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A team of doctors and scientists from the Champalimaud Clinical Centre in Lisbon, Portugal, and the Netherlands Cancer Institute in Amsterdam, has shown that patients with "low" rectal cancer (that is, very close to the anus) who show no sign of their tumors after a course of radio- and chemotherapy can safely choose to postpone invasive and complication-prone surgical procedures. These results have been published in the journal Annals of Surgery.

Agreeing instead to submit to a very close and strict surveillance of their condition during a period of at least two years, in a "Watch-and-Wait" strategy, they might even totally evade surgery without any negative impact on their health outcome, since the majority (around two-thirds) of these patients does not show any regrowth of the tumour after the first two years of "Watch-and-Wait".

What's most important, according to the scientists, is that of the remaining patients (around one-third), whose tumor does regrow within those first years and who undergo exactly the same surgical procedure as was initially planned for them, 97% show the same outcome as if the surgery had been performed immediately after radio-chemotherapy. In other words, no precious time will have been wasted by waiting and watching the patient.

Surgery still is, today, the frontline classical treatment protocol for rectal cancer cases - which represent about 30% of all colorectal cancers, or about six million new cases per year worldwide, according to 2018 estimates. But the fact is that, for certain particularly complicated locations of the tumor in the rectum, a previous course of radio-chemotherapy before surgery is required. Why? Because in these cases, it is necessary to reduce the size of the tumor that might already be invading the pelvic wall structures or even other organs.

This pre-operative treatment comes with its own side effects, increasing the probability of urinary and sexual dysfunction, worse bowel function or even deficient healing process. These could, in turn, have devastating post-operatory consequences, such as suture defects leading to peritonitis.

"For rectal tumors located less than seven centimeters from the anus, the patient is often submitted to radiochemotherapy during five weeks, having a subsequent recovery period of another eight to ten weeks before the surgical intervention", explains Nuno Figueiredo, head of the Champalimaud Surgical Centre and a colorectal surgeon at the Digestive Cancer Unit of the Champalimaud Clinical Centre, who is one of the co-authors of the new study together with his colleagues Marit Van der Sande and Geerard Beets, from the Netherlands Cancer Institute.

Moreover, in more than half of these low rectal cancer cases - which represent 30% to 40% of all rectal cancers, that is, around two million new cases per year worldwide, according to the same 2018 estimates -, the surgery may require removal of the rectum and surrounding tissue (abdominoperineal amputation), a condition that implies permanently redirecting the colon towards an incision made in the abdomen (colostomy). In these cases, the patient is fitted for life with a "bag" to collect stools directly through that artificial orifice.

For all the above reasons, surgery is potentially a very invasive procedure in low rectal cancer. But what if there was a non-invasive option to surgery that did not put eligible patients' lives at risk? The new study shows that this may actually be the case.

Unnecessary surgery?

The Watch-and-Wait strategy for rectal cancer was pioneered by surgeon Angelita Habr-Gama at the University of São Paulo, Brazil, some 20 years ago. Habr-Gama observed that, when patients with low rectal cancer were irradiated to prepare them for surgery due to the proximity of the tumor to the anus, histology results (biopsy) of the tissue harvested during the surgery often showed absolutely no trace of cancer cells. And she wondered whether the surgery, with its cohort of potential complications and life-long impact on patients' quality of life, had actually been necessary in those cases.

In the mid-2000's, surgeons in the Netherlands started proposing the alternative protocol to eligible patients. And in 2013, the Champalimaud Clinical Center and the University of Manchester in the UK were some of the first institutions in the world to follow suit. "Today, 53 centers around the world are using the same Watch-and-Wait protocol", says Figueiredo. "And in 2013, we created the International Watch-and-Wait Database to collect all the data generated by these centers."

The protocol consists in performing, eight to ten weeks after the chemoradiotherapy course, a series of diagnostic tests before deciding if surgery is warranted. "We use clinical and radiological observations to decide whether surgery is needed or not", says Figueiredo. "We perform three exams: digital rectal examination, endoscopy and magnetic resonance imaging." And if the patient's clinical response is "complete" - that is, if the tumor does not show up in any of these exams -, the patient is then told that they can enter the Watch-and-Wait (W&W) protocol. "One hundred percent of our patients at the Champalimaud Center choose this option", Figueiredo points out.

Before they make their decision, the patients are told that if, at any time during the following 24 months, any sign of tumor reappearance (or "regrowth") were to emerge, that would necessarily mean undergoing immediate surgery to remove the tumor in the exact way as initially programmed.

But if the cancer does not regrow during those first 24 months, the patient will then go on to be examined, at least every six months, for three additional years. After that, if it still doesn't reappear, the exams will continue at a rate of once a year.

Is it wise to wait?

Criticism of this protocol has focused, in particular, on the possibility of wasting precious time, during which the tumor could become, if not metastatic, possibly uncontrollable and impossible to remove surgically. It is this deferment of the surgery that the team has now shown to be safe in 97% of cases of tumor regrowth.

The new study involved 385 patients from both centers (83 from the Champalimaud) that were diagnosed between 2005 and 2018 and found to have a complete clinical response following chemoradiotherapy. Of those 385 patients, 89 (23 from Champalimaud) - or around 25% - had tumor regrowth during the first 24 months. And of the patients who experienced regrowth, "97% were rescued, which means operated on as initially programmed", says Figueiredo.

In other words, the W&W period did not compromise the outcome for those patients. The final result was the same they would have obtained if the surgery had been performed immediately.

There were also some patients included in W&W (3%) who were either too frail or too old to sustain a major abdominal operation - or who, experiencing a regrowth after the W&W period, refused to have surgery. These patients were then given the best possible palliative care.

Another line of criticism has to do with the possibility that waiting to see what happens could increase the risk of developing distant metastases, that is, of the initial tumor spreading to other parts of the body, in particular to the liver and lungs. Figueiredo points out that this study was not designed to answer this question.

However, what these researchers have effectively observed is that, compared to historical rectal series in the literature, for which 25% of the patients with rectal cancer go on to develop metastases, this only happened to 8.2% of the patients submitted to the W&W protocol. According to Figueiredo, this could simply reflect the fact that eligible patients for the alternative protocol have a much better prognosis than the general population of rectal cancer patients - and start out with a reduced risk of metastases.

Two next steps, he adds, are already ongoing, namely at the Champalimaud. One is to intensify radiation oncology protocols in order to increase the number of rectal cancer patients who reach a clinical complete response and become eligible for W&W - that is, to contemplate radio and chemotherapy as a standard standalone treatment for these tumours and not just a precursory step for surgery. The other is to improve the diagnostic accuracy of MRI and endoscopy exams in order to reduce the number of "false negatives" - that is, the number of apparently complete responses in which the tumor is actually still there after chemoradiotherapy but fails to be detected.

A new study on how and when the precursors to eggs and sperm are formed during development could help pave the way for generating egg and sperm cells in the lab to treat infertility.

The study, published in the journal Cell Reports, describes the way in which human stem cells evolve into germ cells, the precursors for egg and sperm cells.

"Right now, if your body doesn't make germ cells then there's no option for having a child that's biologically related to you," said Amander Clark, the study's lead author, a member of the Eli and Edythe Broad Center of Regenerative Medicine and Stem Cell Research at UCLA. "What we want to do is use stem cells to be able to generate germ cells outside the human body so that this kind of infertility can be overcome."

It is estimated that infertility affects 10% of the U.S. population, and infertility rates have increased over the past several decades because more people are waiting longer to have children. Many forms of infertility can be treated using procedures that join egg and sperm together outside the body, such as in vitro fertilization and intracytoplasmic sperm injection. But for people whose bodies don't produce eggs or sperm -- because of chemotherapy, radiation, genetics or other unexplained causes -- those treatments aren't an option unless a donor provides the eggs or sperm.

"With donated eggs and sperm, the child is not genetically related to one or both parents," said Clark, who also is a UCLA professor and chair of molecular cell and developmental biology. "To treat patients who want a child who is genetically related, we need to understand how to make germ cells from stem cells, and then how to coax those germ cells into eggs or sperm."

In developing male and female embryos, a subset of pluripotent stem cells -- cells that have the potential to become nearly every type of cell in the body -- become germ cells that will later generate eggs or sperm. Researchers previously demonstrated the ability to make similar stem cells in a laboratory, called induced pluripotent stem cells, or iPS cells, from a person's own skin or blood cells.

Clark and her colleagues used technology that enables them to measure the active genes in more than 100,000 embryonic stem cells and iPS cells as they generated germ cells. Collaborators at the Massachusetts Institute of Technology developed new algorithms to analyze the massive amounts of data.

The experiments revealed a detailed timeline for when germ cells form: They first become distinct from other cells of the body between 24 and 48 hours after stem cells start differentiating into cell types that will ultimately make up all the specialized cells in the adult body.

Clark said that information would help scientists focus their efforts on that particular timeframe in future studies, in order to maximize the number of germ cells they can create.

The study also revealed that the germ cells come from two different populations of stem cells -- amnion cells, which are located in the fluid and membrane that surrounds the embryo during pregnancy, as well as gastrulating cells from the embryo itself.

When the researchers compared the germ cells derived from embryonic stem cells with those derived from iPS cells in the lab, they found that the patterns by which genes were activated were nearly identical.

"This tells us that the approach we're using to begin the process of making germ cells is on the right track," Clark said. "Now we're poised to take the next step of combining these cells with ovary or testis cells."

That next step is critical because molecular signals from ovary or testis tissue are what signal germ cells to mature into eggs and sperm.

If the approach were to be incorporated into a future treatment for infertility, scientists might eventually be able to use a patient's own skin cells to form stem cells that can be coaxed into both germ cells and ovarian or testis tissue -- and those cell types might be able to be used to generate a person's own eggs or sperm in the lab.

"We're going in the right direction but it will take a lot of new innovations to solve infertility related to the loss of germ cells," Clark said.

The techniques described above were used in laboratory tests only and have not been tested in humans or approved by the Food and Drug Administration as safe and effective for use in humans.

A study of East African coral reefs has uncovered an unfolding calamity for the region: plummeting fish populations due to overfishing, which in turn could produce widespread food insecurity.

In a newly published paper in the journal Marine Ecology Progress Series titled "Coral reef fish communities, diversity, and their fisheries and biodiversity status in East Africa," WCS Senior Conservation Zoologist Dr. Tim McClanahan reports that overfishing is widespread across the region.

The remedy, says the sole author of the study, is to recognize the need to rebuild fish stocks to ensure they are providing the maximum possible catch for the developing countries of Kenya, Tanzania, and Mozambique. The African continent has among the highest human population growth rates and associated food security issues.

"Whereas fish stocks within marine parks and areas in distant or turbulent locations were found to be at healthy levels, coastal areas open to fishing were another story," said McClanahan. "We have found that fish catches have been declining in Africa in recent years by a million tons a year, and this study shows that much of this decline in East Africa is due to declining fish stocks."

Based on a sample of 239 sites--data gathered over several years--the study and previous estimates show that 70 percent of the reefs have fish stocks below the levels that will produce the maximum fisheries yields. The few areas above this level were in marine parks, rural areas, and remote or dangerous seas.

The study further shows that low stocks not only affects food production but also the diversity of fish and reef ecology. Numbers of fish species decline rapidly when stocks decline below sustainable levels. This loss of species will have consequences for the long-term recovery and the potential to produce food.

In light of the central finding that fish stocks in East Africa are severely depleted to unsustainable levels, the study suggests that rebuilding fish biomass is the key management action needed for long-term sustainability of the fisheries. Stricter fisheries management and enforcement alongside expanding spatially diverse fishing restrictions are essential to rebuilding stocks, maintaining species diversity, recovering fisheries and ensuring longterm ecosystem services for the East African coast.

The study follows on recent fisheries research that reveals that, where fisheries science is active and evaluating reefs, stocks are rebuilding. The fisheries division of the FAO in Rome recently evaluated their needs in the coming decades and concluded that knowing the stock levels of countries without good fisheries science is undermining efforts to achieve global fisheries sustainability.

A growing body of research shows that the behavior of peers has a significant influence on an individual's energy-related decisions, whether it's choosing to install solar panels or to purchase a hybrid vehicle. In short, personal energy choices can be contagious.

But why exactly that occurs is less clear.

In a new paper, an interdisciplinary team of scholars, including an economist at the Yale School of Forestry & Environmental Studies (F&ES), reviews the latest findings on the role of social influence and then illustrates pathways through which these insights might be used to promote more sustainable energy choices.

"The evidence on peer influence in energy has been growing but people haven't connected it to theories in social psychology that can help provide a deeper understanding of how persuasion works, how that word of mouth works, and what are some of the channels by which peer influence makes an impact," said Kenneth Gillingham, associate professor of environmental and energy economics at F&ES and corresponding author on the paper.

"We wanted to bridge those fields of literatures so that we can better understand how peer effects and contagion work, why they work, and why they're so powerful."

The paper is published in the journal Nature Energy. The co-authors are Kimberly Wolske, a research associate and assistant professor at the University of Chicago's Harris School of Public Policy, and P. Wesley Schultz, a professor of psychology at California State University, San Marcos.

In the paper, the authors review existing scholarship conducted across many disciplines -- including economics, marketing, sociology, and psychology -- on the influence of peer effects. Across these different fields, they write, researchers have found a basic tendency for the energy-related behaviors of individuals to be influenced by members of a peer group; sometimes this influence is an even more important factor than cost or convenience.

For instance, several studies have demonstrated that the chances of an individual deciding to install solar panels increases as more panels are installed in their neighborhood or region. (One study calculated that for each additional installation in one California zip code, the probability of another increased by 0.78 percentage points.)

To better understand why this happens, the authors took a closer look at two areas of research on peer influence that offer important insights:

1. Interpersonal communication and persuasion, which can include observation of energy choices (such as seeing solar panels on a neighbor's roof), word-of-mouth communication, and the influence of trusted community leaders.

2. Normative social influence, in which social norms are passively communicated as shared standards that constrain or guide the behavior within a group.

The authors find the extent to which peer influence affects behavior depends on several factors. These include characteristics of the individual in question (how much have they previously considered a behavior?), the strength of their relationship with their peers, how the individual learns from peer behavior (for example, through conversation, observation, or social comparison), and the depth at which the learned information is processed. "Based on our review of the literature, we hypothesize that certain combinations of these processes are more likely to lead to peer effects in energy than others, depending on the targeted behavior," they write.

For instance, they expect that peer behavior has minimal impact when an individual already has strong beliefs about the behavior in question. If they don't have strong opinions, peer influence can be more powerful.

Also, the effectiveness of different types of peer influence may depend on just how difficult the change in behavior will be. "Receiving a home energy report that shows you consume more energy than your neighbors may be enough to encourage daily conservation," Wolske said. "But we suspect it's less likely to spur investment in durable goods like rooftop solar or electric vehicles."

For behaviors with high upfront costs, people may be more likely to follow suit when they've had an opportunity to talk with existing owners of those technologies. "Friends and family are often among the most trusted sources of information," said Wolske. "Policies and programs that seek to promote low carbon technologies may benefit from enlisting the help of peers who have already adopted them."

The authors suggest that future research should focus on identifying when during the decision-making process social influence is most impactful. They also call for more cross-disciplinary research into the role of peer effects.

"There are surprisingly few conversations across the disciplines about how insights from social psychology and other areas actually underpin the more aggregate findings of contagion in new energy technologies and behavior," said Gillingham. "More interaction between these disciplines can really improve our understanding of why peer effects work and how they can be leveraged to achieve more sustainable energy choices."

Mud wasp nests have helped establish a date for one of the ancient styles of Aboriginal rock art in the Kimberley.

University of Melbourne and ANSTO scientists put the Gwion Gwion art period around 12,000 years old.

"This is the first time we have been able to confidently say Gwion style paintings were created around 12,000 years ago," said PhD student Damien Finch, from the School of Earth Sciences at the University of Melbourne. "No one has been able present the scientific evidence to say that before."

One wasp nest date suggested one Gwion painting was older than 16,000 years, but the pattern of the other 23 dates is consistent with the Gwion Gwion period being 12,000 years old.

The rock paintings, more than twice as old as the Giza Pyramids, depict graceful human figures with a wide range of decorations including headdresses, arm bands, and anklets. Some of the paintings are as small as 15cm, others are more than two metres high.

The details of the breakthrough are detailed in the paper 12,000-year-old Aboriginal rock art from the Kimberley region, Western Australia, now published in Science Advances.

More than 100 mud wasp nests collected from Kimberley sites, with the permission of the Traditional Owners, were crucial in identifying the age of the unique rock art.

"A painting beneath a wasp nest must be older than the nest, and a painting on top of a nest must be younger than the nest," Mr Finch said. "If you date enough of the nests, you build up a pattern and can narrow down an age range for paintings in a particular style."

Lack of organic matter in the pigment used to create the art had previously ruled out radiocarbon dating. But the University of Melbourne and ANSTO scientists were able to use dates on 24 mud wasp nests under and over the art to determine both maximum and minimum age constraints for paintings in the Gwion style.

The project was initiated by Professor Andy Gleadow and Professor Janet Hergt, from the School of Earth Sciences, and started in 2014 with funding from the Australian Research Council and the Kimberley Foundation. It is the first time in 20 years scientists have been able to date a range of these ancient artworks.

"The Kimberley contains some of the world's most visually spectacular and geographically extensive records of Indigenous rock art, estimated to include tens of thousands of sites, only a small fraction of which have been studied intensively," said Professor Gleadow.

Professor Hergt said being able to estimate the age of Gwion art is important as it can now be placed into the context of what was happening in the environment and what we know from excavations about other human activities at the same time.

Dr Vladimir Levchenko, an ANSTO expert in radiocarbon dating and co-author, said rock art is always problematic for dating because the pigment used usually does not contain carbon, the surfaces are exposed to intense weathering and nothing is known about the techniques used thousands of years ago.

"Beeswax or resin have also been used - usually on more modern samples," Dr Levchenko said.

"Although soil is full of carbon, most of it is easily degradable. However, charcoal is more likely to survive for longer periods. There is lots of black carbon in Australian soil because of bushfires."

AMES, Iowa - The so-called "Cocoon Galaxy" not only has a unique shape, it has a rare double-nucleus structure, astronomers report in a new paper.

After studying data from optical and radio telescopes based on the ground and in space, a team of astronomers determined that a galaxy known as NGC 4490 (and nicknamed the "Cocoon Galaxy" because of its shape) has "a clear double nucleus structure," according to their paper.

One nucleus can be seen in optical wavelengths. The other is hidden in dust and can only be seen in infrared and radio wavelengths.

The paper reporting the discovery is now online and has been accepted for publication in the Astrophysical Journal. First author is Allen Lawrence, who earned a master's degree in astronomy from Iowa State University in 2018 and continues to work with Iowa State astronomers.

Co-authors are Iowa State's Charles Kerton, an associate professor of physics and astronomy; and Curtis Struck, a professor of physics and astronomy; as well as East Tennessee State University's Beverly Smith, a professor of physics and astronomy.

Lawrence started the study in 2013 while taking astronomy classes at the University of Wisconsin-Madison. He had the chance to study one of two galaxy systems and picked NGC 4490, which is interacting with a smaller galaxy, NGC 4485. The system is about 20% the size of the Milky Way, located in the Northern Hemisphere and about 30 million light years from Earth.

"I saw the double nucleus about seven years ago," Lawrence said. "It had never been observed - or nobody had ever done anything with it before."

Some astronomers may have seen one nucleus with their optical telescopes. And others may have seen the other with their radio telescopes. But he said the two groups never compared notes to observe and describe the double nucleus.

The new paper says both nuclei are similar in size, mass and luminosity. It says both are similar in mass and luminosity to the nuclei observed in other interacting galaxy pairs. And, it says the double nucleus structure could also explain why the galaxy system is surrounded by an enormous plume of hydrogen.

"The most straightforward interpretation of the observations is that NGC 4490 is itself a late-stage merger remnant" of a much-earlier collision of two galaxies, the authors wrote. A merger could drive and extend the high level of star formation necessary to create such a large hydrogen plume.

The astronomers said there are other reasons they find the study of this system interesting:

Struck, who studies colliding galaxies, said double-nucleus galaxies are very rare, especially in smaller galaxies such as this one. And, he said astronomers think a double nucleus could contribute to the buildup of super massive black holes found in the center of some galaxies.

And Kerton, who researches star formation, said, "This project demonstrates that using multiple wavelengths from space- and ground-based observations together can really help us understand a particular object."

ITHACA, N.Y. - Even just a few days of solitary confinement may significantly increase inmates' risk of death after serving their sentences.

New research from Christopher Wildeman, professor of policy analysis and management at Cornell University, analyzed the Danish prison system and found that 4.5% of former inmates who had spent time in solitary confinement - most for less than a week - died within five years of being released. That was 60% more than those who were not placed in solitary.

"That's a significant increase in the risk of mortality," Wildeman said. "We think it's a pretty substantial effect."

This study tracked everyone - nearly 14,000 people - who began and ended sentences in Danish prisons or jails over a five-year period between 2006 and 2011.

Of the nearly 1,700 inmates who experienced solitary confinement, the average total stay was nearly nine days, but half spent fewer than five days and two-thirds less than a week.

Understanding the effect of such short exposures is important, Wildeman said, because they are often avoidable.

"For somebody who is in disciplinary segregation for 72 hours because of a specific infraction, there's almost always an alternative that a warden or guard could use that wouldn't involve putting someone in solitary," he said.

Alternatives might include a fine, loss of privileges or short increase in sentence length.

The researchers had access to a wealth of data about the former inmates from Danish government registers - not only age, gender, race, ethnicity and education levels, but also information about their family backgrounds, employment and housing histories and prior contacts with the criminal justice system.

That allowed the study to account for many factors that might have made someone more likely to end up in solitary confinement or to die after being released, while acknowledging some gaps in data concerning potential mental health or addiction issues.

Government registers also confirmed dates and causes of death within five years of release. The study determined that the higher death rates for those who had experienced solitary confinement - generally younger inmates serving longer sentences - was driven primarily by non-natural causes such as accidents, suicides and violence.

The finding that just a day or two in solitary confinement appears linked to a higher risk of death after release is somewhat surprising, Wildeman said. More research is needed to understand exactly what amount of exposure elevates mortality, he said.

The study was published in The Lancet Public Health.

Manufacture of chemical sensors and catalysts based on gold nanoclusters gained new light from recent cutting-edge research. Chemists at the University of Jyväskylä, Finland and the University of California succeeded in determining the atomic precise structure of a chain of gold nanoclusters attached to each other. In this study the researchers revealed the disulfide-bridging bond between the bound nanoclusters. Linked gold nanocluster structures advance our understanding of the optical and electronic response of these systems which hold future perspectives in nanoelectronics and bioimaging. The study was published in The Journal of Physical Chemistry Letters publication in January 2020.

These structures - practically huge molecules- were studied four years ago by a researchers at the Nanoscience Center of the University of Jyväskylä. At that time, researchers were the first in the world to build a chains of gold forged with atomic precision, which were named the world's smallest gold chains (Nanoscale, 2016).

In a just released spatially resolved imaging study of individual bonds, researchers investigated the structure of the chain with the precision of atoms and provided experimental confirmation that, the gold nanoparticles are linked together by bridging disulfide bonds. The proof of disulfide linking was to date the subject of speculatithe researchers revealed the disulfide-bridging bond between the bound nanoclusters. Linked gold nanocluster structures advance our understanding of the optical and electronic response of these systems which hold future perspectives in nanoelectronics and bioimaging. The ston.

"Modifying the surface of nanoclusters and the molecules connecting them is a step closer to new biological, medical and electronic applications," says Docent Tanja Lahtinen from the University of Jyväskylä.

A chain of nanoscale gold particles reacts with light.

"In these nanoscale superstructures, the electron clouds of the metal particles of adjacent particles are interconnected, opening up the possibility of studying the interactions between particles with very accurate theoretical calculations, now that we know, for sure, how the structures have formed," says researcher Eero Hulkko.

The atomic precise structure was revealed by combining imaging techniques

The exploration of nanoscale chemical structures has promoted by the rapid development of chemically selective imaging techniques. Atomic resolution of individual molecules requires extremely high resolution and sensitivity of the equipment.

This study utilized the latest transmission electron microscopy technology (TEM).

The measurements were made at the IMRI center, University of California using the JEM-ARM300F Grand ARM TEM equipment, where currently has the best commercially available electron microscopy equipment.

"This study combined high-resolution electron microscopy (TEM) with high-sensitivity electron energy loss spectroscopy (EELS), which allowed simultaneous structural and spectroscopic analysis to determine the nanoscale structure, with X-ray photoelectron spectroscopy (XPS) analysis supported by the above-mentioned data." review by researcher Karolina Sokolowska from the University of Jyväskylä.

Understanding the various molecular interactions and structures that arise among surface water molecules would enable scientists and engineers to develop all sorts of novel hydrophobic/hydrophilic materials or improve existing ones. For example, the friction caused by water on ships could be reduced through materials engineering, leading to higher efficiency. Other applications include, but are not limited to, medical implants and anti-icing surfaces for airplanes. However, the phenomena that occur in surface water are so complicated that Tokyo University of Science, Japan, has established a dedicated research center, called "Water Frontier Science and Technology," where various research groups tackle this problem from different angles (theoretical analysis, experimental studies, material development, and so on). Prof Takahiro Yamamoto leads a group of scientists at this center, and they try to solve this mystery through simulations of the microscopic structures, properties, and functions of water on the surface of materials.

For this study in particular, which was published in the Japanese Journal of Applied Physics, the researchers from Tokyo University of Science, in collaboration with researchers from the Science Solutions Division, Mizuho Information & Research Institute, Inc., focused on the interactions between water molecules and graphene, a charge-neutral carbon-based material that can be made atomically flat. "Surface water on carbon nanomaterials such as graphene has attracted much attention because the properties of these materials make them ideal for studying the microscopic structure of surface water," explains Prof Yamamoto. It had been already pointed out in previous studies that water molecules on graphene tend to form stable polygonal (2D) shapes in both surface water and "free" water (water molecules away from the surface of the material). Moreover, it had been noted that the probability of finding these structures was drastically different in surface water than in free water. However, the differences between surface and free water have to be established, and the transition between the two is difficult to analyze using conventional simulation methods.

Considering this situation, the research team decided to combine a method taken from data science, called persistent homology (PH), with simulations of molecular dynamics. PH allows for the characterization of data structures, including those contained in images/graphics, but it can also be used in materials science to find stable 3D structures between molecules. "Our study represents the first time PH was used for a structural analysis of water molecules," remarks Prof Yamamoto. With this strategy, the researchers were able to obtain a better idea of what happens to surface water molecules as more layers of water are added on top.

When a single layer of water molecules is laid on top of graphene, the water molecules align so that their hydrogen atoms form stable polygonal structures with different numbers of sides through hydrogen bonds. This "fixes" the orientation and relative position of these first-layer water molecules, which are now forming shapes parallel to the graphene layer. If a second layer of water molecules is added, the molecules from the first and second layers form 3D structures called tetrahedrons, which resemble a pyramid but with a triangular base. Curiously, these tetrahedrons are mostly pointing downwards (towards the graphene layer), because this orientation is "energetically favorable." In other words, the order from the first layer translates to the second one to form these 3D structures with a consistent orientation. However, as a third and more layers are added, the tetrahedrons that form don't necessarily point downwards and instead appear to be free to point in any direction, swayed by the surrounding forces. "These results confirm that the crossover between surface and free water occurs within only three layers of water," explains Prof Yamamoto.

The researchers have provided a video of one of their simulations where these 2D and 3D structures are highlighted, allowing one to understand the full picture. "Our study is a good example of the application of modern data analysis techniques to gain new and important insights," adds Prof Yamamoto. What's more, these predictions should not be hard to measure experimentally on graphene through atomic-force microscopy techniques, which would, without a doubt, confirm the existence of these structures and further validate the combination of techniques used. Prof Yamamoto concludes: "Although graphene is a rather simple surface and we could expect more complicated water structures on other types of materials, our study provides a starting point for discussions of more realistic surface effects, and we expect it will lead to the control of surface properties."

Structural variations in genomes can arise from deleting, amplifying, or reordering genomic segments ranging from a few thousand letters of the genetic code to whole chromosomes. These variations have previously been difficult to classify and catalogue due to the complex mechanisms of their formation. Jan Korbel, group leader at EMBL and one of the initiators and coordinators of the Pan-Cancer project, explains: "In this study we have uncovered and classified different ways by which the cancer genome can rearrange. We performed the first detailed classification of structure variation mechanisms in cancer genomes." The researchers uncovered several new processes that can lead to cancer, for instance a complex process in which some fractions of the genome are duplicated more than once. This can lead to cancer genes becoming active, because they are copied in high number and then brought to a region in which they can be switched on.

Linking events to mutations

"Most previous studies have been conducted on the coding 1-2% of the genome," says Joachim Weischenfeldt, group leader in the Biotech Research & Innovation Centre in Copenhagen and a former postdoc in EMBL's Korbel group. "Structural variations have been largely ignored, because most of them are situated in the non-coding part of the genome and are much more complex to comprehend."

Along with colleagues Weischenfeldt developed methods to identify structural variants and the mechanisms of their formation by performing a whole genome sequencing analysis on the Pan-Cancer data. "This paper is one of the first ones to systematically classify very complex types of structural variants that occur in cancer genomes and link them to mechanisms of formation," says Weischenfeldt. "It now gives us a handle to distinguish the different types of structural variants that occur in cancer genomes. We can potentially use these as biomarkers in different cancers, because mutations in certain very potent driver genes give rise to specific types of structural variants." Biomarkers are biological indicators, such as specific molecules or genetic sequences, that can be used to identify certain conditions - in this case cancer.

The paper moves researchers closer to answering some of the basic questions about cancer, as they can now explore the genetics behind genome rearrangements. Complex events can be linked back to a specific mutation, which is very important for better diagnosis of patients. The catalogue can be used both for prognosis and therapy.

A new therapeutic tool

Weischenfeldt explains that this sort of analysis is already being implemented as a clinical tool to identify mutation signatures; combinations of mutations with a characteristic pattern. During his current work at the Biotech Research & Innovation Centre in Copenhagen, Weischenfeldt is applying these analysis methods to understand the genetics of cancer patients and to devise better and more tailored treatment options. "We have a programme in which patients can get precision medicine based on genomic findings. The classification method that will be published in this paper will be an important part of our toolbox," he says.

Weischenfeldt explains that working on the Pan-Cancer project has trained him and many of his colleagues in handling and analysing large and complex datasets to identify recurrent and biologically relevant patterns. "There weren't a lot of these methods when we started. We had to come up with new, reproducible research methods to analyse the genetic information we had," he says. "That was a huge challenge, but also an extremely exciting one. That's why we do research."

Korbel adds that following up on the research presented in this paper will also be very interesting to EMBL scientists. "For us, a very important next step is to identify the molecular cause of all these separate processes," says Korbel.

The Pan-Cancer project

The Pan-Cancer Analysis of Whole Genomes project is a collaboration involving more than 1300 scientists and clinicians from 37 countries. It involved analysis of more than 2600 genomes of 38 different tumour types, creating a huge resource of primary cancer genomes. This was the starting point for 16 working groups to study multiple aspects of cancer development, causation, progression, and classification.

Researchers at EMBL-EBI were among the leaders of a large international consortium that carried out a joint analysis of data from over 1000 donors of more than 25 cancer types, studying data on their whole genomes along with tumour transcriptome data, which indicates the genes that are active within a tumour. These data represent the largest comparative resource to date of cancer-specific RNA alterations matched with whole-genome sequencing data.

Cancer is a disease driven by mutations arising within our DNA, caused by environmental factors or ageing. It is less studied how these alterations in the genome change our RNA. More research is required to understand which of the alterations in RNA are a consequence of the mutations and which contribute to cancer progression.

This research was published in Nature as part of an international collaboration of over 1300 scientists known as the Pan-Cancer Analysis of Whole Genomes (PCAWG). This study involved more then 10 research groups as part of the larger Pan-Cancer project and aimed to develop the most comprehensive catalogue of RNA alterations in cancer including transcript expression, splicing, alternative promoter activity, and fusions.

RNA alterations in cancer

Differences in RNA expression, splicing, and isoform variation are associated with many types of cancer. Here, the researchers used transcriptomic profiling to analyse cancer-specific alterations found in the tumour's RNA. From this they identified many diverse and underappreciated mechanisms of cancer genome alterations yet to be detected by DNA analysis alone.

"Although cancer is caused by changes in an organism's DNA, these changes also manifest via RNA," says Alvis Brazma, Functional Genomics Senior Team Leader and Senior Scientist at EMBL-EBI. "We showed that often it is easier to detect important DNA changes by looking at RNA."

Cancer-specific fusions

"We found hundreds of changes in the cancer genome that we could link to other molecular changes occurring in the cell," says Brazma. "Some of the most interesting were chimera genes, in which part of one gene is fused to part of another. We were able to build a classification of how these chimera genes emerge in cancer."

Gene fusions are known to play an important role in cancer-driving events and can be used for disease diagnosis. This study represents the first comparative analysis of both gene and RNA fusions across a large collection of tumour datasets. The researchers were able to identify over 2000 new cancer-specific gene fusions, 78 of which appeared more than once. This fusion data is freely available to download from Synapse.

Shortly after Tropical Cyclone Francisco formed on Feb. 5 in the Southern Indian Ocean, NASA's Aqua satellite provided a visible image of the storm.

On Feb. 5, 2020, the Moderate Resolution Imaging Spectroradiometer or MODIS instrument that flies aboard NASA's Aqua satellite provided a visible image of Francisco that showed powerful thunderstorms around the low-level center. Satellite imagery showed shallow thunderstorm banding wrapping into the center of the low-level center and strong convective bands of thunderstorms over the eastern semicircle.

On Feb. 5 at 4 a.m. EST (0900 UTC), the Joint Typhoon Warning Center (JTWC) noted that Tropical Cyclone Francisco was located near latitude 17.3 degrees south and longitude 68.5 degrees east, about 647 nautical miles east-southeast of Mauritius. Maximum sustained winds 40 knots (46 mph/74 kph). This storm is moving to the southeastward.

Francisco is forecast to slightly intensify today, Feb. 5. The JTWC expects Francisco will continue to track southeast to south over the next day and a half and turn to the west-southwest after which time it is expected to begin weakening.

Researchers at Albany Medical College in New York have discovered that a specific type of immune cell accumulates in older brains, and that activating these cells improves the memory of aged mice. The study, which will be published February 5 in the Journal of Experimental Medicine (JEM), suggests that targeting these cells might reduce age-related cognitive decline and combat aging-associated neurodegenerative disease in humans.

The brain is highly susceptible to aging, with cognitive functions, such as learning and memory, gradually declining as we get older. Much of the body’s immune system also deteriorates with age, resulting in increased susceptibility to infection and higher levels of inflammation. In their new JEM study, however, a team of researchers led by Qi Yang and Kristen L. Zuloaga at Albany Medical College reveal that aging-related changes in a class of immune cell known as group 2 innate lymphoid cells (ILC2s) could allow doctors to combat the effects of aging on the brain.

ILC2s reside in specific tissues of the body and help to repair them when they are damaged. Recently, for example, ILC2s in the spinal cord were shown to promote healing after spinal cord injury. “However, whether ILC2s also reside in other parts of the central nervous system, and how they respond to aging, was unknown,” Yang says.

The researchers examined the brains of both young and old mice and found that ILC2s accumulated with age in a structure called the choroid plexus. This structure produces cerebrospinal fluid and is close to the hippocampus, a region of the brain that plays a key role in learning and memory. Older mouse brains had up to five times as many ILC2 cells as younger brains. Crucially, the researchers also saw large numbers of ILC2s in the choroid plexus of elderly humans.

The ILC2s in old mouse brains were largely in an inactive, or quiescent, state, but the researchers were able to activate them by treating the animals with a cell signaling molecule called IL-33, causing the cells to proliferate and produce proteins that stimulate the formation and survival of neurons. Compared with ILC2s from younger animals, ILC2s from older mice were able to live longer and produce more ILC2 upon activation, the researchers found.

Remarkably, treating old mice with IL-33, or injecting them with ILC2 cells pre-activated in the lab, improved the animals’ performance in a series of cognitive tests designed to measure their learning and memory. “This suggested that activated ILC2 can improve the cognitive function of aged mice,” says Zuloaga.

One of the proteins produced by activated ILC2s is the signaling molecule IL-5. The research team found that treating old mice with IL-5 increased the formation of new nerve cells in the hippocampus and reduced the amount of potentially damaging inflammation in the brain. Again, IL-5 treatment improved the cognitive performance of aged mice in a number of tests.

“Our work has thus revealed the accumulation of tissue-resident ILC2 cells in the choroid plexus of aged brains and demonstrated that their activation may revitalize the aged brain and alleviate aging-associated cognitive decline,” says Yang.

“Aging is the major risk factor for a variety of neurocognitive and neurodegenerative diseases,” says Zuloaga. “Targeting ILC2 cells in the aged brain may provide new avenues to combat these diseases in humans.”

Using an innovative genome sequencing technology, researchers assembled the complete genetic blueprint of two basmati rice varieties, including one that is drought-tolerant and resistant to bacterial disease. The findings, published in Genome Biology, also show that basmati rice is a hybrid of two other rice groups.

Basmati--derived from the Hindi word for "fragrant"--is a type of aromatic long-grain rice grown in southern Asia. Despite the economic and cultural importance of basmati and related aromatic rice varieties, their evolutionary history is not fully understood.

"Rice is one of the most important staple crops worldwide, and the varieties in the basmati group are some of the most iconic and prized rice varieties. However, until recently, a high-quality reference genome for basmati rice did not exist," said Jae Young Choi, a postdoctoral scholar at NYU and the Genome Biology study's lead author.

Whole-genome sequencing--which determines an organism's complete DNA sequence--is an important tool for studying plants and improving crop varieties. Prior research assembled the genome for basmati rice using short-read sequencing--in which DNA is broken into tiny fragments and then reassembled--but there were missing sequences and gaps in the data.

The researchers in NYU's Center for Genomics and Systems Biology sequenced the genome of two members of the basmati rice group using nanopore sequencing technology. Developed by Oxford Nanopore Technologies, a collaborator on this project, nanopore sequencing is a third-generation sequencing technology that allows long single molecules of DNA to be sequenced quickly, improving on the completeness and efficiency of earlier genome sequencing.

The researchers focused on two basmati rice varieties: Basmati 334 from Pakistan, known to be drought tolerant and resistant to rice-killing bacterial blight, and Dom Sufid from Iran, an aromatic long-grain rice that is one of the most expensive on the market. Using long reads from nanopore sequencing, the researchers assembled high-quality, complete genomes of the two basmati rice varieties that were a significant improvement over earlier genome sequences assembled using short reads.

The sequencing also confirmed that basmati rice is a hybrid of two other rice groups. Most genetic material in basmati comes from japonica (a rice group found in East Asia), followed by the rice group aus (found in Bangladesh).

Now that the genome sequences of basmati rice have been established, the researchers aim to work with the scientific and rice breeding communities to identify important genes, see what makes the basmati group unique, and even develop molecular markers to help breed new varieties.

"By having the sequence of rice varieties like Basmati 334, which can withstand drought conditions and resist bacterial blight, we can start to identify genes that give rise to these valuable traits," said Michael Purugganan, the Silver Professor of Biology at NYU and the study's senior author. "Drought tolerance is something we are particularly interested in, given the challenges we face due to climate change and the implications for food security worldwide."

Physically active older adults benefit from reduced risks of early death, breast and prostate cancer, fractures, recurrent falls, functional limitations, cognitive decline, dementia, Alzheimer's disease, and depression. The findings come from a review of all published reviews of studies that assessed the relationship between physical activity and health in adults aged 60 years or older.

The review, which is published in the Scandinavian Journal of Medicine & Science in Sports, also found that physically active older adults experience healthier ageing trajectories, better quality of life, and improved cognitive functioning.

"This research highlights the benefits of physical activity to our physical and mental health in older age. For some time, we have known of the benefits of physical activity for our physical health; however, what is important about this research is that it highlights compelling emerging evidence of the positive effects of being physically active on our mental health--including depression, cognition, and dementia and Alzheimer's disease," said lead author Conor Cunningham, PhD, of the Institute of Public Health in Ireland.