Earth

The discovery of the mechanics and molecular mechanism that dictate cell shape formation in plants by a team of McGill researchers offers new clues about the fundamental processes governing tissue formation in multicellular organisms.

Plants are made of cells that come in a wide array of shapes and sizes, each of which is closely related and essential to the function of a specific tissue.

"The photosynthetic tissue on the inside of a leaf has a sponge-like architecture formed from star-shaped cells that promotes the passage of oxygen and carbon dioxide. The leaf's 'skin' tissue, the epidermis, on the other hand, is a flat layer of tightly connected, flat cells that doesn't let anything pass through except at designated openings. But we really didn't know how these strikingly different cell shapes come to be," said Anja Geitmann, professor and dean of McGill's Faculty of Agricultural and Environmental Sciences.

Working from the premise that biological organisms must abide by physical laws, Geitmann and her colleagues used engineering principles to run computer simulations of the pressures and forces required to give a plant cell a given shape.

"The typical pressure in a plant cell is higher than that in a car tire," Geitmann explained. "A growing plant cell can, therefore, be compared with a rubber balloon being inflated. If pressure drives plant cell growth, we wondered how it could be possible to generate a balloon (or cell) that is not simply spherical but has a characteristic jigsaw puzzle-like shape, like that of the cells forming the leaf epidermal cells."

The predictions obtained from their computer simulations served as the starting point to find the biological structures that determine a cell's shape.

In studies recently published in Cell Reports and Plant Physiology, the team used cell biology and high-resolution microscopy to show that two well-known molecules - cellulose, a material with which clothing is made, and pectin, the gelatinous substance we use to make jam - play a crucial role in sculpting epidermal leaf cells.

"Our results show that the mechanics of leaf epidermal cells is similar to that of Mylar balloons," Geitmann explained. "Rather than swelling up into a perfect sphere-like a rubber balloon, a Mylar balloon forms wrinkles at its seam and this is what we think happens in the leaf cells; these wrinkles might be the trigger that eventually gives rise to the jigsaw puzzle-like pattern of a leaf's skin."

Geitmann believes that the mechanics involved in giving a leaf cell its distinct shape will likely be similar to those involved in sculpting other types of plant cells.

Her team is now trying to determine the reasons why leaf "skin" has such a complex jigsaw puzzle-like pattern.

"We think plants evolved this way so that the leaves can better resist destructive mechanical stress and we are performing both modelling and experimental tests to show this. Science is slowly unraveling the puzzle of life, one piece at a time," she said.

Scientists have taken the temperature of a huge expanse of seafloor in the Arctic Ocean in new research by the U.S. Geological Survey and the Geological Survey of Canada. The study, published in the Journal of Geophysical Research, is accompanied by the release of a large marine heat flow dataset collected by the USGS from an ice island drifting in the Arctic Ocean between 1963 and 1973. These never-before-published data greatly expand the number of marine heat flow measurements in the high Arctic Ocean.

Marine heat flow data use temperatures in near-seafloor sediments as an indication of how hot Earth's outer layer is. These data can be used to test plate tectonic theories, provide information on oil and gas reservoirs, determine the structure of rock layers and infer fluid circulation patterns through fractures in those rock layers.

"This body of work and the fact that it remains relevant so many years later underscores the enduring contribution that USGS researchers have made to understanding even the most remote corners of the planet," said USGS associate director for natural hazards, David Applegate. "As focus on the Arctic region continues to increase, I look forward to seeing how scientists at the USGS and other institutions build on this valuable research."

Starting in 1963, now-retired USGS scientist Arthur Lachenbruch and his team of researchers conducted 356 marine heat flow measurements and acquired more than 500 seafloor sediment samples while working from a hut installed on Fletcher's Ice Island, a 30-square-mile ice floe also known as T-3. These Arctic Ocean heat flow measurements taken by the USGS over the course of 10 years represent far more than the number available for the U.S. Atlantic margin.

When asked about the release of the T-3 legacy heat flow dataset, Lachenbruch commented, "I am pleased to see the T-3 heat flow results made widely available to researchers and re-analyzed using Arctic seismic data acquired in the past few decades."

T-3 ice island was managed by the U.S. Naval Arctic Research Laboratory and the Office of Naval Research. Researchers from the USGS, the Lamont-Doherty Earth Observatory (LDEO) and other institutions worked on T-3 for months at a time between 1962 and 1974. During this period, the LDEO recorded navigational and geophysical data at one-hour intervals, and the USGS has also released this T-3 dataset in collaboration with former LDEO researcher John K. Hall, Geological Survey of Israel (retired).

During the decade of USGS research, ocean currents and the movement of the polar ice pack carried T-3 Ice Island nearly 21,000 km (13,050 miles) through the western part of the Arctic Ocean, which is known as the Amerasian Basin. This remains one of the most remote and least-studied places on Earth even today, making the large number of heat flow measurements released by the USGS even more remarkable.

The USGS acquired the marine heat flow measurements by lowering a probe equipped with thermal sensors through a permanent hole in the ice until the probe entered the seafloor. The probe recorded temperatures in the sediments and also retrieved a sediment core that was used for other measurements by USGS researchers and colleagues at the University of Wisconsin.

In the Journal of Geophysical Research paper describing these measurements, USGS geophysicist Carolyn Ruppel and co-authors combine the legacy T-3 heat flow data with modern seismic images. These Arctic Ocean seismic data are acquired by icebreakers taking images hundreds to thousands of meters (up to many miles) below the seafloor to reveal sediment and rock structures, faults, and other features.

Some of the modern seismic data used in the paper were collected or compiled by the U.S. and Canadian Extended Continental Shelf projects, whose lead scientists, USGS geophysicist Deborah Hutchinson and Geological Survey of Canada researcher David Mosher, coauthored the new study. Other co-authors include Lachenbruch and retired USGS scientist Robert Munroe, who conducted laboratory thermal measurements on recovered sediment samples while on T-3.

The new paper analyzes the variability in the T-3 heat flow dataset and shows that the temperatures of the seafloor and upper levels of the crust are not dependent on bathymetry or sediment thickness. The analysis also shows that high heat flow variability on Alpha Ridge, which was formed when a mantle hotspot triggered the creation of the High Arctic Large Igneous Province, is consistent with thin sediment cover over fractured basement rock permeated by circulating fluids.

The new study also confirms results obtained in the 1960s by Lachenbruch and USGS colleague B. Vaughn Marshall. They had postulated that differences between the make-up of the rock layers between Canada Basin and Alpha Ridge could account for a heat flow anomaly at the boundary between these provinces.

Treating cancer more selectively and more effectively - this could be achieved with an innovative technology developed by teams of researchers at the Leibniz-Forschungsinstitut für Molekulare Pharmakologie (FMP) and the Ludwig-Maximilians-Universität München (LMU). The process transforms proteins and antibodies into stable, highly functional drug transporters, with which tumor cells can be detected and killed.

Classic chemotherapy for the treatment of cancer is based on toxic substances that are particularly effective for rapidly dividing cells. However, since healthy tissue also depends on cell division, treatment with chemotherapeutic substances is often accompanied by severe side effects. A dose sufficient to completely remove the tumor, would in many cases be too toxic to administer to a diseased person. With more modern approaches, it is now possible to transport active agents (drugs) in the body selectively to the site of action, for example by linking a drug with an antibody that can differentiate cancer cells from healthy tissue through changes on the surface of the cell. Five such Antibody Drug Conjugates (ADCs) are already on the market.

However, these ADCs lose a large part of their "toxic cargo" en route to the cancer cell. The substances (drugs) are released into the bloodstream and dangerous side effects can occur. A stable link between drug and antibody would therefore be highly desirable. This is precisely what the researchers - a team led by Professor Christian Hackenberger from the FMP and Professor Heinrich Leonhardt from the LMU Biocenter - focused on. Their results have been published in the prestigious journal Angewandte Chemie: In two consecutive articles, the development of methods and the application of these methods to selective drug transport are presented.

The new drug transporters enable lower doses and less severe side effects

"We have developed an innovative technology that makes it possible to link native proteins and antibodies to complex molecules, such as fluorescent dyes or drugs more easily and with better stability than ever before," reports Marc-André Kasper, a researcher in Christian Hackenberger's group. The researchers discovered the outstanding properties of unsaturated phosphorus (V) compounds and took advantage of those. These phosphonamidates connect a desired modification - for example, a cancer-fighting agent - exclusively to the amino acid cysteine, in a protein or antibody. Since cysteine is a very rare natural occurring amino acid, the number of modifications per protein can be controlled quite effectively, which is essential for the construction of drug conjugates. In addition, phosphonamidates can easily be incorporated into complex chemical compounds. "The greatest achievement of the new method, however, is that the resulting bond is also stable during blood circulation," says Marc-André Kasper. The ADCs that are on the market cannot achieve this.

To test the applicability on targeted drug delivery, the researchers compared their technology directly with the FDA-approved ADC, Adcetris®. The medication was re-created as precisely as possible with the same antibody and active agent, the only difference was that the innovative phosphonamidate linkage was used. When applied to blood serum, the researchers observed that their modified ADC lost significantly less active ingredient over a period of days. They also used the new technology in experiments with mice to combat Hodgkin's lymphoma. The preparation proved to be more effective than the conventional medication. "From our results, we conclude that phosphonamidate-linked drug transporters can be administered in lower doses, and that side effects can be further reduced. Thus the technology has great potential to replace current methods in order to develop more effective and safer ADCs in the future," says FMP group leader Christian Hackenberger.

In the next step, the research groups will continue their efforts in the development of ADCs based on phosphonamidates. Preclinical studies, which are essential for the treatment of patients, are already underway. In this regard, the promising start-up company Tubulis, which was awarded the Leibniz Start-Up Prize last year, functions as a platform for the further development to market maturity.

Differences in how our brains respond when we're anticipating a financial reward are due, in part, to genetic differences, according to research with identical and fraternal twins published in Psychological Science, a journal of the Association for Psychological Science. The findings suggest that how we experience pleasure and reward is at least partly heritable.

The brain's reward system plays a central role in decision making and emotion, and research suggests that impaired reward processing and the inability to feel pleasure are features of various neuropsychiatric disorders, including schizophrenia, major depressive disorder, and bipolar disorder.

"Being able to quantify the relative influences of genetic and environmental factors on activation of the reward circuit could deepen our understanding on the genesis of the reward system, and further clarify potential causes of the lack of pleasure, or anhedonia, found in mental disorders," says lead researcher Raymond Chan.

To investigate the relative contributions of genetic and environmental factors, Chan and colleagues recruited pairs of identical and fraternal twins from the Twin Registry of the Chinese Academy of Sciences Institute of Psychology. Both identical twin pairs and fraternal twin pairs are thought to share the same environment; while identical twin pairs share the same genes, fraternal twins share only about 50% of the same genes. Comparing how traits vary across identical and fraternal twin pairs is thought to shed light on the degree to which genes explain that variation.

In this study, the researchers focused on a structure buried in the middle of the brain called the nucleus accumbens. The nucleus accumbens is part of the ventral striatum, an area that facilitates aspects of decision making, motivation, and reward processing. Chan and colleagues wanted to examine whether nucleus accumbens activation in anticipation of a financial reward differed between identical twin pairs and fraternal twin pairs.

The participants - 43 pairs of same-sex identical twins and 44 pairs of same-sex fraternal twins - completed a computer task while their brain activity was measured via functional MRI. On each trial, the participants pressed a button as soon as they saw a target and an on-screen cue told them what type of trial it would be: a triangle meant they would gain 5 points for hitting the target and a square meant they would lose 5 points for missing it. A circle indicated that they wouldn't gain or lose any points, regardless of their performance. In total, they completed two runs of the task, each of which contained 10 gain trials, 10 loss trials, and 10 neutral trials.

The participants also completed Chinese versions of validated measures for physical anhedonia, social anhedonia, and experience of pleasure.

On trials when the participants expected an award, activation of the nucleus accumbens appeared to moderately heritable, as were scores for physical anhedonia and pleasure. Furthermore, nucleus accumbens activation and physical anhedonia scores appeared to be influenced by shared genes; physical anhedonia and pleasure also appeared to share some of the same genes.

Activation of the nucleus accumbens on loss trials did not appear to be heritable, however.

The fact that activation of the reward system and self-reported pleasure seem to share genetic influence provides further support for the role of the nucleus accumbens in pleasure, the researchers note.

"We plan to clarify how the genetic and environmental factors shape the reward system - in other words, we would like to link gene expression and specific environmental factors to the reward circuit," says Chan.

Continued research examining the heritability of brain and behavioral reward responses "could help researchers identify shared regions of the genome and explore interventions fore amotivation and anhedonia, both of which are associated with poor prognosis and are resistant to treatments that are currently available," Chan and colleagues conclude.

A comprehensive functional analysis of TP53 mutations in human leukemia may refute a working hypothesis - primarily based on mouse studies - that missense mutations confer new cancer-causing functions to the p53 tumor suppressor protein; the new study instead suggests that these mutations exert a "dominant-negative" effect that reduces the cancer-suppressing activity of wild-type p53, the authors say. The TP53 gene was discovered 40 years ago and it now known to be the most frequently mutated gene in human cancer. Initially, TP53 was mischaracterized as an oncogene but human genetic studies ultimately established that it encodes a tumor suppressor. But how cancer-associated mutations in TP53 alter the function of wild-type p53 has continued to be the subject of debate. The vast majority of TP53 mutations across all cancer types are missense mutations, which can result in non-functional or dysfunctional p53. Based largely on mouse model experiments, it has been hypothesized that certain missense mutations can transform the p53 tumor suppressor into a tumor promoter via so-called oncogenic "gain of function" (GOF) effects. To explore the functional consequences of p53 mutations, Steffen Boettcher and colleagues performed a comprehensive analysis of TP53 mutations in human myeloid leukemia. Using CRISPR/Cas9 gene editing technology, the authors generated isogenic human leukemia cell lines featuring the most common p53 missense variants. This isogenic analysis - as well as comprehensive mutational screening, in vivo experiments in mice and an analysis of clinical data - did not support the notion that missense mutations confer new oncogenic functions to the p53 tumor suppressor protein, according to Boettcher et al. Instead, the authors discovered that the mutations confer either loss of function effects or dominant-negative effects (DNE) that reduce the tumor-supressing efficacy of wild-type p53 in human leukemia. In a related Perspective, David Lane discusses the new results as well as the possible ways in which they can be reconciled with the findings of previous studies.

Female adolescents are experiencing relationship abuse at alarming rates, according to a new Michigan State University study that specifically researched reproductive coercion - a form of abuse in which a woman is pressured to become pregnant against her wishes.

Heather McCauley, assistant professor in the School of Social Work, and co-researchers found nearly one in eight females between ages 14 and 19 experienced reproductive coercion within the last three months. Forms of such abuse included tampering with condoms and a partner threatening to leave.

The study, published in the journal Obstetrics & Gynecology this month, is the largest adolescent study on the issue. It uses data from a previously conducted randomized trial at eight school-based health centers in California during the 2012-13 school year and assessed 550 sexually active female teens.

To date, most research has focused on young adult women. But because adolescent relationships differ so much from adult relationships, clinicians need to know how to spot reproductive coercion in their younger patients and tailor clinical assessment and intervention for this population, McCauley said.

"We looked at whether adolescents who experience reproductive coercion displayed the 'red flags' we typically teach clinicians to look for - like coming into the clinic multiple times for emergency contraception or pregnancy testing," McCauley said. "We found no difference in care-seeking behaviors between girls who experienced reproductive coercion and girls who didn't, so those red flags may not be present. Therefore, clinicians should have conversations with all their adolescent patients about how relationships can impact their health."

Previous research has also identified disparities in reproductive coercion by race/ethnicity, with black women more likely than white women to experience such abuse, she said. But, again, that wasn't the case in this study, highlighting the need for researchers and clinicians to understand how to talk about relationship abuse with female teens.

Other takeaways from the study:

17% of teens reported physical or sexual abuse.

Females who experienced reproductive coercion had four times the odds of also experiencing other forms of relationship abuse.

Females exposed to both relationship abuse and reproductive coercion were more likely to have a sexual partner who is five or more years older.

"These findings highlight how common reproductive coercion and other forms of abuse are in adolescent relationships, yet the signs of a teen's unhealthy relationship may be tricky for clinicians, parents and other adults to spot," McCauley said. "So, parents could open the door for their teen to disclose abuse by having a conversation with them about healthy and unhealthy relationship behaviors, including those that interfere with their decision making about their own reproductive health."

It's a classic question in contemporary politics: Does partisan news media coverage shape people's ideologies? Or do people decide to consume political media that is already aligned with their beliefs?

A new study led by MIT political scientists tackles this issue head-on and arrives at a nuanced conclusion: While partisan media does indeed have "a strong persuasive impact" on political attitudes, as the researchers write in a newly published paper, news media exposure has a bigger impact on people without strongly held preferences for partisan media than it does for people who seek out partisan media outlets.

In short, certain kinds of political media affect a cross-section of viewers in varying manners, and to varying degrees -- so while the influence of partisan news is real, it also has its limits.

"Different populations are going to respond to partisan media in different ways," says Adam Berinsky, the Mitsui Professor of Political Science and director of the Political Experiments Research Lab (PERL) at MIT, and a co-author of the study.

"Political persuasion is hard," Berinsky adds. "If it were easy, the world would already look a lot different."

The paper, "Persuading the Enemy: Estimating the Persuasive Effects of Partisan Media with the Preference-Incorporating Choice and Assignment Design," is now available in advance online form from the American Political Science Review.

In addition to Berinsky, the authors are Justin de Benedictis-Kessner PhD '17, an assistant professor of political science at Boston University; Mathew A. Baum, a professor at the Harvard Kennedy School; and Teppei Yamamoto, an associate professor in MIT's Department of Political Science.

Breaking down the problem

A substantial political science literature has debated the question of media influence; some scholars have contended that partisan media significantly shapes public opinion, but others have argued that "selective exposure," in which people watch what they already agree with, is predominant.

"It's a really tricky problem," Berinsky says. "How do you disentangle these things?"

The new research aims to do that, in part, by disaggregating the viewing public. The study consists of a series of experiments and surveys analyzing the responses of smaller subgroups, which were divided according to media consumption preferences, ideology, and more.

That allows the researchers to tease apart the cause-and-effect issues surrounding media consumption by looking more specifically at the impact of media on people with different ideologies and different levels of willingness to view media. The researchers call this approach the Preference-Incorporating Choice and Assignment design, or PICA.

For instance, one experiment within the study gave participants the option of reading web posts from either the conservative Fox News channel; MSNBC, which has several shows leaning in a significantly more liberal-left direction; or the Food Network. Other participants were assigned to watch one of the three.

By examining viewer responses to the content, the scholars found that people who elected to read materials from partisan news channels were less influenced by the content. By contrast, participants who gravitated to the Food Network but were assigned to watch cable news, were more influenced by the content.

How big is the effect? Quantitatively, the researchers found, a single exposure to partisan media can change the views of relatively nonpolitical citizens by an amount equal to one-third of the average ideological gap that exists between partisans on the right and left sides of the political spectrum.

Thus, the influence of cable news depends on who it is reaching. "People do respond differently based on their preferences," Berinsky says.

And while the impact of partisan cable news on people who elect to watch it is smaller, it does exist, the researchers found. For instance, in another of the study's experiments, the researchers tested cable news' effects on viewers' beliefs about marijuana legislation. Even among regular cable-news viewers, partisan content influenced people's views.

Overall, Yamamoto states, the PICA method is novel because it "allows us to make inferences about what is never [otherwise] directly observable," that is, the impact of partisan media on people who would normally choose not to consume it.

"Most people just don't want news"

To put the findings in the context of daily news viewership in the U.S., consider the recent congressional hearings in which special counsel Robert Mueller testified about his presidential investigation. Fox News led the cable ratings with an average of 3 million viewers during most of the day, while MSNBC had an average of 2.4 million viewers. Overall, 13 million people watched. But the Super Bowl, for example, regularly pulls in around 100 million viewers.

"Most people just don't want to be exposed to political news," Berinsky notes. "These are not bad people or bad citizens. In theory, a democracy is working well when you can ignore politics."

One implication of the larger lack of interest in politics, consequently, is that any audience gains that partisan media outlets experience can produce relatively greater influence -- since that growth would apply to formerly irregular consumers of news, who may be more easily influenced. Again, though, such audience gains are likely to be limited, due to the reluctance of most Americans to consume partisan media.

"We only learned those people are persuadable because we made them watch the news," Berinsky says.

The study was supported by a National Science Foundation grant and the Political Experiments Research Lab at MIT; Berinsky's contribution was partly supported by a Joan Shorenstein Fellowship.

HOUSTON -- A key difference between the few pancreatic cancer patients who survive long-term and the many whose disease overcomes all treatments is the bacterial signatures on their tumors that either stimulate or suppress immune response, a team led by researchers from The University of Texas MD Anderson Cancer Center reports in the journal Cell.

The researchers also showed that fecal microbiota transplants (FMT) from long-term survivors prompted immune response and stifled tumors in a mouse model of the disease by altering the bacteria on the tumor - its microbiome.

"Results of the FMT experiments represent a significant therapeutic opportunity to improve pancreatic cancer treatment by altering the tumor immune microenvironment," said senior author Florencia McAllister, M.D., assistant professor of Clinical Cancer Prevention at MD Anderson. "There is promise here but we have a lot of work ahead."

MD Anderson's Pancreatic Cancer Moon Shot™ has provided McAllister with funding to develop a clinical trial of fecal transplants for pancreatic cancer. The Moon Shots Program™ is a collaborative effort to accelerate the development of scientific discoveries into clinical advances that save patients' lives.

Most patients with pancreatic ductal adenocarcinoma - the most common form of pancreatic cancer - have late-stage disease when diagnosed. Just 9% survive to five years. Those with earlier stage cancer that can be surgically removed have a high recurrence rate and median survival of 24-30 months.

No genomic biomarkers have been identified that shed light on the reasons for long-term survival in that fraction of patients, McAllister said.

Long-term survivors have diverse tumor microbiome

While recent research has shown that the composition and diversity of microbes living in the digestive tract - the gut microbiome - can affect how cancer immunotherapy works, little research has focused on the bacteria in the tumor and how it might affect prognosis and survival, McAllister said. "We've known there are bacteria on pancreatic tumors, so we asked 'do these bacteria have a role in cancer?'"

To launch the first such study in pancreatic cancer, McAllister and colleagues analyzed the bacterial DNA in tumors of long-term survivors matched to short-term survivors from two independent cohorts at MD Anderson and Johns Hopkins Hospital. In the MD Anderson cohort, median survival was 10 years for the long-term survivors (22 patients) and 1.6 years for the short-term survivors (21 patients). In the validation cohort from Johns Hopkins, 15 patients had overall survival greater than 10 years, and 10 survived fewer than five years.

Using 16S rRNA gene sequencing, the team found the long-term survivors had much greater diversity of bacterial species than the short-term survivors. Stratifying the MD Anderson patients only by this diversity measure showed those with high diversity had median survival of 9.66 years and those with low diversity had median survival of 1.66 years.

The diversity results were independent of other factors, such as previous therapies, body mass index, and antibiotics use, making it a predictor of survival for surgical patients and indicating the potential importance of the tumor microbiome in cancer progression.

Researchers also found marked differences in the bacterial communities found in each survivor group. The long-term survivors showed a relative abundance of Pseudoxanthomonas, Saccharropolyspora and Streptomyces. The presence of all three taxa, as well as the species Bacillus Clausii, predicted better outcomes for patients in both MD Anderson and Johns Hopkins cohorts.

Specific microbiome boosts immune attack on tumors

Immunohistochemistry showed a greater density of T cells, including the CD8-positive cell-killing variety, in the tumors of long-term survivors in both the MD Anderson and Johns Hopkins cohorts, consistent with previous research that showed more active immune response in long-term survivors.

McAllister and colleagues found a strong correlation between immune cell infiltration and the microbiome diversity of the tumors. Additional analysis showed immune infiltration and activation of T cells was associated with the three enriched bacterial types discovered on long-term survivors' tumors.

With an apparent connection between the tumor microbiome and immune response, the team set out to find a way to change the tumor microbiome.

Using the gut microbiome to alter tumor microbiome

"You cannot modulate the tumor microbiome directly, but you can modulate the gut microbiome, and if there's cross-talk between the gut and the tumor microbiomes, you could change the tumor microbiome indirectly," McAllister said.

The team compared the bacteria in the gut, in the tumor and in adjacent tissue in three surgery patients. They found the gut microbiome represents about 25% of the tumor microbiome, but is absent from the normal, adjacent tissue, suggesting bacteria in the gut can colonize pancreatic tumors.

The researchers transplanted fecal microbiota from patients with advanced cancer into mice and found that the donor microbiome represented about 5% of the resultant tumor microbiome but that 70% of the overall tumor microbiome had been otherwise altered by the transplant.

"Now we know you can completely change the bacterial composition of the tumor microbiome by doing FMT," McAllister said.

Reversing immune suppression with fecal transplants

Next, they performed stool transplants into mice from patients who had advanced pancreatic cancer, patients who had survived more than five years and had no evidence of disease, and healthy controls.

Five weeks after tumor implementation, mice that had received FMT from patients with advanced disease had much larger tumors than those that received FMT from long-term survivors (70% smaller average size) or healthy controls (50% smaller average size).

Immune profiling showed the mice that received the FMT from long-term survivors had significantly higher numbers and greater activation of CD8-positive T cells compared to the other two groups. Those who received FMT from advanced-stage patients had increased regulatory T cells and myeloid-derived suppressor cells, both of which suppress immune response.

To evaluate whether the effect of FMT relies on the immune system, the team depleted T cells in a group of mice treated with the long-term survivor FMT, which completely blocked the anti-tumor effect of the transplant.

Marine heatwaves are a much bigger threat to coral reefs than previously thought, research revealing a previously unrecognized impact of climate change on coral reefs has shown.

In the study, scientists show for the first time what really happens to corals during marine heatwaves, and they reveal that it's not just coral animals that are affected - their skeletons start to decay within weeks, too. This means that the 3D coral framework which provides home to many other animals on the reef is also at risk.

The study by a team of researchers from UNSW Sydney, The University of Newcastle, The University of Technology Sydney, James Cook University and The National Oceanographic and Atmospheric Administration (NOAA), USA was published today in journal Current Biology.

In 2016 the team's research showed that just a 0.5OC increase in ocean temperature changes the extent of mortality that happens in coral during bleaching.

In this study, the team now find that severe marine heatwaves not only trigger bleaching events as we have known them - a breakdown of symbiosis - but in fact can lead to heat-induced mortality of the coral animal itself. They suggest that severe heatwave-induced mortality events should therefore be considered a distinct biological phenomenon, with more direct damage different from coral bleaching.

"Until now, we have described coral bleaching as an event where the symbiotic relationship between coral and its microbes breaks down and corals lose their main source of nutrition, and the coral can die if the symbiosis is not restored," author Associate Professor Tracy Ainsworth from UNSW says.

"But what we are now seeing is that severe marine heatwave events can have a far more severe impact than coral bleaching: the water temperatures are so warm that the coral animal doesn't bleach - in terms of a loss of its symbiosis - the animal dies and its underlying skeleton is all that remains."

"We find that the skeleton is immediately overgrown by rapid growth of algae and bacteria," says Associate Professor Bill Leggat of the University of Newcastle, a co-author on the paper.

"We were able to study the consequences of this process of rapid colonisation using CT scanning of the coral skeleton - as would be used in medical imaging. We show that this process is devastating not just for the animal tissue, but also for the skeleton that is left behind, which is rapidly eroded and weakened."

University of Technology Sydney scientists A/Professor David Suggett and Dr Emma Camp explain how they were also able to use novel bio-optical techniques that allow them to visualise and study the rapid transition in the coral microbiome for the first time.

"With this technique, we can see microbial communities go from symbionts to harmful coral skeleton-dissolvers. Adopting these techniques more broadly will be central to understanding how this process occurs on reefs globally - we anticipate that heatwave mortality events, and rapid reef decay, will become more frequent as the intensity of marine heatwaves increase."

Dr Scott Heron from James Cook University says this rapid dissolving of coral skeletons following severe heatwaves hasn't been known to date.

"Climate scientists talk about 'unknown unknowns' - impacts that we haven't anticipated from existing knowledge and experience. This discovery fits into this category. As we begin now to understand this impact, the question is how many more of these 'unknown unknowns' might there still be that could bring faster and greater damage to coral reefs from climate change," he says.

Dr Mark Eakin, Coordinator of NOAA's Coral Reef Watch, says such events are predictable.

"We already use climate models and satellite data to predict and detect conditions that cause coral bleaching. By focusing on especially severe marine heatwaves, we should be able to predict this direct coral death, too."

A/Prof Ainsworth says that the team hopes that this research will motivate the public to tell decision makers how important coral reefs are to them, and voice the immediate need to preserve coral reefs now.

"Across the globe coral reefs are still a source of inspiration and awe of the natural world, as well as being critically important to the communities that rely upon them. Given that the degradation of coral reefs will result in the collapse of ecosystem services that sustain over half a billion people, we urgently need actions both globally and locally that protect and conserve these truly wonderful places."

When ocean temperatures rise, corals are put at risk of a phenomenon known as bleaching, in which corals expel the algae living in their tissues and turn white. Bleached corals are at increased risk of disease and death. But, researchers reporting in the journal Current Biology on August 8 now show that more severe marine heatwaves--as occurred on Australia's Great Barrier Reef (GBR) in 2016--are even worse for corals. They don't just lead to bleaching but to the immediate death and decay of coral reefs.

"The water temperatures are so warm that the coral doesn't bleach, it dies," says Tracy Ainsworth of The University of New South Wales, Sydney, Australia. "We still see the coral become white as the animal dies and its skeleton is exposed to the water, and then we see it very rapidly become overgrown by colonizing algae from both the inside out and the outside in. This process of rapid colonization and decay is devastating not just for the animal tissue, but also for the skeleton that is left behind, which is the three-dimensional framework of the reef."

Ainsworth's team earlier showed that just a 0.5C increase in water temperature changes the extent of mortality in corals during bleaching. In the new study, they examined GBR corals following the 2016 mass bleaching event. At that time, reefs of the northern GBR were exposed to a rapid and severe rise in sea surface temperatures, with more than 30 percent experiencing temperatures above the established threshold for coral survival. After the heatwave, the corals showed rapid degradation and mortality as microbial biofilms took over.

To better understand this phenomenon in the new study, Ainsworth and colleagues simulated the severe heatwave conditions seen on the GBR in 2016 with two coral species that showed high mortality that year. Their studies show that marine heatwave events on coral reefs are entirely different from the way coral bleaching has been understood.

Heatwave conditions lead to an immediate heat-induced mortality of the coral colony, as the coral skeleton rapidly dissolves and its structure is lost. Within days, a complex microbial biofilm encases the exposed coral skeleton, further accelerating the loss of calcium carbonate from the reef to weaken it even further.

The findings suggest that severe heatwave- induced mortality events should be considered as a distinct biological phenomenon from coral bleaching, the researchers say. They say that such heatwave mortality events, and the rapid reef decay that results, likely will become more frequent as the intensity of marine heatwaves increases in the coming years.

"This work provides very clear evidence that the intense heatwave conditions, which are now becoming a feature of bleaching events, are far more severe and are changing how we understand the impact of climate change on coral reefs and the consequences of severe heat-wave events," said says William Leggat, first author of the study from the University of Newcastle, Australia.

An international collaboration of researchers from the RIKEN Center for Biosystems Dynamics Research (BDR) in Japan and Gladstone Institutes in the USA have generated 3D blastocyst-like structures from stem cells. Published in the journal Stem Cell Reports, the study shows that the blastocyst-like structures very closely resemble actual blastocysts, and even induce proper changes in the uterus after being implanted in pseudo-pregnant mice.

After an egg is fertilized, it begins to divide and passes through several stages. Cells in the two-cell stage are totipotent--they can become any type of cell. After many more cell divisions, the embryo turns into a blastocyst that is implanted in the womb where it differentiates and grows into a fetus. A blastocyst is like an almost hollow ball. Inside are pluripotent cells--cells that can become any type of cell in the body, but not the placenta--while the outer shell is made from trophoblasts--cells that eventually form the placenta.

For several years, scientists have been able to convert somatic cells--like skin cells--into pluripotent cells. However, nobody has been able to convert differentiated cells into totipotent cells. In an earlier study conducted at Gladstone, authors Cody Kime and Kiichiro Tomoda were able to convert pluripotent mouse cells from an implanted-like state to a pre-implanted state. In doing so, they noticed structures that looked like early embryo blastocysts. As Kime explains, "over seven years ago, our reprogramming experiments suggested that we had found a way to increase cell potency beyond pluripotency, which was unlikely and had not been seen before. Instead of discarding what we had found because it was not our primary objective, we decided to find out if it was real."

In the new report, the team has refined their reprogramming technique to produce embryo-like structures that are more similar to real embryos. According to Kime, "perhaps our most important finding was that natural molecules found in the early mouse embryo can reprogram cultured cells to become surprisingly similar in function to early embryos." After seven days of conversion treatment, the new process can produce 5-30 floating self-assembled blastocyst-like structures.

When they examined small clusters of cells a few days before they matured into the blastocyst-like structures, they found that the cells contained gene expression for totipotency that are found in two-cell embryos. A further test comparing the blastocyst-like structures with their precursors showed that cells in the matured structures were bound close together--a hallmark of blastocyst formation and polarization that is the result of a process called compaction. Cells within the precursors resembled embryos at an earlier stage before compaction, which was good evidence that the precursor clusters might include totipotent cells.

Next the group investigated how genetically and functionally similar their blastocyst-like structures were to actual blastocysts. They found that many genes related to the outer/inner cell fates of blastocysts were present in the induced structures, but at lower than natural levels, indicating that the new technique does not perfectly reproduce blastocysts. Nevertheless, when transplanted to the womb of pseudo-pregnant mice, the blastocyst-like structures often induced changes to the uterus that are necessary for successful blastocyst implantation, including the integration of the maternal blood supply. The implanted structures often grew and produced many types of cells that resembled those naturally found in early developing embryos. Eventually, the embryos were resorbed, and the surrounding tissue showed signs that were similar to instances of natural resorption.

"Totipotency is the highest order of cell potency: one totipotent cell can form the placenta and the body...everything," says Kime. "If our system can be improved to fully reach that state we will be able to improve basic research in the fields of embryogenesis and fertility, as well as basic and clinical research in regenerative medicine."

The inability to tolerate light touch is a telltale feature of autism and one of the disorder's many perplexing symptoms. It has defied treatment, and its precise origins have remained somewhat of a mystery.

Now a study led by investigators at Harvard Medical School's Blavatnik Institute has not only identified the molecular aberrations that give rise to heightened touch sensitivity in autism spectrum disorders but also points to a possible treatment for the condition.

The research, conducted in mice and published Aug. 8 in Cell, shows that an old experimental compound that exclusively targets the peripheral nerve cells not only mitigated abnormal touch sensitivity, but also improved body mass, alleviated anxiety and, in a subset of mice, prevented the development of certain brain abnormalities that arise from altered touch response.

If affirmed in further studies, the findings could help pave the way toward much-needed treatments, the research team said.

Current therapies, while somewhat effective, remain suboptimal because they cross the blood-brain barrier and cause sedation and memory problems.

"More and more people are diagnosed with autism and related disorders and the need to identify effective therapies with minimal or no side effects is acute. We believe our findings set the stage for the development of a new class of medicines that may not only treat sensory overreactivity but some of the other core behaviors seen in autism spectrum disorders," said study senior investigator David Ginty, professor of neurobiology in the Blavatnik Institute at Harvard Medical School and a Howard Hughes Medical Institute investigator.

Additionally, the findings underscore just how important the peripheral nervous system is to brain development, the team said, providing a key clue into now-classic observations that young children deprived of normal touch during infancy have a greater risk of behavioral abnormalities in later life.

"Our findings help provide a molecular basis for a phenomenon that physicians and scientists have observed for decades," said study first author Lauren Orefice, assistant professor of genetics in the Blavatnik Institute at Harvard Medical School and the Department of Molecular Biology at Massachusetts General Hospital. "Our results add to a growing body of evidence demonstrating that abnormalities in peripheral neurons can hamper the development of key areas of the brain in newborn animals and contribute to behavioral problems later in life."

Earlier work by the same team identified defects in two specific genes--Mecp2 and Gabrb3--as the underlying drivers of abnormal touch sensitivity. Their absence in peripheral neurons, the work showed, decreases the activity of a key neurotransmitter, GABA, a chemical known to tamp down nerve signaling and regulate nerve-to-nerve communication in the spinal cord and brain. These findings also showed that low GABA-receptor activity in peripheral sensory neurons underlies aberrant neuronal signaling and overactive nerve-cell firing in the spinal cords of mice lacking Mecp2 or Gabrb3, thus leading to heightened touch sensitivity. Building on these findings, Ginty, Orefice and colleagues conducted a series of experiments demonstrating that each of these, as well as other genes linked to autism spectrum disorders, regulate distinct properties of peripheral neurons. When absent or defective, they give rise to altered sensitivity to light touch.

The new study additionally demonstrates that mice lacking yet another gene, Shank3, also had abnormal touch responses. However, the malfunction in neurons lacking Shank3 was different from the dysfunction seen in neurons lacking the other two genes, the study showed. Shank3-deficient neurons retained normal GABA signaling but had altered function in these cells' potassium channels, which rendered them more excitable. Animals whose peripheral neurons lacked Shank3 also exhibited traits associated with autism, including anxiety and social impairment.

Next, the researchers examined the interplay between peripheral neuronal genes and the central nervous system. They turned their attention to key areas in the brain that receive and process touch signals from the peripheral nerves. The experiments revealed that animals lacking Mecp2, Gabrb3 and Shank3 genes only in their peripheral neurons had marked alterations in brain circuits that regulate and process touch sensation. Conversely, restoring the presence of these genes in the peripheral neurons improved circuit development and function in the brains of newborn mice and restored normal touch sensitivity--an observation that underscores the critical role that peripheral nerve activity plays in brain development, the researchers said.

Notably, the scientists observed that mice that showed the most serious alterations in brain development and exhibited the most serious symptoms were the animals in whom gene mutations had occurred early in development. The finding, the team said, highlights the critical importance of normal peripheral nerve function early in life to ensure proper brain development.

Given that alterations in Mecp2 and Gabrb3 genes cause abnormal touch sensitivity and impact brain development by modulating signaling by the neurotransmitter GABA, the researchers decided to test whether increasing GABA-receptor activity would reduce the aberrant neuronal firing and normalize touch sensitivity. Indeed, boosting GABA activity nearly normalized the animals' response to touch.

One of the central challenges in treating touch hypersensitivity stems from the fact that current GABA-modulating drugs sometimes used to treat the condition cross the blood-brain barrier and cause sedation and, at times, cognitive problems. The researchers needed a way to precision-target peripheral nerves without affecting the brain.

They turned to isoguvacine, an experimental compound from the 1970s that activates GABA receptors but is believed to be incapable of permeating the blood-brain barrier.

"Years ago, we started thinking 'Wouldn't it be lovely to be able to harness the power of these GABA drugs but restrict their activity to peripheral nerves?" Ginty said.

They were able to do precisely that.

Indeed, a series of experiments showed that treatment with isoguvacine normalized touch sensitivity in animals with features of autism-spectrum disorders and even attenuated anxiety and abnormalities in certain social behaviors.

The results, the researchers said, could help set the stage for developing treatments that recapitulate the drug's effects.

"What we would like to see happen is the development of a new class of compounds that are chemically altered to act selectively on peripheral nerves while sparing the brain," Ginty said. "That's the simple dream we've had, and our findings bring it just a bit closer within reach."

Thin films made of carbon nanotubes hold a lot of promise for advanced optoelectronics, energy and medicine, however with their manufacturing process subject to close supervision and stringent standardization requirements, they are unlikely to become ubiquitous anytime soon.

"A major hindrance to unlocking the vast potential of nanotubes is their multiphase manufacturing process which is extremely difficult to manage. We have suggested using artificial neural networks (ANN) to analyze experimental data and predict the efficiency of single-walled carbon nanotubes synthesis," explains one of the authors of the study and Skoltech researcher, Dmitry Krasnikov.

In their work published in the prestigious Carbon journal, the authors show that machine learning methods, and, in particular, ANN trained on experimental parameters, such as temperature, gas pressure and flow rate, can help monitor the properties of the carbon nanotube films produced.

"The development of human civilization and the advancement of the materials manufacturing and application technologies are closely interlinked in the era of information and technology, with both materials and computational algorithms and their applications shaping our day-to-day life. This is equally true for ANN that have evolved into an indispensable tool for dealing with multi-parameter tasks, which run the gamut from object recognition to medical diagnosis. Over the last 25 years, little headway was made in the development of electronics based on carbon nanotubes due to the complex nature of the nanotube growth process. We believe that our method will help create an effective carbon nanotube production framework and open new horizons for their real-life applications," says Head of Skoltech's Laboratory of Nanomaterials, Professor Albert Nasibulin.

A new sensor, that can detect ice accumulation in real-time, might be a game-changer when it comes to airline safety and efficiency.

Two distinctly different research teams-one that designs microwave sensors and microelectronics systems, and the other that investigates ice-repellent materials and extreme liquid repellency-joined forces for this latest research coming out of UBC Okanagan's School of Engineering.

The researchers aimed to develop a sensor that could detect the precise moment when ice begins to form on a surface. Due to their high sensitivity, low power, ease of fabrication, and planar profile, the team chose to use microwave resonators. The device, explains Assistant Professor Kevin Golovin, will make it easier to detect and manage ice accumulation on aircraft, noting there have been quite a few airline tragedies directly linked to icy airplane wings.

"The ice detection systems used today are quite rudimentary. For example, pilots visually detect ice on aircraft wings before de-icing in flight," says Golovin, who runs the Okanagan Polymer Engineering Research and Applications Lab. "And on the tarmac, certifying that the aircraft is free of ice after de-icing is also done by visual inspection, which is susceptible to human error and environmental changes."

Planar microwave resonator sensors are simple traces of metal deposited onto a plastic, and yet they are mechanically robust, sensitive and easy to fabricate explains Assistant Professor Mohammad Zarifi, head of UBCO's Microelectronics and Advanced Sensors Laboratory.

"The sensors give a complete picture of the icing conditions on any surface, like an airplane wing. They can detect when water hits the wing, track the phase transition from water to ice, and then measure the thickness of the ice as it grows, all without altering the aerodynamic profile of the wing."

The pair, along with graduate students Benjamin Wiltshire and Kiana Mirshahidi, have recently published their research findings in Sensors and Actuators B: Chemical. This is the first report on using microwave resonators to detect frost or ice accumulation, says Zarifi. The reverse is also possible, and the sensors can detect when ice is melted away during de-icing, he adds.

And the sensitivity and precision of the sensors means the detection occurs in real time. That could make both ground and in-flight de-icing faster, cheaper and much more efficient.

"The resonator detected frost formation within seconds after the sensor was cooled below freezing," explains Wiltshire, the first author of the study. "It took about two minutes at -10C for the frost to become visible on the resonator with the naked eye--and that's in one small area in ideal lab conditions. Imagine trying to detect ice over an entire wingspan during a blizzard."

Planar microwave resonator devices have recently demonstrated significant performance in sensing, monitoring and characterizing solid, liquid and gaseous materials. However, research on the detection of ice and frost has not been undertaken until now, says Zarifi, despite the clear benefits of real-time, sensitive and robust ice detection for transportation and safety applications.

"This is a brand-new method for detecting ice formation quickly and accurately," says Zarifi. "The radiofrequency and microwave technology can even be made wireless and contactless. I wouldn't be surprised if airlines start adopting the technology even for this upcoming winter."

Scientists are increasingly warning that prescription drugs can affect wildlife and ecosystems when they find their way into the environment. In a new Environmental Toxicology and Chemistry study, investigators found that the anxiety and depression drug Escitalopram--at concentrations similar to those measured in the environment--can inhibit fish foraging and eating behavior.

Interestingly, the team noted that the two sexes respond differently to the drug. Specifically, the inhibitory effect of the drug was more pronounced in males than in females.

"It is disturbing that psychoactive drugs affect vital life processes in aquatic wildlife," said corresponding author Erik Baatrup, PhD, of Aarhus University, in Denmark.