Culture

Research sheds new light on how brain stem cells are activated

image: A confocal microscope image showing small/ quiescent and enlarged/ reactivating Neural Stem Cells expressing membrane-tagged GFP (green) and the cell cycle marker Cyclin B (red) in the young Drosophila larval brain.

Image: 
Dr. Claudia Barros, University of Plymouth

Our brains are notoriously bad at regenerating cells that have been lost through injury or disease. While therapies using neural stem cells (NSCs) hold the promise of replacing lost cells, scientists need to better understand how NSCs behave in the brain in order to develop effective treatments.

Now research led by the University of Plymouth helps to shed new light on the mechanisms used by NSCs to 'wake up' - going from their usual dormant state to one of action.

NSCs produce neurons (nerve cells) and surrounding glial cells in the brain. By understanding how NSCs work, it could pave the way for therapies to speed up the neurons' and glial cells' regeneration.

The new study, conducted using Drosophila fruit flies, shows that molecules that form a complex called STRIPAK are essential to promote reactivation in NSCs. STRIPAK (Striatin-interacting phosphatase and kinase) is found in organisms from fungi to humans, and the team uncovered it when comparing the genetic messages of dormant and reactivated NSCs in live fly brains.

The researchers then discovered that STRIPAK components act as a switch to turn off dormancy (or quiescence) and turn on reactivation.

Lead author Dr Claudia Barros, from the Institute of Translational and Stratified Medicine at the University of Plymouth, acknowledges there is still a long way to go until such findings can be translated into human treatments. But she explains the significance of the new work:

"So little is currently known about how neural stem cells coordinate cues to become active and direct the production of more brain cells," she said. "These stem cells last throughout life mainly in a dormant state, so learning how they work is critical to our understanding of cell regeneration.

"This study reveals that STRIPAK molecules are essential to enable reactivation in NSCs, and we are very pleased with the outcomes. But we are only at the beginning. We are working to expand our findings and bring us closer to the day when human neural stem cells can be controlled and efficiently used to facilitate brain damage repair, or even prevent brain cancer growth that is fuelled by stem-like cells."

The full study, entitled STRIPAK Members Orchestrate Hippo and Insulin Receptor Signaling to Promote Neural Stem Cell Reactivation, is available to view now in the journal Cell Reports (doi: 10.1016/j.celrep.2019.05.023).

Credit: 
University of Plymouth

Study shakes up sloth family tree

image: New studies rearrange the sloth family tree, which includes the two existing sloths (center and right in the tree) as well as extinct giant ground sloths (bottom).

Image: 
Illustration by Jorge Blanco

Sloths once roamed the Americas, ranging from tiny, cat-sized animals that lived in trees all the way up to massive ground sloths that may have weighed up to six tons. The only species we know and love today, however, are the two-toed and three-toed sloths--but paleontologists have been arguing how to classify them, and their ancestors, for decades.

A pair of studies published June 6 have shaken up the sloth family tree, overturning a longstanding consensus on how the major groups of sloths are related. According to the results, the three-toed sloth is more closely related to a large family that included ancient elephant-sized ground sloths; meanwhile, the two-toed sloth appears to be the last survivor of an ancient lineage previously thought extinct.

"The results are surprising on many levels," said Graham Slater, an assistant professor of geophysical sciences at the University of Chicago who co-authored one of the papers. "Not only do they rewrite sloth classification, they suggest much of what we thought we knew about how sloths evolved may be wrong."

Slater's study, published in Nature Ecology & Evolution, uses a pioneering approach that uses proteins in fossils to discover evolutionary relationships--marking the first time an entire lineage has been mapped with the method.

"All of these ancient sloths must have occupied really important roles in grazing and browsing the landscape, and so they're important to understanding how these ecosystems worked, but getting a handle on their evolution has been difficult," said Slater, who specializes in analyzing the patterns of evolution in mammals.

The existing hierarchy is built on how physically similar the fossils look to one another. But Slater, working with Ross MacPhee with the American Museum of Natural History and Samantha Presslee at the University of York, wanted to explore the possibilities of an emerging field called paleoproteomics--extracting information from proteins inside fossilized bone.

Instead of DNA, which is a fragile molecule that needs specific conditions to survive inside fossils--"getting ancient DNA is a bit of a lottery," Slater said--scientists have been looking at proteins instead. Protein molecules are sturdier, and since DNA is translated directly into proteins, they hold much of the same information. So the scientists extracted collagen from multiple fossils, analyzed it to reconstruct the sequences of amino acids, and then compared these to one another to piece together relationships between the species.

"What came out was just remarkable. It blew our minds--it's so different from anything that's ever been suggested," Slater said.

Previously, scientists thought that the unau--the three-toed sloth with cute black lines around its eyes--was an outlier species that diverged early in the group's evolution. But based on the new evidence, it actually appears to be nested within a large group of different ground sloths that includes those gigantic, elephant-sized sloths.

Meanwhile, the ai (or two-toed sloth) had been classified in with a family called Megalonychidae, which includes everything from Central American and Caribbean sloths to an Ice Age-era American ground sloth that was first described by Thomas Jefferson (due to the fossil's large claws, he thought it was a lion). But according to the findings, two-toed sloths are actually the last survivors of a branch previously thought to be extinct, which likely split off about 20 million years ago.

The protein evidence also revealed that those extinct Caribbean sloths were the descendants of an early branch that split from other sloths around 30 million years ago. This is interesting evidence for another longstanding question: whether there was a short-lived land bridge connecting South America and what would become the West Indies, many millions of years ago. If wanderlust drove ancient sloths across the bridge, their presence in the islands would support that idea. Thus far no conclusive fossil evidence has turned up, but the genetic split 30 million years ago makes sense if those sloths were then geographically isolated after the land bridge disappeared.

The new conclusions also cast doubt on our picture of how sloths evolved, because the West Indian sloths look as though they lived in trees. "We've been used to thinking that today's sloths each evolved independently for life in the trees from a ground-dwelling ancestor, but our results suggest that the ancestral sloth may have been at home in both," Slater said.

Though revolutionary, the results square with a DNA analysis released the same day by a group with the French National Centre for Scientific Research and other institutions. That group was able to pull mitochondrial DNA from several critical fossils, and the two independent analyses align very closely. "Exceptional results demand exceptional verification," said MacPhee, so the two groups agreed to publish simultaneously.

The team is excited about pushing the boundaries of the field of paleoproteomics. Evolutionary paleobiology is greedy for more and older data, and proteins could provide it.

"The very oldest DNA you can get is 800,000 years old, but in theory we should be able to get protein data from specimens that are millions of years old," Slater said. "A whole bunch of questions suddenly come into reach. It opens doors that we were only dreaming of."

Credit: 
University of Chicago

New model predicts impact of invasive lionfish predators on coral reefs

image: A lionfish in the Bahamas. Invasive lionfish are wreaking havoc among native fish populations in the Atlantic and Caribbean.

Image: 
Mark Albins, Ohio State University

A new model is providing insight into the impact of invasive lionfish on coral reefs in the Atlantic Ocean and Caribbean Sea. The venomous predatory fish has invaded more than 7.3 million square kilometres in the Atlantic and Caribbean, wreaking havoc among native fish populations.

The method, developed and tested with coral reef fish in the Bahamas through an international collaboration of scientists in Canada, the United States, and United Kingdom, is based on the behaviours used by prey to avoid being eaten by predators that use different hunting tactics.

"Many scientists have speculated that invasive lionfish are so successful in the Atlantic because prey don't recognize them as a predator," explained Stephanie Green, assistant professor in the University of Alberta's Department of Biological Sciences and lead author.

Stephanie Green, assistant professor in the Department of Biological Sciences, swims alongside a lionfish.

"However, we found that reef fish enter the 'danger zone'--close enough to be eaten--around invasive lionfish at similar rates to native predators. But for those prey that stray too close to lionfish, they are up to twice as likely to be captured than by predators that are naturally found on Caribbean reefs."

The ranges of many predators are expected to grow, due to climate change and future invasions. The new method is designed to help both scientists and conservationists better understand how predators select their prey. In the case of lionfish, the scientists' hope the model can help them identify areas where native species are most vulnerable to the novel stalking hunting strategy of lionfish as the invasion spreads.

"As invasions take hold, scientists have few tools to help them predict what the effects will be,and as a result, we often don't understand how invasive predators have changed environments until it is too late," added Mark Hixon, professor at the University of Hawai'i and co-author of the study.

The authors hope their approach can be used by researchers in the Mediterranean who are keen to understand which kinds of fishes and fisheries there will be most affected by the recent invasion of lionfish in this region. Green is also adapting the model to examine predator-prey interactions for albacore tuna with respect to climate change. "We hope that using knowledge of species behaviours can help scientists and managers predict who will eat whom when predators and prey encounter one another in new settings," added Green, who is also a Sloan Research Fellow.

Credit: 
University of Alberta

LGBT-identifying females are at increased risk of substance use in early adolescence

CORVALLIS, Ore. - Females who identify as sexual minorities face an increased risk of substance use that shows up as early as age 13, suggesting early adolescence is a critical period for prevention and intervention efforts, a new study from Oregon State University has found.

The odds of substance use among females who identify as sexual minorities - an umbrella term for those who identify with any sexual identity other than heterosexual or who report same-sex attraction or behavior - is 400% higher than their heterosexual female peers.

"We saw this striking difference in substance use at age 13 and there was rapid increase in the rate of cigarette and alcohol use from there," said Sarah Dermody, an assistant professor in the School of Psychological Science in OSU's College of Liberal Arts and the study's lead author. "That tells us we need to find ways to intervene as early as possible to help prevent substance use in this population."

The findings were published recently in the Journal of LGBT Youth. Co-authors are James McGinley of McGinley Statistical Consulting and director of behavioral analytics at the Vector Psychometric Group; Kristen Eckstrand, a physician at the University of Pittsburgh Medical Center; and Michael P. Marshal of the University of Pittsburgh.

Among youth, alcohol, marijuana and nicotine are the three most commonly used drugs. That is a concern because youth who use those substances are at risk of negative health and social outcomes, including addiction and poor cognitive, social and academic function.

Past research has shown that sexual minority youth reported nearly three times more substance use than heterosexual youth. The disparity may be due in part to stress from discrimination, violence and victimization rooted in their sexual minority status, Dermody said.

The pattern of increased substance use for youth who identify as sexual minorities is magnified significantly for females. In the new study, researchers hoped to gain better understanding of how substance use rates develop over time for this group in particular, Dermody said.

Using data from about 2,200 participants in the Pittsburgh Girls Study, a large, longitudinal study of the lives of urban girls, researchers examined substance use among females over time from age 13 to 20, comparing those who identified as heterosexual to those identifying as lesbian/gay or bisexual.

They looked at when disparities in use between heterosexual and sexual minority identifying females began to emerge; rates of change over time for both groups; and how rates change as the girls approach young adulthood.

The researchers found that disparities in substance use between heterosexual and sexual minority girls were already present at age 13. The difference in use between heterosexual and sexual minority girls persisted and increased as they entered their 20s.

The findings suggest that early prevention and intervention efforts may be needed to reduce initial use and slow the escalation of substance use among the population. Such efforts could also help decrease substance use disparities over time, Dermody said.

"It's already a risky and vulnerable period for youths' social development, and it's also a vulnerable time for brain development," Dermody said.

It's also important to remember that within the population of youths who identify as sexual minorities, there are many youths who are not using any substances at all, or who are not using them as heavily, Dermody said.

"This is a subgroup that we are concerned about," she said. "In future research, it would useful to explore how individual youths' experiences influence where they fall on the spectrum of substance use."

Credit: 
Oregon State University

The mystery of the galaxy with no dark matter: Solved!

image: The ultra-diffuse galaxy KKS2000]04 (NGC1052-DF2), towards the constellation of Cetus, considered previously a galaxy with no dark matter. Credit: Trujillo et al.

Image: 
Trujillo et al.

Galaxies with no dark matter are impossible to understand in the framework of the current theory of galaxy formation, because the role of dark matter is fundamental in causing the collapse of the gas to form stars. In 2018, a study published inNature magazine announced the discovery of a galaxy that lacked dark matter, which made a strong impact, and occupied the covers of popular scientific magazines.

Now, according to an article published in the Monthly Notices of the Royal Astronomical Society (MNRAS) a group of researchers at the Instituto de Astrofísica de Canarias (IAC) has solved this mystery via a very complete set of observations of KKS2000]04 (NGC1052-DF2), previously nicknamed "the galaxy without dark matter".

In this study the researchers, perplexed because all the parameters that depended on the distance of the galaxy were anomalous; have revised the available distance indicators. Using five independent methods to estimate the distance of the object they found that all of them coincided in one conclusion: the galaxy is much nearer than the value presented in the previous research.

The original article published in Nature stated that the galaxy is at a distance of some 64 million light years from the Earth. However, this new research has revealed that the real distance is much less, around 42 million light years.

Thanks to these new results, the parameters of the galaxy inferred from its distance have become "normal" and fit the observed trends traced by galaxies with similar characteristics.

The most relevant datum that has been found via the new distance analysis is that the total mass of this galaxy is around a half of the mass estimated previously, but the mass of its stars is only about quarter of the previously estimated mass. This implies that a significant part of the total mass must be made up of dark matter. The results of this work show the fundamental importance of the correct measurement of extragalactic distances. It has always been one of the most challenging tasks in astrophysics: how to measure the distances to objects which are very far away and which we cannot touch.

Credit: 
Instituto de Astrofísica de Canarias (IAC)

Bird personalities influenced by both age and experience, study shows

image: The study investigated red knots, like the one pictured here, at the NIOZ Royal Netherlands Institute for Sea Research in Texel, the Netherlands.

Image: 
Jan J. Wijmenga

For birds, differences in personality are a function of both age and experience, according to new research by University of Alberta biologists.

The study examined the red knot, a medium-sized shorebird that breeds in the Canadian Arctic and winters in North Western Europe. The researchers studied 90 birds over a two year period, comparing behavioural and physiological traits of two age cohorts: adult and juvenile birds. Studying two age groups allowed the researchers to determine which changes were due to age versus time in captivity.

"During this time, birds had the same type of life experience, including varied diet," explained Kim Mathot, assistant professor in theDepartment of Biological Sciences and Canada Research Chair in Integrative Ecology. "At the start of the experiments, individuals showed differences in their behaviour. We looked at whether these differences disappeared in the course of the study, which would suggest that there is something about individually variable experiences that helps maintain differences, because in our experiments, all these birds had the same experience."

Exploring nature and nurture

The results? Well, it's complicated.

The causes of variation among individual birds were different for different traits. For the birds in this study, individual differences in behaviour were maintained over the course of the study. But physiological traits, such as the size of each bird's gizzard, became more similar.

"The world isn't simple, so it makes sense that there isn't a straightforward answer for how and why individuals differ," added Mathot. "Nature is wonderfully complex. This is yet another example of that at play."

In the next leg of the research, PhD student Eva Kok will follow a smaller subset of the study's birds after they've been released back into the wild in order to examine how the traits measured in the lab translate to real life.

"We're curious to see if physiological differences will reappear after release back into the wild," explained Mathot. "For instance, if an individual had a relatively large gizzard when we initially captured it but that became smaller in captivity, will it grow to be relatively large again when re-released? Or did we shuffle the deck, and now birds can go onto different trajectories than what they were on before?"

Credit: 
University of Alberta

How flow shapes bacterial biofilms

image: Remains of cyanobacteria biofilms (stromatolites) in Australia's Shark Bay World Heritage Area.

Image: 
© Philippe Barraud

Although we tend to think of them as solitary sojourners of the world, bacteria are actually very social organisms. In fact, the vast majority of bacteria live on surfaces by forming "biofilms": three-dimensional communities hosting thousands to millions of bacteria of such bustling activity that scientists describe them as "bacterial cities".

Bacteria form biofilms by attaching to each other on a wide variety of surfaces: the bottom of oceans, lakes or rivers, medical equipment and even internal organs, like the intestine, lungs, and teeth - the latter is the familiar dental plaque, a large source of income for dentists.

In short, biofilms are the preferred lifestyle of bacteria. They grow wide and thick, forming a new, social dynamic among their member microorganisms, while also defending them: biofilms can be notoriously inaccessible to antibiotics, which is why they have drawn a lot of medical research.

But looking at biofilms can also give us clues about broader social dynamics that have shaped the evolution of species across the entire planet, like cooperation, competition etc. And it is such questions that drive the work of Alexandre Persat, director of EPFL's Microbial Mechanics Lab.

"About ninety percent of bacterial life at the surface of Earth is found in the form of biofilms" he says. "Because these structures are so dense, they bring many species in proximity, which makes them interact socially and consequently drives their evolution. The outcome of social interactions such as competition or cooperation thus depends on the spatial arrangement of these cells. But what shapes the architecture and the organization of cells in biofilms, for example to mix or segregate, is still unclear."

In a new study, Tamara Rossy, a PhD student in Persat's group, expands our view of biofilms to look at how physical cues affect their development - more specifically, how they are affected by flow of the surrounding fluid. "Whether in oceans, lung infections skin, gut microbiota - the physics of fluids are ubiquitous to biofilms," says Rossy. "We wanted to study how flow changes their spatial organization."

To do this, Rossy had to first create a model biofilm that could be studied under controllable flow conditions. She chose two different clones of the bacterium Caulobacter crescentus, which is commonly found in freshwater lakes and streams, and undergoes a "stalked" cell stage that allows it to anchor on surfaces, colonize them, and form biofilms. Rossy grew the bacteria in microfluidic chips within which she could carefully control minute amounts of liquid flowing through channels just half a millimeter wide.

Rossy imaged the formation of biofilms at the level of single bacteria to monitor the effects of each flow rate on the bacterial colonies. The results showed dramatic differences in architecture between different flows: in weak flows, biofilms were very dense. In stronger flows, bacteria grew in sparse, cluster-like biofilms.

To understand this process, Rossy built a physical model that is reminiscent of the transport of molecules in fluidic systems. Using it, she found that stronger flows can dramatically impair the ability of bacteria to swim towards a surface and colonize it, resulting in sparse colonies.

But some results were also counter-intuitive. "High flow rates lower the probability of swimming bacteria to invade existing colonies," says Rossy. "In order to grow in such high flows, single cells rely on immediate attachment of daughter cells close to their mother cells."

Stronger flows also segregated the two populations, with potentially significant effects on the overall social dynamics between biofilm-dwelling bacteria. "Low and high flow really matter to the arrangement and structure of the biofilm," says Persat. "This shows that flow and, more generally, the physical environment of biofilms can affect the evolutionary history of a bacterial species; this is true at least between different bacterial clones like the ones we used, but it is very likely to apply across different bacterial species."

"Biofilms are a really fascinating and important facet of microbial life," he concludes. "We are only now appreciating how physical principles guide their architecture and how this feeds back into bacterial physiology and evolution. But we have only here scratched the surface -- there is still so much to learn."

Credit: 
Ecole Polytechnique Fédérale de Lausanne

Talking to each other -- how forest conservation can succeed

image: Life and Death: Natural forest dynamics in the Hainich National Park as part of the UNESCO World Natural Heritage Site "Ancient and Primeval beech forests of the Carpathians and other regions of Europe."

Image: 
Laura Demant

Forest conservation can be a source of tension between competing priorities and interests from forestry, science, administration and nature conservation organisations. The different stakeholders can create the public impression of disagreement with regard to the objectives and measures in forest conservation. Scientists from the University of Göttingen, the HAWK University of Applied Sciences and Arts Hildesheim/Holzminden/Göttingen and the Northwest German Forest Research Institute have developed a framework of conservation objectives whereby targets for nature conservation can be compared and analysed. The study was published in Nature Conservation.

The research team developed a reference framework to systematically classify conservation objectives. It considered the following: "living" biotic natural resources such as genes, species, ecosystems and landscapes; and "non-living" abiotic natural resources such as soil, water and climate; in addition to social factors such as recreation, tourism and awareness-raising. The suitability of the conceptual framework was applied to 79 biodiversity and forest conservation concepts. The researchers assigned the stakeholders to three reference areas - international, Germany-wide and regional - in order to search for commonalities and differences with regard to the transfer of knowledge and conservation objectives across stakeholders and reference areas.

"There is a broad consensus concerning forest conservation amongst di?erent stakeholders in Germany," says first author Laura Demant, PhD student in the Department of Vegetation Analysis and Phytodiversity at the University of Göttingen and research associate at the Northwest German Forest Research Institute. Stakeholders agree that the protection and preservation of diverse and self-sustaining structures in forest ecosystems should be a key objective in forest conservation. The protection of species, deadwood and habitat trees, all of which provide special habitats for other living organisms, are also without doubt recognised as important objectives in forest conservation.

"Nevertheless, there are shortcomings and a need for improvement regarding the conservation of abiotic natural resources, genetic diversity, landscape conservation and the consideration of socio-cultural targets. In these areas, forest conservation concepts should be improved and harmonised," says Professor Erwin Bergmeier, Head of Department. The authors write that the existing trade-offs between objectives in forest conservation point to a lack of coordination, across both institutions and reference areas, and between the stakeholders. "Nature conservation concepts should integrate the concerns of various stakeholders, instruments and scales into conservation practices, taking into account their specific needs and requirements," Demant says, "so that forest conservation can be successful."

Credit: 
University of Göttingen

Robotic surgery for throat cancer not superior to radiation therapy, study finds

image: From left: Dr. David Palma (Lawson Associate Scientist), Betty Ostrander (Research Participant) and Dr. Anthony Nichols (Lawson Associate Scientist).

Image: 
Lawson Health Research Institute

LONDON, ON - In 2012, scientists at Lawson Health Research Institute launched the world's first clinical trial comparing robotic surgery to radiation therapy for the treatment of oropharyngeal cancer (cancer at the back of the throat). The team is now reporting findings from the seven-year study which challenges beliefs that surgery leads to better swallowing outcomes, suggesting instead that radiation results in better quality of life for patients.

For Betty Ostrander, an operating room nurse from Tillsonburg, Ontario, a throat cancer diagnosis was life-changing. Betty was 59 when she discovered a small lump on the right side of her neck. After seeking medical care and testing, she was told she had oropharyngeal cancer.

"I remember thinking 'I'm healthy, I eat right and I exercise; this can't be happening to me.' But it was, and it was scary," recalls Betty. "One of the first questions I asked was whether there were any clinical trials available."

Betty was one of 68 research participants in the ORATOR trial. The study included six centres from across Canada and Australia, including London Health Sciences Centre's (LHSC) London Regional Cancer Program. Participants were randomized to receive either precision radiation therapy, often combined with chemotherapy, or transoral robotic surgery (TORS).

TORS is a surgical method for treating throat cancer which uses a small 3D camera and miniature robotic instruments to remove tumours. LHSC was the first centre in Canada to offer TORS in 2011.

"Early studies suggested TORS might reduce the risk of swallowing problems historically associated with radiation and it therefore rose quickly in popularity," explains Dr. Anthony Nichols, Associate Scientist at Lawson and Head and Neck Cancer Surgeon at LHSC. "But there was no randomized trial to compare patients' swallowing outcomes. As the first centre in Canada to offer TORS, we decided to tackle this problem through the ORATOR trial."

The research team found no difference in survival between the two groups but, surprisingly, participants in the radiation group experienced better swallowing outcomes. A mild decline in swallowing function was observed in 40 per cent of the surgery participants compared to 26 per cent of radiation participants. All participants were able eat a full diet after treatment but 16 per cent from the surgery group said they needed to specially prepare their food.

"Our findings challenge the notion that TORS leads to better swallowing outcomes," says Dr. David Palma, Associate Scientist at Lawson and Radiation Oncologist at LHSC. "While radiation was previously associated with poor swallowing outcomes, treatments have advanced considerably and are now much more precise, which may be leading to better patient outcomes."

Patients in the surgery group were also at risk for dangerous bleeding during surgery. One year after treatment, patients in the surgery group were more likely to experience pain (22 per cent versus eight per cent in the radiation group), use painkillers (45 per cent versus 15 per cent), have issues with their teeth (12 per cent versus one per cent), and experience shoulder impairment.

The team found that patients in the radiation group experienced more short-term constipation and a temporary drop in blood counts. They also experienced an increased risk of tinnitus (ringing in the ears) and high frequency hearing loss when receiving chemotherapy, with some needing hearing aids.

"Each therapy has its different potential side effects but our findings suggest that TORS is not superior to modern radiation," says Dr. Nichols. "We hope this research can be used by patients and their oncologists to help inform treatment decisions."

Cases of oropharyngeal cancer have more than doubled since the 1990s. While throat cancer was more common in elderly patients with a history of heavy smoking or drinking, physicians have seen a dramatic rise in cases caused by human papilloma virus (HPV).

There is fortunately a high survival rate in patients with HPV-related throat cancer, leading researchers to study quality of life after treatment.

Drs. Nichols and Palma recently launched the ORATOR 2 trial which will further compare TORS against radiation and chemotherapy. The goal is to reduce the intensity of radiation and chemotherapy to improve quality of life while maintaining survival rates. The team aims to recruit 140 participants.

Results from the ORATOR trial were shared by Dr. Nichols at the American Society of Clinical Oncology's Annual Meeting on May 31, 2019. The study was funded by the Canadian Cancer Society.

Credit: 
Lawson Health Research Institute

Leopard coral grouper: Overexploited

image: Researchers measured the population stock of the commercially valuable leopard coral grouper (Plectropomus leopardus), a species subject to population collapse due to high fishing pressure.

Image: 
Dhani

Researchers measured the population stock in Saleh Bay, Indonesia of the commercially valuable leopard coral grouper (Plectropomus leopardus), a species subject to population collapse due to high fishing pressure.

The researchers used yield-per-recruit modeling to evaluate population stock and to estimate a biological reference point finding that the species is in fact over-exploited in Saleh Bay.

To reduce fishing mortality, they recommend limiting the catch size and control on spear gun fishing.

Credit: 
Wildlife Conservation Society

Taking stock of Indonesia's reef fishes

image: Using an underwater visual census method, the team recorded a total of 176 species belonging to 19 families of economically important reef fishes.

Image: 
Fakhrizal Setiawan

A research team estimated the natural stock of reef fishes from three regencies in the lesser Sunda-Banda Seascape in Indonesia to fill gaps in knowledge of species composition and biodiversity.

Using an underwater visual census method, the team recorded a total of 176 species belonging to 19 families of economically important reef fishes.

Community structure of target fish in the three regencies is still in a relatively good condition, and there is not much difference in terms of target fish community structure between the three regencies.

Credit: 
Wildlife Conservation Society

Breathing in black carbon from polluted air linked to alterations in lung blood vessels

Evidence that breathing in tiny particles of black carbon, typically a result of burning diesel, is linked to an increased volume of peripheral, smaller blood vessels in the lungs has been observed for the first time in new research published in the European Respiratory Journal [1].

The study adds to the evidence that exposure to diesel pollutants at what are considered relatively low levels may contribute to subtle changes in the lungs that may make people more prone to developing chronic lung disease, the third leading cause of death globally.

The researchers say the differences observed in people exposed to higher levels of black carbon were comparable in magnitude to those associated with smoking a pack of cigarettes a day for 15 years.

The project was based in the US National Heart, Lung, and Blood Institute’s Multi-Ethnic Study of Atherosclerosis (MESA) Lung and Air Pollution Studies. Lead researcher Dr Carrie Pistenmaa Aaron performed this work as an Assistant Professor at Columbia University in New York, USA. She said: “A few previous studies have suggested a link between air pollution and the pulmonary circulation, but we wanted to evaluate whether there were associations between chronic air pollution exposure and the vascular structure of the lungs. We were interested in the lung vasculature as we think it may be related to chronic lung conditions.”

The researchers analysed data for more than 3,000 people from six metropolitan areas in the USA. A team led by scientists at the University of Washington calculated participants’ long-term exposure to outdoor air pollutants using specific monitoring data from the US Environmental Protection Agency’s (EPA) monitoring database, and by analysing traffic, weather patterns and land use data.

The participants’ pulmonary blood vessels were then measured using chest CT scans between 2010-12. Each participant’s age, height, weight, sex, race and ethnicity, pack-years of cigarette smoking, exposure to secondhand smoke, medical history and other socioeconomic factors were also accounted for in the analyses, as these factors can also have an impact on lung health.

The researchers estimated that on average, study participants were exposed to annual levels of black carbon of 0.8 micrograms per cubic meter and fine particulate matter (PM2.5), another measure of air pollution that includes black carbon particles, of 11 micrograms per cubic meter.

These levels are below the current air pollution limits for PM2.5 as set by the EPA in the USA, and lower than current EU limit values for pollution. Despite this relatively low average exposure, the analyses showed that exposures to a higher level of black carbon was associated with a greater volume of blood vessels in the periphery of the lungs.

Dr Aaron explained: “Our findings suggest that long-term exposure to black carbon may impact the pulmonary circulation. No previous research has looked specifically at whether these changes in humans lead to disease, so we cannot say for certain how this may be affecting health. However, other studies of similar pulmonary vascular measures on CT and MRI in humans, in addition to a number of studies in animals, suggest that differences in the pulmonary vasculature might make people more likely to develop chronic lung disease.”

The researchers say the main contributors to black carbon levels in the cities of developed countries are diesel-fuelled vehicles, oil furnaces and coal power plants, and worldwide the major sources of black carbon are from wood burning stoves, forest fires and forest clearing.

Dr Aaron added: “There are many ways to reduce outdoor air pollution levels – they start with energy efficiency, switching to clean or renewable energy sources, and by using technology to make fossil-fuel based energy as clean as possible.”

The researchers say the study’s design may limit their conclusions, as they relied on cross-sectional observational data rather than findings from direct experiments carried out with participants. They plan to conduct further research that will look in more detail at how pulmonary blood vessels relate to chronic lung disease, and understand the biological processes involved in remodeling of the pulmonary vessels.

Professor Thierry Troosters is President Elect of the European Respiratory Society and was not involved in the research. He said: “A large proportion of the European population lives in areas with unhealthy outdoor air quality and those people are unable to avoid exposure to the harmful effects of pollution. Lots of previous research has shown that in the long term, outdoor air pollution can reduce life expectancy, affect lung development, increase asthma incidence and lead to other chronic respiratory diseases.

“This study provides interesting data on how exposure to black carbon—likely a result of burning diesel—may be damaging the lungs, and highlights further how we need strict policies for cleaner air in order to reduce the impact of pollution on health of European citizens and patients. Together with the World Health Organization, the European Respiratory Society advocates for such policies at both a European and global level.”

Credit: 
European Respiratory Society

Brain disorder leaves lasting legacy of disability, study finds

Four out of five people with a hidden brain condition that causes limb weakness or paralysis experience lasting physical difficulties.

Research to assess long-term effects of the disorder, called Functional Neurological Disorder (FND) - found 80 per cent of patients still had symptoms in their arms and legs 14 years after initial diagnosis.

Experts, who tracked outcomes of more than 100 patients, hope the study - the largest of its kind - will help doctors provide realistic prognoses in future and encourage more work on treatment.

In their initial studies 14 years ago, researchers found that FND is as common and disabling as better known conditions, such as multiple sclerosis. It has, however, suffered from stigma because it cannot be seen on conventional brain scans.

Doctors often describe it as a 'software' problem of the brain rather than a 'hardware' one - a condition related to how the brain processes information rather than a physical defect in its structure.

For the follow-up study, patients filled in questionnaires to assess their physical and psychiatric symptoms, quality of life and perception of their illness.

Their answers revealed that levels of physical disability and distress remained high, even after 14 years, leading to persistent and sometimes, disabling problems.

Doctors can sometimes be reluctant to give a diagnosis of FND for fear of making a mistake, the researchers say. But the team found mistakes are rare and this should not prevent them making a diagnosis using clinical signs, even if tests are normal.

The study was carried out by the Universities of Edinburgh and Groningen in the Netherlands and is published in the journal Brain.

Professor Jon Stone, of the University of Edinburgh's Centre for Clinical Brain Sciences, said perceptions of FND have changed dramatically over the past 20 years but that doctors are still likely to dismiss patients as 'imagining' or 'putting on' the condition.

He said: "Thankfully with better research and treatment those attitudes are changing. This study shows the importance of neurologists staying involved with the long-term management of patients to guide treatment and detect additional neurological conditions, which can rarely occur years after the start of FND.

"It should also help clinicians provide a more realistic prognosis for patients with FND when it causes limb weakness and stresses the importance of active and targeted treatment which many of these patients didn't have."

Credit: 
University of Edinburgh

Most-detailed-ever simulations of black hole solve longstanding mystery

video: Simulation shows the inner region of the accretion disk aligns with the black hole's equatorial plane, signaling the long-sought Bardeen-Petterson alignment.

Image: 
Sasha Tchekhovskoy/Northwestern University; Matthew Liska/University of Amsterdam

EVANSTON, Ill. -- An international team has constructed the most detailed, highest resolution simulation of a black hole to date. The simulation proves theoretical predictions about the nature of accretion disks -- the matter that orbits and eventually falls into a black hole -- that have never before been seen.

The research will publish on June 5 in the Monthly Notices of the Royal Astronomical Society.

Among the findings, the team of computational astrophysicists from Northwestern University, the University of Amsterdam and the University of Oxford found that the inner-most region of an accretion disk aligns with its black hole's equator.

This discovery solves a longstanding mystery, originally presented by Nobel Prize-winning physicist John Bardeen and astrophysicist Jacobus Petterson in 1975. At the time, Bardeen and Petterson argued that a spinning black hole would cause the inner region of a tilted accretion disk to align with its black hole's equatorial plane.

After a decades-long, global race to find the so-called Bardeen-Petterson effect, the team's simulation found that, whereas the outer region of an accretion disk remains tilted, the disk's inner region aligns with the black hole. A smooth warp connects the inner and outer regions. The team solved the mystery by thinning the accretion disk to an unprecedented degree and including the magnetized turbulence that causes the disk to accrete. Previous simulations made a substantial simplification by merely approximating the effects of the turbulence.

"This groundbreaking discovery of Bardeen-Petterson alignment brings closure to a problem that has haunted the astrophysics community for more than four decades," said Northwestern's Alexander Tchekhovskoy, who co-led the research. "These details around the black hole may seem small, but they enormously impact what happens in the galaxy as a whole. They control how fast the black holes spin and, as a result, what effect black holes have on their entire galaxies."

Tchekhovskoy is an assistant professor of physics and astronomy in Northwestern's Weinberg College of Arts and Sciences and a member of CIERA (Center for Interdisciplinary Exploration and Research in Astrophysics), an endowed research center at Northwestern focused on advancing astrophysics studies with an emphasis on interdisciplinary connections. Matthew Liska, a researcher at the University of Amsterdam's Anton Pannenkoek Institute for Astronomy, is the paper's first author.

"These simulations not only solve a 40-year-old problem, but they have demonstrated that, contrary to typical thinking, it is possible to simulate the most luminous accretion disks in full general relativity," Liska said. "This paves the way for a next generation of simulations, which I hope will solve even more important problems surrounding luminous accretion disks."

Elusive alignment

Nearly everything researchers know about black holes has been learned by studying accretion disks. Without the intensely bright ring of gas, dust and other stellar debris that swirls around black holes, astronomers would not be able to spot a black hole in order to study it. Accretion disks also control a black hole's growth and rotation speed, so understanding the nature of accretion disks is key to understanding how black holes evolve and function.

"Alignment affects how accretion disks torque their black holes," Tchekhovskoy said. "So it affects how a black hole's spin evolves over time and launches outflows that impact the evolution of their host galaxies."

From Bardeen and Petterson until present day, simulations have been too simplified to find the storied alignment. Two main issues have acted as a barrier for computational astrophysicists. For one, accretion disks come so close to the black hole that they move through warped space-time, which rushes into the black hole at immense speed. Complicating matters further, the black hole's rotation forces space-time to spin around it. Properly accounting for both of these crucial effects requires general relativity, Albert Einstein's theory that predicts how objects affect the geometry of space-time around them.

Second, astrophysicists have not had computing power to account for magnetic turbulence, or the stirring inside of the accretion disk. This stirring is what causes the disk's particles to hold together in a circular shape and what causes gas eventually to fall into the black hole.

"Imagine you have this thin disk. Then, on top of that, you have to resolve the turbulent motions inside the disk," Tchekhovskoy said. "It becomes a really difficult problem."

Without being able to resolve these features, computational scientists were unable to simulate realistic black holes.

Cracking the code

To develop a code capable of carrying out simulations of titled accretion disks around black holes, Liska and Tchekhovskoy used graphical processing units (GPUs) instead of central processing units (CPUs). Extremely efficient at manipulating computer graphics and image processing, GPUs accelerate the creation of images on a display. They are much more efficient than CPUs for computing algorithms that process large swaths of data.

Tchekhovskoy likens GPUs to 1,000 horses and CPUs to a 1,000-horsepower Ferrari.

"Let's say you need to move into a new apartment," he explained. "You will have to make a lot of trips with this powerful Ferrari because it won't fit many boxes. But if you could put one box on each horse, you could move everything in one go. That's the GPU. It has a lot of elements, each of which is slower than those in the CPU, but there are so many of them."

Liska also added a method called adaptive mesh refinement, which uses a dynamic mesh, or grid, that changes and adapts to the flow of movement throughout the simulation. It saves energy and computer power by focusing only on specific blocks in the grid where movement occurs.

The GPUs substantially accelerated the simulation, and the adaptive mesh increased resolution. These improvements allowed the team to simulate the thinnest accretion disk to date, with a height-to-radius ratio of 0.03. When the disk was simulated this thin, the researchers could see alignment occur right next to the black hole.

"The thinnest disks simulated before had a height-to-radius ratio of 0.05, and it turns out that all of the interesting things happen at 0.03," Tchekhovskoy said.

In a surprise finding, even with these incredibly thin accretion disks, the black hole still emitted powerful jets of particles and radiation.

"Nobody expected jets to be produced by these disks at such slight thicknesses," Tchekhovskoy said. "People expected that the magnetic fields that produce these jets would just rip through these really thin disks. But there they are. And that actually helps us resolve observational mysteries."

Credit: 
Northwestern University

New method for engineering metabolic pathways

Cells are incredibly adept at creating complex molecules, like therapeutics, and can do so much better than many of our best factories.

Synthetic biologists look to re-engineer cells to make these molecules for specific needs, including pharmaceuticals and energy applications. But the trial-and-error process is difficult and time-consuming, and often competes with the cell's other goals and processes, like growth and survival.

A new method developed at Northwestern University combines two state-of-the-art research approaches to create a fast, efficient way to engineer and analyze metabolic pathways.

The approaches -- cell-free protein synthesis and self-assembled monolayer desorption ionization (SAMDI) mass spectrometry -- combine to make a new tool to help engineers better understand the pathways to create molecules.

"With these two methods, we can build thousands of potential mixtures and test them all in a single day, a much faster process that will give new insights and design rules for synthetic biologists," said Milan Mrksich, the Henry Wade Rogers Professor of Biomedical Engineering, Chemistry, and Cell and Molecular Biology at Northwestern's McCormick School of Engineering. He is also the co-director of Northwestern's Center for Synthetic Biology.

The results were published June 5 in the journal Science Advances. Michael Jewett, the Charles Deering McCormick Professor of Teaching Excellence, professor of chemical and biological engineering, and co-director of the Center for Synthetic Biology, is a co-corresponding author of the research.

Creating enzymes through cell-free synthesis

Cells develop complex molecules through enzymes, the protein that is used to convert one molecule to another. Through a series of these conversions, a metabolite becomes a complex molecule, one that often is associated with societal benefit.

For engineers to mimic this process, they need to identify which enzymes are required to give them the desired molecule. Once they understand that metabolic pathway, they can engineer a cell -- often a bacteria cell -- to make the enzymes to create the target molecule. For example, Coenzyme A (CoA) is a central molecule in metabolism, and synthetic biologists have used its dependent pathways to engineer antimalarial drugs, brewer's yeast, and advanced biofuels.

But finding these pathways is a trial-and-error process that can take days of effort to both engineer and then test the outcome. To get past this, Jewett's lab has developed a process of cell-free protein synthesis that creates just the enzymes needed to make the target product molecules, but without having to use the whole cell itself. Here, the lab created enzymes, which allows them to mix and match potential enzymes in reaction tubes without having their ultimate goals compete with a cell's other goals, like maintaining its metabolism.

"Cell-free protein synthesis is really an exciting technology," Jewett said. "The cocktail-based approach for constructing biosynthetic functions using cell-free systems we describe here is achieving an unprecedented freedom of design to expand the capabilities of natural biocatalysts."

Analyzing quickly with SAMDI

Once these solutions are created, testing their success requires at least a half hour per sample. Because there are so many possible solutions, that manual process is not efficient enough to search for the optimal outcomes.

That's where Mrksich's SAMDI mass spectrometry comes in. The technology measures biochemical reactions extremely quickly and cheaply. "We can easily test 10,000 reaction mixtures in a single day to determine which molecules were synthesized and how much of each is present in the reaction mixtures," Mrksich said.

Additionally, the method allows them to observe all the molecules present in the reaction, which means they can find molecules that they weren't necessarily searching for in the first place. "That's pretty exciting," Mrksich said. "It's a powerful scientific tool that teaches us about how these reactions are balanced and trade off each other in the cell."

Creating factories with cells

To prove this method, the researchers synthesized hydroxymethylglutaryl-CoA (HMG-CoA), a common metabolite used in the synthesis of many complex molecules, including a class of important molecules known as isoprenoids (including steroids and cancer drugs), and mapped more than 800 unique reaction conditions.

"Today, a typical synthetic biology project might explore dozens of variants of a pathway," Jewett said. "With our method, we show it's possible to test hundreds to thousands of pathway variations. This is important because it will enable new types of data driven design to facilitate pathway optimization."

Because the SAMDI method creates so many data points for each test, the researchers hope to employ more machine learning and artificial intelligence methods going forward to help them analyze and make sense of all the data.

The ultimate goal is to have enough of an understanding to harness the power of a cell to create next-generation pharmaceuticals and sustainable chemicals for energy. Just as rapid increases in the performance of computational devices -- described by Moore's law -- has had a profound impact on the entire computation and consumer electronics industry, "this approach represents the next step in engineering that will have an analogous impact on synthetic biology for all of its applications," Jewett said.

"Imagine replacing entire factories with a barrel of bacteria," Mrksich said. "Those bacteria cells can be engineered to produce our target molecules, without the high temperatures and unsafe solvents and chemicals that are normally required.. It's an attractive route to manufacturing chemicals, and with this new process, we've significantly improved the efficiency with which the pathways can be discovered and optimized."

Credit: 
Northwestern University