Earth

Many have assumed that the rates of major abdominal surgeries in adults over 65 is increasing over time as the U.S. population ages and as new technology renders surgical procedures safer for older adults. Contrary to this popular belief, a new study from the University of Chicago Medicine found the frequency of abdominal surgery in older adults is decreasing, especially among adults over the age of 85. The study, which examined data from 2002 to 2014, was published May 10 in the Journal of the American Geriatric Society.

While the research was not able to determine the exact reasons for this shift, the results indicate that improvements in medical treatments and cancer screening for older adults may be reducing the need for invasive surgeries, which can have negative impacts on patient's long-term quality of life.

"There was a really stark decrease in the number of surgeries among older adults over the age of 65 throughout the study period," said first author Daniel Rubin, MD, Associate Professor of Anesthesia and Critical Care at UChicago Medicine. "This suggests we're getting better at determining who would benefit most from a surgery, and also possibly that we've developed better and less invasive alternative treatments."

Rubin was inspired to investigate this question after reading a 2019 New York Times article discussing "routine" surgeries in adults over 85.

"This is a very personal topic for me because I was very close to my grandparents, and I saw their experiences with geriatric surgeries," said Rubin. "My grandmother had an emergency hysterectomy at 92. Despite a stay in the intensive care unit and delirium she was able to go home and live independently afterward. My 89-year-old grandfather, on the other hand, declined a Whipple procedure for treating pancreatic cancer. So I could see early on how these big surgical interventions can really affect older adults."

While the researchers found the overall frequency of surgery in older adults is decreasing, they did note some exceptions.

"The biggest surprise was that we saw a redistribution of surgical procedures to certain types of hospitals," Rubin said. "There was a large shift away from rural and non-teaching urban hospitals to major academic medical centers; these were the only hospitals that saw an increase in the frequency of procedures performed on older adults. We think this may be due to increased specialization and that some procedures that may not be available at a smaller or rural institution are more likely to be offered at a larger, academic hospital."

Another trend that was less surprising was the increase in certain procedures, such as the Whipple procedure for treating pancreatic cancer. "With pancreatic cancer, there aren't really many less-invasive options available, and outcomes are generally good even for older adults," Rubin said. "We perform Whipple procedures on 85- or 90-year-old adults here at UChicago Medicine simply because it is usually the most effective option."

The researchers say these results are important because older adults often struggle to recover after major surgeries. The study found that over half of adults over 85 will require at least some transitional, post-acute medical care after a surgical procedure.

"Older adults really want to get back to their normal life after an operation," said Rubin. "But recovery can be difficult, and the rates at which older adults require post-acute care -- such as time in a rehabilitation facility or long-term care -- is high. These results can help inform the decisions made by patients and providers on whether or not a surgery is the right choice for them."

Understanding how trends in surgical procedures change over time can help illuminate which options are the most likely to lead to optimal outcomes -- and determine which patients will most benefit from specific interventions.

"We're very good at understanding overall mortality for certain procedures, but not as good at identifying which individual patients will have poor outcomes," said Rubin. "It's important for patients and their families to understand that these surgeries can lead to a challenging recovery trajectory for older adults, even if the surgery goes well. My hope is that this research, and other studies like it, will help us better understand how to help older adults prepare for major surgeries, and help us identify which individual patients will benefit the most from surgical intervention."

Unlike the oscillations of sound waves, the oscillations of light are so fast that extremely complex equipment is needed to observe them directly. However, it is possible to measure the frequencies of these oscillations indirectly with frequency combs. These combs are made up of a set of regularly spaced "teeth" where each tooth corresponds to a frequency. Used as a graduated ruler, they offer the possibility of measuring an optical frequency with great precision. This makes it possible, among other things, to measure variations in the distance between the Earth and the Moon with an accuracy equivalent to the size of a hair!

It can be shown that the time signal corresponding to a frequency comb consists of a regular succession of light pulses, called a pulse train. These pulses are ultra-short and have a duration of one millionth of a billionth of a second or less.

There are currently two main methods of generating a pulse train either via a pulsed laser or via a passive optical cavity.

"Some lasers can directly generate a pulse train. Some lasers can directly generate a very energetic pulse train but the delay between two successive pulses is subject to variations even in the absence of external disturbances," explains Nicolas Englebert - OPERA-Photonics Laboratory - Ecole polytechnique de Bruxelles.

The other solution is based on passive optical resonators, made, for example, using optical fibres. It allows the generation of a pulse that propagates indefinitely, a cavity soliton, when a continuous laser beam is injected at its input. The period of the resulting train, in the absence of any external disturbance, is fixed here, unlike with pulsed lasers. Unfortunately, its energy is limited.

Each platform therefore has its advantages and disadvantages. However, for certain applications (LiDAR), it is necessary to have a pulse train that is both energetic and ultra-stable.

Recent research carried out by the ULB OPERA-Photonics Laboratory, published in the journal Nature Photonics, shows the existence of new ultra-stable, high-power cavity solitons: active cavity solitons.

"These solitons emerge within a signal-injected resonator in which there is a finely designed amplification section. The purpose of this section is to compensate for some of the losses that the wave (the soliton) experiences at each roundtrip. If the amplification is too low compared to the losses, the soliton cannot exist. On the other hand, if the amplification is greater than the losses, a laser emission will occur. Thanks to this partial compensation of the losses, it is possible to extract a large part of the soliton's energy (more than 30%!) without compromising its existence," Nicolas Englebert points out.

Moreover, as the amplification section is chosen such that lasing does not occur, the pulse train inherits the stability properties of passive resonators. The active cavity soliton thus combines the advantages of pulse trains generated by pulsed lasers and passive resonators.

This new type of universal and hybrid soliton could trigger many experiments on different platforms, especially in the field of integrated optics where passive resonators dominate the landscape but applications lag behind because very little power can be extracted from the chips. This new concept is not limited to the generation of solitons. Thanks to this new hybrid cavity, components that induce a lot of losses (crystal, particular fibre, etc.) can now be placed in a resonator, opening the way to the study of phenomena that were previously inaccessible experimentally. The invention is the subject of a patent application filed in the name of ULB.

URBANA, Ill. - Sweet corn growers and processors could be bringing in more profits by exploiting natural density tolerance traits in certain hybrids. That's according to 2019 research from USDA Agricultural Research Service (ARS) and University of Illinois scientists.

But since root systems get smaller as plant density goes up, some in the industry are concerned about the risk of root lodging with greater sweet corn density. New research says those concerns are unjustified.

"Root lodging can certainly be a problem for sweet corn, but not because of plant density. What really matters is the specific hybrid and the environment, those major rainfall and wind events that set up conditions for root structural failure," says Marty Williams, USDA-ARS ecologist, affiliate professor in the Department of Crop Sciences at Illinois, and author on a new study in Crop Science.

Williams and his co-authors used multiple approaches to understand the effects of planting density on root lodging in sweet corn. First, they planted sweet corn hybrid DMC 21-84 - a density-tolerant type that happens to be one of the most widely grown commercial hybrids - at five densities in experimental plots on U of I farms. When plants were at the tasseling stage, the researchers simulated a natural lodging event by flooding the field and knocking the corn over with a two-by-four.

"We mimicked a root lodging event with pure brute force," Williams says.

When corn is flattened in the process of root lodging, it can, depending on the growth stage, right itself through the plant's natural inclination to grow toward the light. As corn grows back upward from its repose, the base of the stem often carries a curved reminder of its lodging legacy, known as a gooseneck.

Williams and his team found most plants recovered to a near vertical position, albeit with a bit of goosenecking, within a few days of the artificial lodging event. They also measured yield metrics, and found no statistical difference in sweet corn yield between lodged and non-lodged plants.

But a two-by-four and brute force can't replace nature.

"Testing a crop's root lodging potential experimentally is inherently difficult. Simply put, a natural root lodging event may not happen in any given field experiment. As such, phenotyping crops for root lodging often employs the use of artificially created lodging events, like the ones we created," Williams says. "While artificially created root lodging events are helpful, used alone they often fail to capture a broad range of environments in which the crop is grown."

That's why the research team leveraged data from on-farm sweet corn trials across Illinois, Minnesota, and Wisconsin. Between 2013 and 2017, the team evaluated economic optimum density for DMC 21-84 and 10 other hybrids under real-world farm management. And during that time, natural lodging events happened to occur in six of the 30 fields.

"We happened to take notes on lodging severity. It wasn't our specific focus at the time, but we figured, let's go ahead and score this and maybe we'll use it later. Turns out it was great that we collected root lodging data, because we were able to use it for this study," Williams says.

Those fortuitous notes showed that when sweet corn density increased from the current standard to the economic optimum density, typically a few thousand more plants per acre, there was absolutely no difference in the severity of lodging.

"What excited me about this work is that we combined an experiment where we created lodging artificially and looked at the response, and then we also tapped into this network of naturally occurring events. Together, they told a pretty convincing story," Williams says. "Simply put, root lodging potential should not keep us from using plant density tolerant hybrids and growing them at their correct density. I mean, there's always the possibility that root lodging could occur, but it's not going to be due to planting a few more plants."

Recurrent, metastatic breast cancer resists treatment and is usually fatal.

These tumors often have low numbers of immune cells in them, which renders immune therapies less effective for the disease.

This preclinical study suggests that drugs called CDK4 and CDK6 inhibitors may make immune-cell therapies an effective option for treating recurrent ER-positive metastatic breast cancer.

COLUMBUS, Ohio - A class of drugs that inhibits breast cancer progression when used with hormonal therapy might also boost the effectiveness of immune therapy in cases of recurrent, metastatic breast cancer, according to a new study led by researchers at The Ohio State University Comprehensive Cancer Center - Arthur G. James Cancer Hospital and Richard J. Solove Research Institute (OSUCCC - James).

Published in the journal Cell Reports, the findings of the animal study suggest that drugs called CDK4 and CDK6 (CDK4/6) inhibitors might improve the effectiveness of immune therapies for metastatic, estrogen-receptor-positive (ER+) breast cancer.

"We know that CDK4/6 inhibitors effectively slow the progression of newly diagnosed breast cancer, but they don't kill cancer cells," says principal investigator Anna Vilgelm, MD, a member of the OSUCCC - James Translational Therapeutics Program and assistant professor at the Ohio State College of Medicine. "Consequently, the disease often recurs, and then it is usually fatal because we have no effective therapies for recurrent disease.

"Our findings suggest that combining CDK4/6 inhibitors with immunotherapy might offer an effective treatment for recurrent, metastatic ER+ breast cancer," Vilgelm says.

Specifically, the study shows that CDK4/6 inhibitors can improve the efficacy of T-cell-based therapies such as adoptive T-cell transfer or T-cell-activating antibodies in animal models of breast cancer.

Immune therapies are proving to be effective treatments for a variety of cancers but not for advanced breast cancer. One problem is that breast tumors often have low numbers of cancer-killing T lymphocytes within the tumor. Such tumors tend to respond poorly to immune therapies.

"In addition, breast cancer patients with low numbers of tumor-infiltrating lymphocytes often have worse survival compared to patients with high numbers of infiltrating lymphocytes in their tumors," says Vilgelm.

The new study shows that CDK4/6 inhibitors cause breast tumors to secrete small proteins called chemokines that attract T cells. This can help to improve patients' response to cancer immunotherapies.

For this study, Vilgelm and her colleagues used the oral CDK inhibitor palbociclib, mouse models, breast cancer cell lines and analyses of The Cancer Genome Atlas (TCGA) to study the influence of CDK4/6 inhibitors and chemokine production in the tumor immune microenvironment and on patient outcomes.

Key findings include:

Pre-treatment with a CDK4/6 inhibitor improves recruitment of T cells into tumors and improved the outcome of adoptive cell therapy in animal models;

CDK4/6 inhibitor-treated human breast cancer cells produce T-cell-recruiting chemokines;

TCGA analysis showed that chemokine expression is a favorable prognostic factor in breast cancer patients;

mTOR-regulated metabolic activity is required for chemokine induction by CDK4/6 inhibition;

T-cell-recruiting chemokines may be useful prognostic markers for stratifying patients for immunotherapy treatment.

"Overall," Vilgelm says, "our findings suggest that CDK4/6 inhibitors may offer a therapeutic strategy that can attract T cells into breast cancer tumors, which mayincrease their sensitivity to immune therapies."

MISSOULA - University of Montana Professor Mark Hebblewhite has joined an international team of 92 scientists and conservationists to create the first-ever global atlas of ungulate (hoofed mammal) migrations.

Working in partnership with the Convention on the Conservation of Migratory Species of Wild Animals, a U.N. treaty, the Global Initiative on Ungulate Migration (GIUM) launches May 7 with the publication of a commentary in Science titled "Mapping out a future for ungulate migrations."

The atlas provides detailed maps of the seasonal movements of herds worldwide. The maps will help stakeholders like governments, Indigenous peoples, communities, planners and wildlife managers identify current and future threats to migrations and create conservation measures to sustain them.

"A global migration atlas is urgently needed because there has never been a worldwide inventory of these phenomenal seasonal movements," said lead author Matthew Kauffman, a wildlife biologist with the U.S. Geological Survey in Wyoming and a former UM post-doctorate researcher. "As landscapes become more difficult to traverse, the maps can help conservationists pinpoint threats, identify stakeholders and work together to find solutions."

Migratory ungulates include species like Mongolian gazelles and saiga in Asia, wildebeest in the African Serengeti, guanacos in South America, red deer in Europe and many more. More familiar North American species include pronghorn, elk, mule deer and caribou.

Around the globe, these species undertake arduous seasonal journeys to find food, escape harsh conditions and breed - each journey as unique as the individual species. Wherever they're located, ungulates are an essential part of natural ecosystems. Migrations also contribute to local and regional economies through harvest and tourism, and they are woven into the culture of numerous communities.

But many ungulate migrations are declining or threatened because of human disturbances like roads, fences and other types of development.

Mongolian gazelle migrations, which can cover hundreds of kilometers, are sharply constrained by border fences and new railroads. Over the last few decades, researchers in Kenya's Kajiado County have witnessed the near collapse of the migrations of wildebeest, zebra and Thompson's gazelle due to unplanned roads, fences and other infrastructure. In other cases, migrations have been lost even before they have been documented.

"The same sort of problems that ungulates in Montana and North America face like fences, highways and expanding human development are playing out on a global scale in a huge way," said Hebblewhite, professor of ungulate ecology in UM's Wildlife Biology Program. "We're trying to raise awareness at a global level of the issues they face and also that we need new international guidance."

The new global migration atlas will help decision-makers plan and implement infrastructure projects to mitigate or eliminate their barrier effects and will help decision-makers prioritize which areas along migration routes to conserve.

The effort builds on previous conservation successes made possible by migration mapping. Around the world, actions such as protected-area expansion, road-crossing structures and working-lands conservation initiatives have been catalyzed by tracking the actual migration routes of the herds. The scientists and conservationists involved in the initiative hope that detailed maps of migrations around the world will spark similar conservation actions to sustain wildlife migrations.

To coordinate this large effort, the international team partnered with the U.N. Secretariat of CMS to create the GIUM.

An environmental treaty of the U.N., CMS provides a global platform for the conservation and sustainable use of migratory animals and their habitats. This unique treaty brings countries and wildlife experts together to address the conservation needs of terrestrial, aquatic and avian migratory species and their habitats around the world.

The new global initiative hosted by CMS will use the latest GPS tracking technology, mapping software and data-sharing platforms, combined with local and Indigenous knowledge. The team also will endeavor to map lost migrations and document local and historical knowledge of animal movements.

While the paper offers a global perspective, Hebblewhite said it's relevant in Montana as a reminder of the importance of coordination of conservation across boundaries -including state, federal and private lands - and even internationally across the Canadian border.

"In some ways, Montana and Wyoming really are leading the world in how to conserve migratory ungulates," Hebblewhite said. "Montana is already undertaking a lot of conservation work to understand the needs of their migratory ungulates. But even in places like the Greater Yellowstone ecosystem, there's continued threats and continued risks to losing migrations to expanding human development.

This is a very globally relevant issue that we here in Montana have a lot to offer the rest of the world," he said. "And that carries a lot of responsibility. It's not just about preserving ungulates in Montana. If we do that here and lose them in the rest of the world, we've failed."

Breast cancer has recently overtaken lung cancer to become the most common cancer globally, according to the World Health Organization. Advancing the fight against breast cancer, the BreastPathQ Challenge was launched at SPIE Medical Imaging 2019 to support the development of computer-aided diagnosis for assessing breast cancer pathology.

BreastPathQ Challenge participants were tasked with developing an automated method for analyzing microscopy images of breast tissue and ranking them according to their tumor cell content, to provide a reliable assessment score. As reported in SPIE's Journal of Medical Imaging (JMI), the challenge produced encouraging results that indicate a path toward integrating artificial intelligence (AI) to streamline clinical assessment of breast cancer.

Medical imaging for neoadjuvant treatment

Treatment for large or aggressive breast cancers has often turned to mastectomy as the most reliable therapy. However, therapy known as "neoadjuvant treatment" can result in reduced tumor size, density, and spread, making patients candidates for breast-conserving surgery rather than mastectomy.

Medical imaging allows doctors to assess the effects of neoadjuvant treatment. While the processes of analyzing medical images for cancer detection are typically performed manually and rely on expert interpretation of complex tissue structures, machine-learning algorithms for identifying cancer may increase the reliability and efficiency of those processes. In addition to reducing variability, which is inherent to human pathologists, fully automated methods like these are expected to increase the speed of image analysis.

Intensive focus, international effort

A total of 39 teams from 12 different countries worldwide engaged in the BreastPathQ Challenge. A total of 100 algorithms were developed, validated, and tested. Teams were able to compare their algorithms with those of others from academia, industry, and government, as structured by the Grand Challenge framework, which requires a shared set of source data.

Most of the teams used an ensemble of machine-learning algorithms instead of limiting themselves to a single AI architecture. Top algorithms performed at levels comparable to the pathologists who provided the reference standards for the study, and the best performing algorithm slightly surpassed the scores of the pathologists. The algorithms generally performed well on easier patches of images but struggled on the difficult patches - those for which AI would be especially beneficial to pathologists.

The BreastPathQ Challenge was successful because the organizing committee brought together experts in multiple fields. According to Nicholas Petrick, deputy director for the Division of Imaging, Diagnostics and Software Reliability in the US FDA Center for Devices and Radiological Health, and representative for the BreastPathQ Challenge Group, advance collaborative groundwork meant that participants were able to move quickly and efficiently to address the task, access the data set, and develop their algorithms.

After years of criticism for their lack of diversity, programs for high achievers may not be adequately serving their Black and low-income students, a new study shows.

"The potential benefits aren't equally distributed," said lead author and University of Florida College of Education professor Christopher Redding, Ph.D., who evaluated data from gifted programs in elementary schools nationwide. "The conversation up to this point has been about access, with less emphasis on how students perform once in gifted programs."

While academic achievement gains for students overall were modest -- going from the 78th to 80th percentile in reading and rising only a third as much in math -- low-income and Black gifted students, on average, saw no achievement gains. When the researchers looked at factors beyond scores, including engagement, attendance, and whether a student left or stayed in a school, they found little evidence to suggest gifted participation influenced those measures for any group.

"We're not saying these programs don't have benefits," Redding said. "But as states and school districts evaluate them, we need to ask, 'How can we do this best both for all gifted students and for diverse student populations?'"

A barrier to effectively serving a diverse gifted population could be the programs' content. If the curriculum only reflects the affluent, predominantly white population that gifted has traditionally served, it might not meet the needs of its other students, Redding says. As a success story, he points to the example of Illinois' second-largest school district, which diversified its curriculum -- but the impetus for that shift was a federal class-action suit.

"Unfortunately, unless there's this strong pressure from the courts, lots of districts aren't taking these steps that could be taken," Redding said.

Another culprit could be the structure of the programs. While some students receive all-day gifted instruction, others might only get an hour every other week. In "light touch" programs like those, a better option might be what education researchers call acceleration: skipping a grade or taking fifth grade math while in fourth grade, for example.

Redding doesn't want to see gifted programs go away, but he wants educators to take a hard look at how their curriculum meshes with the students they're trying to reach -- and for policymakers to have a better understanding of what the programs are actually achieving.

"It's not just about access," he said.

Clavelina oblonga, an invasive marine fouling species, not only reduces diversity in communities it invades, it also interferes in their recovery following natural disasters - a process known as "succession."

Succession refers to how an ecosystem recovers after a disturbance or natural disaster - does the system come back more or less the same as it was in terms of species composition, or is it different?

"The classic example of succession is a forest that experiences a wildfire," says Kayla Christianson, former NC State graduate student and first author of a paper describing the research. "As the community recovers from the fire, it proceeds through a predictable pattern of community development - starting with grasses and ending with trees and a mature forest. This predictable order of succession is due mainly to the seed bank beneath the soil, which allows the community to recover regardless of when the disturbance occurs."

However, marine fouling communities don't follow the same pattern as terrestrial ecosystems. Marine fouling species are invertebrate filter-feeding organisms - like barnacles or mussels - that settle on hard substrates, like docks, pilings, or ship hulls. Soft-bodied tunicates such as the invasive C. oblonga are also fouling species.

"Marine fouling environments are different because different species of larvae are present at different times of the year, so what the ecosystem looks like after a disturbance depends on when it occurs," says David Eggleston, professor of marine, earth and atmospheric sciences at North Carolina State University and corresponding author of the research. "For marine species, disturbances enhance community diversity."

Given the recent introduction and proliferation of C. oblonga along the North Carolina coast, Eggleston and Christianson wanted to see how this invasive species would affect succession in a fouling environment.

Christianson and Eggleston duplicated succession experiments performed 50 years ago in Beaufort, N.C. They submerged terra cotta settlement plates every four weeks from May 2017 to September 2018 along the docks and observed the communities that settled there.

Over the course of the study, 22 different fouling species settled on the plates. But in each case, when C. oblonga settled, they rapidly crowded out the other species. The study period also included an unseasonably cold winter, as well as landfall from Hurricane Florence in September 2018, enabling the researchers to look at succession after a natural disturbance. While both the cold and the hurricane succeeded in removing C. oblonga, it quickly regrew and crowded out other species, eliminating species diversity.

"In retesting succession theory we found that it holds in the absence of invasive species but not in their presence," Eggleston says. "For these fouling species, regardless of when a disturbance occurs, the community always reverts back to the invasive species.

"C. oblonga has only been here since 2015, but it seems to have no real natural predators, it crowds out native species and it has a foothold. We will have to monitor this species and be sure that it doesn't impact our local shellfish industry."

FRANKFURT. When the SARS-CoV-2 virus mutates, this initially only means that there is a change in its genetic blueprint. The mutation may lead, for example, to an amino acid being exchanged at a particular site in a viral protein. In order to quickly assess the effect of this change, a three-dimensional image of the viral protein is extremely helpful. This is because it shows whether the switch in amino acid has consequences for the function of the protein - or for the interaction with a potential drug or antibody.

Researchers at Goethe University Frankfurt and TU Darmstadt began networking internationally from the very start of the pandemic. Their goal: to describe the three-dimensional structures of SARS-CoV-2 molecules using nuclear magnetic resonance spectroscopy (NMR). In NMR spectroscopy, molecules are first labelled with special types of atoms (isotopes) and then exposed to a strong magnetic field. NMR can then be used to look in detail and with high throughput at how potentially active compounds bind to viral proteins. This is done at the Centre for Biomolecular Magnetic Resonance (BMRZ) at Goethe University and other locations. However, the basic prerequisite is to produce large quantities of the proteins in high purity and stability, and with their correct folding, for the large amount of tests.

The network, coordinated by Professor Harald Schwalbe from the Institute of Organic Chemistry and Chemical Biology at Goethe University, spans the globe. The elaboration of laboratory protocols for the production of proteins is already the second milestone. In addition to proteins, the virus consists of RNA, and the consortium already made all important RNA fragments of SARS-CoV-2 accessible last year. With the expertise of 129 colleagues, it has now been possible to produce and purify 23 of the total of almost 30 proteins of SARS-CoV-2 completely or as relevant fragments "in the test tube", and in large amounts.

For this purpose, the genetic information for these proteins was incorporated into small, ring-shaped pieces of DNA (plasmids). These plasmids were then introduced into bacteria for protein production. Some special proteins were also produced in cell-free systems. Whether these proteins were still correctly folded after their isolation and enrichment was confirmed, among other things, by NMR spectroscopy.

Dr Martin Hengesbach from the Institute of Organic Chemistry and Chemical Biology at Goethe University explains: "We have isolated functional units of the SARS-CoV-2 proteins in such a way that their structure, function and interactions can now be characterised by ourselves and others. In doing so, our large consortium provides working protocols that will allow laboratories around the world to work quickly and reproducibly on SARS-CoV-2 proteins and also the mutants to come. Distributing this work from the beginning was one of our most important priorities. In addition to the protocols, we are also making the plasmids freely available."

Dr Andreas Schlundt from the Institute for Molecular Biosciences at Goethe University says: "With our work, we are speeding up the global search for active agents: Scientific laboratories equipped for this work do not have to first spend several months establishing and optimising systems for the production and investigation of SARS-CoV-2 proteins, but can now start their research work within two weeks thanks to our elaborated protocols. Given the numerous mutations of SARS-CoV-2 to come, it is particularly important to have access to reliable, rapid and well-established methods for studying the virus in the laboratory. This will, for example, also facilitate research on the so-called helper proteins of SARS-CoV-2, which have remained under-investigated, but which also play a role in the occurrence of mutations."

Researchers at Linköping University, Sweden, have made several discoveries on the functioning mechanisms of the inner hair cells of the ear, which convert sounds into nerve signals that are processed in the brain. The results, presented in the scientific journal Nature Communications, challenge the current picture of the anatomical organisation and workings of the hearing organ, which has prevailed for decades. A deeper understanding of how the hair cells are stimulated by sound is important for such matters as the optimisation of hearing aids and cochlear implants for people with hearing loss.

In order to hear sounds, we must convert sound waves, which are compressions and decompressions of air, into electrical nerve signals that are transmitted to the brain. This conversion takes place in the part of the inner ear known as the cochlea, due to its shape, which is reminiscent of a snail shell. The cochlear duct houses the hearing organ, with many hair cells that are divided into outer and inner hair cells. The outer hair cells amplify sound vibrations, which enables us to hear faint sounds and perceive the various frequencies in human speech better. The inner hair cells convert the sound vibrations into nerve signals. In the current study, the researchers have investigated how the conversion takes place. It is, namely, still unclear how the inner hair cells are stimulated by sound vibrations in order to produce nerve signals.

It has long been known that the outer hair cells are connected to a membrane that rests on top of them. The outer hair cells have hair-like protrusions known as stereocilia that are bent and activated when sound causes the membrane and the hearing organ to vibrate. However, the current view is that the stereocilia of the inner hair cells are not in contact with this membrane, which is known as the tectorial membrane, and that they are stimulated by sounds by a completely different mechanism. It is this model that the new study challenges.

The relationship between the hair cells and the tectorial membrane has been studied in detail by electron microscopy since the 1950s. But it is extremely difficult to investigate how this gelatinous membrane functions, since it shrinks as soon as it is removed from the ear. This makes it extremely difficult to preserve the relationship between the inner hair cells and the tectorial membrane. In addition, this membrane is transparent, and has therefore been essentially invisible. Until now. The LiU researchers noticed that the tectorial membrane reflected green light. This discovery made it possible to visualise the tectorial membrane by microscope.

"We cannot see any gap between the tectorial membrane and the hair cells. In contrast, the stereocilia on both outer and inner hair cells are completely embedded in the tectorial membrane. Our results are incompatible with the generally accepted idea that only the outer hair cells are in contact with the tectorial membrane", says Pierre Hakizimana, principal research engineer at the Department of Biomedical and Clinical Sciences at Linköping University, and principal author of the article.

Pierre Hakizimana and his colleagues have studied the inner ear of guinea pigs, which is very similar to that of humans. When the researchers investigated the relationship between the membrane and the hair cells in more detail, they made a further discovery.

"We found calcium ducts with an appearance that we've never seen before. These calcium ducts span the tectorial membrane and connect to the stereocilia of both the inner and the outer hair cells", says Pierre Hakizimana.

The research group, led by Professor Anders Fridberger, has previously discovered that the tectorial membrane functions as a reservoir for calcium ions, which are needed for the hair cells to convert the sound-evoked vibrations into nerve signals. The researchers followed the motion of the calcium ions in the ducts, and their results suggest that the calcium ions flow through the ducts to the hair cells. This may explain how the hair cells obtain the large amounts of calcium ions needed for their function. The study has also shown that the stereocilia on the inner and outer hair cells are bent by the tectorial membrane in similar ways. The next step of the research will be to understand in more detail how the calcium ions are transported, and identify the protein or proteins that make up the newly discovered calcium ducts.

"Our results allow us to describe a mechanism for how hearing functions, that is incompatible with the model that has been accepted for more than fifty years. The classic illustrations in the textbooks showing the hearing organ and how it functions must be updated. The mathematical models used in research to study hearing should also be updated to include these new findings", says Pierre Hakizimana.

New information about how our hearing functions may in the long term be important for the development of cochlear implants. These are hearing aids that are inserted into the cochlea and which use electrical stimulation to make it possible for children and adults with hearing loss to perceive sounds.

"Cochlear implants are an amazing solution for treating hearing loss, but they can be improved. A deeper understanding of how the inner hair cells are stimulated by sounds is important to optimise how cochlear implants stimulate the auditory nerve", says Pierre Hakizimana.

Thousands of sharks have been illegally caught in a Marine Protected Area (MPA) in the Indian Ocean, new research shows.

The MPA was created in 2010 around the Chagos Archipelago, also known as the British Indian Ocean Territory (BIOT), banning all fishing there.

The new study examined information on illegal fishing in the MPA - a vast (640,000 km²/250,000 mi2) area containing pristine and remote reefs.

Enforcement data suggests more than 14,000 sharks were caught in the MPA from 2010-20, but discussions with fishers in the region suggest the true number was "considerably higher".

The study was carried out by the University of Exeter and ZSL (Zoological Society of London), Oceanswell and MRAG Ltd.

"Enforcement of MPA rules in a large, remote area such as this is extremely difficult," said lead author Claire Collins, of the University of Exeter.

"Our findings highlight the threat of illegal fishing to sharks in the BIOT MPA, which is home to critically endangered species such as the oceanic whitetip and scalloped hammerhead.

"Fishers often target reef areas, where many of the sharks are juveniles, and taking sharks at this life stage could be especially damaging to species numbers.

"However, it's important to note that - despite evidence of shark fishing - the MPA still provides a vital refuge in the Indian Ocean, and shark numbers there are still much higher than most other places.

"Many shark species in this region are under intense pressure from fishing.

"Following the recent news that the Maldives was considering lifting its shark-fishing ban, the importance of large areas within the Indian Ocean where shark fishing is banned was brought to everyone's attention.

"This study emphasises the need to ensure that sharks within these important areas are fully protected."

As part of the study, Oceanswell researchers carried out interviews and ran focus groups with fishers in two Sri Lankan communities previously associated with illegal fishing in the BIOT MPA.

Fishers told the researchers that vessels often fished in the MPA without being detected, providing "clear evidence that total extraction was considerably higher" than the estimate of 14,340 based on detected vessels, the study says.

"It is crucial to work with fishing communities to understand where, when and why people fish illegally - and how we can improve deterrence," said final author Tom B Letessier.

"For example, we found fishers had very different ideas of the fines they could face, and some felt there were very unlikely to be caught - so improving awareness of the sanctions, in addition to increasing the probability of being caught, could be beneficial."

Efforts are under way to improve enforcement in the MPA, including by increased use of satellite tracking of vessels and ensuring enforcement is responsive to the threat of illegal fishing.

This study highlights the value of interacting with fishers themselves to obtain information about the pressures they are facing and what motivates their behaviours.

Of the 188 vessels investigated by the BIOT MPA patrol boat from 2010-20, 126 were suspected of illegal fishing - and 97% of these targeted sharks.

More than three quarters of suspected vessels were from Sri Lanka, but a growing minority came from India - and these tended to be larger and could therefore take many more sharks.

"The threats to a large MPA like this one are constantly changing, so management of the MPA has to adapt too," Collins said.

The study was funded by grant ID is BPMS 2017-12 from the Bertarelli foundation, as part of the Bertarelli Programme of Marine Science.

The paper, published in the journal Frontiers in Marine Science, is entitled: "Understanding persistent non-compliance in a remote, large-scale marine protected area."

The morphological compatibility between flowers and insects was given in the famous textbook example of Darwin's orchids and hawkmoths. As in this example, many studies have shown that geographical variations in flower size match the size of insects in each region. In other words, studies have shown "flower-sized regional adaptation" in which large flowers evolve in areas pollinated by large insects and small flowers evolve in areas pollinated by small insects.

However, when examining the genetic similarity between populations, are plants in each region more similar, or are plants with large (or small) flower sizes across nearing regions more similar? This has remained unknown until this study led by doctoral candidate Tsubasa Toji of Shinshu University's Professor Takao Itino lab. The team used white nettle to show this classic flower-insect size agreement, and by combining population genetic analysis, examined the actual evolution of flower size.

The flower traits of white dead-nettle (Lamium album var. barbatum) were clearly correlated with bee size. On the other hand, the genetic structure was similar between plants of each region. In other words, the flower size was independently large and small in each mountain area or a parallel evolution of flower size developed independently between mountain areas.

This study was conducted very simply, combining two methods: field research and population genetic analysis. Field studies showed geographical variation in flower size, showing that flower size was clearly correlated with the bee size visited in the population. Genetic analysis showed that there is an overarching genetic structure or genetic divergence between mountains.

When the two results are combined, the flower size of each population is independent of the genetic structure, and the flower size differs greatly even between genetically similar populations, or groups belonging to the same mountain range. In some cases, flower sizes were similar even between populations that were genetically distant, or species belonging to different mountain areas. This suggests that flower size evolved independently in each mountain area.

The group is in the process of confirming the parallel evolution of flower traits between mountainous areas for other plant species using the same approach. They are also trying to find out about other plant species and are exploring the possibility that the parallel evolution of this flower trait between mountains is a fairly common phenomenon. Ultimately, by extending the trait comparison between mountain areas to organisms of other taxa other than plants and combining it with population genetic analysis, they hope to elucidate the actual state of evolution of various species occurring in mountain regions.

A Flinders University researcher has finally fathomed why large numbers of killer whales gather at a single main location off the Western Australian southern coastline every summer.

In a new paper published in Deep Sea Research, physical oceanographer Associate Professor Jochen Kampf describes the conditions which have produced this ecological natural wonder of orcas migrating to the continental slope near Bremer Bay in the western Great Australian Bight from late austral spring to early autumn (January-April).

"The aggregation is connected to the local marine food web that follows from the upwelling of benthic particulate organic matter (POM) in a confined region near the seafloor plateau near the head of the Hood Canyon," says Associate Professor Kampf, from the Flinders University College of Science and Engineering.

But how and why does this feeding aggregation occur?

Detailed modelling of the three submarine canyons in the region has demonstrated how the process favours the Hood Canyon over the adjoining Bremer and Whale canyons.

"We showed that the shape and position of the Hood Canyon on the continental slope enables it to funnel significantly more benthic particles onto surrounding areas, and this is supported by smaller scale undulations which cause the slope upwelling of POM."

Whale watching is a popular pursuit at the Bremer Bay Canyon hotspot, located 70km offshore from Bremer Bay in the Fitzgerald River National Park.

Naturaliste Charters whale watching tour operators in Bremer Bay says the eco-wilderness expeditions over several years have identified more than 275 regular killer whales at the location, between January and April, with this year's aggregation attracting some new animals.

"This large aggregation of killer whales at Bremer Bay come to the same confined region every year over a seafloor plateau near the head of the Hood Canyon where the total water depth is between 800m and 1000m.

The hydrodynamic modelling framework of the 'Orca Plateau' explains how the Hood Canyon produces a concentrated flow of POM at great depth that provides the diet for deep-sea crabs, squids and other filter feeders upon which killer whales feed.

"Explaining the feeding aggregation of these populations is an important step forward in explaining this natural phenomenon," he says.

The Naturaliste Charters website says: "Every year in summer, this newly discovered remote marine wilderness hot spot off the WA coast becomes the epicentre for an unbelievable intensity of life, including whaler sharks, giant squid, sperm whales, masses of sea birds and the largest aggregation of killer whales in the Southern Hemisphere".

A novel approach to immunotherapy design could pave the way for new treatments for people with an aggressive form of brain cancer called glioblastoma.

Using specifically designed receptors, researchers were able to completely clear brain cancer tumours in preclinical models, using chimeric antigen receptor (CAR) T cell therapy.

Published today in Clinical & Translational Immunology and led by Associate Professor Misty Jenkins, the research is a crucial step towards developing new immunotherapy treatments for this devastating illness.

More than 1800 Australians are diagnosed with brain cancer every year. Brain cancer is the leading cause of cancer death in children and adults under 40. Adults diagnosed with glioblastoma have a five-year survival rate of just five per cent.

At a glance

Using specifically designed receptors, researchers were able to completely clear brain tumours in preclinical models in the laboratory.

Chimeric antigen receptor (CAR) T cell therapy works by harnessing the body's own white blood cells to recognise and destroy their own cancer.

The research team will now look to progress this research to clinical trials, which would be the first of their kind in Australia for brain cancer.

CAR T cell therapy could offer solution

CAR T cell therapy is a new type of immunotherapy that uses the body's own T cells to fight infection. It is one of the greatest advancements in cancer therapy in decades and has proven to be effective against blood cancers such as B-cell acute lymphoblastic leukaemia (ALL) and adult diffuse large B-cell lymphoma (DLBCL). There are currently more than 600 CAR T cell therapy clinical trials worldwide.

Associate Professor Jenkins said results from the research were incredibly promising.

"This approach of immunotherapy harnesses the patient's white blood cells to recognise and destroy their own cancer," she said.

"Current CAR T cell approaches have relied on repurposing existing antibodies. We have created our own, high-affinity specific receptors, which enable them to bind very tightly to the cells."

"We found this approach completely cleared the tumour in preclinical models of brain cancer in the laboratory."

Associate Professor Jenkins said the research team was now looking to progress the 'proof of concept' research through to clinical trials.

"If we can progress this to clinical trials, it would be Australia's first CAR T clinical trial for brain cancer," she said.

"CAR T cell immunotherapy is still very new, but it has enormous potential, and we are excited about its future applications," she said.

"This won't necessarily be the silver bullet for brain cancer, but I envision this treatment could potentially be used in combination with other therapies in the future, offering hope to people diagnosed with this insidious disease."

Fast-tracking therapeutic development

The research was supported by grants from Carrie's Beanies 4 Brain Cancer Foundation and the Robert Connor Dawes Foundation. With this support, Associate Professor Jenkins spearheaded a new immunotherapy brain cancer program at WEHI, enabling WEHI to make further advances and breakthroughs for brain cancers in both adults and children. Her research uses a new type of CAR T cell receptor that has superior properties to other versions of the therapy.

"We now have the techniques, tools and platforms established to advance immunotherapies and other brain-cancer-tailored approaches, allowing us to very rapidly test and translate these into the clinic," she said.

"These therapies could provide hope for many patients, for whom current standard therapies have dismal outcomes."

In conjunction with this research, the team is also working on developing further enhanced CAR T candidates, which will be the first of their kind, paving the way for novel therapies for patients with solid tumours.

This work, undertaken in collaboration with Myrio Therapeutics, was made possible with funding from Carrie's Beanies 4 Brain Cancer, the Isabella and Marcus Foundation, the Robert Connor Dawes Foundation, the National Health and Medical Research Council and the Victorian Government.

Lugano, Switzerland, 8 May 2021 - The finding that breast tumours can evolve to express low HER2 potentially widens the number of patients who can benefit from new investigational agents, typically novel antibody-drug conjugate therapies, that are currently in clinical trials for HER2-low tumours.

The first study of its kind exploring how breast cancers change from the primary to the recurrent tumour has revealed that nearly 30% of breast cancer patients convert from, or to, human epidermal growth factor receptor (HER)2-low status. Specifically, the study found that 14% of triple-negative breast cancers with HER2-negative expression (also referred to as HER2-0) in the primary tumour converted to HER2-low expression in the recurrent tumour possibly offering an option to such hard-to-treat tumours.

Traditionally, breast cancers are categorised as: hormone receptor positive (HR+)/HER 2-negative, (also known as luminal-like), HER2-positive, or triple negative (negative for oestrogen receptors, progesterone receptors, and excess HER2 protein). HER2-low refers to HER2-negative tumours with low HER2 biomarker expression. About half of breast cancers classified as HER2-negative show low HER2 expression.

Presenting the findings at this year's ESMO Breast Cancer Virtual Congress is Dr Federica Miglietta, School of Oncology, University of Padua, Italy. (1) "The results provide a whole new insight on how HER2-low tumours might evolve as a subgroup, possibly challenging the current dichotomy between HER2-positive and HER2-negative breast cancer," she said. "Our findings stress the importance of re-testing HER2 expression on tumour relapse since it might provide the option of new therapeutic opportunities, currently in a trial, and hopefully in the near future, in the clinic." Several clinical trials are ongoing in HER2-low breast cancer.

In total, 29% of recurrent breast cancer biopsies showed conversion either from, or to, HER2-low expression. In primary tumours and relapse tumours, HER2-low expression was seen in 34% and 38% of tumours, respectively. A total of 15% HER2-negative tumours switched to HER2-low tumours, and 14% HER2-low switched to HER2-negative.

The study also confirmed that HER2-low expression was more frequent in HR+/HER2-negative tumours compared to triple negative tumours (47% vs 36% on primary tumour samples, 54% vs 36% on relapse samples). Plus, the switch from HER2-negative to HER2-low in primary to recurrent tumours was 21% vs 14% in luminal-like and triple negative, respectively.

Commenting on the findings, Professor Aleix Prat, Head Medical Oncology, at the Hospital Clinic of Barcelona, Spain said: "These changes on HER2-low levels are substantial. There could be a biological rationale for this, or a technical one, given that there is currently no standardisation of how to determine levels of the HER2 biomarker in metastatic biopsies, which could be biopsied from skin, liver or bone and give different results."

"We need to work out how the HER2 status determines response to therapies - is it the HER2 status in the primary tumour, or in the metastatic biopsy that is important? Maybe some patients have HER2-low expression in metastatic tumours and now respond when they didn't previously, and this might change again over time and further relapses."

"This all speaks to a much greater need to biopsy metastatic tumours. Importantly, we need to determine who will benefit from treatments for HER2-low, because patients will be asking about this in the clinic soon if trial results are positive," said Prat.