Tag Archives: #iron

Investigation of the Enigma of the Iron Routes (Astronomy)

If you want to understand how the universe evolves, follow the iron. And it is precisely by reconstructing the quantity and distribution of iron in 12 clusters of galaxies that a team led by Simona Ghizzardi of INAF in Milan managed to discover three significant anomalies. One above all: to explain the abundance of iron estimated by astronomers, there should be seven times more stars, than those observed, capable of producing it. Or they should be seven times more efficient

In the end there is iron. It is there, in box 26 of the periodic table, that you can push the pieces of that goose game that is the stellar nucleosynthesis to the maximum. Elements beyond iron cannot form through the normal nuclear fusion processes that occur in stars: they require special processes triggered by extreme events – such as supernova explosions or neutron star collisions . But the life of a star cannot go beyond that threshold – iron. And it is precisely this dead end, not being able to go beyond iron, which – with the sudden cessation of nuclear fusion – leads to the collapse of the nucleus of large-mass stars, therefore to the dizzying increase in its density andexplosion as a supernova – resulting in the scattering of iron all around in interstellar space and beyond to intergalactic space.

In the end there is iron, then. And about the process that leads to its production – this rough summary above – there is now little doubt. But by studying its distribution in the universe – and in particular by estimating how much iron there is in the clusters of galaxies and on their periphery – the astronomers realized that the picture is not complete. And that there are still many open questions.

«What is known for sure is who are responsible for the production of iron and metals in general: the ‘iron makers’ are the most massive stars that will then explode as supernovae. But how and when they enriched the gas of the intracluster medium is still to be understood “, tells Media Inaf Simona Ghizzardi , astrophysicist at INAF in Milan and first author of a study , published last February in Astronomy & Astrophysics , which investigates the distribution of iron in 12 clusters of galaxies. “Furthermore, preliminary estimates published in recent years in the literature show that the stars contained in a cluster appear not to be able to produce all the iron measured.”

And it is precisely on the mystery of this excess of iron – as well as on its strangely uniform distribution along the entire extension of galaxy clusters – that the census undertaken by the team led by Ghizzardi tries to clarify. Observing the 12 clusters with the Xmm-Newton European space telescope , sensitive to X emission, and from the ground with the Canada-France-Hawaii Telescope and Wide Isaac Newton Telescope , Ghizzardi and colleagues surveyed the relative abundance of iron. 56 up to what in jargon is called R500. That is to say, pushing to the periphery of the 12 clusters of their sample until the density of matter falls below the threshold of 500 times thecritical density of the entire universe – roughly 3 or 4 million light years from the center. Thanks to their investigation, three significant anomalies were confirmed.

As can be seen from the graph, moving away from the center of the masses (therefore moving to the right along the horizontal axis) the profile of the iron abundance curve is flat, a sign that the relative quantity of iron remains more or less constant.  The shower head in the background represents an analogy with the mechanisms of dispersion of iron, evidently very efficient, since they have managed to spread it over enormous distances. Graphic credits: S. Ghizzardi et al., A&A, 2021. Image credits: Pixabay

“First of all, we observed that iron abundance profiles are – apart from the most central regions – extremely flat,” says Ghizzardi. In other words, the abundance of iron is uniform over most of the volume of the clusters, and moreover it varies very little from one cluster to another. This result leads to a very interesting scenario: it is plausible that enrichment essentially occurred in “ancient” times, at about 2 redshifts , when the clusters were not yet formed. Supernovae would have produced most of the iron and expelled it out of galaxies already in the protocluster phase, enriching the surrounding gas which will subsequently be increased to form the cluster. The iron would thus have had time to spread and dilute in a homogeneous way, so as to provide a similar metallicity for all the clusters and uniform within each cluster ».

In addition to this unexpected uniformity in its distribution, iron was then surprisingly abundant in the apparently “empty” spaces, those outside the galaxies that populate the clusters. Spaces that are not empty, however: the space between galaxies is in fact permeated by a very hot gas (millions of degrees), called intracluster gas , invisible to the eye but emitting X-rays. It is mainly made up of hydrogen and helium but contains traces heavier elements – “metals”, in the jargon of astronomers – including iron. “The amount of iron in the intracluster gas  is about ten times greater than the amount of iron that is trapped inside galaxies. This implies that the feedback mechanisms(Agn, stellar winds …) that expel iron from galaxies must be extremely efficient “, explains Ghizzardi,” because 90 percent of the iron produced inside galaxies is expelled and disperses in the intracluster gas “. To make an analogy, it is a bit like coming across a nation in which only one in ten inhabitants live in the city, while all the others have been expelled from urban centers and live scattered among rural, mountainous or desert areas.

The graph highlights the difference between the efficiency that stars should have in producing iron to reach the levels found in the study (pink band at the top) compared to the efficiency expected from stellar evolution models and data. 
(yellow band at the bottom).  In the background, an image of Xmm-Newton with the mosaic of the Abell 2319 cluster, one of the twelve in the X-Cop sample analyzed in the study.  Graphic credits: S. Ghizzardi et al., A&A, 2021. Image credits: The Xmm Cluster Outskirts Project (X-Cop)

But the most intriguing result is perhaps what concerns the amount of iron, which resulted – as we said at the beginning – inexplicably high. «Our work confirms the preliminary measurements in the literature: apparently the stars present in the galaxies that form the clusters are not able to manufacture all the revealed iron: to do this they would have to be 7 times more, or 7 times more efficient. But obviously there are no other “iron makers”: supernovae are the only ones able to synthesize it. So the enigma of who produced the iron is not solved », concludes Ghizzardi.

Among the hypotheses to explain this last anomaly, one of the most intriguing is that the stars responsible for the enrichment that are missing are today in regions even more peripheral than those observed in the course of the study – or perhaps even beyond of what astronomers call the virial radius of the cluster . In practice, beyond its borders, that is to say in regions where gas and stars are already affected by the gravitational attraction of the cluster but have not yet been captured within its potential well. In short, the investigation is not yet closed.

Featured image: Simona Ghizzardi, astrophysicist at the INAF IASF in Milan and first author of the study on the distribution of iron in 12 galaxy clusters published in Astronomy & Astrophysics © INAF

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Provided by INAF

Study Sheds Light on Stellar Origin Of 60Fe (Chemistry)

Researchers from the Institute of Modern Physics (IMP) of the Chinese Academy of Sciences and their collaborators have recently made great progress in the study of the stellar beta-decay rate of 59Fe, which constitutes an important step towards understanding 60Fe nucleosynthesis in massive stars. The results were published in Physical Review Letters on April 12.

Radioactive nuclide 60Fe plays an essential role in nuclear astrophysical studies. It is synthesized in massive stars by successive neutron captures on a stable nucleus of 58Fe and, during the late stages of stellar evolution, ejected into space via a core-collapse supernova.

The characteristic gamma lines associated with the decay of 60Fe have been detected by space gamma-ray detectors. By comparing the 60Fe gamma-ray flux to that from 26Al, which shares a similar origin as 60Fe, researchers should be able to obtain important information on nucleosynthesis and stellar models. However, the observed gamma-ray flux ratio 26Al/60Fe does not match theoretical predictions due to uncertainties in both stellar models and nuclear data inputs.

60Fe yield in 18 solar mass star. Blue lines (LMP) are calculations based on previous decay rate, red lines (present work) are those based on the new measurement. © Physical Review Letters

The stellar beta-decay rate of 59Fe is among the greatest uncertainties in nuclear data inputs. During the nucleosynthesis of 60Fe in massive stars, 59Fe can either capture a neutron to produce 60Fe or beta decay to 59Co. Therefore, the stellar beta-decay rate of 59Fe is critical to the yield of 60Fe.

Although the decay rate of 59Fe has been accurately measured in laboratories, its decay rate may be significantly enhanced in stellar environments due to contributions from its excited states. However, direct measurement of the beta-decay rate from excited states is very challenging since one has to create a high-temperature environment as in stars to keep the 59Fe nuclei in their excited states.

To address this problem, researchers at IMP proposed a new method for measuring the stellar beta-decay rate of 59Fe. “The nuclear charge-exchange reaction is an indirect measurement alternative, which provides key nuclear structure information that can determine those decay rates.” said GAO Bingshui, a researcher at IMP.

The researchers carried out their experiment at the Coupled Cyclotron Facility at Michigan State University. In the experiment, a secondary triton beam produced by the cyclotrons was used to bombard a 59Co target. Then the reaction products, 3He particles and gamma rays, were detected by the S800 spectrometer and GRETINA gamma-ray detection array. Using this information, the beta-decay rates from the 59Fe excited states were determined. This measurement thus eliminated one of the major nuclear uncertainties in predicting the yield of 60Fe.

By comparing stellar model calculations using the new decay rate data with previous calculations, the researchers found that, for an 18 solar mass star, the yield of 60Fe is 40% less when using the new data. The result points to a reduced tension in the discrepancy in 26Al/60Fe ratios between theoretical predictions and observations.

“It is an important step towards understanding 60Fe nucleosynthesis in massive stars and it will provide a more solid basis for future astrophysical simulations,” said LI Kuoang, the collaborator of Gao.

This work was supported by the National Key Research and Development program and the Strategic Priority Research Program of CAS.

Featured image: 60Fe nucleosynthesis in massive stars. © LI Yutian

Reference: B. Gao et al., “New 59Fe Stellar Decay Rate with Implications for the 60Fe Radioactivity in Massive Stars”, Phys. Rev. Lett. 126, 152701 – Published 12 April 2021. DOI: https://doi.org/10.1103/PhysRevLett.126.152701

Provided by Chinese Academy of Sciences

Study Explores Crosstalk between Iron and Copper Homeostasis in Arabidopsis (Botany)

Iron (Fe) and copper (Cu) are indispensable for the growth and development of plants. Although Fe and Cu are crucial for plants, excessive Fe or Cu can be toxic to plants. Therefore, plants must maintain the homeostasis of Fe and Cu. 

Despite that the crosstalk between Fe and Cu homeostasis signaling networks exists in plants, the underlined molecular mechanism remains unclear. 

In a study published in Plant, Cell & Environment, researchers from the Xishuangbanna Tropical Botanical Garden (XTBG) explored the crosstalk between Cu and Fe signaling pathways in Arabidopsis. They revealed that FER-LIKE IRON DEFICIENCY-INDUCED TRANSCRIPTION FACTOR (FIT) and basic helix-loop-helix (bHLH) Ib are involved in the Cu uptake under Fe deficiency conditions.   

Fe deficiency induced the expression of Cu uptake genes (e.g. copper transporter 2 (COPT2), ferric reductase oxidase 4 (FRO4) and FRO5) in an FIT and bHLH Ib dependent manner.

Further investigation revealed that FIT and bHLH Ib activate the expression of COPT2FRO4, and FRO5. Moreover, Cu application improved the growth of the fit-2 and bhlh4x mutants under –Fe conditions. 

Furthermore, they revealed that SQUAMOSA promoter-binding protein-like 7 is not required for the induction of Cu uptake genes by Fe deficiency. FIT and bHLH Ib TFs mediate the crosstalk between Fe and Cu homeostasis by targeting COPT2FRO4, and FRO5

“Our finding represents a new aspect of Fe and Cu interaction, and also provides a new node linking signals from the Cu pathway into the Fe deficiency regulation network,” said Dr. LIANG Gang, principal investigator of the study. 

“Through the link between bHLH Ib/FIT and COPT2/FRO4/FRO5 under Fe deficiency conditions, this work establishes a new relationship between Cu and Fe homeostasis,” said LIANG.

Reference: Cai, Y., Li, Y. and Liang, G. (2021), FIT and bHLH Ib transcription factors modulate iron and copper crosstalk in Arabidopsis. Plant Cell Environ. Accepted Author Manuscript. https://doi.org/10.1111/pce.14000

Provided by Chinese Academy of Sciences

Gene Regulator Pumps Iron To Control Sleep, Inflammation and More, Study Finds (Biology)

A key process in cells that affects immunity and circadian rhythms is illuminated in detail for the first time.

Scientists at Scripps Research have clarified the molecular workings of an important signaling mechanism involved in a host of biological processes including immunity, cholesterol metabolism, and circadian rhythms.

The discovery, reported January 27 in the journal Science Advances, is a significant advance in basic cell biology, and opens up the possibility of designing drug molecules that target this mechanism to treat diseases.

The signaling mechanism illuminated in the study includes an iron-containing molecule called heme, and two molecular switches called REV-ERBα and REV-ERBβ, which work deep within cells to control the activities of large groups of genes. The scientists resolved a long-running conundrum in the field by showing in detail how heme triggers the activation of these switches.

“The REV-ERB receptors are critical regulators of many biological processes and knowing at last how heme interacts with them enables us to start thinking about the design of drugs to target that interaction, potentially to treat sleep disorders, diabetes, atherosclerosis, autoimmune diseases, perhaps even cancers,” says study senior author Douglas Kojetin, PhD, associate professor in the Department of Integrative Structural and Computational Biology at Scripps Research’s Florida campus.

Douglas Kojetin, PhD, associate professor in the Department of Integrative Structural and Computational Biology, collaborated with first author Sarah Mosure on a study of heme’s role in bringing together nuclear receptors involved in sleep and other processes. © SCRIPPS

Scientists have known since 2007 that REV-ERB receptors can be activated by heme, a distinctively four-cornered, red-tinted molecule that contains an iron atom and—though it has many functions in mammals—is best known for its oxygen-carrying role in red blood cells.

Knowing the molecular details of how heme switches on the REV-ERBs would, in principle, enable researchers to engineer drugs to enhance or disrupt the interaction. But those molecular details have been elusive. To work properly, the REV-ERBs have to bind to another protein called NCoR, and experiments to illuminate how heme helps the REV-ERBs hook up with NCoR have yielded conflicting results. In particular, tests using fluorescent tags on the molecules have suggested confusingly that heme prevents the REV-ERBs from coupling to NCoR.

In the new study, Kojetin and colleagues, including first author Sarah Mosure, a PhD candidate in the Kojetin lab who performed most of the experiments, found a flaw in the standard fluorescence-based tests that had caused so much confusion: Heme’s unusual optical properties result in a big distortion of the fluorescence readout and essentially a false picture of heme’s effects. Using two alternative, non-fluorescence-based methods, Mosure showed that heme does in fact help bring REV-ERB and NCoR together.

The team also used X-ray crystallography to reveal at atomic scale how heme and NCoR bind to a REV-ERB receptor.

The experiments used REV-ERBβ, but the researchers expect essentially the same results for the sister receptor REV-ERBα.

“We were able in this study to make sense of more than a decade’s contradictory experiments, by demonstrating the detailed structural basis for this three-way interaction,” Mosure says.

The results mean that the Kojetin lab and other investigators can start designing molecules to interrupt or otherwise alter heme-based activation of the REV-ERBs, to aid the study of this process and its role in disease, and pave the way for future drugs that target it.

Based on the success of this research so far, Mosure has been awarded a two-year predoctoral fellowship from the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) to study the heme-REV-ERB role in inflammatory disorders.

Structural basis for heme-dependent NCoR binding to the transcriptional repressor REV-ERBβ” was co-authored by Sarah Mosure, Timothy Strutzenberg, Jinsai Shang, Paola Munoz-Tello, Laura Solt, Patrick Griffin, and Douglas Kojetin.

Funding was provided by the National Institutes of Health (R01GM114420, F31GM126842, R01AI116885, and R01CA241816) and a Richard and Helen DeVos graduate fellowship award.

Featured image: The three-dimensional structure of REV-ERB-beta protein (yellow) bound to heme (red ball and sticks) and NCoR (blue) reveals the molecular basis for a three-way interaction that affects transcription of genes involved in sleep, immunity, and more. Visualizing the complex enables scientists to design potential medicines to affect the interaction.

Provided by SCRIPPS

Iron Deficiency Can be Managed Better (Medicine)

Australian and European researchers have released updated, evidence-based guidance for managing iron deficiency, a serious worldwide health problem.

Iron deficiency is a major cause of anaemia, a deficiency in oxygen-carrying red blood cells or hemoglobin in the blood. New guidance published by Australian and European researchers outlines the best practice for managing iron deficiency. ©Wehi Australia

Iron deficiency is a major cause of anaemia, a lack of oxygen-carrying red blood cells or haemoglobin, which is experienced by two billion people worldwide – including almost one in 20 Australian adults. Iron deficiency and anaemia can have serious long-term health consequences, particularly for young children. They can also be a sign of other serious health conditions that should be treated.

Recent research has led to significant updates in the best practice for clinicians to diagnose and manage iron deficiency, and implementing these would lead to significant long-term health benefits both in Australia and around the world.

The new guidance has been published today in a review in The Lancet, by WEHI clinician scientists Associate Professor Sant-Rayn Pasricha and Associate Professor Jason Tye-Din, who are both also physicians at The Royal Melbourne Hospital, together with Professor Martina Muckenthaler from University of Heidelberg, Germany, and Professor Dorine Swinkels from Radboud University Medical Center, the Netherlands.

At a glance

  • Iron deficiency is a very common health condition both in Australia and around the world, and is a common cause of anaemia in people of all ages.
  • Anaemia and iron deficiency have serious long-term health consequences, and it is important that they are appropriately diagnosed and managed.
  • A new review in The Lancet has outlined cutting-edge, evidence-based guidance for how iron deficiency should be detected and managed, to ensure long-term health benefits.

A serious health concern

Iron deficiency is a common problem worldwide, including in Australia, where it impacts all ages from young children through to the elderly: twelve per cent of Australian women are currently iron deficient, and one in 10 Australians has been iron deficient at some point of their lives.

A range of health problems can be caused by iron deficiency, including heart problems or, when pregnant women or children are iron deficient, the child is at risk of developmental problems, said Associate Professor Pasricha, who is also a haematologist at The Royal Melbourne Hospital.

“Being able to diagnose iron deficiency, and to understand and manage the causes of that anaemia, can provide a critical boost to the health of people of all ages,” he said.

“Our review has provided clear guidelines for how to test for iron deficiency, and the best approaches to treat it both in Australia and internationally.”

Associate Professor Pasricha leads the World Health Organisation (WHO) Collaborating Centre for Anaemia Detection and Control at WEHI, which provides up-to-date, evidence-based advice to the WHO. His research has included leading large-scale clinical trials of iron supplementation in low-income countries.

“We recently discovered that approaches to treating iron deficiency should be tailored to different countries,” he said.

“In Australia, there have been many advances in how iron deficiency is managed in the last two decades, but as a haematologist I can see that some people are still not getting the best care. For example, some people whom might benefit from intravenous iron are not being offered this, despite clear evidence it can quickly restore iron levels.

“We hope this review will provide clear information for doctors in Australia and around the world, improving the management of iron deficiency – which will have widespread benefits on people’s health.”

More than a dietary problem

While iron deficiency is often caused by a lack of iron in the diet, it can also be a sign of serious health problems including bowel cancer or coeliac disease, said Associate Professor Tye-Din, who is a gastroenterologist at the Royal Melbourne Hospital.

“It’s really important that the cause of iron deficiency is properly investigated, rather than patients just being instructed to take iron supplements,” he said. “If doctors don’t take iron deficiency seriously and investigate why it is happening, serious health problems could be overlooked. In some cases these can be potentially life-threatening. This is something we’ve really highlighted in the review.”

Associate Professor Pasricha’s research is supported by the Gates Foundation, the Australian National Health and Medical Research Council, The RACP Foundation, and the Victorian Government.

Provided by Walter and Eliza Hall Institute

More Evidence That Cellular ‘Death by Iron’ Could be Promising Avenue of Cancer Treatment (Medicine)

If there is a silver lining in cancer’s chaotic biology, it’s that the same traits that give cancer cells a growth advantage often present opportunities for sabotaging them.

That’s the central idea behind a new research paper published November 23 in Proceedings of the National Academy of Sciences (PNAS) by Xuejun Jiang, a cell biologist in the Sloan Kettering Institute, and Craig Thompson, President and CEO of Memorial Sloan Kettering. They found that cancer cells often exhibit metabolic changes that make them vulnerable to a particular type of cell death called ferroptosis.

Ferroptosis — literally, death by iron — is often triggered by oxidative stress, the buildup in cells of free radicals and other corrosive chemicals that are byproducts of using oxygen to burn fuel for energy. But many cancer cells, which need abundant amounts of energy to grow and divide, have found a way around this problem.

“Genetic mutations that allow cancer cells to cope with oxidative stress make them more resistant to ferroptosis,” Dr. Jiang says. “Another way to say this is that without the benefit of those mutations, cancer cells might be very, very sensitive to ferroptosis.”

He and his colleagues, including postdoctoral fellows Junmei Yi and Jiajun Zhu, tested this idea by giving mice a combination of drugs — one that promotes ferroptosis and one that blocks the effect of the mutations. The results of this one-two punch were dramatic.

A Commonly Mutated Pathway

The particular mutations Dr. Jiang and colleagues studied affect a signal-sending pathway called PI3K-AKT-mTOR, which controls metabolism. Mutations in this pathway are among the most common found in cancer. That likely reflects the fact that cancer cells have increased metabolic demands owing to how quickly they reproduce. Cancers with mutations in the PI3K-AKT-mTOR pathway are some of the most difficult to treat.

The team found that tumor cells with these mutations demonstrated a hardy resistance to an experimental ferroptosis-inducing drug that was administered to cells growing in a dish. When the scientists added drugs that block the action of this metabolic pathway to the ferroptosis-inducing drug, the cancer cells died.

Next, they tested whether this same effect would be seen in mouse models of breast and prostate cancers containing these mutations. Indeed, the drug combination resulted in near-complete tumor destruction in the mice.

“These were some of the most significant tumor regressions I’ve ever seen coming from experiments in my lab,” Dr. Jiang says.

He and his collaborators further showed that the way the mutated PI3K-AKT-mTOR pathway protects cancer cells is by increasing the activity of a protein that is involved in making lipids for the cell’s outer membrane. These extra lipids help to protect the cells against oxidative stress, and therefore ferroptosis. Blocking PI3K-AKT-mTOR prevents this lipid synthesis and re-sensitizes the cells to ferroptosis.

The new findings complement previous work from the Jiang lab, published in 2019 in the journal Nature. In that paper, Dr. Jiang found the some cancers have mutations that make them more sensitive to ferroptosis, even without administering metabolism-altering drugs. In a sense, the new results represent the flipside of the equation.

“The key point is that many cancers have genetic alterations that can be exploited to trigger ferroptosis and kill the cells. It’s an exciting way to think about developing new cancer treatments.”

The team has applied for a patent related to this work. Their next step is to test the drug combination in tumor samples obtained from patients being treated at MSK.

This work was supported by the National Institutes of Health (grants R01CA204232 and R01CA201318), the Leukemia and Lymphoma Society, and the National Cancer Institute (core grant P30 CA008748). Dr. Thompson is a founder of Agios Pharmaceuticals and a member of its scientific advisory board. He is also a former member of the Board of Directors and stockholder of Merck and Charles River Laboratories. He holds patents related to cellular metabolism. Dr. Jiang holds patents related to autophagy and cell death.

References: Junmei Yi, Jiajun Zhu, Jiao Wu, Craig B. Thompson, Xuejun Jiang, “Oncogenic activation of PI3K-AKT-mTOR signaling suppresses ferroptosis via SREBP-mediated lipogenesis”, Proceedings of the National Academy of Sciences Nov 2020, 202017152; DOI: 10.1073/pnas.2017152117 https://www.pnas.org/content/early/2020/11/17/2017152117

Provided by MSK

About Memorial Sloan Kettering (MSK):

As the world’s oldest and largest private cancer center, Memorial Sloan Kettering has devoted more than 135 years to exceptional patient care, influential educational programs and innovative research to discover more effective strategies to prevent, control and, ultimately, cure cancer. MSK is home to more than 20,000 physicians, scientists, nurses and staff united by a relentless dedication to conquering cancer. Today, we are one of 51 National Cancer Institute-designated Comprehensive Cancer Centers, with state-of-the-art science and technology supporting groundbreaking clinical studies, personalized treatment, and compassionate care for our patients. We also train the next generation of clinical and scientific leaders in oncology through our continually evolving educational programs, here and around the world. Year after year, we are ranked among the top two cancer hospitals in the country, consistently recognized for our expertise in adult and pediatric oncology specialties.

Microbes Help Unlock Phosphorus for plant growth (Botany)

Phosphorus is a necessary nutrient for plants to grow. But when it’s applied to plants as part of a chemical fertilizer, phosphorus can react strongly with minerals in the soil, forming complexes with iron, aluminum and calcium. This locks up the phosphorus, preventing plants from being able to access this crucial nutrient.

Poplar trees such as these along the Snoqualmie River able to thrive on rocky riverbanks, despite low availability of nutrients like phosphorus in their natural habitat. Microbes help these trees capture and use the nutrients they need for growth. ©Sharon Doty/University of Washington

To overcome this, farmers often apply an excess of chemical fertilizers to agricultural crops, leading to phosphorus buildup in soils. The application of these fertilizers, which contain chemicals other than just phosphorus, also leads to harmful agricultural runoff that can pollute nearby aquatic ecosystems.

Now a research team led by the University of Washington and Pacific Northwest National Laboratory has shown that microbes taken from trees growing beside pristine mountain-fed streams in Western Washington could make phosphorus trapped in soils more accessible to agricultural crops. The findings were published in October in the journal Frontiers in Plant Science.

Endophytes, which are bacteria or fungi that live inside a plant for at least some of their lifecycle, can be thought of as “probiotics” for plants, said senior author Sharon Doty, a professor in the UW School of Environmental and Forest Sciences. Doty’s lab has shown in previous studies that microbes can help plants survive and even thrive in nutrient-poor environments — and help clean up pollutants.

In this new study, Doty and collaborators found that endophytic microbes isolated from wild-growing plants helped unlock valuable phosphorus from the environment, breaking apart the chemical complexes that had rendered the phosphorus unavailable to plants.

“We’re harnessing a natural plant-microbe partnership,” Doty said. “This can be a tool to advance agriculture because it’s providing this essential nutrient without damaging the environment.”

Doty’s research scientist, Andrew Sher, and UW undergraduate researcher Jackson Hall demonstrated in lab experiments that the microbes could dissolve the phosphate complexes. Poplar plants inoculated with the bacteria in Doty’s lab were sent to collaborator Tamas Varga, a materials scientist at the Environmental Molecular Sciences Laboratory at Pacific Northwest National Laboratory in Richland, Washington. There researchers used advanced imaging technologies at their lab and at other U.S. Department of Energy national laboratories to provide clear evidence that the phosphorus made available by the microbes did make it up into the plant’s roots.

As an endophytic strain dissolves tricalcium phosphate, a clear halo is produced around the milky-white phosphate circles, as seen in this image of the process occurring in an agar medium. ©Sharon Doty/University of Washington

The imaging also revealed that the phosphorus gets bound up in mineral complexes within the plant. Endophytes, living inside plants, are uniquely positioned to re-dissolve those complexes, potentially maintaining the supply of this essential nutrient.

While previous work in Doty’s lab demonstrated that endophytes can supply nitrogen, obtained from the air, to plants, such direct evidence of plants using phosphorus dissolved by endophytes was previously unavailable.

The bacteria used in these experiments came from wild poplar trees growing along the Snoqualmie River in Western Washington. In this natural environment, poplars are able to thrive on rocky riverbanks, despite low availability of nutrients like phosphorus in their natural habitat. Microbes help these trees capture and use the nutrients they need for growth.

These findings can be applied to agriculture crops, which often sit, unused, on an abundance of “legacy” phosphorus that has accumulated in the soil, unused, from years of fertilizer applications. Microbes could be applied in the soil among young crop plants, or as a coating on seeds, helping to unlock phosphorus held captive and making it available for use by plants to grow. Reducing the use of fertilizers and employing endophytes — such as those studied by Doty and Varga — opens the door for more sustainable food production.

“This is something that can easily be scaled up and used in agriculture,” Doty said.

UW has already licensed the endophyte strains used in this study to Intrinsyx Bio, a California-based company working to commercialize a collection of endophyte microbes. The direct evidence provided by Doty and Varga’s research of endophyte-promoted phosphorus uptake is “game-changing for our research on crops,” said John Freeman, chief science officer of Intrinsyx Bio.

Reference: Tamas Varga et al., “Endophyte-Promoted Phosphorus Solubilization in Populus”, Front. Plant Sci., 21 October 2020 | https://doi.org/10.3389/fpls.2020.567918 https://www.frontiersin.org/articles/10.3389/fpls.2020.567918/full?

Provided by University of Washington

Taking Out the Trash is Essential for Brain Health (Neuroscience)

A research team at Tokyo Medical and Dental University (TMDU) find that Wipi3, a protein involved in cellular waste disposal, is crucial for neuronal health.

A little mess never killed anyone, right? Wrong. Researchers at Tokyo Medical and Dental University (TMDU) have recently shown that a build-up of cellular “trash” in the brain can actually cause neurodegeneration, and even death.

Abnormal motor performance in Wipi3cKO mice at 10 weeks of age. In (a), the limb-clasping reflex is observed in Wipi3cKO mice. In (b), the footprint assay indicated a motor deficit in Wipi3cKO mice. ©Department of Pathological Cell Biology,TMDU

Reporting their findings in Nature Communications, the researchers describe how defects in a cellular waste disposal mechanism, called “alternative autophagy”, can lead to a lethal build-up of iron and protein in brain cells.

“Cells are constantly clearing out dysfunctional or unnecessary components, which are then degraded and recycled,” explains study lead author Hirofumi Yamaguchi. “Autophagy is the process whereby unwanted cellular components and proteins are contained within a spherical doubled-membraned vesicle called an autophagosome, which fuses with an enzyme-filled lysosome to form an autolysosome. The waste material is then broken down and reused by the cell.”

This common form of autophagy, called “canonical autophagy”, is well characterized and involves a suite of autophagy-related proteins, such as Atg5 and Atg7. More recently though, several Atg5-independent alternative autophagy pathways have also been described, the biological roles of which remain unclear.

Cryosections of the cerebellum from Wipi3cKO mice and WT mice were stained with Prussian blue (a) and were immunostained with anti-ceruloplasmin (green) and anti-calbindin (red) antibodies (b). Blue puncta indicate iron deposition in (a). ©Department of Pathological Cell Biology,TMDU

After identifying alternative autophagy-related proteins in yeast, the team at TMDU focused on a mammalian ortholog called “Wipi3”, which had previously been implicated in canonical autophagy. “When we deleted Wipi3 in a mouse cell line and induced alternative autophagy, we no longer observed the formation of double-membraned autophagosomes or single-membraned autolysosomes, confirming that Wipi3 is essential for alternative autophagy,” says Yamaguchi.

Mice containing a brain-specific deletion of Wipi3 demonstrated growth and motor defects most commonly seen in patients with neurodegeneration, with the researchers also noting an accumulation of iron and the iron-metabolizing protein ceruloplasmin in the brain cells of affected mice.

“Iron deposition has been flagged as a possible trigger in various neurodegenerative disorders, and is usually associated with the abnormal accumulation of iron-binding proteins,” explains study senior author Shigeomi Shimizu. “Our findings are strong evidence that alternative autophagy, and Wipi3 specifically, may be essential for preventing this toxic build-up of iron.”

Wipi3 is translocated from the cytosol to the trans-Golgi, and manipulates the trans-Golgi membrane to generate autophagic vacuoles. In vivo, Wipi3-dependent alternative autophagy degrades excess ceruloplasmin, and prevents abnormal iron deposition in brain cells. ©Department of Pathological Cell Biology,TMDU

Interestingly, although Wipi3-deficient and Atg7 (canonical autophagy)-deficient mice showed similar motor defects, they exhibited very different sub-cellular changes, suggesting that alternative autophagy and canonical autophagy act independently to protect neurons. Supporting this, deletion of both Wipi3 and Atg7 in mice was almost always fatal.

The researchers are hopeful that this research could lead to the development of neuroprotective drugs. Preliminary tests indicate that over-expression of Dram1, another alternative autophagy-associated protein, can reverse the effects of Wipi3 deletion, and may form the basis of future therapies for various neurodegenerative diseases. The article, “Wipi3 is essential for alternative autophagy and its loss causes neurodegeneration,” was published in Nature Communications (DOI: 10.1038/s41467-020-18892-w).

References: Yamaguchi, H., Honda, S., Torii, S. et al. Wipi3 is essential for alternative autophagy and its loss causes neurodegeneration. Nat Commun 11, 5311 (2020). https://www.nature.com/articles/s41467-020-18892-w https://doi.org/10.1038/s41467-020-18892-w

Provided by Tokyo Medical and Dental University

How an Odd Property of Acid Created Self-Healing Iron? (Chemistry)

An odd quirk of iron led, eventually, to the first self-healing materials. An iron bar, dipped in strong acid, was just fine. Dipped in weak acid, it was eaten away to nothing. Here’s why a diluted acid will succeed when a strong acid fails.

The Industrious Michael Faraday

Michael Faraday spent the first half of the 19th century doing, roughly, everything. The amount of things, in science, that are named “Faraday,” is frankly obscene and something should be done about it. What with the Faraday cage and the Faraday constant and the Faraday effect, few people know of the relatively minor phenomenon known as the Faraday paradox of electrochemistry, also called the Faraday paradox of passivation. The “electrochemistry,” and “passivation,” differentiate it from the more well-known Faraday Paradox which is named for Faraday, and illustrates Faraday’s Law of Electromagnetic Induction – because apparently Faraday did not go on even one single vacation during his lifetime.

This particular Faraday phenomenon was noted by Michael Faraday when he dipped an iron bar in very concentrated nitric acid. He had also dipped iron in weakened nitric acid, and the acid ate away at the metal quickly, so he must have expected a huge reaction. He was disappointed. After a little bubbling, the iron bar sat there, at rest in concentrated acid. Faraday guessed that some reaction with the strong acid had caused the outer surface of the iron to form a film that protected the rest of the bar. Being Michael Faraday he was right. What he didn’t realize, that he had taken the first step towards the creation of the first kind of self-healing materials.

The Process of Passivation

When he was conducting his experiment, Faraday had luck on his side. Most of the time this particular process takes a bit more rigging than lowering a metal into acid, but Faraday had stumbled on two materials that managed to go through passivation at room temperature. Passivation is the creation of a coating over a metal surface that renders it unresponsive, or passive, in the face of elements that would otherwise corrode it.

Concentrated nitric acid has an interesting property. It promotes oxidization. In biology, oxidization happens when materials combine with oxygen – in other words, when they burn. Chemistry has a slightly different definition for the same word. A material is oxidized when it gives up an electron. The more electrons it gives up, the more it is oxidized. Concentrated nitric acid is an oxidizing agent, an rips electrons off materials dipped in it. Iron is particularly susceptible to nitric acid’s effects. After its electrons are ripped away, the biological sense of oxidization takes over, and oxygen does combine with the iron on the surface to create an iron oxide layer. The layer is impervious to the acid, and the interior iron is protected until the oxide layer is scraped off. Dilute nitric acid can’t get the same oxidization reaction going, and so it will continue to eat away at the iron until the iron is dissolved.

Electrochemistry and Self-Healing Materials

Over time people other than Michael Faraday saw fit to involve themselves in science. They began looking at the results that Faraday had achieved with iron and acid – and electrochemistry was born. Iron, when treated only with strong nitric acid, was not particularly useful. The slightest scratch and the patina was scraped away. There was also the unfortunate fact that acid didn’t work on just any metal.

What worked on lots of other metals was electricity. Nothing rips electrons away like a process designed to rip electrons away. Dipping metals in solution and applying a voltage that “pumps” electrons away oxidizes the outer layers of a metal quickly. Meanwhile, metals that receive electrons are “reduced.” Oxidation and reduction are often enough to put a coating on a metal, but chemists took it one step further. They started adding chemicals to the solutions that would combine with the metals while they were in their reduced, or oxidized, state, and plate the surface. This can be done for decoration, as in “gold-plating,” but there are more useful applications. This is what lead to the original self-healing materials.

As low-tech as it is, one of the most common self-healing materials was invented back in 1913, when someone figured out that adding a little chrome to iron made it less likely to get stained and corroded. Iron alone stains, and then pits, and then is eaten away. Not so when chrome is added. The iron and chrome grab oxygen atoms and form an oxide that coats and protects the surface. Scratch the surface, and the iron and chrome beneath grab on to oxygen, re-forming the protective layer. Because of Faraday’s experiment in the 19th century, people at the beginning of the 20th century understood the principles of how to make a self-healing material.

In a nod to Faraday’s original experiment, often the process of making or repairing stainless steel involves his original experiment. Immersing the whole thing in strong nitric acid oxidizes any free iron on the surface of the steel, allowing it to be removed, so the self-healing steel can be repaired and shine.

This article is republished here from Gizmodo under common creative licenses