Earth

Water molecules are gold for nanocatalysis

Nanocatalysts made of gold nanoparticles dispersed on metal oxides are very promising for the industrial, selective oxidation of compounds, including alcohols, into valuable chemicals. They show high catalytic activity, particularly in aqueous solution. A team of researchers from Ruhr-Universität Bochum (RUB) has been able to explain why: Water molecules play an active role in facilitating the oxygen dissociation needed for the oxidation reaction. The team of Professor Dominik Marx, Chair of Theoretical Chemistry, reports in the high-impact journal ACS Catalysis on 14 July 2020.

Rushing for gold

Most industrial oxidation processes involve the use of agents, such as chlorine or organic peroxides, that produce toxic or useless by-products. Instead, using molecular oxygen, O2, and splitting it to obtain the oxygen atoms needed to produce specific products would be a greener and more attractive solution. A promising medium for this approach is the gold/metal oxide (Au/TiO2) system, where the metal oxide titania (TiO2) supports nanoparticles of gold. These nanocatalysts can catalyse the selective oxidation of molecular hydrogen, carbon monoxide and especially alcohols, among others. A crucial step behind all reactions is the dissociation of O2, which comprises a usually high energy barrier. And a crucial unknown in the process is the role of water, since the reactions take place in aqueous solutions.

In a 2018 study, the RUB group of Dominik Marx, Chair of Theoretical Chemistry and Research Area coordinator in the Cluster of Excellence Ruhr Explores Solvation (Resolv), already hinted that water molecules actively participate in the oxidative reaction: They enable a stepwise charge-transfer process that leads to oxygen dissociation in the aqueous phase. Now, the same team reveals that solvation facilitates the activation of molecular oxygen (O2) at the gold/metal oxide (Au/TiO2) nanocatalyst: In fact, water molecules help to decrease the energy barrier for the O2 dissociation. The researchers quantified that the solvent curbs the energy costs by 25 per cent compared to the gas phase. "For the first time, it has been possible to gain insights into the quantitative impact of water on the critical O2 activation reaction for this nanocatalyst - and we also understood why," says Dominik Marx.

Mind the water molecules

The RUB researchers applied computer simulations, the so-called ab initio molecular dynamics simulations, which explicitly included not only the catalyst but also as many as 80 surrounding water molecules. This was key to gain deep insights into the liquid-phase scenario, which contains water, in direct comparison to the gas phase conditions, where water is absent. "Previous computational work employed significant simplifications or approximations that didn't account for the true complexity of such a difficult solvent, water," adds Dr. Niklas Siemer who recently earned his PhD at RUB based on this research.

Scientists simulated the experimental conditions with high temperature and pressure to obtain the free energy profile of O2 in both liquid and gas phase. Finally, they could trace back the mechanistic reason for the solvation effect: Water molecules induce an increase of local electron charge towards oxygen that is anchored at the nanocatalyst perimeter; this in turn leads to the less energetic costs for the dissociation. In the end, say the researchers, it's all about the unique properties of water: "We found that the polarizability of water and its ability to donate hydrogen bonds are behind oxygen activation," says Dr. Munoz-Santiburcio. According to the authors, the new computational strategy will help to understand and improve direct oxidation catalysis in water and alcohols.

Credit: 
Ruhr-University Bochum

Study shows three medications currently on the market may have unexpected effects

A new study of 1,443 medications found that three prescription drugs currently on the market caused unexpected changes in worms that could point to potential, unrecognized effects in humans.

The study shows that a microscopic nematode worm called C. elegans, which is commonly used in biology experiments, can serve as a quick, inexpensive tool to identify targets for drug safety or efficacy studies. This work also highlights the need for continued evaluation of medications even after Food and Drug Administration (FDA) approval. The research was published online on July 23, 2020 in the journal Chemosphere.

"We did not expect to see anything so dramatic and obvious, but three medications caused distinct physiological changes in these worms," said Antony Jose, an associate professor of cell biology and molecular genetics at the University of Maryland and senior author of the study. "This really highlights how underexplored these drugs are."

Jose emphasized that the study does not conclude that the three drugs, which have been approved by the FDA, are toxic to humans or have unidentified side effects in humans. The research showed these drugs, which are currently on the market, may have impacts on cellular processes that haven't been previously explored according to the scientific literature.

C. elegans has thousands of genes that are similar to human genes and share similar biological functions, which is why the worms are sometimes used in early toxicity tests for new compounds. If further investigation reveals that the compounds affect genes or cellular processes in C. elegans that are shared with humans, additional studies may identify potential side effects or provide insights into how the drugs work on a molecular level that could improve future drug development.

In the current study, the anticoagulant ticlopidine and the antifungal sertaconazole caused bubbles that appear to be accumulated medication in the worms' throats, physically distorting that part of their bodies. In some cases, the worms died after exposure to the drugs, but it is unclear whether death was caused by the accumulation in the throat or some other mechanism. Ticlopidine is sometimes used for preventing blood clots when a stent is inserted to open a patient's blood vessel, and sertaconazole is used to treat athlete's foot.

The third medication, dexlansoprazole, is a proton-pump inhibitor used to treat heartburn. This medication caused molting defects in the worms. Although humans don't molt, the C. elegans genes involved in molting are similar to human genes involved in secreting collagen, which is the main structural component of connective tissues, such as skin and cartilage. This means the molecular processes that enable molting in C. elegans could be similar to those that enable collagen secretion in humans, and if the medication interrupts one of those processes, it may also affect collagen secretion in humans.

The researchers made their discovery serendipitously while lead author, Kyle Galford (B.S. '19, biological sciences), who is now employed at Novogene, was searching for drug compounds that could disrupt gene regulation. To conduct the study, Galford applied drops of 1,443 different FDA-approved medications into different petri dishes containing C. elegans worms.

The worms had been engineered in the lab to have a fluorescent gene that was turned off. Two days later, the researchers inspected the worms under a microscope to see if any of the medications turned the fluorescent gene on, meaning they had successfully disrupted regulation of the fluorescent gene. None of the medications turned the fluorescent gene on, but the scientists immediately noticed other changes in three batches of worms--those exposed to ticlopidine, sertaconazole and dexlansoprazole. All 1,443 medications were tested at the same concentration, and these were the only three that produced observable changes in the worms, supporting the need for further investigations.

Although almost all drugs are tested for toxicity in mammals such as mice before being advanced to human trials, it is currently impossible to screen for every potential physiological effect of a drug before it is allowed on the market. This sometimes means side effects are discovered years after a drug is in use.

The current study suggests that evaluating medications already on the market using a simple, well-studied organism like C. elegans could provide an easy, inexpensive method to identify areas where further research could be useful.

"To think about unforeseen risk, we need a different mindset," Jose said. "Even the most commonly used drugs aren't exhaustively studied before they make it to market. But we may think that just because they are so commonly used, we must already know everything about them. The more people are exposed to a drug, the more we need to study it."

Jose intends to continue investigating the effect of these drugs in C. elegans to better understand how they interacts with animals and whether they could affect biological processes such as collagen secretion in humans.

Credit: 
University of Maryland

Molecular cause underlying rare genetic disorder revealed

image: Paras Patel (left), a student in Virginia Tech's translational biology, medicine, and health graduate program, and Konark Mukherjee, a faculty member and research team leader with the Fralin Biomedical Research Institute at VTC, have revealed how a nonfunctioning version of an ordinary gene associated with intellectual disability impairs brain structure and function. File photos

Image: 
Virginia Tech

Virginia Tech scientists have revealed how a nonfunctioning version of an ordinary gene impairs brain structure and function. The findings help explain a genetic form of microcephaly -- a condition where babies' heads are small and grow more slowly than their peers.

The study, in the July print edition of Experimental Neurology, for the first time provides a global picture of the effects of the gene called CASK on the molecular activity within brain cells and the connections between brain cells.

CASK is found across the animal kingdom, including in worms, fruit flies, mice, and people, but dysfunctional variants of the CASK gene in children result in microcephaly with pontine and cerebellar hypoplasia, or impaired growth, which may contribute to intellectual disability, microcephaly, abnormal brain and optic nerve development, and seizures in girls.

The new research indicates that seizures are not a likely cause for the smaller brain size.

"There are drastic changes in brain development in these children, and whenever that happens, the prospect of seizures and cellular toxicity due to epileptic activity becomes a concern," said Paras Patel, a student in Virginia Tech's translational biology, medicine, and health graduate program and lead author on the published study.

"We developed and studied a 'face-valid' genetic animal model and determined that global electrical activity in the brain is not affected," said Patel, who is also with the Fralin Biomedical Research Institute at VTC Center for Neurobiology Research, where he carries out his research with the mentorship of Konark Mukherjee, a primary faculty member and research team leader with the Fralin Biomedical Research Institute who leads perhaps the only research team in the world devoted to exploring CASK's role in neurological disorders. "We confirmed that epilepsy is indeed of very low frequency, suggesting that it is not underlying the cellular death and abnormality in brain volume."

The human CASK gene lies on the X chromosome and contains instructions for producing the CASK protein molecule, which is necessary for brain growth and function. Boys without a functional CASK gene develop a severe encephalopathy and may not survive. Girls with one mutated copy express this mutation in half of their cells and the non-mutated copy in the other half.

To understand the functional changes caused by CASK-related disorder, the researchers studied a mouse model where half of the cells did not have mouse CASK and the other half had normal mouse CASK, which is a genetically similar profile to the majority of human cases to understand the functional changes caused by CASK-related disorder

The scientists discovered abnormalities that would affect communication between brain cells, as well as molecular changes that affect processes cells use to make protein.

In addition, the findings point to an unexpected role for CASK in the regulation of energy production in cells, including the mitochondria, which are structures that convert nutrients into energy.

"Strikingly, significant numbers of molecular changes that we observed occur in proteins related to cellular energy production and other aspects of mitochondrial function," said Mukherjee, the corresponding author on the manuscript. "The role for CASK at the mitochondria provides interesting future directions into how this function could explain diminished brain size and dysregulated function in cases of CASK mutation in humans."

"The interest from parents whose children are affected by CASK gene mutations is very inspiring," said Patel. "They search the web for all the new studies and read extremely complex papers, so it is exciting to provide a step forward for them which comes from an extensive, unbiased investigation relevant to the disorder."

Credit: 
Virginia Tech

Artificial intelligence finds patterns of mutations and survival in tumour images

image: A mosaic of tumour microscopy images forming broken DNA molecules.

Image: 
Yu Fu, Moritz Gerstung, Spencer Phillips/EMBL

Researchers at EMBL's European Bioinformatics Institute (EMBL-EBI), the Wellcome Sanger Institute, Addenbrooke's Hospital in Cambridge, UK, and collaborators have developed an artificial intelligence (AI) algorithm that uses computer vision to analyse tissue samples from cancer patients. They have shown that the algorithm can distinguish between healthy and cancerous tissues, and can also identify patterns of more than 160 DNA and thousands of RNA changes in tumours. The study, published today in Nature Cancer, highlights the potential of AI for improving cancer diagnosis, prognosis, and treatment.

Cancer diagnosis and prognosis are largely based on two main approaches. In one, histopathologists examine the appearance of cancer tissue under the microscope. In the other, cancer geneticists, analyse the changes that occur in the genetic code of cancer cells. Both approaches are essential to understand and treat cancer, but they are rarely used together.

"Clinicians use microscopy slides for cancer diagnosis all the time. However, the full potential of these slides hasn't been unlocked yet. As computer vision advances, we can analyse digital images of these slides to understand what happens at a molecular level," says Yu Fu, Postdoctoral Fellow in the Gerstung Group at EMBL-EBI.

Computer vision algorithms are a form of artificial intelligence that can recognise certain features in images. Fu and colleagues repurposed such an algorithm developed by Google - originally used to classify everyday objects such as lemons, sunglasses and radiators - to distinguish various cancer types from healthy tissue. They showed that this algorithm can also be used to predict survival and even patterns of DNA and RNA changes from images of tumour tissue.

Teaching algorithms to detect molecular changes

Previous studies have used similar methods to analyse images from single or a few cancer types with selected molecular alterations. However, Fu and colleagues generalised the approach on an unprecedented scale: they trained the algorithm with more than 17 000 images from 28 cancer types collected for The Cancer Genome Atlas, and studied all known genomic alterations.

"What is quite remarkable is that our algorithm can automatically link the histological appearance of almost any tumour with a very broad set of molecular characteristics, and with patient survival," explains Moritz Gerstung, Group Leader at EMBL-EBI.

Overall, their algorithm was capable of detecting patterns of 167 different mutations and thousands of gene activity changes. These findings show in detail how genetic mutations alter the appearance of tumour cells and tissues.

Another research group has independently validated these results with a similar AI algorithm applied to images from eight cancer types. Their study was published in the same issue of Nature Cancer.

A potential tool for personalised medicine

The integration of molecular and histopathological data provides a clearer picture of a tumour's profile. Detecting the molecular features, cell composition, and survival associated with individual tumours would help clinicians tailor appropriate treatments to their patients' needs.

"From a clinician's point of view, these findings are incredibly exciting. Our work shows how artificial intelligence could be used in clinical practice," explains Luiza Moore, Clinician Scientist and Pathologist at the Wellcome Sanger Institute and Addenbrooke's Hospital. "While the number of cancer cases is increasing worldwide, the number of pathologists is declining. At the same time, we strive to move away from the 'one size fits all' approach and into personalised medicine. A combination of digital pathology and artificial intelligence can potentially alleviate those pressures and enhance our practice and patient care."

Sequencing technologies have propelled genomics to the forefront of cancer research, yet these technologies remain inaccessible to most clinics around the world. A possible alternative to direct sequencing would be to use AI to emulate a genomic analysis using data that is cheaper to collect, like microscopy slides.

"Getting all that information from standard tumour images in a completely automatic manner is revolutionary," says Alexander Jung, PhD student at EMBL-EBI. "This study shows what might be possible in the coming years, but these algorithms will have to be refined before clinical implementation."

Credit: 
European Molecular Biology Laboratory - European Bioinformatics Institute

Model links patterns in sediment to rain, uplift and sea level change

image: A source-to-sink model run illustrating changes in elevation (left) and erosion/deposition (right).

Image: 
Jinyu Zhang/ The University of Texas at Austin.

Forces that shape the Earth's surface are recorded in a number of natural records, from tree rings to cave formations.

In a recent study, researchers from The University of Texas at Austin show that another natural record - sediments packed together at basin margins - offers scientists a powerful tool for understanding the forces that shaped our planet over millions of years, with implications on present day understanding

The study was published in the journal Geology and uses a computer model to connect distinct patterns in the sedimentary deposits to shifts in climate and tectonic activity.

"We are trying to find a way to distinguish the tectonics and the climate signals," said lead author Jinyu Zhang, a research associate at UT's Bureau of Economic Geology. "By using this numerical model we suddenly have this power to simulate the world under different tectonics and climate."

Zoltán Sylvester and Jacob Covault, both research scientists at the bureau, co-authored the paper.

Geoscientists have long looked to sedimentary basins for clues about Earth's past climate. That's because sediment supply is closely linked to environmental factors, such as rainfall or snowfall, that influence sediment creation through erosion and sediment transport across a landscape and into a basin. Tectonic factors also influence sediment creation, with increasing uplift associated with more sediment and decreasing uplift with less.

However, despite knowledge of sediment supply being linked with climate and tectonics, the researchers said little is known about how changes in these phenomena directly influence how sediment is deposited along basin margins over long time scales.

This study changes that, with Zhang using the open-source computer program pyBadlands to create a "source-to-sink" 3D model that tracks how changes in precipitation, tectonic uplift and sea level influence sediment erosion and deposition. The model uses topography inspired by the Himalaya Mountains and Indus River Delta to track the sediment as it makes its way from the mountains, through a river system, and settles into a basin margin over millions of years.

"This is one of the first [models] to put the landscape evolution part with the stratigraphic response, depositional response, and do it in 3D," Covault said. "Jinyu has made a really great step in putting this all together."

The researchers ran 14 different scenarios - each with a different climatic, tectonic, and sea level settings - over a simulated time period of 30 million years to investigate changes in landscape topography and sediment deposition.

The different scenarios created distinct patterns in sediment deposition, which allowed the researchers to draw general conclusions about how tectonic and climatic factors affect basin margin growth. For example, changes in uplift take millions of years to affect change in the basin margin sediments, but once those changes are in effect, they set a new baseline for behavior. In contrast, changes in precipitation cause much more abrupt change, followed by a return to the depositional behavior observed before the climate shift.

The scenarios showed that sea level could potentially complicate the delivery of the signal of tectonic change into the basin. For example, an increase in sea level flooded coastal regions and interfered with sediment reaching a basin margin. But when this scenario was paired with increased precipitation, the sediment supply was large enough to make it to the basin margin.

Gary Hampson, a professor at Imperial College London who was not part of the study, said that the model provides important guidelines for geoscientists looking to reconstruct Earth's past.

"The results increase the confidence with which geoscientists can interpret tectonic and climatic histories in the geologic archives of basin margins," he said.

Zhang spent the past two years learning the programming language Python so he could use the pyBadlands software, which was developed by the University of Sydney's Tristan Salles.

Sylvester, who leverages similar tools to study erosion and sedimentation in river systems, said that the computing tools available to geoscientists are making long-standing yet fundamental questions in geosciences more accessible than ever.

"It's an exciting time," he said. "It's increasingly easier to investigate the stratigraphic record in a quantitative way."

Credit: 
University of Texas at Austin

NASA sees hurricane Douglas brush Hawaii

image: Visible imagery from MODIS instrument aboard NASA's Terra satellite was compiled from July 25 to 26 and made into an animation using NASA's Worldview application. The imagery showed Douglas' movement past the Hawaiian Islands.

Image: 
NASA Worldview, Earth Observing System Data and Information System (EOSDIS)

Imagery from NASA's Terra satellite was used to create an animation showing Douglas' movement past the Hawaiian Islands.

Although the Hawaiian Islands missed a landfall from Hurricane Douglas, the storm was certainly close enough to bring strong surf, heavy rains and gusty winds to the islands. NASA's Terra satellite imagery showed the storm's track as it moved just north of the islands.

Visible imagery of Hurricane Douglas from July 25 to 26, taken from the Moderate Resolution Imaging Spectroradiometer or MODIS instrument aboard NASA's Terra satellite was compiled and made into an animation using NASA's Worldview application. The imagery showed Douglas' center staying just off shore from the Hawaiian Islands.

NASA's Earth Observing System Data and Information System (EOSDIS) Worldview application provides the capability to interactively browse over 700 global, full-resolution satellite imagery layers and then download the underlying data. Many of the available imagery layers are updated within three hours of observation, essentially showing the entire Earth as it looks "right now."

Warnings in Effect on July 27

NOAA's Central Pacific Hurricane Center (CPHC) posted several updates to the warnings on July 27. A Hurricane Warning is in effect for portions of the Papahanaumokuakea Marine National Monument from Nihoa to French Frigate Shoals. A Tropical Storm Warning is in effect for portions of the Papahanaumokuakea Marine National Monument from French Frigate Shoals to Maro Reef. A Hurricane Watch is in effect for portions of the Papahanaumokuakea Marine National Monument from French Frigate Shoals to Maro Reef, and a Tropical Storm Watch is in effect for portions of the Papahanaumokuakea Marine National Monument from Maro Reef to Lisianski.

Douglas' Status on July 27, 2020

NOAA's CPHC noted at 11 a.m. EDT (5 a.m. HST/1500 UTC), the center of Hurricane Douglas was located near latitude 22.9 degrees north and longitude 160.4 degrees west. Douglas is moving toward the west-northwest near 17 mph (28 kph), and this general motion will continue the next couple of days, with a slight turn toward the west. Maximum sustained winds are near 90 mph (150 kph) with higher gusts. The estimated minimum central pressure is 987 millibars.

In Hawaii, rainfall associated with Douglas is expected to affect portions of the main Hawaiian Islands today. Total rain accumulations of 3 to 6 inches with locally higher amounts are possible, with the greatest rainfall in elevated terrain on Kauai. Heavy rainfall will also affect portions of the Papahanaumokuakea Marine National Monument the next couple of days.

Douglas' Forecast

NOAA's CPHC noted, "Hurricane force winds are expected over portions of the Papahanaumokuakea Marine National Monument from Nihoa to French Frigate Shoals later today and tonight. Tropical storm conditions are expected from French Frigate Shoals to Maro Reef Tuesday and Tuesday night, with hurricane conditions possible.

Tropical storm conditions are possible from Maro Reef to Lisianski Tuesday night and Wednesday.

Large swells generated by Douglas will affect a large swath of the Papahanaumokuakea Marine National Monument the next couple of days. Weakening is forecast during the next couple of days.

For more than five decades, NASA has used the vantage point of space to understand and explore our home planet, improve lives and safeguard our future. NASA brings together technology, science, and unique global Earth observations to provide societal benefits and strengthen our nation. Advancing knowledge of our home planet contributes directly to America's leadership in space and scientific exploration.

Credit: 
NASA/Goddard Space Flight Center

How airway cells work together in regeneration and aging

image: Microscopic image showing stem cells in young (left) and old (right) airways with cell nuclei seen in blue, airway basal stem cells seen in red and ciliated cells seen in green.

Image: 
Broad Stem Cell Research Center

Researchers at the Eli and Edythe Broad Center of Regenerative Medicine and Stem Cell Research at UCLA have identified the process by which stem cells in the airways of the lungs switch between two distinct phases -- creating more of themselves and producing mature airway cells -- to regenerate lung tissue after an injury.

The study, published in Cell Stem Cell, also sheds light on how aging can cause lung regeneration to go awry, which can lead to lung cancer and other diseases.

"There currently are few therapies that target the biology of lung diseases," said Dr. Brigitte Gomperts, a professor and vice chair of research in pediatric hematology-oncology at the UCLA Children's Discovery and Innovation Institute and the paper's senior author. "These findings will inform our efforts to develop a targeted therapy to improve airway health."

The airways, which carry the air that is breathed in from the nose and mouth to the lungs, are the body's first line of defense against airborne particles -- like germs and pollution -- that can cause illness.

Two types of airway cells play a vital role in this process: mucus cells, which secrete mucus to trap harmful particles, and ciliated cells, which use their finger-like projections to sweep the mucus-engulfed particles up to the back of the throat, where they can be cleared out of the lungs.

The infectious or toxic particles that people breathe in every day can injure the airways and when that happens, airway basal stem cells -- which are capable of self-renewing and producing the mucus and ciliated cells that line the airways -- activate to repair the damage.

To keep the right balance of each cell type, airway basal stem cells must transition from the proliferative phase, during which they produce more of themselves, to the differentiation phase, during which they give rise to mature airway cells.

"These stem cells have to maintain a really delicate equilibrium," said Gomperts, who is also co-director of the cancer and stem cell biology program at the UCLA Jonsson Comprehensive Cancer Center. "They have to produce just the right amount of mucus and ciliated cells to keep harmful particles out of the lungs, but they also have to self-replicate to ensure there will be enough stem cells to respond to the next injury."

In the new study, the researchers examined mice with lung injuries, analyzing how the different types of cells found in the niche -- the supportive environment that surrounds airway basal stem cells -- work together to orchestrate the repair response.

They found that a group of molecules known as the Wnt/beta-catenin signaling pathway activates to stimulate the airway basal stem cells to respond to injury. The researchers were surprised to discover that this group of molecules originates in one cell type to initiate proliferation and another cell type to initiate differentiation.

In the proliferation phase of repair, a connective tissue cell called a fibroblast secretes the Wnt molecule, which signals to the stem cells that it's time to self-renew. In the differentiation phase of repair, the Wnt molecule is secreted by an epithelial cell, which make up the lining of tissues and organs, to signal to the stem cells that it's time to produce mature airway cells.

Understanding how regeneration occurs in healthy lungs is a critical first step to understanding how disease can arise when the process goes wrong. Seeking insights into what role this process and the cells that activate it might play in disease, the scientists studied its activity in older mice.

"We were surprised to find that in the aging airways, the Wnt/beta-catenin signaling pathway is active in the stem cells even when there is no injury, in contrast to the young airways where it is only activated when necessary," said Cody Aros, the paper's first author, a UCLA medical student who recently completed his doctoral research. "When this pathway is active, it stimulates the stem cells to produce more of themselves and more airway cells -- even if they're not needed."

Previous research by Gomperts' lab has established a link between a more active Wnt/beta-catenin pathway and lung cancer.

"The more a cell divides, the more likely it is that a proofreading error or mutation can occur and lead to cancer," Gomperts said.

The new paper builds on that work by establishing not just what goes wrong but precisely when it goes wrong in otherwise healthy people as part of the aging process.

"These findings give us insight into which cell types are important, which pathway is important and when we might want to think about intervening with therapies to prevent the formation of cancer," Aros said.

Credit: 
University of California - Los Angeles Health Sciences

Heat smarter, not harder -- How microwaves make catalytic reactions more efficient

image: (Top) Whereas conventional heating results in a mostly uniform temperature between the platinum nanoparticle and support, microwave heating creates a marked temperature difference. This is revealed by the either gradual or sharp changes in the XAFS spectra as temperature changes. (Bottom) Microwaves selectively heat the metallic nanoparticles in the catalyst and create a temperature gradient that can be indirectly measured via XAFS spectroscopy. In this work, the external and internal temperature differences between nanoparticle and support were determined for two different catalysts, as well as their catalytic performance.

Image: 
Tokyo Tech

Many reactions that we use to produce chemical compounds in food, medical, and industrial fields would not be feasible without the use of catalysts. A catalyst is a substance that, even in small quantities, accelerates the rate of a chemical reaction and sometimes allows it to occur at milder conditions (lower temperature and pressure). A good catalyst can sometimes multiply the throughput of an industrial-scale reactor or shave more than 100°C off of its operating temperature.

It is no surprise, then, that catalyst research is crucial for making chemical reactions more efficient. One emerging approach that has been observed to provide these benefits is heating the metal nanoparticles in some catalysts directly using microwaves instead of conventional uniform heating techniques. Metal nanoparticles in catalysts interact strongly with microwaves and are believed to be heated selectively. However, scientists have reported conflicting results when using this approach, and understanding the effect that selectively heating the nanoparticles has on chemical reactions is difficult because no methods for measuring their local temperature have been found yet.

Now, scientists at Tokyo Tech led by Prof Yuji Wada tackle this problem and demonstrate a novel approach for measuring the local temperature of platinum nanoparticles in a solid catalyst. Their method, as detailed in their study published in Communications Chemistry, relies on X-ray absorption fine structure (XAFS) spectroscopy, which, as the name implies, provides information on the small local structures of a material using X-rays.

In extended XAFS oscillations, a value called the Debye-Waller factor can be derived. This factor is comprised of two terms; one related to structural disorder, and one related to thermal disorder. If the structure of the catalyst does not change upon microwave heating, any variation in the Debye-Waller factor has to be due to thermal variations. Therefore, XAFS can be used to indirectly measure the temperature of metal nanoparticles, as shown in Figure 1.

The team of scientists tested this approach in "platinum on alumina" and "platinum on silica" catalysts to find out to what extent microwaves can selectively heat the platinum nanoparticles instead of their supporting material. Microwave heating was found to produce a marked temperature difference between NP and support. A series of comparative experiments demonstrated that a higher local temperature of the metal nanoparticles in catalysts is crucial to obtaining higher reaction rates at the same temperature.

Excited about the results, Prof Wada remarks: "This work is the first to present a method for the assessment of the local temperatures of nanoparticles and their effect on catalytic reactions. We conclude that the local heating of platinum nanoparticles is efficient for accelerating chemical reactions that involve platinum itself, presenting a practical approach to obtain a dramatic enhancement in catalytic reactions using microwave heating."

These findings represent a breakthrough for improving our understanding of the role of microwave heating in enhancing catalytic performance. Dr. Tsubaki adds, "Efficient energy concentration at the active sites of catalysts--the metal nanoparticles in this case--should become a critical strategy for exploring microwave chemistry to achieve efficient energy use for reactions and to enable milder conditions for reaction acceleration." This new insight into catalytic processes will hopefully save tons of energy in the long run by making reactors work smarter, not harder.

Credit: 
Tokyo Institute of Technology

Temporary salt crystals may provide a permanent solution to Alzheimer's

image: Images showing the precipitation-dissolution event of a salt crystal observed by the liquid-state transmission-electron micrography.

Image: 
Osaka University

Osaka, Japan - Alzheimer's disease is the leading cause of dementia worldwide and a major cause of disability. Now, researchers at Osaka University and Hokkaido University have shown that repeated precipitation-dissolution events of salt crystals do occur even at low salt concentrations in nanoscales, and that it can accelerate the aggregation of the neurotoxic amyloid-β peptides implicated in its pathogenesis.

The human brain comprises around 86 billion neurons, roughly as many grains of sand as in a large dump truck. These neurons juggle electrochemical information as signals among the brain, muscles and organs to orchestrate the symphony of life from survival to self-awareness. Alzheimer's disease disrupts this complex neuronal networking, causing functional disability and cell death. As yet uncurable, available treatments are symptomatic, supportive, or palliative; a breakthrough in understanding its pathogenesis may brighten the prospects for medication, diagnosis and prevention.

The role of amyloid in Alzheimer's disease has long been recognized. Amyloid-β peptides are derived from amyloid precursor protein and they self-assemble into sizes ranging from low-molecular-weight aggregates and larger oligomers to amyloid fibrils. These last are known to be neurotoxic but recent research suggests that oligomeric disordered aggregates are also toxic, possibly even more than fibrils.

"Fibril aggregation begins with nucleation followed by an elongation stage," explains Kichitaro Nakajima, lead author of this study. "Until now, the early stages of oligomer evolution have been difficult to study because of their morphologic variability, the timeframe for nucleation, and the lack of a suitable fluorescent assay."

Using liquid-state transmission electron microscopy, the researchers analyzed the aggregation of protein molecules, acquiring time-resolved nanoscale images and electron diffraction patterns. "Remarkably, we discovered that a salt crystal can precipitate even at a concentration well below its solubility due to local density fluctuation, and its rapid dissolution accelerates the aggregation reaction of amyloid-β peptides," says Professor Hirotsugu Ogi, the corresponding author. "This formation of temporary salt crystals provides a mechanism whereby proteins adhere to the surface of the crystal; as it dissolves, the interface shrinks, condensing the proteins at the vanishing point. This phenomenon resembles the aggregation acceleration by ultrasonic cavitation bubble. Proteins are attached on the bubble surface during the expansion phase, and they are highly condensed by the subsequent bubble collapses by the positive pressure of ultrasonic wave at its center. This is the artificial catalytic effect. Thus, in an autocatalytic-like nanoscopic aggregation mechanism, salt dissolution accelerates the aggregation reaction, and the aggregate itself can promote salt nucleation."

Ogi explains the implications of their results: "The aggregation of amyloid-β peptides is slow and this has been a hindrance to pharmaceutical research. Establishing an effective acceleration method will help clarify their structural evolution from monomer to fibril. This knowledge is key to understanding the pathogenesis of Alzheimer's disease."

Credit: 
Osaka University

Lead white pigments on Andean drinking vessels provide new historical context

image: Lead researcher Allison Curley with qeros from the collection of the Smithsonian National Museum of the American Indian.

Image: 
Alyson Thibodeau

(Carlisle, Pa.) - Researchers studying lead white pigments on Andean ceremonial drinking vessels known as qeros have found new similarities among these artifacts that could help museums, conservators, historians and scholars better understand the timeline and production of these culturally significant items during the colonial period (1532-1821). In a study published in the journal Heritage Science, researchers used isotope measurements of lead white pigments in the decorative patterns on 20 colonial qeros to reveal linkages among vessels that were unknown previously.

The analysis identified only three isotope signatures among the lead white pigments decorating the qeros. Two of these isotopic signatures, present on a total of eight qeros, are the same as found in lead white paints used in European artwork from the same period. This match suggests these qeros are decorated with pigments imported to the Andes from Europe. The third signature, found on 12 of the qeros, suggests that the lead white was manufactured locally in the Andes.

The analysis was carried out by Allison Curley, a former Dickinson College undergraduate who is now a graduate student in earth & environmental sciences at the University of Michigan, and her mentor, geochemist Alyson Thibodeau, assistant professor of earth sciences at Dickinson, along with a team of researchers from the Smithsonian National Museum of the American Indian; the Metropolitan Museum of Art; the UCLA/Getty Program in Conservation of Archaeological and Ethnographic Materials; and the American Museum of Natural History.

"Little is known about the history of colonial qeros now in museum or private collections. The results could lead to a better understanding of the objects' chronology and production," explained Thibodeau. "For example, it is possible that qeros made earlier in the colonial period are decorated with European lead white, while qeros made later are decorated with lead white made from Andean ores. Further, the results strongly suggest some form of centralization in pigment acquisition, manufacture and distribution in the colonial period."

"The consistency of the data was both surprising and satisfying," said Curley, who has been collaborating with Thibodeau on this project since 2017. "It is exciting to see geochemistry provide insights into some longstanding historical and archaeological questions, and I was absolutely thrilled to present these findings to the Society for American Archaeology and to the conservators at the Smithsonian."

"It's important for those studying qeros all over the world to have a better understanding of the Andean people who made and used qeros during a time of colonial rule," said Emily Kaplan, conservator for the Smithsonian National Museum of the American Indian, which has the largest collection of qeros in the United States. Kaplan hopes the research will lead to more radiocarbon dating, which will reveal more about the chronology of qero production. "Style and iconography have been used to help establish production timelines, but there's a lot of guesswork involved," she said.

Ceremonial drinking vessels have been used for toasting rituals in the Andes for millennia. Wooden qeros made in the colonial period were typically fabricated in identical pairs to make ceremonial toasts for social, political and religious occasions. These items retain their cultural significance to this day and are recognized as a symbol of the Inka Empire. Because they provide a window into the Andean indigenous colonial experience, qeros have been studied by art historians, archaeologists and anthropologists.

Credit: 
Dickinson College

Trapping tiny particles: A versatile tool for nanomanipulation

image: Using a metamaterial, the group traps nanoparticles.

Image: 
OIST

Nanoparticles are tiny. At just 1/1000th of a millimeter, they're impossible to see with the naked eye. But, despite being small, they're extremely important in many ways. If scientists want to take a close look at DNA, proteins, or viruses, then being able to isolate and monitor nanoparticles is essential.

Trapping these particles involves tightly focusing a laser beam to a point that produces a strong electromagnetic field. This beam can hold particles just like a pair of tweezers but, unfortunately, there are natural restrictions to this technique. Most notable are the size restrictions - if the particle is too small, the technique won't work. To date, optical tweezers have been unable to hold particles like individual proteins, which are only a few nanometers in diameter.

Now, due to recent advances in nanotechnology, researchers in the Light-Matter Interactions for Quantum Technologies Unit at the Okinawa Institute of Science and Technology Graduate University (OIST) have developed a technique for precise nanoparticle trapping. In this study, they overcame the natural restrictions by developing optical tweezers based on metamaterials - a synthetic material with specific properties that do not occur naturally. This was the first time that this kind of metamaterial had been used for single nanoparticle trapping.

"Being able to manipulate or control these small particles is crucial for advances in biomedical science," explained Dr. Domna Kotsifaki, staff scientist in the OIST Unit and first author of the research paper published in Nano Letters. Dr. Kotsifaki went on to explain that trapping these nanoparticles could enable researchers to see the progression of cancer, to develop effective drugs, and to advance biomedical imaging. "The potential applications for society are far-reaching."

This novel technique has two sought after abilities - it can stably trap the nanoparticles using low intensity laser power and it can be used for a long period whilst avoiding light damage to the sample. The reason for this was the metamaterial that the researchers chose to use. This metamaterial is highly sensitive to changes in the surrounding environment and, therefore, allows for the use of low intensity laser power.

"Metamaterials have unusual properties due to their unique design and structure. But this makes them very useful. Over the last few years, a whole new era of devices with novel concepts and potential applications has been created from them," explained Dr. Kotsifaki. "From the metamaterial, we fabricated an array of asymmetric split rings using a beam of ions - tiny, charged particles - on a 50 nm gold film."

To test whether the technique worked, the research group illuminated the device with near infrared light and trapped 20 nm polystyrene particles at certain regions on it.

Dr. Kotsifaki and colleagues were looking for the trap stiffness, which is a measurement of trapping performance. "The achieved trapping performance was several times better than that of conventional optical tweezers and the highest reported to date as far as we know," she explained. "As the first group to use this device for precision nanoparticle trapping, it has been rewarding to contribute to such progress in this research area."

The research team now plans to tweak their device to see if these tweezers can be used in real-world applications. Specifically, in the future, this device could be utilized to create lab-on-chip technologies, which are hand-held, diagnostic tools that can provide results efficiently and economically. Alongside its applications in biomedical science, this research has provided new and fundamental insights into nanotechnology and light behavior at the nanoscale.

As well as Dr. Domna Kotsifaki, the research group consisted of Professor Síle Nic Chormaic, who leads the OIST Unit, and staff scientist, Dr. Viet Giang Truong.

Credit: 
Okinawa Institute of Science and Technology (OIST) Graduate University

Knowledge, concerns, behaviors of individuals during 1st week of COVID-19 pandemic in Italy

What The Study Did: This is a survey study that examined the knowledge, concerns and behaviors of people living in different COVID-19 exposure zones during the first week of the pandemic in Italy.

Authors: Francesco Pagnini, Psy.D., Ph.D., of the Università Cattolica del Sacro Cuore in Milan, Italy, is the corresponding author.

To access the embargoed study: Visit our For The Media website at this link https://media.jamanetwork.com/

(doi:10.1001/jamanetworkopen.2020.15821)

Editor's Note: The article includes conflict of interest disclosures. Please see the article for additional information, including other authors, author contributions and affiliations, conflict of interest and financial disclosures, and funding and support.

Credit: 
JAMA Network

T cells can shift from helping to harming in atherosclerosis

image: Everyone produces T cells that can recognize ApoB, the protein backbone of LDL cholesterol, better knowns as "bad" cholesterol. Close-up of a T cell receptor (green) and an MHC molecule (pink), which presents a fragment of an ApoB molecule (light grey).

Image: 
Ley Laboratory, La Jolla Institute for Immunology

LA JOLLA--High cholesterol kills. In fact, one in four Americans will die from the consequences of atherosclerosis, the buildup of plaques of fat and cholesterol in the arteries. Statins have helped reduce mortality, but millions are still at risk.

At La Jolla Institute for Immunology (LJI) researchers are dedicated to finding a way to stop plaques from forming in the first place. In a new study, LJI scientists show that certain T lymphocytes, a type of white blood cell, that start out trying to fight the disease can end up increasing inflammation and making atherosclerosis cases even worse.

"Your immune response to self is normally anti-inflammatory, but once the disease process starts, it turns against you," says LJI Professor Klaus Ley, M.D., who led the study published July 24, 2020 in the journal Circulation.

Ley's lab specializes in studying T cells, immune cells that recognize specific peptides, or pieces of a protein. Ley's lab has found that everyone produces T cells that can recognize ApoB, the protein backbone of LDL cholesterol. LDL, sometimes called "bad" cholesterol, is important for transporting fat molecules to where they are needed in the body, but too much LDL can contribute to the plaques that narrow arteries in atherosclerosis.

Ley is hoping to someday harness the power T cells by designing a vaccine that could target LDL and prevent dangerous plaques from ever forming. In a 2018 study, Ley's team showed that an atherosclerosis vaccine could reduce plaque levels in mice.

To design a safe vaccine for human patients, Ley and his colleagues need a deep understanding of how T cells function in atherosclerosis.

For the new study, Ley worked with the lab of LJI Professor Alessandro Sette, Dr. Biol. Sci., to find the epitopes--the T cell targets--on the ApoB protein. This allowed the researchers to then build "tetramers," or molecules that they could use to find the very small population of T cells that can actually recognize those epitopes.

Using this new tracking method, Ley and his colleagues identified a group of regulatory T cells that would normally help reduce inflammation in the body. But it appears that something goes haywire in atherosclerosis that turns the function of these cells on its head. Instead of reducing inflammation, the regulatory T cells start secreting immune molecules, called cytokines, that increase inflammation and further narrow diseased arteries.

"These T cells don't cause plaques in the arteries, but they can accelerate the disease," says Ley.

The researchers saw the same phenomenon in mouse models of atherosclerosis and in human patients with coronary artery disease, caused by atherosclerosis.

"The reasons why this happens are unclear," says Ley. "We know that ApoB goes up as your cholesterol goes up, and these cells turn into pro-inflammatory cells."

The researchers found that both genetics and diet can play a role in shifting regulatory T cells from helpers to pathogenic cells. In fact, diet led to the harmful T cell shift in mice after only four weeks. This suggests a metabolic change might be behind this T cell behavior, but it is too early to know for sure.

"Obviously, we cannot have T cells switching like this after we vaccine against ApoB, so we need to better understand what is happening when the cells switch," Ley says.

Ley and his colleagues are now using a new technology (called single-cell RNA sequencing with cell-surface phenotype) to study T cells from many more patients in even more detail. They are working to understand exactly what drives the regulatory T cells to become pathogenic. "You can only protect patients if you know the mechanism," Ley says.

Credit: 
La Jolla Institute for Immunology

Genetic mutations help MRSA to become highly resistant to antibiotics

Scientists from the University of Sheffield have found that genetic mutations in MRSA allow it to evolve and become more resistant to antibiotics such as penicillin.

The research, published in PLOS Pathogens, found that genetic mutations in MRSA are allowing the bacteria to become highly resistant to antibiotics without reducing the bacteria's ability to cause disease.

Most clinical MRSA exhibits a low level of antibiotic resistance, due to the cells acquiring a new gene encoding a protein (MecA) that makes its cell wall, some strains can evolve high-level resistance and pose a serious threat.

Antibiotics, such as penicillin and methicillin, do not bind well to the new protein (MecA) meaning they cannot 'kill' the bacteria. The next phase of this research is to understand how this protein works with other factors within the bacteria to allow a higher level of antibiotic resistance.

Findings from the research pave the way for more understanding of the cause and evolution of antibiotic resistance, and will help researchers develop new treatments and drugs for MRSA.

Simon Foster, Professor of Molecular Microbiology at the University and Principal Investigator of the research, said: "Antibiotics have been a mainstay of human healthcare for over 70 years, but the emergence of antimicrobial resistance is now a global catastrophe. In order to combat antimicrobial resistant organisms, we have to understand them. Our work uncovers the complex mechanisms that underpin resistance, giving insight into how we might tackle this global challenge."

The research is part of a collaborative project called the Physics of Antimicrobial Resistance which involves the Universities of Sheffield, Newcastle, Edinburgh and Cambridge, funded by UK Research and Innovation (UKRI).

Dr Viralkumar Panchal, Postdoctoral Researcher at the University of Sheffield and leader of the research, said: "The research provides a new outlook into the process of evolution of resistance and reveals important details of how MRSA is so resistant. We can now exploit these findings to develop new cures."

Globally, the effectiveness of antimicrobial compounds is decreasing as infectious species become increasingly resistant. The University of Sheffield's Florey Institute for Host-Pathogen Interactions aims to create a world-leading focus on antimicrobial resistance from fundamental science to translation and brings together scientists and clinicians to tackle this problem.

Credit: 
University of Sheffield

Ocean features and changes in the past are explored to anticipate future climate

image: A core being extracted from the floor of the Bay of Biscay taken on board an oceanographic vessel.

Image: 
Julio Rodríguez-UPV/EHU

The climate represents the set of atmospheric conditions that characterize a region. Yet these conditions are the result of global interaction between dry land, vegetation, ice, atmosphere and ocean. "Bearing in mind that the oceans cover 75% of the earth's surface, the influence they exert on the climate is very strong, and conversely, the oceans are strongly influenced by climate changes. In our group we are involved in the study of palaeoceanography in which we seek and analyse evidence on how the ocean has changed during various climatic periods or intervals. Our study focusses on the Bay of Biscay, a part of the ocean we have off our coasts," said Julio Rodríguez-Lázaro, professor of the Department of Stratigraphy and Palaeontology at the UPV/EHU's Faculty of Science and Technology and one of the authors of the study.

In a piece of work recently published in the Quaternary International journal, this group mainly comprising female researchers detailed with great precision many of the climatic events occurring in the last 37,000 years. To do this they resorted to the study of the microfossils of 176 species of benthic foraminifera obtained from cores of the ocean floor. The foraminifera studied are tiny marine organisms (a single, but very large cell), characterised by a carbonate shell the size of a grain of sand widely used in palaeoceanography because "we can find out the conditions prevailing in a specific location and during a specific period in terms of the species that are plentiful in one geological epoch or another. This faunal analysis is possible because many of the foraminifera species are highly sensitive to basic environmental parameters, such as temperature, oxygen concentration or organic matter content," said the researcher.

So in the sediment of the Bay of Biscay they were able to identify evidence of known climatic episodes, not only cold periods, such as the Younger Dryas or Heinrich events, but also warm intervals, such as the Bolling-Allerod or the Holocene, occurring throughout recent geological history, including recent millennia. In addition, they regard the identification of the 176 benthic foraminifera described as "a contribution towards knowledge about the biodiversity existing in the Bay of Biscay during the Quaternary period".

Involvement of oceans in global climate

Beyond the last 37,000 years the research group in the UPV/EHU's Department of Stratigraphy and Palaeontology is working on detecting the climate changes that took place in the Bay of Biscay 150,000 years ago. Rodriguez sums it up thus: "The climate on the planet during this period of time is characterised by the sharp alternation of warm and cool periods, and these climate changes appear to have taken place about every 1,500 years. Warming (up to 10 ºC) takes place within a few decades while cooling occurs over the course of several centuries. When cooling occurs, what happens is that the water in the north Atlantic Ocean cools down coinciding with massive iceberg discharges originating from the breaking up of ice sheets in the Arctic Ocean, and the result is a cool climate period in the northern hemisphere."

These rapid climate changes are caused by alterations in the so-called AMOC (Atlantic Meridional Overturning Circulation); this is when heat is carried northwards from the south Atlantic by the movements of ocean water bodies, where warm, less dense tropical waters move northwards, while cold, denser waters of the north Atlantic head southwards at a depth. On their way these water movements modify not only the climate of Europe (making it milder), but also that of the planet as a whole. AMOC is altered when not very salty waters head into the Arctic owing to the melting of permafrost and also as a result of changes caused by the thickness of the ice in these Arctic latitudes.

The geological moment we are experiencing right now is an interglacial "or warm" (Holocene) epoch, and "if we were progressing at the rate at which previous intervals of cold and heat took place, we should be moving towards a cooling down, but this is not happening," warned Rodriguez. "As a result of human activity, we are altering this cycle, we are modifying the natural balance. And that could have serious consequences during the forthcoming climate cycles in the near future".

Credit: 
University of the Basque Country