Innovative Cancer Treatment Found To Be A Promising Approach To the Control of Fungal Infections (Medicine)

An innovative cell-based treatment for cancer has been found promising for the control of infections caused by fungi. A study published in the journal Cytotherapy reports that the use of CAR (chimeric antigen receptor) T-cells programmed to “recognize” Cryptococcus spp. fungi was effective in combating infection in vitro and in mice.

C. gattii and C. neoformans are present in soil with dead organic matter and places contaminated by the droppings of pigeons and other birds. They cause systemic mycoses in the human organism. They can infect the lungs and central nervous system, causing meningitis or meningoencephalitis. The symptoms vary according to the site of the infection, which can be fatal. Transmission occurs by inhalation of the fungi. 

About 1 million cases of Cryptococcus infection are reported worldwide every year, according to the US Centers for Disease Control and Prevention (CDC). The mortality rate ranges from 20% to 70%, and 220,000 cases of cryptococcal meningitis occur annually, affecting mainly people living with HIV-AIDS.

To escape the host’s immune response, Cryptococcus covers itself in a capsule made up primarily of glucuronoxylomannan (GXM), a polysaccharide considered its main virulence factor. It is difficult for the human immune system, especially T CD4+ and T CD8+ cells, to recognize and prevent the infection.

In the study, the group redirected T CD8+ cells to target the GXM in the capsule via expression of a GXM-specific CAR, in order to have the cells recognize the pathogen directly and contain its growth.

“The findings show that GXMR-CAR T-cells can be redirected to recognize C. neoformans. Future studies will focus on determining the therapeutic efficacy of such cells in an animal model of cryptococcosis,” the authors conclude in the article.

The first author is Thiago Aparecido da Silva, a Brazilian researcher affiliated with the University of São Paulo’s Ribeirão Preto Medical School (FMRP-USP). In an interview given to Agência FAPESP, Silva explained that the infusion of GXMR-CAR T-cells not only contained the fungus’s growth but also reduced the number of so-called titan cells that make the infection more virulent. These are abnormally large yeast cells with a diameter of more than 45 micrometers. 

Silva is a researcher in FMRP-USP’s Department of Cellular and Molecular Biology and Pathogenic Bioagents (Biocel) and is supported by FAPESP via a postdoctoral fellowship and a research internship abroad

“This reduction in titan cells points to a good prognosis for new treatments for cryptococcosis,” Silva said. “CAR T-cells can be used to treat other fungal infections and can be associated with conventional drugs to reduce their side-effects. CAR T-cells can establish immune memory and protect the patient against reinfection by invasive fungi.” 

Silva is now working on ways to optimize the protective response of CAR T-cells to fungal disease, including infections caused by Candida albicans and Histoplasma capsulatum, with support from FAPESP via a Young Investigator Grant.

Direct death of fungi

Researchers at MD Anderson Cancer Center in Texas (USA) who collaborate with Silva were the first to explore the direct death of fungi from redirected T CD8+ cells with a CAR targeting a carbohydrate found in the cell wall of Aspergillus fumigatus.

Interest in the use of CAR T-cells to treat cancer and other diseases has increased in several countries. In most studies involving the technique, the researchers targeted the antigen CD19 to contain multiplication of abnormal B-cells causing lymphoma or other kinds of severe disease (read more at: agencia.fapesp.br/31675). 

CAR T-cell therapy in various forms has been approved since 2017 by the US Food and Drug Administration (FDA), especially to treat leukemia and lymphoma.

In Brazil, a group of researchers at the Center for Cell-Based Therapy (CTC), hosted by FMRP-USP, tested this innovative cancer treatment with reprogrammed cells from the patient for the first time in 2019. CTC is a Research, Innovation and Dissemination Center (RIDC) supported by FAPESP.

The technique was used to treat an advanced case of diffuse large B-cell lymphoma (DLBCL), a type of non-Hodgkin lymphoma (read more at: agencia.fapesp.br/31675). In February 2020, CDC launched a book with practical information on the production of CAR T-cells. 

Target recognition

Silva and the other authors of the latest study raise the hypothesis that redirecting GXMR-CAR T-cells induces cytotoxic activity against fungi that express GXM in the cell wall. The study shows that modified human T-cells expressing GXMR-CAR were capable of binding to GXM in vitro and interacting with the yeast form of C. neoformans.

“The most critical part of the construction of a CAR is the target recognition portion, in which we use monoclonal antibodies that interact with Cryptococcus,” Silva said. “We use the DNA sequence that encodes the part of the antibody that recognizes the fungus and combine it with the DNA sequence that encodes the other portions of the CAR.”

The article “Glucuronoxylomannan in the Cryptococcus species capsule as a target for chimeric antigen receptor T-cell therapy” can be retrieved from: www.isct-cytotherapy.org/article/S1465-3249(20)30933-6/fulltext

Featured image: The use of CAR T-cells reprogrammed to “recognize” Cryptococcus spp. proved effective to combat the infection in vitro and in mice (pulmonary cryptococcosis; image: Wikimedia Commons)


Provided by FAPESP

Scientists Find New Cell Type Implicated in Chronic Pain, Inflammation (Medicine)

The discovery, from the UNC School of Medicine lab of Mark Zylka, PhD, offers pain researchers a new, precise target to treat inflammation associated with neuropathic pain.

One of the hallmarks of chronic pain is inflammation, and scientists at the UNC School of Medicine have discovered that anti-inflammatory cells called MRC1+ macrophages are dysfunctional in an animal model of neuropathic pain. Returning these cells to their normal state could offer a route to treating debilitating pain caused by nerve damage or a malfunctioning nervous system.

The researchers, who published their work in Neuron, found that stimulating the expression of an anti-inflammatory protein called CD163 reduced signs of neuroinflammation in the spinal cord of mice with neuropathic pain.

“Macrophages are a type of immune cell that are found in the blood and in tissues throughout the body. We found a class of anti-inflammatory macrophages that normally help the body to resolve pain. But neuropathic pain appears to disable these macrophages and prevent them from doing their job,” said senior author Mark Zylka, PhD, director of the UNC Neuroscience Center and Kenan Distinguished Professor of Cell Biology and Physiology. “Fortunately they don’t appear to be permanently disabled, as we were able to coax them to ramp up their anti-inflammatory actions and reduce neuropathic pain. We suspect it will be possible to develop new treatments for pain by boosting the activities of these macrophages.”

Mark Zylka, PhD

Roughly one-fifth of the U.S. population has chronic pain, according to the Centers for Disease Control and Prevention. Often the underlying causes are elusive, and patients need pain alleviated so they can function in life. While opioids are great at treating pain in the short term, these drugs can have severe side effects when used for extended periods, such as addiction, respiratory depression, dizziness, nausea, and death due to overdose.

One reason why strong pain relievers work well but can have dramatic side effects has to do with a basic biological fact: pain involves a highly diverse set of cells and current treatments lack cell type specificity. So, any given medication may resolve adverse changes in some cells to alleviate pain, but the medication might exacerbate a particular function in other cells, leading to adverse side effects.

With an emerging technology called single-cell RNA-sequencing, scientists can now interrogate thousands of cells at once to see which cells are altered during chronic pain, and in which ways the cells change.

Jesse Niehaus

“Knowing which cells to target allows us to design very specific therapies. Targeted therapies in theory should have fewer adverse side-effects,” said Jesse Niehaus, graduate student in the Zylka lab and first author of the Neuron paper.

To figure out which cells were changing and in what ways, Zylka’s lab performed single-cell RNA-sequencing on the spinal cords of mice with neuropathic pain, a type of chronic pain caused by nerve damage. The spinal cord undergoes many long-term changes that contribute to neuropathic pain.

From those experiments, the researchers found a population of anti-inflammatory cells called MRC1+ macrophages that were dysfunctional.

“This was incredibly interesting because long-term inflammation in the spinal cord is commonly seen in animals with neuropathic pain,” Niehaus said.

With the identity of the cells revealed, Zylka’s lab delivered a gene therapy designed to stimulate the expression of an anti-inflammatory protein called CD163 in MRC1+ macrophages. With this approach, a single treatment reduced spinal cord inflammation and relieved pain-related behavior for up to a month.

“This discovery is quite exciting,” Zylka said, “As it immediately suggests multiple distinct ways to boost the function of these macrophages. Any one of these therapeutic approaches could provide a more precise way to treat neuropathic pain.”

Other authors of the Neuron paper are Jeremy Simon, PhD, research assistant professor; Bonnie Taylor-Blake, research specialist, and Lipin Loo, PhD, a former postdoc in the Zylka Lab who is now a research fellow at the University of Sidney.

The National Institute of Neurological Disorders and Stroke funded this research. Sequencing was performed at the UNC High Throughput Sequencing Core. Microscopy was performed at the UNC Neuroscience Center Microscopy Core.

Featured image: Spinal cord illustration of pro-inflammatory cells (red) and anti-inflammatory MRC1+ macrophages (blue).


Reference: Jesse K. Niehaus, Bonnie Taylor-Blake et al., “Spinal macrophages resolve nociceptive hypersensitivity after peripheral injury”, Neuron, 2021. DOI: https://doi.org/10.1016/j.neuron.2021.02.018


Provided by UNC School of Medicine

Volcanoes Might Light Up the Night Sky of This Planet (Planetary Science)

Until now, researchers have found no evidence of global tectonic activity on planets outside our solar system. Under the leadership of the University of Bern and the National Center of Competence in Research NCCR PlanetS, scientists have now found that the material inside planet LHS 3844b flows from one hemisphere to the other and could be responsible for numerous volcanic eruptions on one side of the planet.

On Earth, plate tectonics is not only responsible for the rise of mountains and earthquakes. It is also an essential part of the cycle that brings material from the planet’s interior to the surface and the atmosphere, and then transports it back beneath the Earth’s crust. Tectonics thus has a vital influence on the conditions that ultimately make Earth habitable.

Dr. Dan J. Bower, Center for Space and Habitability (CSH) and NCCR PlanetS, University of Bern© Universität Bern / University of Bern, Photo: D. Bower

Until now, researchers have found no evidence of global tectonic activity on planets outside our solar system. A team of researchers led by Tobias Meier from the Center for Space and Habitability (CSH) at the University of Bern and with the participation of ETH Zurich, the University of Oxford and the National Center of Competence in Research NCCR PlanetS has now found evidence of the flow patterns inside a planet, located 45 light-years from Earth: LHS 3844b. Their results were published in The Astrophysical Journal Letters.

An extreme contrast and no atmosphere

“Observing signs of tectonic activity is very difficult, because they are usually hidden beneath an atmosphere”, Meier explains. However, recent results suggested that LHS 3844b probably does not have an atmosphere. Slightly larger than Earth and likely similarly rocky, it orbits around its star so closely that one side of the planet is in constant daylight and the other in permanent night – just like the same side of the Moon always faces the Earth. With no atmosphere shielding it from the intense radiation, the surface gets blisteringly hot: it can reach up to 800°C on the dayside. The night side, on the other hand, is freezing. Temperatures there might fall below minus 250°C. “We thought that this severe temperature contrast might affect material flow in the planet’s interior”, Meier recalls.

Tobias G. Meier, Center for Space and Habitability (CSH) and NCCR PlanetS, University of Bern© Universität Bern / University of Bern, Photo: Felix Meier

To test their theory, the team ran computer simulations with different strengths of material and internal heating sources, such as heat from the planet’s core and the decay of radioactive elements. The simulations included the large temperature contrast on the surface imposed by the host star.

Flow inside the planet from one hemisphere to the other

“Most simulations showed that there was only upwards flow on one side of the planet and downwards flow on the other. Material therefore flowed from one hemisphere to the other”, Meier reports. Surprisingly, the direction was not always the same. “Based on what we are used to from Earth, you would expect the material on the hot dayside to be lighter and therefore flow upwards and vice versa”, co-author Dan Bower at the University of Bern and the NCCR PlanetS explains. Yet, some of the teams’ simulations also showed the opposite flow direction. “This initially counter-intuitive result is due to the change in viscosity with temperature: cold material is stiffer and therefore doesn’t want to bend, break or subduct into the interior. Warm material, however, is less viscous – so even solid rock becomes more mobile when heated – and can readily flow towards the planet’s interior”, Bower elaborates. Either way, these results show how a planetary surface and interior can exchange material under conditions very different from those on Earth.

A volcanic hemisphere

Such material flow could have bizarre consequences. “On whichever side of the planet the material flows upwards, one would expect a large amount of volcanism on that particular side”, Bower points out.  He continues “similar deep upwelling flows on Earth drive volcanic activity at Hawaii and Iceland”.  One could therefore imagine a hemisphere with countless volcanoes – a volcanic hemisphere so to speak – and one with almost none.

“Our simulations show how such patterns could manifest, but it would require more detailed observations to verify. For example, with a higher-resolution map of surface temperature that could point to enhanced outgassing from volcanism, or detection of volcanic gases.  This is something we hope future research will help us to understand”, Meier concludes.

Featured image: This artist’s illustration represents the possible interior dynamics of the super-Earth exoplanet LHS 3844b. The planet’s interior properties and the strong stellar irradiation might lead to a hemispheric tectonic regime.© Universität Bern / University of Bern, Illustration: Thibaut Roger


Publication details:

T. G. Meier et al.: Hemispheric Tectonics on LHS 3844b, The Astrophysical Journal Letters, 2021. DOI: https://doi.org/10.3847/2041-8213/abe400


Provided by University of Bern

This Frog Has Lungs That Act Like Noise-canceling Headphones (Biology)

To succeed in mating, many male frogs sit in one place and call to their potential mates. But this raises an important question familiar to anyone trying to listen to someone talking at a busy cocktail party: how does a female hear and then find a choice male of her own species among all the irrelevant background noise, including the sound of other frog species? Now, researchers reporting March 4 in the journal Current Biology have found that they do it thanks to a set of lungs that, when inflated, reduce their eardrum’s sensitivity to environmental noise in a specific frequency range, making it easier to zero in on the calls of their mates.

“In essence, the lungs cancel the eardrum’s response to noise, particularly some of the noise encountered in a cacophonous breeding ‘chorus,’ where the males of multiple other species also call simultaneously,” says lead author Norman Lee of St. Olaf College in Minnesota.

The researchers explain that what their lungs are doing is called “spectral contrast enhancement.” That’s because it makes the frequencies in the spectrum of a male’s call stand out relative to noise at adjacent frequencies.

“This is analogous to signal-processing algorithms for spectral contrast enhancement implemented in some hearing aids and cochlear implants,” says senior author Mark Bee of the University of Minnesota-Twin Cities. “In humans, these algorithms are designed to amplify or ‘boost’ the frequencies present in speech sounds, attenuate or ‘filter out’ frequencies present between those in speech sounds, or both. In frogs, the lungs appear to attenuate frequencies occurring between those present in male mating calls. We believe the physical mechanism by which this occurs is similar in principle to how noise-canceling headphones work.”

It’s long been known to scientists that vocal signals are key to reproduction in most frogs. In fact, frogs possess a unique sound pathway that can transmit sounds from their air-filled lungs to their air-filled middle ears through the glottis, mouth cavity, and Eustachian tubes. But the precise function of this lung-to-ear sound transmission pathway had been a puzzle. Earlier studies suggested that the frog’s lungs might play a role in increasing the degree to which eardrum vibrations were direction dependent, thereby improving the ability of listeners to locate a sexually advertising male. But Bee’s team has found that wasn’t the case.

Further analysis of the data suggested a different explanation: while the state of the lungs’ inflation had no effect on directional hearing, there was a substantial impact on the sensitivity of the eardrum. With inflated lungs, the eardrum vibrated less in response to sounds in a specific frequency range. It led them to a new idea: that the lungs were dampening vibrations, thereby canceling out noise.

This image shows a pair of Green treefrogs mating © Norman Lee

Indeed, their studies using laser vibrometry showed that the resonance of inflated lungs selectively reduces the eardrum’s sensitivity to frequencies between the two spectral peaks present in the mating calls of frogs of the same species. It confirmed that a female can hear males of her own species no matter the state of her lungs’ inflation. So, the lungs had no impact on the “signals” of interest to a female. But what about the “noise”?

They already knew that a major source of noise for any given species of frog is the calls of other frog species breeding at the same time and calling in the same choruses. But they had no idea how many or which other species might “co-call” in a mixed species chorus with green treefrogs across its geographic range, much less how the frequency spectrum of their calls looked. To find out, they turned to publicly available data from a citizen science project called the North American Amphibian Monitoring Program. Their analysis of those data suggests that the green treefrog’s inflated lungs would make it harder to hear the calls of other species while leaving their ability to hear the calls of their own species intact.

“Needless to say, we think this result–a frog’s lungs canceling the eardrum’s response to noise created by other species of frogs–is pretty cool!” Bee says.

Finally, they created a physiological model of sound processing by the green treefrog’s inner ear to examine how the lung’s impact on the eardrum might be converted into more robust neural responses to the calls of their own species. They think it works like this: the inner ear is, in some ways, “tuned” to respond best to the frequencies in the species’ own calls. But that tuning is not perfect. The authors suggest that a primary function of the lungs in hearing is to sharpen or improve this tuning, allowing the inner ear to generate relatively stronger neural responses to the species’ own calls by reducing the neural responses driven by the calls of other species.

The findings demonstrate the power of evolution to co-opt pre-existing adaptations for new functions, the researchers say. In future work, they want to find out more about the physical interaction between the three sources of sound (external, internal via the opposite ear, and internal via the lungs) that determine the eardrum’s vibration response. They also want to know more about how widespread noise cancellation is in frogs.

This work was supported by the U.S. National Science Foundation.

Featured image: This image shows a male Green treefrog calling © Norman Lee


Reference: Lee et al.: “Lung Mediated Auditory Contrast Enhancement Improves the Signal-to-Noise Ratio for Communication in Frogs”, Current Biology, 2021.
https://www.cell.com/current-biology/fulltext/S0960-9822(21)00113-5


Provided by Cell Press

Reconstructing Historical Typhoons From a 142-year Record (Earth Science)

A team of scientists has, for the first time, identified landfalls of tropical cyclones (TCs) in Japan for the period from 1877 to 2019; this knowledge will help prepare for future TC disasters.

In recent years strong TCs have been making landfalls in Japan, such as Typhoon Jebi in 2018, which severely hit the Kinki region, and Typhoon Hagibis in 2019, which severely hit eastern Japan. While Japan has suffered from a number of TC impacts throughout its history, meteorological data for these events has been sparse.

The team, including Specially Appointed Associate Professor Hisayuki Kubota of the Faculty of Science, Hokkaido University, investigated TC activity over the western North Pacific and TC landfalls in Japan by analyzing a combination of TC tracking and meteorological data observed at weather stations and lighthouses, including rescued and recovered historical observations.

The team has collected and recovered TC track and landfall data and meteorological observations in the mid-19th century and later through an approach that rescues, collects and digitizes weather data across the world that has been stored away and often forgotten. To give the data useful consistency, the team developed a new, unified definition for TCs, based on minimum pressure.

Photo of a weather map when a typhoon hit Japan on 30 August 1896. Now archived in the Taiwan Central Weather Bureau (Photo: Hisayuki Kubota).

According to their analysis, TC landfall locations tend to shift to the northeast and then southwest regions of Japan at roughly 100-year intervals. The analysis also shows that annual TC landfall numbers and their intensities have been increasing in recent years, while noting that these increases may be part of an oscillated fluctuation operating on interdecadal time scales.

The landfall numbers were relatively small in the late 20th century, and larger at other times. The Tohoku and Hokkaido regions, which experienced small numbers of TC landfalls in the late 20th century, may experience more landfalls in the future.

Annual TC landfall numbers in Japan from 1877 to 2019 (bars). The thick blue line is 11-year running means and the thin blue line indicates an average of 3.09 TC landfalls a year. (Hisayuki Kubota, et al. Climatic Change. February 5, 2021).

Japan’s first official meteorological observation was conducted in Hakodate, Hokkaido, in 1872. There is very little earlier meteorological data obtained by meteorological instruments at terrestrial stations, which makes it difficult to perform long-term meteorological variability analyses. In a new approach, the team focused on foreign ship log weather records from the mid-19th century made with meteorological instruments on vessels sailing through East- and Southeast Asian waters.

The team used records from the US Navy expedition fleet to Japan led by Commodore Matthew C. Perry and from British Navy ships that also sailed to Japan to accurately identify the track of a TC moving over the ocean around the Okinawa Islands from 21 to 25 July 1853, and the track of a TC moving north over the East China Sea from 15 to 16 August 1863.

Estimated TC track during 15-16 August 1863 (red dashed arrow), based on weather records from the logs British Navy ships that participated in the Bombardment of Kagoshima (Hisayuki Kubota, et al. Climatic Change. February 5, 2021).

The results of the study show for the first time the usefulness of such marine data in identifying weather patterns after the mid-19th century in Asia, where there is much less meteorological data for that time period compared with Western countries. “It is projected that stronger TCs will hit Japan in the future due to global warming. The long-term data from our research is indispensable for knowing the variabilities of TC activities in the past and to prepare for future TCs,” says Hisayuki Kubota.

Original Article:

Hisayuki Kubota, et al. Tropical cyclones over the western north Pacific since the mid-19th centuryClimatic Change. February 5, 2021 DOI: 10.1007/s10584-021-02984-7

Funding:

This research was supported by Grants-in-Aid for Scientific Research (25282085, 15KK0030, 18H05307, 20240075, 23240122, 26220202, 19H00562, 16H03116, 18H01278) and by the Young Scientific Research (21684028) of the MEXT; the UK

Newton Fund, which is managed by the UK Department for Business, Energy and Industrial Strategy (BEIS), under its CSSP China and WCSSP South Africa projects; and the EU Copernicus C3S Data Rescue Service.

Featured image: Hurricane Isabel, a tropical cyclone that occured 2003, as seen from the International Space Station (Ed Lu, ISS/NASA).


Provided by Hokkaido University

Researchers Discover How To Control Zinc in Plants: Could Help the World’s Malnourished (Agriculture)

Over 2 billion people worldwide are malnourished due to zinc deficiency. Led by the University of Copenhagen, an international team of researchers has discovered how plants sense zinc and use this knowledge to enhance plant zinc uptake, leading to an increase in seed zinc content by 50 percent. The new knowledge might one day be applied towards the cultivation of more nutritious crops.

A deficiency of zinc and other essential dietary nutrients is one of the greatest causes of malnutrition worldwide. More than two billion people are estimated to suffer from zinc deficiency, a problem that can lead to impaired immune systems, mental disorders and stunting. Among other things, malnutrition can be caused by infertile agricultural land, which affects the nutritional content of staple crops such as rice, wheat and maize.

But imagine that it was possible to flip a switch in crops, at the seed stage, that prompted them to turbocharge their intake of zinc, iron or other nutrients, and cause them to absorb more nutrients than they would otherwise. Researchers at the University of Copenhagen’s Department of Plant and Environmental Sciences have done just that using the thale cress plant (Arabidopsis thaliana).

“For the first time ever, we have demonstrated that, by using a molecular ‘switch’ in the plant, we can cause the plant to absorb more zinc than it would otherwise, without apparent negative impact on the plant,” states the study’s lead author, Associate Professor Ana Assunção of the University of Copenhagen’s Department of Plant and Environmental Sciences.

Plants absorbed 50 percent more zinc

Zinc benefits humans by helping to maintain a wide array of chemical processes and proteins running within our bodies. Should these processes cease to function properly, we become prone to illness. For plants, the absence of zinc primarily impacts growth, which is adversely affected in the absence of zinc.

Researchers have long attempted to understand how plants increase and decrease their zinc uptake. Ana Assunção and her colleagues have become the first to identify two specific proteins from thale cress that act as zinc sensors and determine the plant’s ability to absorb and transport zinc throughout plant tissue.

By changing the properties of these sensors, or molecular “switch”, that control a tightly connected network of zinc transporters, the researchers succeeded in getting them to absorb more zinc.

“Simply put, by making a small change in the sensor, we’ve led the plant to believe that it was in a permanent state of zinc deficiency. This kept the plant’s zinc uptake machinery swiched-on and resulted in an increase of zinc content in the seeds by as much as 50 percent compared to a normal plant,” explains Grmay Lilay, the study’s first author, Postdoc at Assunção’s Lab .

Up next: rice and beans

The researchers have demonstrated that it is possible to increase zinc-absorption in their experimental plant, but the next step is to reproduce the results in real crops. And the researchers are already well on the way to doing so.

“We’re currently working to recreate our results in bean, rice and also tomato plants. Should we succeed, we’ll realize some interesting opportunities to develop more nutritious and biofortified crops. Biofortification is a sustainable solution to improve micronutrient content in human diet,” says Associate Professor Assuncao.

In the long term, the researchers’ results could be applied by using CRISPR gene editing or by selecting naturally occurring crop varieties with a particularly good ability to absorb nutrients like zinc. “The availability of enormous genomic resources will assist our efforts in finding crop varieties that are likely to display higher zinc accumulation, ” concludes Grmay Lilay.

The result was achieved in collaboration with Wageningen University and the University of Porto and has just been published in the renowned journal Nature Plants.

Fact box:

* Zinc is a key structural and catalytic component of a large number of proteins. For all proteins to function properly, an optimal zinc supply needs to be maintained, avoiding deficiency or toxicity.

* In humans, the risk of zinc deficiency alone can lead to different degrees of growth retardation, immune dysfunction, and cognitive impairment.


Reference: Lilay, G.H., Persson, D.P., Castro, P.H. et al. Arabidopsis bZIP19 and bZIP23 act as zinc sensors to control plant zinc status. Nat. Plants 7, 137–143 (2021). https://www.nature.com/articles/s41477-021-00856-7 https://doi.org/10.1038/s41477-021-00856-7


Provided by University of Copenhagen

Fluorescent Nanodiamonds Successfully Injected Into Living Cells (Physics)

As odd as it sounds, many scientists have attempted to place extremely small diamonds inside living cells. Why? Because nanodiamonds are consistently bright and can give us unique knowledge about the inner life of cells over a long time. Now physics researchers at Lund University in Sweden have succeeded in injecting a large number of nanodiamonds directly to the cell interior.

Diamonds are not only sought after for their beauty, but also for their uniquely luminescent properties, at least among scientists. Unlike other fluorescent materials, they do not bleach.

”We actually think of them as a dye. In addition, they are biocompatible”, says Elke Hebisch, researcher at solid state physics at Lund University.

Together with Professor Christelle Prinz, she has “injected” fluorescent nano-sized diamonds into living cells.

As a researcher, having such a reporter from inside a cell has many advantages: gaining new knowledge about the cell, as well as monitoring what happens inside the cell over time.

”Especially the latter would be a great step forward, as it is currently possible to take snapshots of, for example, proteins in a cell, but difficult to follow changes over time”, explains Elke Hebisch.

What would researchers want to know? It could be about separating healthy cells from diseased ones, targeting disease-causing proteins and other proteins within a specific cell, or monitoring variations in temperature and pH-levels. The knowledge gained could be pure basic research but can also be used to understand diseases and develop drugs.

Other researchers have previously tried to do the same thing, but the diamonds were then taken care of by the cell’s “cleaners”, the so-called lysosomes, that quickly encapsulated the foreign substance.

”In that scenario,they are not useful since they are trapped in lysosomes and unable to interact with the cell components. Others have managed to get the diamonds into the cell one cell at a time, but that is far too time-consuming to become a realistic alternative”, says Christelle Prinz.

The same technique could eventually be used to transport other molecules in order to alter cells or heal diseased cells.

On a final note: is using nanodiamonds expensive? No, Elke Hebisch explains – the quantities needed are extremely small. They are bought in a bottle where they are suspended around in water, and cost the same as regular antibodies.

How it works:

The researchers built nanostraws onto a substrate. They then added cells on the nanostraws , and when mild electrical pulses were applied across the subtrate, the ”pores” of the cell membrane dilated and the nanodiamonds went through the nanostraws  into the cells. The method was inspired by a similar method developed at Standford University for a different purpose.

Publication:

Link to publication in research journal Small:

Nanostraw‐Assisted Cellular Injection of Fluorescent Nanodiamonds via Direct Membrane Opening


Provided by Lund University

Doubling Creation Of Antimatter Using Same Laser Energy (Physics)

Lawrence Livermore National Laboratory (LLNL) scientists have achieved a near 100 percent increase in the amount of antimatter created in the laboratory.

Using targets with micro-structures on the laser interface, the team shot a high-intensity laser through them and saw a 100 percent increase in the amount of antimatter (also known as positrons). The research appears in Applied Physics Letters.

Previous research using a tiny gold sample created about 100 billion particles of antimatter. The new experiments double that.

“These successful experimental results are important for the Livermore positron project, whose grand goal is to make enough electron-positron antimatter to study the physics of gamma-ray bursts,” said Hui Chen, the project lead and a co-author of the paper. “But we found that the experiments also created a high energy (MeV) X-ray backlighter that can penetrate very dense objects, which is important for many aspects of high energy density science.”

When enough energy is squeezed into a very small space, such as during high-energy particle collisions, particle-antiparticle pairs are produced spontaneously. When energy transforms into mass, both matter and antimatter are created in equal amounts. In these experiments, intense laser-plasma interactions produce very high energy electrons whose energy, when interacting with the gold target, can generate electron-positron pairs. 

The researchers used previous results and new simulations to design micro-structures, which could either enhance or diminish this interaction, leading to enhanced or suppressed positron generation relative the previous state of the art. Co-author Anthony Link said that “the agreement between the simulations and the experiment is remarkable, giving us confidence that we’re capturing the most important physical mechanisms.”

The ability to create numerous positrons in a small laboratory opens the door to new avenues of anti-matter research, including an understanding of the physics underlying various astrophysical phenomena such as black holes and gamma-ray bursts as well as a pathway toward a dense electron-positron plasma in the laboratory.

“Adding front surface micro-structures to the typical gold target constitutes a cost-effective approach to substantially increase the positron yield while keeping the same laser conditions. It is one step further toward using laser-generated positron sources for the variety of applications,” said Jiang Sheng, the lead author of the paper.

Other Livermore scientists include Shaun Kerr, Russell Wallace and Jackson Williams as well as researchers from the Laboratory for Laser Energetics at Rochester, General Atomics, California Institute of Technology and the University of California, San Diego. The research was funded by LLNL’s Laboratory Directed Research and Development program.

Featured image: Laser light enters the micro-structure in front of the gold target, driving high energy gamma photons (orange) and particles, including the electron-positron antimatter pairs (blue and green). The experimental data shows that the micro-structure doubled the energy conversion from lasers to antimatter (relative to a target with no structure).


Reference: S. Jiang, A. Link et al., “Enhancing positron production using front surface target structures”, Appl. Phys. Lett. 118, 094101 (2021); https://doi.org/10.1063/5.0038222


Provided by LLNL

Does a Vegan Diet Lead To Poorer Bone Health? (Food)

The vegan diet is on trend. How this type of diet affects health is the subject of scientific studies. In a new study from the German Federal Institute for Risk Assessment (BfR), the bone health of 36 vegans as well as 36 people following a mixed-food diet was determined with an ultrasound measurement of the heel bone. The result: on average, people following a vegan diet had lower ultrasound values compared to the other group. This indicates poorer bone health. In the study, the scientists also determined biomarkers in blood and urine. This aims to identify nutrients that might be related to diet and bone health. Out of 28 parameters of nutritional status and bone metabolism, it was possible to identify twelve biomarkers most strongly associated with bone health – for example, the amino acid lysine and vitamins A and B6. The results show that in most cases, the combination of these biomarkers was present in lower concentrations in vegans. This could be a possible explanation for the poorer bone health. “A vegan diet is often considered health-conscious. However, our scientific findings indicate that a vegan diet does affect bone health,” says BfR President Professor Dr. Dr. Andreas Hensel.

Nutrition plays an important role in bone health. This was more closely investigated in the BfR’s cross-sectional “Risks and benefits of a vegan diet” study. 72 men and women participated in the study. The bone health of all participants was assessed at the heel bone using ultrasound measurements. Information on age, smoking status, education, body mass index, physical activity and alcohol consumption was also collected. By using a statistical model, the BfR was able to identify a pattern of twelve biomarkers that play an important role in bone health from 28 nutrition- and bone-relevant parameters from blood or urine. It was shown that in combination vitamins A and B6, the amino acids lysine and leucine, omega-3 fatty acids, selenoprotein P, iodine, thyroid-stimulating hormone, calcium, magnesium and α-Klotho protein were positively associated with bone health. Conversely, lower concentrations of the hormone FGF23 were observed at higher ultrasound levels in this pattern.

Taking into account other scientific studies, the results indicate that vegans intake fewer nutrients that are relevant for the skeleton and are mainly found in food of animal origin. Further studies are needed for clarification.

Link to publication: Menzel, Juliane; Abraham, Klaus; Stangl, Gabriele I.; Ueland, Per M.; Obeid, Rima; Schulze, Matthias B.; Herter-Aeberli, Isabelle; Schwerdtle, Tanja; Weikert, Cornelia. 2021. “Vegan Diet and Bone Health—Results from the Cross-Sectional RBVD Study” Nutrients 13, no. 2: 685. https://doi.org/10.3390/nu13020685 https://www.mdpi.com/2072-6643/13/2/685/htm


Provided by BFR