It’s possible that I shall make an ass of myself. But in that case one can always get out of it with a little dialectic. I have, of course, so worded my proposition as to be right either way (K.Marx, Letter to F.Engels on the Indian Mutiny)
Thursday, August 06, 2020
Identifying and contending with radioisotopes of concern at Fukushima
AMERICAN ASSOCIATION FOR THE ADVANCEMENT OF SCIENCE
In this Perspective, Ken Buesseler describes the enormous challenges that remain in doing clean-up on land in Japan following the Fukushima Daiichi Nuclear Power Plant disaster in 2011, even as some progress has been made offshore. Buesseler notes that among the biggest unresolved issues is what to do with the more than 1,000 tanks at the plant site that contain contaminated water. One possible option for dealing with it is to release it into the ocean. It contains Tritium, 3H, which is notoriously difficult to remove because it is a radioactive form of hydrogen that is part of the water molecule itself. But, says Buesseler, while tritium has received much attention to date, the tank water also contains other radioactive isotopes that behave differently in the ocean and are more readily incorporated into marine biota or seafloor sediments. Buesseler argues that, to assess the consequences of releasing the tanks, "a full accounting ... of what isotopes are left in each tank is needed." Buesseler also suggests that options other than ocean discharge should be considered, moving forward. And he notes that public fears about the clean-up process "should not be dismissed" because these decisions may have negative impacts on local fisheries that are just now rebuilding.
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Why shaving dulls even the sharpest of razors
Human hair is 50 times softer than steel, yet it can chip away a razor's edge, a new study shows
MASSACHUSETTS INSTITUTE OF TECHNOLOGY
Razors, scalpels, and knives are commonly made from stainless steel, honed to a razor-sharp edge and coated with even harder materials such as diamond-like carbon. However, knives require regular sharpening, while razors are routinely replaced after cutting materials far softer than the blades themselves.
Now engineers at MIT have studied the simple act of shaving up close, observing how a razor blade can be damaged as it cuts human hair -- a material that is 50 times softer than the blade itself. They found that hair shaving deforms a blade in a way that is more complex than simply wearing down the edge over time. In fact, a single strand of hair can cause the edge of a blade to chip under specific conditions. Once an initial crack forms, the blade is vulnerable to further chipping. As more cracks accumulate around the initial chip, the razor's edge can quickly dull.
The blade's microscopic structure plays a key role, the team found. The blade is more prone to chipping if the microstructure of the steel is not uniform. The blade's approaching angle to a strand of hair and the presence of defects in the steel's microscopic structure also play a role in initiating cracks.
The team's findings may also offer clues on how to preserve a blade's sharpness. For instance, in slicing vegetables, a chef might consider cutting straight down, rather than at an angle. And in designing longer-lasting, more chip-resistant blades, manufacturers might consider making knives from more homogenous materials.
"Our main goal was to understand a problem that more or less everyone is aware of: why blades become useless when they interact with much softer material," says C. Cem Tasan, the Thomas B. King Associate Professor of Metallurgy at MIT. "We found the main ingredients of failure, which enabled us to determine a new processing path to make blades that can last longer."
Tasan and his colleagues have published their results in the journal Science. His co-authors are Gianluca Roscioli, lead author and MIT graduate student, and Seyedeh Mohadeseh Taheri Mousavi, MIT postdoc.
A metallurgy mystery
Tasan's group in MIT's Department of Materials Science and Engineering explores the microstructure of metals in order to design new materials with exceptional damage-resistance.
"We are metallurgists and want to learn what governs the deformation of metals, so that we can make better metals," Tasan says. "In this case, it was intriguing that, if you cut something very soft, like human hair, with something very hard, like steel, the hard material would fail."
To identify the mechanisms by which razor blades fail when shaving human hair, Roscioli first carried out some preliminary experiments, using disposable razors to shave his own facial hair. After every shave, he took images of the razor's edge with a scanning electron microscope (SEM) to track how the blade wore down over time.
Surprisingly, the experiments revealed very little wear, or rounding out of the sharp edge over time. Instead, he noticed chips forming along certain regions of the razor's edge.
"This created another mystery: We saw chipping, but didn't see chipping everywhere, only in certain locations," Tasan says. "And we wanted to understand, under what conditions does this chipping take place, and what are the ingredients of failure?"
A chip off the new blade
To answer this question, Roscioli built a small, micromechanical apparatus to carry out more controlled shaving experiments. The apparatus consists of a movable stage, with two clamps on either side, one to hold a razor blade and the other to anchor strands of hair. He used blades from commercial razors, which he set at various angles and cutting depths to mimic the act of shaving.
The apparatus is designed to fit inside a scanning electron microscope, where Roscioli was able to take high-resolution images of both the hair and the blade as he carried out multiple cutting experiments. He used his own hair, as well as hair sampled from several of his labmates, overall representing a wide range of hair diameters.
Regardless of a hair's thickness, Roscioli observed the same mechanism by which hair damaged a blade. Just as in his initial shaving experiments, Roscioli found that hair caused the blade's edge to chip, but only in certain spots.
When he analyzed the SEM images and movies taken during the cutting experiments, he found that chips did not occur when the hair was cut perpendicular to the blade. When the hair was free to bend, however, chips were more likely to occur. These chips most commonly formed in places where the blade edge met the sides of the hair strands.
To see what conditions were likely causing these chips to form, the team ran computational simulations in which they modeled a steel blade cutting through a single hair. As they simulated each hair shave, they altered certain conditions, such as the cutting angle, the direction of the force applied in cutting, and most importantly, the composition of the blade's steel.
They found that the simulations predicted failure under three conditions: when the blade approached the hair at an angle, when the blade's steel was heterogenous in composition, and when the edge of a hair strand met the blade at a weak point in its heterogenous structure.
Tasan says these conditions illustrate a mechanism known as stress intensification, in which the effect of a stress applied to a material is intensified if the material's structure has microcracks. Once an initial microcrack forms, the material's heterogeneous structure enabled these cracks to easily grow to chips.
"Our simulations explain how heterogeneity in a material can increase the stress on that material, so that a crack can grow, even though the stress is imposed by a soft material like hair," Tasan says.
The researchers have filed a provisional patent on a process to manipulate steel into a more homogenous form, in order to make longer-lasting, more chip-resistant blades.
"The basic idea is to reduce this heterogeneity, while we keep the high hardness," Roscioli says. "We've learned how to make better blades, and now we want to do it."
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Written by Jennifer Chu, MIT News Office
Small towns have highest risk of intimate partner violence
WASHINGTON STATE UNIVERSITY
VANCOUVER, Wash. - Despite common perceptions that big cities have more violence, women living in small towns are most at risk of violence from current or former spouses and partners, according to a recent study by Washington State University criminologist Kathryn DuBois.
For the study, published in the Journal of Interpersonal Violence, DuBois analyzed the responses of more than 570,000 women from the National Crime Victimization Survey from 1994 to 2015. She found that women from small towns were 27% more likely to be victims of intimate partner violence than women from the center of big cities and 42% more likely than suburban women.
"In criminology, we often have this urban bias. We assume big cities are the worst and paint other places as idyllic," said DuBois, associate professor at WSU Vancouver. "We tend to think in a continuum from urban to suburban to rural, but for intimate partner violence, it's actually the suburban areas that are the safest, and small towns that have the highest risk."
The National Crime Victimization Survey collects information through a large sample of interviews about a range of personal crimes committed every year. Part of the intent of the survey is to uncover the "dark figure" of crime, DuBois said, those crimes that may not be reported to police.
While the survey defines many locations as simply urban or rural, DuBois analyzed the data by population density to delineate urban, suburban, small town and rural areas. Small towns were defined as urbanized portions of non-metropolitan counties with populations up to 50,000. They are distinct from suburban areas that exist just outside of big cities.
"Many surveys assume that everyone in those nonmetropolitan counties are the same, but there's a lot more heterogeneity across them," Dubois said.
DuBois originally undertook the study to try and reconcile the inconsistency between national surveys, which typically find rural areas have less or similar rates of intimate partner violence to urban areas--and ethnographic research, in-depth qualitative studies that have indicated that rural isolation can exacerbate gender-based violence.
While the study data cannot reveal the reasons behind the violence, the finding about the high rate of intimate partner violence in small towns indicates that there may be a different set of factors at play, DuBois said.
"Small towns have populations large enough to have the difficult problems of a big city, while at the same time these are some of the hardest hit areas economically, so they don't have specialized services and policing needed to deal with family violence," DuBois said.
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Impact of climate change on tropical fisheries would create ripples across the world
Tropical oceans and fisheries are threatened by climate change, generating impacts that will affect the sustainable development of both local economies and communities, and regions outside the tropics.
UNIVERSITY OF BRITISH COLUMBIA
Tropical oceans and fisheries are threatened by climate change, generating impacts that will affect the sustainable development of both local economies and communities, and regions outside the tropics through 'telecoupling' of human-natural systems, such as seafood trade and distant-water fishing, says a scientific review from UBC and international researchers.
Seafood is the most highly traded food commodity globally, with tropical zone marine fisheries contributing more than 50 per cent of the global fish catch, an average of $USD 96 billion annually. Available scientific evidence consistently shows that tropical marine habitats, fish stocks and fisheries are most vulnerable to oceanic changes associated with climate change. However, the scientific review highlights that telecoupling, or linkages between distant human-natural systems, could generate cascades of climate change impacts from the tropics that propagate to other 'extra-' tropical natural systems and human communities globally.
"Telecoupling interactions between two or more linked areas over distance between tropical fisheries and elsewhere include distant-water fishing, the international seafood supply chain, transboundary fisheries resources and their governance would allow benefits derived from tropical fisheries to transfer to the people in the extratropical regions," said Vicky Lam, lead author and research associate in the UBC's Institute for the Oceans and Fisheries. "Although these linkages could enable the flow of benefits, including food, livelihoods and government revenue, from tropical fisheries to extratropical locations, their dependence on tropical fisheries also exposes them to the negative consequences of climate change in tropical regions. The effects of climate change on tropical fisheries also affect the profitability and employment opportunities of fish-processing industries in extratropical regions."
"Pacific Island countries and territories, for example, are expected to see a redistribution of skipjack and yellowfin tuna - their two most exported fish species - that could see decreased catches of between 10 and 40 per cent by 2050 in many countries such as Palau and the Solomon Islands, while catches are expected to increase by 15 to 20 per cent in Kiribati and the Cook Islands. This will have a tremendous effect on the economies of these small island developing states," said Rashid Sumaila, co-author and professor at UBC's Institute for the Oceans and Fisheries and School of Public Policy and Global Affairs. "There are similar projections in African nations, where climate-related changes are expected to decrease the value of landed catch by approximately 20 per cent by 2050, as well as reduce fisheries-related jobs by 50 per cent."
To reduce the effect of climate change on the benefits derived from tropical fisheries, both locally and in extra-tropical regions, the root causes of climate-driven problems in tropical fisheries need to be recognized and rectified. Effective and practical adaptation and mitigation solutions with stakeholder commitment and involvement, as well as supporting policies, are therefore necessary in the tropics.
"We already see that there are close linkages between the tropical regions and the extra-tropical nations through trade and distant-water fishing" said William Cheung, co-author and professor at UBC's Institute for the Oceans and Fisheries. "Solving climate change impacts in the tropics will benefit the whole world; this provides an additional argument for non-tropical countries to support climate mitigation and adaptation in tropical countries."
Economic Telecoupling of Tropical Fisheries (IMAGE)
Annual average value (US$ million) of fish exports from Pacific Island countries and territories (PICTs) (panel a), Brazil (panel b) and Africa (panel c) to their main trading partners for 2014-2018 (left), and annual average landed values (US$ billions) of fish caught in the three corresponding groups of exclusive economic zones (EEZs) by the countries and territories in those regions and by distant-water fishing nations between 2007 and 2016 (right). There are close linkages between the tropical regions and the extratropical nations through trade and distant-water fishing, indicating that any climate-related changes to tropical fisheries have socio-economic implications for many extratropical nations. Note that values from the Pacific Islands region are for tuna only, and the catch values refer to tuna caught from the Western and Central Pacific Fisheries Convention Area, which is larger than the combined EEZs of PICTs (see Supplementary Tables 1,4-8). Source of data for panel a: Pacific Islands Forum Fisheries Agency.###
The article "Climate change, tropical fisheries and prospects for sustainable development" appeared in Nature Reviews Earth & Environment.
New insight into the evolution of complex life on Earth
LANCASTER UNIVERSITY
A novel connection between primordial organisms and complex life has been discovered, as new evidence sheds light on the evolutionary origins of the cell division process that is fundamental to complex life on Earth.
The discovery was made by a cross-disciplinary team of scientists led by Professor Buzz Baum of University College London and Dr Nick Robinson of Lancaster University.
Their research, published in Science, sheds light on the cell division of the microbe Sulfolobus acidocaldarius, which thrives in acidic hot springs at temperatures of around 75?C. This microbe is classed among the unicellular organisms called archaea that evolved 3.5 billion years ago together with bacteria.
Eukaryotes evolved about 1 billion years later - likely arising from an endosymbiotic event in which an archaeal and bacterial cell merged. The resulting complex cells became a new division of life that now includes the protozoa, fungi, plants and animals.
Now a common regulatory mechanism has been discovered in the cell division of both archaea and eukaryotes after the researchers demonstrated for the first time that the proteasome - sometimes referred to as the waste disposal system of the cell - regulates the cell division in Sulfolobus acidocaldarius by selectively breaking down a specific set of proteins.
The authors report: "This is important because the proteasome has not previously been shown to control the cell division process of archaea."
The proteasome is evolutionarily conserved in both archaea and eukaryotes and it is already well established that selective proteasome-mediated protein degradation plays a key role in the cell cycle regulation of eukaryotes.
These findings therefore shed new light on the evolutionary history of the eukaryotes.
The authors summarise: "It has become increasingly apparent that the complex eukaryotic cells arose following an endosymbiotic event between an ancestral archaeal cell and an alpha-proteobacterium, which subsequently became the mitochondria within the resulting eukaryotic cell. Our study suggests that the vital role of the proteasome in the cell cycle of all eukaryotic life today has its evolutionary origins in archaea."
Its neck was three times as long as its torso, but had only 13 extremely elongated vertebrae: Tanystropheus, a bizarre giraffe-necked reptile which lived 242 million years ago, is a paleontological absurdity. A new study led by the University of Zurich has now shown that the creature lived in water and was surprisingly adaptable.
For over 150 years, paleontologists have puzzled over Tanystropheus, its strangely long neck and whether it lived mostly underwater or on land. An international team led by the University of Zurich has now reconstructed its skull in unprecedented detail using synchrotron radiation micro-computed tomography (SRμCT), an extremely powerful form of CT scanning. In addition to revealing crucial aspects of its lifestyle, this also shows that Tanystropheus had evolved into two different species.
Underwater ambush predator
The researchers were able to reconstruct an almost complete 3D skull from a severely crushed fossil. The reconstruction reveals that the skull of Tanystropheus has several very clear adaptations for life in water. The nostrils are located on the top of the snout, much like in modern crocodilians, and the teeth are long and curved, perfectly adapted for catching slippery prey like fish and squid. However, the lack of visible adaptations for swimming in the limbs and tail also means that Tanystropheus was not a particularly efficient swimmer. "It likely hunted by stealthily approaching its prey in murky water using its small head and very long neck to remain hidden," says lead author and UZH paleontologist Stephan Spiekman.
Two species living together
Tanystropheus remains have mainly been found at Monte San Giorgio on the border between Switzerland and Italy, a place so unique for its Triassic fossils that it has been declared a UNESCO World Heritage Site. Two types of Tanystropheus fossils are known from this location, one small and one large. Until now, these were believed to be the juveniles and adults of the same species.
However, the current study disproves this assumption. The reconstructed skull, belonging to a large specimen, is very different from the already known smaller skulls, particularly when it comes to its dentition. In order to see whether the small fossils actually belonged to young animals, the researchers looked at cross sections of limb bones from the smaller type of Tanystropheus. They found many growth rings which form when bone growth is drastically slowed down. "The number and distribution of the growth rings tells us that these smaller types were not young animals, as previously considered, but mature ones," says last author Torsten Scheyer. "This means that the small fossils belonged to a separate, smaller species of Tanystropheus."
Specialists in different food sources
According to Spiekman, these two closely related species had evolved to use different food sources in the same environment: "The small species likely fed on small shelled animals, like shrimp, in contrast to the large species which ate fish and squid." For the researchers, this is a really remarkable finding: "We expected the bizarre neck of Tanystropheus to be specialized for a single task, like the neck of a giraffe. But actually, it allowed for several lifestyles."
Reconstructions of the skeletons of Tanystropheus hydroides (large species, newly named) and Tanystropheus longobardicus (small species). The outline of a 170 cm tall diver serves as the scale.###
Fossil mystery solved: Super-long-necked reptiles lived in the ocean, not on land
Twenty-foot-long specimens described as separate species from their cousins, named after mythology's Hydra
FIELD MUSEUM
A fossil called Tanystropheus was first described in 1852, and it's been puzzling scientists ever since. At one point, paleontologists thought it was a flying pterosaur, like a pterodactyl, and that its long, hollow bones were phalanges in the finger that supported the wing. Later on, they figured out that those were elongated neck bones, and that it was a twenty-foot-long reptile with a ten-foot neck: three times as long as its torso. Scientists still weren't sure if it lived on land or in the water, and they didn't know if smaller specimens were juveniles or a completely different species--until now. By CT-scanning the fossils' crushed skulls and digitally reassembling them, researchers found evidence that the animals were water-dwelling, and by examining the growth rings in bones, determined that the big and little Tanystropheus were separate species that could live alongside each other without competing because they hunted different prey.
"I've been studying Tanystropheus for over thirty years, so it's extremely satisfying to see these creatures demystified," says Olivier Rieppel, a paleontologist at the Field Museum in Chicago and one of the authors of a new paper in Current Biology detailing the discovery.
Tanystropheus lived 242 million years ago, during the middle Triassic. On land, dinosaurs were just starting to emerge, and the sea was ruled by giant reptiles. For a long time, though, scientists weren't sure whether Tanystropheus lived on land or in the water. Its bizarre body didn't make things clear one way or the other.
"Tanystropheus looked like a stubby crocodile with a very, very long neck," says Rieppel. The larger specimens were twenty feet long, with their necks making up ten feet of that length. Oddly for animals with such long necks, they only had thirteen neck vertebrae, just really elongated. (We see the same thing with giraffes, which have only seven neck bones, just like humans.) And their necks were rather inflexible, reinforced with extra bones called cervical ribs.
In the same region where many of the big Tanystropheus fossils were found, in what's now Switzerland, there were also fossils from similar-looking animals that were only about four feet long. So not only were scientists unsure if these were land-dwellers or marine animals, but they also didn't know if the smaller specimens were juveniles, or a separate species from the twenty-footers.
To solve these two long-standing mysteries, the researchers used newer technologies to see details of the animals' bones. The large Tanystropheus fossils' skulls had been crushed, but Stephan Spiekman, the paper's lead author and a researcher at the University of Zurich, was able to take CT scans of the fossil slabs and generate 3D images of the bone fragments inside.
"The power of CT scanning allows us to see details that are otherwise impossible to observe in fossils," says Spiekman. "From a strongly crushed skull we have been able to reconstruct an almost complete 3D skull, revealing crucial morphological details."
The skulls had key features, including nostrils on top of the snout like a crocodile's, that suggested Tanystropheus lived in the water. It probably lay in wait, waiting for fish and squid-like animals to swim by, and then snagged them with its long, curved teeth. It may have come to land to lay eggs, but overall, it stayed in the ocean.
Rieppel wasn't surprised that evidence pointed to a water-dwelling Tanystropheus. "That neck doesn't make sense in a terrestrial environment," he says. "It's just an awkward structure to carry around.
The digitially reconstructed skull of Tanystropheus, using CT scans of the crushed skull pieces.
So that answered one question, about where Tanystropheus lived. To learn whether the small specimens were juveniles or a separate species, the researchers examined the bones for signs of growth and aging.
"We looked at cross sections of bones from the small type and were very excited to find many growth rings. This tells us that these animals were mature," says Torsten Scheyer, the study's senior author and a researcher at University of Zurich.
"The small form is an adult, which basically sealed the case," says Rieppel. "It's proven now that these are two species." The researchers named the larger one Tanystropheushydroides, after the long-necked hydras in Greek mythology. The small form bears the original name Tanystropheuslongobardicus.
"For many years now we have had our suspicions that there were two species of Tanystropheus, but until we were able to CT scan the larger specimens we had no definitive evidence. Now we do," says Nick Fraser, Keeper of Natural Sciences at National Museums Scotland and a co-author of the paper. "It is hugely significant to discover that there were two quite separate species of this bizarrely long-necked reptile who swam and lived alongside each other in the coastal waters of the great sea of Tethys approximately 240 million years ago."
The animals' different sizes, along with cone-shaped teeth in the big species and crown-shaped teeth in the little species, meant they probably weren't competing for the same prey.
"These two closely related species had evolved to use different food sources in the same environment," says Spiekman. "The small species likely fed on small shelled animals, like shrimp, in contrast to the fish and squid the large species ate. This is really remarkable, because we expected the bizarre neck of Tanystropheus to be specialized for a single task, like the neck of a giraffe. But actually, it allowed for several lifestyles. This completely changes the way we look at this animal."
This "splitting up" of a habitat to accommodate two similar species is called niche partitioning. "Darwin focused a lot on competition between species, and how competing over resources can even result in one of the species going extinct," says Rieppel. "But this kind of radical competition happens in restricted environments like islands. The marine basins that Tanystropheus lived in could apparently support niche partitioning. It's an important ecological phenomenon."
"Tanystropheus is an iconic fossil and has always been," adds Rieppel. "To clarify its taxonomy is an important first step to understanding that group and its evolution."
Racial disparities in high-cost cancer treatment for children
JAMA ONCOLOGY
What The Study Did: This observational study looked at whether race and socioeconomic factors were associated with children enrolled in national clinical trials receiving high-cost proton radiotherapy for treatment of cancer.
Authors: Daphne A. Haas-Kogan, M.D., of the Dana-Farber Cancer Institute in Boston, is the corresponding author.
Editor's Note: The article includes conflicts of interest and funding/support disclosures. Please see the article for additional information, including other authors, author contributions and affiliations, conflict of interest and financial disclosures, and funding and support.
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Media advisory: The full study is linked to this news release.
Tasmanian devil research offers new insights for tackling cancer in humans
WASHINGTON STATE UNIVERSITY
PULLMAN, Wash. - A rare, transmissible tumor has brought the iconic Tasmanian devil to the brink of extinction, but new research by scientists at Washington State University and the Fred Hutchinson Cancer Research Center in Seattle indicates hope for the animals' survival and possibly new treatment for human cancers.
The study, published in Genetics on Aug. 1, found a single genetic mutation that leads to reduced growth of a transmissible cancer in Tasmanian devils in the wild.
"This gene is implicated in human prostate and colon cancers," said Andrew Storfer, professor of biological sciences at WSU. "While the findings hold the most immediate promise to help save the world's few remaining Tasmanian devils, these results could also someday translate to human health."
The research team, led by Storfer and Mark Margres, now a postdoctoral fellow at Harvard University, studied the genomes of cases of devil facial tumor disease, or DFTD, that regressed spontaneously -- that is, the cancer began disappearing on its own.
They were surprised to find the mutation contributing to tumor regression doesn't change the gene function but instead, turns on a gene that slows cell growth in the tumor. At least, it behaves that way in the lab.
Current human cancer therapies focus on removing every trace of a tumor, often through toxic or debilitating treatments, said David Hockenbery, a cancer biologist at Fred Hutch who contributed to the study.
"If there were ways that tumors could be tricked into regressing without having to administer cytotoxic drugs or deforming surgeries, it would be a major advance," he said.
While infections cause up to 20 percent of all human cancers - such as gastric cancer from Helicobacter pylori and cervical cancer from human papillomavirus - for Tasmanian devils, the cancer is the infection.
DFTD spreads between the animals when they bite each other during common social behaviors. Since the mid-1990s, the disease has decimated the natural population of the carnivorous marsupials, which are now found only on the island state of Tasmania, off the southeastern coast of Australia.
Storfer's lab leads a National Institutes of Health-funded team of researchers from the U.S. and Australia to improve conservation efforts for Tasmanian devils and increase understanding of the co-evolution of the tumor and its host.
Though ferocious with each other, Tasmanian devils take mild handling by people without much fuss, making it easy for investigators to humanely capture the animals, collect tissue samples and tag them for monitoring before release back into the wild.
As the researchers work to save the devils, they also have an unprecedented opportunity to watch tumors naturally evolve and sometime regress without drugs or surgery.
"Although this disease is largely fatal, we're seeing tumors just disappear from an increasing number of individual animals," Storfer said.
The team is looking at the effects of other promising mutations in regressed tumors as well.
"We hope to learn something that could be applied to understanding and possibly treating a number of human cancers in the future," Storfer said.
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This research was supported by the National Institutes of Health, the National Science Foundation and the Washington Research Foundation.
NTU develops peptide that makes drug-resistant bacteria sensitive to antibiotics again
Peptide also kills multidrug-resistant bacteria on its own
NANYANG TECHNOLOGICAL UNIVERSITY
Scientists at Nanyang Technological University, Singapore (NTU Singapore) have developed a synthetic peptide that can make multidrug-resistant bacteria sensitive to antibiotics again when used together with traditional antibiotics, offering hope for the prospect of a combination treatment strategy to tackle certain antibiotic-tolerant infections.
On its own, the synthetic antimicrobial peptide can also kill bacteria that have grown resistant to antibiotics.
Every year, an estimated 700,000 people globally die of antibiotic-resistant diseases, according to the World Health Organisation. In the absence of new therapeutics, infections caused by resistant superbugs could kill an additional 10 million people each year worldwide by 2050, surpassing cancer[1]. Antibiotic resistance arises in bacteria when they can recognise and prevent drugs that would otherwise kill them, from passing through their cell wall.
This threat is accelerated by the developing COVID-19 pandemic, with patients admitted to hospitals often receiving antibiotics to keep secondary bacterial infections in check, amplifying the opportunity for resistant pathogens to emerge and spread[2].
The NTU Singapore team, led by Associate Professor Kimberly Kline and Professor Mary Chan, developed an antimicrobial peptide known as CSM5-K5 comprising repeated units of chitosan, a sugar found in crustacean shells that bears structural resemblance to the bacterial cell wall, and repeated units of the amino acid lysine.
The scientists believe that chitosan's structural similarity to the bacterial cell wall helps the peptide interact with and embed itself in it, causing defects in the wall and membrane that eventually kill the bacteria.
The team tested the peptide on biofilms, which are slimy coats of bacteria that can cling onto surfaces such as living tissues or medical devices in hospitals, and which are difficult for traditional antibiotics to penetrate.
In both preformed biofilms in the lab and biofilms formed on wounds in mice, the NTU-developed peptide killed at least 90 per cent of the bacteria strains in four to five hours.
In separate experiments, when CSM5-K5 was used with antibiotics that the bacteria are otherwise resistant to, more bacteria was killed off as compared to when CSM5-K5 was used alone, suggesting that the peptide rendered the bacteria susceptible to antibiotics. The amount of antibiotics used in this combination therapy was also at a concentration lower than what is commonly prescribed.
The findings were published in the scientific journal ACS Infectious Diseases in May.
Assoc Prof Kimberly Kline, a Principal Investigator at the Singapore Centre for Environmental Life Sciences Engineering (SCELSE) at NTU, said: "Our findings show that our antimicrobial peptide is effective whether used alone or in combination with conventional antibiotics to fight multidrug-resistant bacteria. Its potency increases when used with antibiotics, restoring the bacteria's sensitivity to drugs again. More importantly, we found that the bacteria we tested developed little to no resistance against our peptide, making it an effective and feasible addition to antibiotics as a viable combination treatment strategy as the world grapples with rising antibiotic resistance."
Prof Mary Chan, director of NTU's Centre of Antimicrobial Bioengineering, said: "While efforts are focussed on dealing with the COVID-19 pandemic, we should also remember that antibiotic resistance continues to be a growing problem, where secondary bacterial infections that develop in patients could complicate matters, posing a threat in the healthcare settings. For instance, viral respiratory infections could allow bacteria to enter the lungs more easily, leading to bacterial pneumonia, which is commonly associated with COVID-19."
How the antimicrobial peptide works
Antimicrobial peptides, which carry a positive electric charge, typically work by binding to the negatively-charged bacterial membranes, disrupting the membrane and causing the bacteria to die eventually. The more positively charged a peptide is, the more efficient it is in binding to bacteria and thus killing them.
However, the peptide's toxicity to the host also increases in line with the peptide's positive charge - it damages the host organism's cells as it kills bacteria. As a result, engineered antimicrobial peptides to date have met with limited success, said Assoc Prof Kline, who is also from the NTU School of Biological Sciences.
The peptide designed by the NTU team, called CSM5-K5, is able to cluster together to form nanoparticles when it is applied to bacteria biofilms. This clustering results in a more concentrated disruptive effect on the bacterial cell wall when compared to the activity of single chains of peptides, meaning it has high antibacterial activity but without causing undue damage to healthy cells (See Image 1 in Note to Editors).
To examine CSM5-K5's efficacy on its own, the NTU scientists developed separate biofilms comprising methicillin-resistant Staphylococcus aureus, commonly known as the MRSA superbug; a highly virulent multidrug-resistant strain of Escherichia coli (MDR E. Coli); and vancomycin-resistant Enterococcus faecalis (VRE). MRSA and VRE are classified as serious threats by the US Centers for Disease Control and Prevention[3].
In lab experiments, CSM5-K5 killed more than 99 per cent of the biofilm bacteria after four hours of treatment. In infected wounds on mice, the NTU-developed antimicrobial peptide killed more than 90 per cent of the bacteria.
When CSM5-K5 was used with conventional antibiotics, the NTU team found that the combination approach led to a further reduction in the bacteria in both lab-formed biofilms and infected wounds in mice as compared to when only CSM5-K5 was used, suggesting that the antimicrobial peptide made the bacteria sensitive to the drugs they would otherwise be resistant to.
More importantly, the NTU team found that the three strains of bacteria studied (MRSA, VRE and MDR E. coli) developed little to no resistance against CSM5-K5. While MRSA developed low-level resistance against CSM5-K5, this made MRSA more sensitive to the drug it is otherwise resistant to.
Prof Chan said: "Developing new drugs alone is no longer sufficient to fight difficult-to-treat bacterial infections, as bacteria continue to evolve and outsmart antibiotics/ It is important to look at innovative ways to tackle difficult-to-treat bacterial infections associated with antibiotic resistance and biofilms, such as tackling the bacteria's defence mechanisms. A more effective and economic method to fight bacteria is through a combination therapy approach like ours."
The next step forward for the team is to explore how such a combination therapy approach can be used for rare diseases or for wound dressing.
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The research on the CSM5-K5 antimicrobial peptide was funded by NTU, the National Research Foundation, the Ministry of Education, and the Ministry of Health.
Note to Editors:
Paper 'Combined Efficacy of an Antimicrobial Cationic Peptide Polymer With Conventional Antibiotics to Combat Multidrug-Resistant Pathogens' published in ACS infectious diseases, 6(5), 1228-1237.
DOI: 10.1021/acsinfecdis.0c00016
Media contact:
Foo Jie Ying Manager, Corporate Communications Office Nanyang Technological University Email: jieying@ntu.edu.sg
About Nanyang Technological University, Singapore
A research-intensive public university, Nanyang Technological University, Singapore (NTU Singapore) has 33,000 undergraduate and postgraduate students in the Engineering, Business, Science, Humanities, Arts, & Social Sciences, and Graduate colleges. It also has a medical school, the Lee Kong Chian School of Medicine, set up jointly with Imperial College London.
NTU is also home to world-class autonomous institutes - the National Institute of Education, S Rajaratnam School of International Studies, Earth Observatory of Singapore, and Singapore Centre for Environmental Life Sciences Engineering - and various leading research centres such as the Nanyang Environment & Water Research Institute (NEWRI) and Energy Research Institute @ NTU (ERI@N).
Ranked amongst the world's top universities by QS, NTU has also been named the world's top young university for the past seven years. The University's main campus is frequently listed among the Top 15 most beautiful university campuses in the world and it has 57 Green Mark-certified (equivalent to LEED-certified) building projects, of which 95% are certified Green Mark Platinum. Apart from its main campus, NTU also has a campus in Singapore's healthcare district.
Bone-anchored leg prostheses also prove to be a valuable procedure after 5-year follow-up
Despite 'stoma' problems it has lasting benefits in terms of daily functioning, mobility and quality of life
RADBOUD UNIVERSITY MEDICAL CENTER
After above-knee amputation, there is the option of a prosthesis that is placed in the thigh bone (osseointegration). Despite the fact that bone-anchored prostheses have been used for thirty years, researchers at the Radboud University Medical Center have now published the first long-term evaluation of such a prosthesis. It turns out that the procedure is not without stoma problems, but that these can usually be treated with simple measures and that the osseointegration implant system leads to a permanent improvement in mobility and quality of life.
This study was published yesterday in the latest edition of Journal Of Bone And Joint Surgery.
Options for the attachment of the prosthetic leg after amputation
Bone-anchored prostheses offer a number of important advantages over traditional 'socket' prosthetics, which must fit snugly over the stump and be held in place by a suction or suspension system. To place a bone-anchored prosthesis, a 14 cm steel pin must first be inserted into the remaining portion of the femur bone. In a few weeks this coated pin grows into the bone, after which an adapter is attached that protrudes a few centimeters through the skin (via a stoma). The wearer can attach or detach the artificial leg to this part with a quick coupling connector.
Strong improvement in mobility and quality of life despite complications
In this study, clinical researcher David Reetz and surgeon Jan Paul Frölke, along with their colleagues from the rehabilitation and orthopedics department at Radboudumc, looked at 42 patients who had received such a prosthesis, and performed a follow-up study of the five years after surgery. A full follow-up was obtained in 39 of the 42 patients. The most common complication was infection, in 77% of patients - mostly superficial and in the first two years. The vast majority (95%) were mild to moderate infections that did not require surgical treatment. Fourteen patients experienced irritation around the stoma where the pin protrudes through the skin, and they underwent minor surgery to re-shape the soft tissue.
After receiving their implants, patients increased the number of hours per week they could use their prosthesis: from an average of 56 hours with their previous socket prosthesis to 101 hours with the bone-anchored prosthesis. The bone-anchored prostheses also improved health-related quality of life (HRQoL): on a 100-point scale, the average score increased from 33 to 75.
Frölke: "We received a lot of skeptical reactions from colleagues who didn't believe in it, even after we published excellent results after 2 years of follow-up. Thanks to the trust that patients placed in us, we have continued and we can now conclude that this is the new gold standard in people with sleeve-related problems including about half of all people with a leg amputation. "
Next steps
This study adds to existing evidence showing other benefits of bone anchored prostheses, including more natural and stable control of the prosthesis, improved walking and sitting conditions and avoidance of the many problems associated with the sleeve prosthesis, such as blisters.
Reetz notes, "Next steps in clinical research should include studies aimed at optimizing the stoma using a unified registry system, and further developing the implant design and safety of bone-anchored prostheses in patients with vascular disease. This is by far the largest group but has not been taken into account in this study. "