated by using different types of proteins. Furthermore, the used density of the membrane-bound proteins was rather low which leaves ample space for other proteins to be accommodated on the artificial cell membranes. Therefore, the membrane-protein systems introduced here provide a promising and versatile module for the bottom-up approach to synthetic biology. Finally, the division process of artificial cells described here also sheds new light on cell division in vivo. Even though all modern cells seem to rely on a complex protein machinery, our cellular ancestors may have used much simpler mechanisms for their division as Jan Steinkühler, the first author of the study, explains: "Certain bacteria can also divide without the known protein machinery. It has already been speculated that membrane mechanics might play an important role in the latter division processes. Our study demonstrates that mechanically controlled cell division is indeed possible."

NEW YORK- "For those who have faced exploitation and discrimination at the hands of physicians, the medical profession, and medical institutions, trust is a tall order and, in many cases, would be naïve," writes Laura Specker Sullivan in "Trust, Risk, and Race in American Medicine." Specker Sullivan calls on medical providers to take action, writing that caring and competence are not always enough to earn patient trust. People in advantageous positions must work to gain knowledge of those who are more marginalized, the author writes, particularly in the context of American medicine, where many African American patients have experienced unjust treatment.

In "Trust in American Medicine: A Call to Action for Health Care Professionals," Dinushika Mohottige and L. Ebony Boulware complement Specker Sullivan's call by recommending that health professionals commit to five actions: explore and understand patients' mistrust, work with patients to develop individual and institutional efforts to mend and prevent mistrust, strive to be culturally humble, make empathy part of relationships, and engage in continuous self-education. In "Earning Patient Trust: More Than a Question of Signaling," Alan Elbaum advises that health providers can work to overcome their implicitly racist perceptions by adopting an "orientation of empathic curiosity in every patient encounter."

In "Equity Care", Joseph Geskey takes us into a patient's home to explain how her health care system, like many in the United States, is acting against the patient's best interests by placing technology in her home. The Ohio physician notes that, paradoxically, the health system's attempt to use technology to reduce health disparities may end up creating further inequalities in outcomes for elderly, less technologically facile patients with limited literacy. He finds that focusing on equitable outcomes with a personalized understanding of patients allows patients to creatively incorporate their individual goals in managing their health. Geskey asks, "When will this become the standard of care rather than being viewed as charitable care?"

In "Medically Assisted Dying and Suicide: How Are They Different, and How Are They Similar?," Phoebe Friesen goes beyond the semantics to argue that there is no clear justification for emphasizing either the differences or similarities between suicide and medically assisted dying and that more harm may be done in attempts to distance the two acts.

Also in this issue, Benjamin S. Wilfond writes of the ethical considerations involved in adding information to drug labeling in "Pediatric Drug Labeling and Imperfect Information." In "Hans Jonas and the Ethics of Human Subjects Research," Douglas S. Diekema marks 50 years of bioethics by discussing the continued relevance of a landmark 1969 article. And Robert Sparrow and Joshua Hatherley write in "High Hopes for 'Deep Medicine'? AI, Economics, and the Future of Care" that if we want to ensure that "AI increases, rather than erodes, the opportunities for care in medicine, we will need to think more deeply, not just about AI but also about the business of medicine and the institutional and economic contexts in which it is practiced today."

In an article coming from the project, recently published in the Teoría y Derecho magazine, the efficiency of the Spanish system of economic compensation for victims of sexual violence is analysed through the two procedures aimed at this purpose: on one hand, the payment of compensations established in judgement of conviction and on the other hand, grants given to the victims directly from the State, and they note solutions to improve the situation. The results of this analysis prove "the inefficiency of the procedural system and especially the lack of interest on the part of the State on compensating the victims through public assistance".

"We have observed that the State compensation system for victims is an absolute disaster and that victims of sexual crimes rarely receive compensation", points out Helena Soleto, leader of the study and professor of Procedural Law at the UC3M. These grants are usually used to pay for therapy to overcome the victims' trauma and it has been proven that they do not normally cost more than 800 Euros per victim, who are minors in many cases.

Victims of sexual violence are usually women (in 80 per cent of cases). The rest are men, in this case mostly children. The worst crimes in this context are abuse, sexual aggression (rape) and human trafficking for the purposes of prostitution.

"The State, in theory, provides some compensation to victims of sexual crimes that are regulated in a law from 1995. In practice we have seen that nearly half of these requests come from children and the State refuses to give them compensation which, moreover, could only be used for therapy", explains Helena Soleto.

Studying the compensation system in Europe

This study carried out in Spain is part of FAIRCOM (Towards a fair and effective compensation scheme for victims of sexual violence; GA 847360), a research project funded by The European Union Justice Programme (2014 - 2020) which bring six partners together from five countries (Spain, Greece, Italy, Latvia and the Netherlands). The project is led by the UC3M under the management of Helena Soleto, with the participation of researchers from various fields such as Statistics and IT, as well as Law.

The main aim of this project is to design and promote an efficient and effective model for a fair and adequate compensation for victims of sexual crimes. The committee proposes to modify the current deficient compensation model for victims of sexual violence in each country through the identification of legal and organisational obstacles that prevent victims from claiming and accessing their right to effective compensation. In addition, they intend to identify and develop good practices to overcome these barriers and allow the victims to exercise their rights in an efficient manner. "A rule that theoretically protects is not enough; it also needs to put this into practice. Ultimately, we want a fair compensation system to exist for victims of sexual crimes", concludes Soleto.

INDIANAPOLIS -- Admission to the hospital and being seen by a neurologist are factors associated with better quality care for people with a transient ischemic attack (TIA), also known as mini-stroke, according to new research led by scientists from the U.S. Department of Veterans Affairs, Regenstrief Institute, Purdue University, and Indiana University. The study looked at patients treated in the U.S. Veterans Health Administration (VHA).

"There has been a movement to avoid hospital admission for patients with TIAs and instead create observation units to allow patients to get care quickly and be sent home," said Dawn Bravata, M.D., senior author of the paper and a research scientist at the VA and Regenstrief. "However, this study supports the idea that admission may still lead to improved care."

Patients with TIA are at high risk of more vascular events, including repeated TIAs, stroke and death. Timely care has been shown to substantially reduce those risks. However, because TIAs are considered less serious than strokes and there is often uncertainty about diagnosis, patients with TIA are less likely to be admitted to the hospital for treatment than patients with stroke.

The researchers undertook this study to understand both the patient and facility factors that influence care quality, which includes characteristics such as a patient's health history, date and time of the visit to the emergency department, and staffing at the VA facility.

The research team, which also included scientists from Yale School of Medicine and Michigan State University, analyzed data from 3,052 VHA patients with a TIA treated between October 2010 and September 2011. They looked at four indicators to measure care quality: brain imaging, carotid artery imaging, statin therapy and antithrombotic therapy. Then they developed a multilevel, structural equation model that allowed them to evaluate the complex relationship between both patient and facility characteristics and the association with composite quality of care measure.

Findings showed:

Care quality was most strongly affected by admission to the hospital,

Patients who received a neurological consultation had overall higher care quality,

Speech impairment was associated with higher hospital admittance,

Weekend arrivals lowered the likelihood of neurological consultation but increased the likelihood of inpatient admission,

Fewer neurologists on staff was associated with fewer consultations and admissions,

And a higher Charlson Comorbidity Index (higher burden of comorbid diseases such as cancer or heart disease) was associated with higher hospital admittance but lower neurological consultation.

"The patients who are admitted to the hospital have the highest quality of care, and are more likely to have a neurological consultation, which is also a strong driver of care quality," said Dr. Bravata. "The next steps are to determine the best approach to ensuring that all TIA patients get access to the necessary neurological treatment, regardless of the facility where they receive care. The VA recently instituted a teleneurology program to expand access to neurology across facilities, but it is too soon to tell its effect on care."

Study authors say an alternative to hospital admission could be comprehensive follow-up TIA care in the outpatient setting, however these care models have not been widely adopted in the U.S.

Older adults often face new disabilities after a hospital stay for a serious illness. Among the problems they may need to adjust to are difficulties with bathing and dressing, shopping and preparing meals, and getting around inside and outside the home. These new disabilities can lead to being hospitalized again, being placed in a nursing home, and more permanent declines in well-being. The longer a serious disability lasts, the worse it can be for an older adult.

To learn more about this issue, a research team studied information about a particular group of people. They looked at individuals who were hospitalized for a medical issue but did not require critical care. The study was based on data from the Precipitating Events Project (PEP), an ongoing study of 754 people, aged 70 or older, who lived at home at the beginning of the study. At that time, the participants were not disabled and did not need assistance in four basic activities: bathing, dressing, walking inside the house, and getting out of a chair. The researchers published their study in the Journal of the American Geriatrics Society.

The participants were examined at home at the start of the PEP study and then again every 18 months, while telephone interviews were completed monthly through June 2016.

In all, 515 participants were included in the study. They were mostly around 83 years of age and had a medical hospitalization. The participants shared medical problems related to their age, living alone, and having little social support.

At months one and six after hospitalization, disability was common for study participants and interfered with their ability to leave home for medical care. Disabilities included being unable to get dressed, walk across a room, get in or out of a chair, walk a quarter-mile, climb a flight of stairs, and drive a car.

Disability at months one and six after hospitalization was also common for the kinds of activities people need to take care of themselves, including meal preparation and taking medications.

Of the people in the study, many had new disabilities after hospitalization:

31 percent were newly unable to bathe themselves

42 percent couldn't do simple housework

30 percent had problems taking their medications

43 percent were unable to walk a quarter-mile

For those who did recover from a disability, it took between one to two months following hospitalization. Recovering also appears to have a connection to being able to perform most daily tasks, except driving. Recovering the ability to drive following a hospitalization was less common.

In many cases, recovery was incomplete even six months after hospital discharge. For example, the proportion of people who were not disabled at six months was just 65 percent for bathing, 65 percent for meal preparation, 58 percent for taking medications, and 55 percent for driving.

The research team concluded that many older adults discharged from the hospital after a serious medical illness are disabled in specific activities important for leaving the home to access care and self-manage their health conditions. They also noted that these disabilities are often new following hospitalization. Recovery from disability is frequently incomplete six months after discharge, even among persons who return home in the month after hospitalization.