Culture

Oncotarget published "Perioperative changes in the plasma metabolome of patients receiving general anesthesia for pancreatic cancer surgery" which reported that little is known about the impact of anesthesia on the plasma metabolome, although many metabolites have been shown to modulate the function of various immune cells, making it particularly interesting in the context of oncological surgery.

In this study longitudinal dynamics in the plasma metabolome during general anesthesia in patients undergoing pancreatic surgery were analyzed.

Prospective, observational study with 10 patients diagnosed with pancreatic malignancy and subjected to elective resection surgery under general anesthesia.

Plasma metabolites were quantified at eight consecutive perioperative timepoints using mass spectrometry-based targeted metabolomics.

The major finding of this Oncotarget study was perioperative tryptophan depletion and increased taurine synthesis.

The major finding of this Oncotarget study was perioperative tryptophan depletion and increased taurine synthesis.

Dr. Johanna Mock-Ohnesorge from The Heidelberg University Hospital said, "Although general anesthesia using intravenous and volatile anesthetics is well and safely established for extended abdominal surgery, little is known about the effects of anesthesia on perioperative metabolism."

While in the past, anesthetic procedures were considered sole prerequisites of surgery, modern anesthesia evolved to become more individualized in an effort to address a patient's individual needs regarding the metabolic, physiological and immunological integrity in sight of long-term clinical outcome.

Since immune cells as natural killer cells or CD8 T-cells have the capability to identify and eliminate these malignant cells, the perioperative immune status plays an essential role for anti-tumor activities.

A plethora of factors contribute to a complex modulation of immune function during surgery, e.g., the release of damage-associated molecular patterns from injured tissue and the organism's release of metabolites in response to anesthesia and surgical stress.

The objective of this prospective, exploratory study is to gain information on longitudinal perioperative alterations in the plasma metabolome during general anesthesia in patients diagnosed with pancreatic malignancies leading to a better understanding for personalized perioperative management.

The Mock-Ohnesorge Research Team concluded in their Oncotarget Research Output that metabolomics represent a phenotype of all genetic, transcriptomic and posttranslational modifications.

Perioperative metabolomic analysis enables to get a more accurate insight on perioperative processes.

This will answer individual needs enabling personalized anesthetic management.

In the field of surgical oncology, it might be even possible to identify therapeutic windows with best conditions for perioperative immunotherapy or chemotherapy.

Further controlled studies are desperately needed to compare the impact of different anesthetic procedures on the plasma metabolome to identify beneficial or detrimental influences on long-term clinical outcome.

Oncotarget published "Genome wide DNA methylation landscape reveals glioblastoma's influence on epigenetic changes in tumor infiltrating CD4+ T cells" which reported that whole-genome bisulfite sequencing of tumor infiltrating and blood CD4 T-cell from GBM patients showed 13571 differentially methylated regions and a distinct methylation pattern of methylation of tumor infiltrating CD4 T-cells with significant inter-patient variability.

The methylation changes also resulted in transcriptomic changes with 341 differentially expressed genes in CD4 tumor infiltrating T-cells compared to blood.

Analysis of specific genes involved in CD4 differentiation and function revealed differential methylation status of TBX21, GATA3, RORC, FOXP3, IL10 and IFNG in tumor CD4 T-cells.

Interestingly, the authors observed dysregulation of several ligands of T cell function genes in GBM tissue corresponding to the T-cell receptors that were dysregulated in tumor infiltrating CD4 T-cells.

These Oncotarget results suggest that GBM might induce epigenetic alterations in tumor infiltrating CD4 T-cells there by influencing anti-tumor immune response by manipulating differentiation and function of tumor infiltrating CD4 T-cells.

These Oncotarget results suggest that GBM might induce epigenetic alterations in tumor infiltrating CD4 T-cells

Dr. Mahua Dey from The University of Wisconsin-Madison as well as The Indiana University School of Medicine said, "Naïve CD4+ helper T cell population is known for its polyfunctionality and highly plastic characteristics."

In the tumor microenvironment, lineage commitments of CD4 T cells reflect initiation of new programs of gene expression within tumor infiltrating naïve T cells.

The GBM tumor microenvironment is known to be extremely immunosuppressive, possessing multiple unique properties including:

Impaired cellular immunity no dearth of tumor infiltrating T cells
High levels of TGFβ secreted by resident as well as circulating microglia and
Expression of several inhibitory ligands, eliciting anergy and apoptosis of cytotoxic lymphocytes in the TME, immune checkpoints expression, and increased infiltration of immunosuppressive cells.

Genome wide methylation sequencing showed 13571 uniquely differentially methylated regions , mostly concentrated around the TSS, in the CD4 T cells from GBM patient tumor compared to blood.

Furthermore, combining transcriptomic data from RNAseq analysis with DNA methylation, we observed differential methylation of gene sets specific for CD4 T cells including Th1, Th2, Th17 and iTregs in GBM tumors, although with significant interpatient variability.

In conclusion, this data for the first time, report unique DNA methylation pattern and gene expression profiles in GBM associated tumor infiltrating CD4 T cells compared to CD4 T-cell from the blood of the same patient and some of their ligands on the GBM cells suggesting that CD4 T cells function and differentiation may be influenced by the GBM TME by way of epigenetic mechanisms such as, DNA methylation.

The Dey Research Team concluded in their Oncotarget Research Output, "in the present clinical corelative report, we demonstrated that differential DNA methylation pattern might influence gene expression in tumor infiltering CD4+ T cells as compared to circulating blood CD4+ T cells in GBM patients. Our findings provide evidence that GBM might be influencing the state of tumor infiltrating CD4+ T cells by epigenetic modification in the form of DNA methylation of key immune function regulating genes and influencing the fate of helper T cells in the GBM TME. Based on our observations we believe that perhaps epigenetic interaction between GBM and tumor infiltrating CD4+ T cells is responsible for the immunosuppressed state seen in the GBM patients. Our data convincingly show that there is significant inter-patient variability in the GBM tumor ligand expression of various T-cell modulating ligands and consequently striking differences in the methylation pattern and gene expression in tumor infiltrating CD4+ T-cells. This has a very strong implication for selecting future patients for immunotherapy trials who will have better likelihood of responding to immunotherapy than others based on their tumor immune signature. The findings from our corelative study needs to be further validated in the experimental setting."

Scientists have found an unexplained cache of fossilised shark teeth in an area where there should be none - in a 2900 year old site in the City of David in Jerusalem. This is at least 80 km from where these fossils would be expected to be found. There is no conclusive proof of why the cache was assembled, but it may be that the 80 million-year-old teeth were part of a collection, dating from just after the death of King Solomon*. The same team has now unearthed similar unexplained finds in other parts of ancient Judea.

Presenting the work at the Goldschmidt Conference, lead researcher, Dr. Thomas Tuetken (University of Mainz, Institute of Geosciences) said:

"These fossils are not in their original setting, so they have been moved. They were probably valuable to someone; we just don't know why, or why similar items have been found in more than one place in Israel".

The teeth were found buried in material used to fill in a basement before conversion to a large Iron-Age house. The house itself was situated in the City of David, one of the oldest parts of Jerusalem, found nowadays in the largely Palestinian village of Silwan. They were found together with fish bones thrown away as food waste 2900 years ago, and other infill material such as pottery. Intriguingly, they were found together with hundreds of bullae - items used to seal confidential letters and packages - implying a possible connection with the administrative or governing class at some point. Normally archaeological material is dated according to the circumstances where it is found, and so at first it was assumed that the teeth were contemporary with the rest of the find. Dr. Tuetken said:

"We had at first assumed that the shark teeth were remains of the food dumped nearly 3000 years ago, but when we submitted a paper for publication, one of the reviewers pointed out that the one of the teeth could only have come from a Late Cretaceous shark that had been extinct for at least 66 million years. That sent us back to the samples, where measuring organic matter, elemental composition, and the crystallinity of the teeth confirmed that indeed all shark teeth were fossils. Their strontium isotope composition indicates an age of about 80 million years. This confirmed that all 29 shark teeth found in the City of David were Late Cretaceous fossils - contemporary with dinosaurs. More than that, they were not simply weathered out of the bedrock beneath the site, but were probably transported from afar, possibly from the Negev, at least 80 km away, where similar fossils are found".

Since the first finds, the team have found other shark teeth fossils elsewhere in Israel, at the Maresha and Miqne sites. These teeth are also likely to have been unearthed and moved from their original sites.

Dr. Tuetken said:

"Our working hypothesis is that the teeth were brought together by collectors, but we don't have anything to confirm that. There are no wear marks which might show that they were used as tools, and no drill holes to indicate that they may have been jewellery. We know that there is a market for shark's teeth even today, so it may be that there was an Iron Age trend for collecting such items. This was a period of riches in the Judean Court. However, it's too easy to put 2 and 2 together to make 5. We'll probably never really be sure".

The shark teeth which have been identified come from several species, including from the extinct Late Cretaceous group Squalicorax. Squalicorax, which grew to between 2 and 5 metres long, lived only during the Late Cretaceous period (which was the same period as the late dinosaurs), so acts as a reference point in dating these fossils.

Commenting, Dr. Brooke Crowley (University of Cincinnati) said:

"This research by Dr. Tuetken and colleagues is an excellent example of why it is so important to approach a research question with as few assumptions as possible, and how sometimes we have to revisit our initial assumptions. It also highlights how beneficial it can be to apply multiple tools to answer a research question. In this case, the authors used both strontium and oxygen isotopes, as well as x-ray diffraction and trace element analysis to establish most likely age and origin of the fossil teeth. It was a monumental of work but these efforts have revealed a much more interesting story about the people who lived in this region in the past. I am very excited by this work and hope that one day, we might be able to unravel the mystery of why these fossil teeth are being recovered from cultural deposits".

When the analysis of digital data reaches its limits, methods that focus on observations made by individuals can be useful. In contexts such as the coronavirus pandemic, a method called human social sensing can elicit information that is difficult to obtain from digital trace data. Prof. Frauke Kreuter at Ludwig-Maximilians-Universitaet (LMU) in Munich is now using this method with the global "Covid Trends & Impact Survey" to predict the course of the pandemic.

Despite today's researchers in the social sciences having access to historically unparalleled amounts of data, many aspects of contemporary social developments have proven difficult to predict. National elections and the ongoing coronavirus pandemic are highly visible examples where current systems have been challenged to provide accurate forecasts.

"We shouldn't focus too narrowly on the analysis of digital trace data. It's a mistake to ignore the fact that people are equipped with sensory capacities. Those can be particularly useful in areas that are difficult to capture with data from behavioral traces", says Frauke Kreuter, Professor of Statistics and Data Science in the Social Sciences and the Humanities at LMU. Many social phenomena develop very rapidly - and often in unexpected directions. This makes it impossible to collect enough up-to-date passive data to enable researchers to trace the trajectories of such trends.

The individual as a human sensor plays a central role

In a research paper that has just appeared in the journal Nature, Kreuter and her international co-authors demonstrate that interviews with individual informants still have a crucial role to play, even in an era where big data generates the biggest headlines. "One should never lose sight of the fact that surveys can serve as a very valuable source of supplementary information", she says.

An individual interviewee is in a position to supply information not only about her own situation, but also, "individual interviews allow one to ask individuals about themselves and also about things in their local environment. However, the latter possibility has long been overlooked." And now, in this current context, it is beneficial to make use of the fact that the individual can be viewed as a potentially informative 'social sensor' for what is happening around him.

The development of the coronavirus pandemic as a test case

As a statistician, Frauke Kreuter chose to employ together with her colleagues this approach in the current global "Covid Trends & Impact Survey", which attempts to forecast the trajectory of the coronovirus pandemic. The survey began in April 2020, and over 55 million people globally have been interviewed. One of  the queries asks interviewees whether they personally know anyone in their local community with COVID-19 symptoms.

This is of particular salience as, "the answers to this question turn out to be a strong predictor of the further development of the pandemic", says Kreuter. Preliminary results of the study have already appeared as a preprint on MedRxiv. "The crucial prerequisite for the use of individuals as sensors in social-science surveys is that the informants chosen must constitute a controlled and representative sample of the population of interest."

The seasonal flu kills up to 600 000 people a year worldwide and has a century-long history of pandemics. Examples include the Spanish flu in the late 1910's or the H1N1 in 2009, which together claimed more than 50 million lives. "The way the stage is set tells us that it is not a matter of if but rather of when there will be a next pandemic. And preparing ourselves for that demands intensive fundamental research and constant accumulation of knowledge about these viruses and the diseases they cause", says Maria João Amorim, IGC principal investigator and leader of the team that conducted the study.

When a virus like influenza enters our lungs, it is quickly faced with cocktails of molecules that recognize it and alert the host of its presence. Signals flow back and activate the immune response, calling in an army of cells and inflammation sidekicks. Any exaggeration can destabilize the equilibrium needed to clear the virus and spare our tissues from damage. For most people, clearance arrives a few days after infection and leaves very few traces. But for some, influenza infection entails severe complications, resulting from an exacerbated response that damages the lungs.

"We found that DAF, which stands for decay accelerating factor, aggravates influenza A infection and increases damage to the lungs in mice. This virulence mechanism of influenza, and the molecular regulation that underpins it, are new for us", Maria João Amorim reveals. DAF is a receptor found at the surface of most cells that functions to protect them from being attacked by one of our own immune surveillance systems--the complement. This system protects us against invading pathogens once it detects them in circulation, by inactivating the pathogen itself, or inside infected cells, by mounting a strategy to eliminate them.

"But this can work as double-edged sword because if complement destroys cells from the host, there is the associated danger of provoking excessive self-injury by eliminating too many bystander cells and promoting inflammation. In fact, disease severity and mortality have been associated with both lack or excess of complement activation, which is tuned by regulators such as DAF", remarks Nuno Santos, first author of the study. Contrary to expectations, the team found that influenza A virus exploits DAF to potentiate complement activation as an immune evasion mechanism, increasing the recruitment of immune cells. "By doing so, it can exacerbate the immune response, and this is what damages the lungs. Remarkably, this occurs in a way that is independent of viral load, telling us that it directly affects resilience to infection", says Zoé Vaz da Silva, coauthor of the study.

The role of DAF upon influenza infection can depend on how it interacts with some parts of the virus, leading to more or less aggravated responses. "The complement system is important, but not the only component that determines the outcome of the infection. These interactions have functional implications and are an unprecedented way of a virus, via altering a host protein from within the infected cell, to modulate the immune response. Studying this further in the future is crucial", Maria João Amorim says.

Researchers based in Munich and Tuebingen have developed an open-source camera system that images natural habitats as they appear to rodents.

During the course of evolution, animals have adapted to the particular demands of their local environments in ways that increased their chances of survival and reproduction. This is also true of diverse aspects of the sensory systems that enable species to perceive their surroundings. In the case of the visual system, these adaptations have shaped features such as the positioning of the eyes and the relative acuity of different regions of the retina.

However, our knowledge of the functional evolution of visual systems in mammals has remained relatively sparse. "In the past 10 or 15 years, the mouse has become the favored model for the investigation of the processing of visual information," says Professor Laura Busse of the Department of Biology II at Ludwig-Maximilians-Universitaet (LMU) in Munich. "That's a somewhat surprising development, given that it was previously thought that these rodents primarily sensed the world using their whisker system and smell." However, color vision in mammals is known to have an effect on the ability to find food, evade predators, and choose mating partners.

"It occurred to us that we don't really know how mice perceive their natural environment visually," says Busse, who is a member of the transregional Collaborative Research Center (CRC) 1233  on "Robust Vision". Here, the term "robust" refers the fact that animals (including humans) are able to draw inferences from limited amounts of visual information, even in environments that are constantly changing. Busse decided to close this gap by studying the visual input and the processing of neuronal signals in mice", In collaboration with Professor Thomas Euler of Tuebingen University, the Coordinating University of the CRC.

A camera that captures the mouse's view

Mice are dichromate - in other words, they have two types of cone cells (the photoreceptors that are responsible for color vision) in their retinas. These cells detect electromagnetic radiation in the green and ultraviolet regions of the spectrum, centered on wavelengths of 510 nanometers (nm) and 350 nm, respectively. "We wanted to know what range of color information is available to mice in their natural habitats, and whether the prevalence of these colors can explain the functional characteristics of the neural circuits in the mouse retina," Busse explains.

Together, the teams in Munich and Tuebingen set out to develop an low-cost, open-source camera which, unlike conventional cameras, was specifically designed to cover the spectral regions in the green and ultraviolet to which the mice retina is sensitive. To facilitate its use in the field, the hand-held camera is equipped with a gimbal, which automatically orients the picture frame, thus avoiding sudden, unintentional shifts in perspective.

The researchers used this camera to image the environment as it would appear to a mouse, at different times of the day, in fields that showed clear signs of their presence. "We knew that the upper hemisphere of the mouse retina, with which they can see the sky, is especially sensitive to UV light," says Busse. "The lower half of the mouse retina, which is normally oriented towards the ground, shows a higher sensitivity in the green region. The team confirmed that these two spectral ranges closely match the color statistics of the natural environments that are favored by mouse populations. This adaptation could be a result of evolutionary processes - and for example help the animal to perceive birds of prey in the sky - and take evasive action. Experiments using artificial neural nets that mimic the processing characteristics of cone cells in the mouse retina confirm this conjecture.

Elisa Cordero, a doctor at the Virgen del Rocío University Hospital, researcher at the Institute of Biomedicine of Seville (IBiS) and professor in the Department of Medicine at the University of Seville, led a study involving researchers from 12 Spanish hospitals to study the clinical characteristics and facilitate the prognosis of solid organ transplant recipients with COVID-19.

The study provides a more precise description of the complications caused by Covid-19 in organ transplant recipients and has provided useful clinical indicators to identify the disease early. This makes it possible to determine therapeutic and care measures based on an individual assessment of each patient. The study highlights the need to take preventive measures with recently transplanted patients to avoid all risk of Covid-19 infection.

"This study found that SARS-CoV-2 infection is more severe in patients who have received a solid organ transplant, especially in the first months after transplantation. It is thus very important to take strict precautionary measures," stresses Dr. Cordero.

The project received support from the Carlos III Health Institute (ISCIII), Spanish Ministry of Science and Innovation, through the call for Research Projects on SARS-CoV-2 and Covid-19 (COV20/00370) and the Clinical Research Support Platform of the ISCIII.

The study in figures

A total of 210 patients with Covid-19 were analysed, of whom 140 (70.5%) were male with an average age of 63 years. It found that 90% of the patients suffered pneumonia, with the most frequent symptoms presented being fever, cough, gastrointestinal disorders and dyspnoea.

Seventeen percent of patients required admission to intensive care units and 5.7% suffered graft dysfunction. The study concluded with a mortality rate among the patients in the sample of 21.4%, i.e. 45 of the 210 patients studied died. Some of the factors associated with the need to admit patients to intensive care or, indeed, mortality were advanced age, respiratory failure, a drop in lymphocytes and elevated lactate dehydrogenase enzyme.

A new study disputes the prevailing hypothesis on why Mercury has a big core relative to its mantle (the layer between a planet's core and crust). For decades, scientists argued that hit-and-run collisions with other bodies during the formation of our solar system blew away much of Mercury's rocky mantle and left the big, dense, metal core inside. But new research reveals that collisions are not to blame--the sun's magnetism is.

William McDonough, a professor of geology at the University of Maryland, and Takashi Yoshizaki from Tohoku University developed a model showing that the density, mass and iron content of a rocky planet's core are influenced by its distance from the sun's magnetic field. The paper describing the model was published on July 2, 2021, in the journal Progress in Earth and Planetary Science.

"The four inner planets of our solar system--Mercury, Venus, Earth and Mars--are made up of different proportions of metal and rock," McDonough said. "There is a gradient in which the metal content in the core drops off as the planets get farther from the sun. Our paper explains how this happened by showing that the distribution of raw materials in the early forming solar system was controlled by the sun's magnetic field."

McDonough previously developed a model for Earth's composition that is commonly used by planetary scientists to determine the composition of exoplanets. (His seminal paper on this work has been cited more than 8,000 times.)

McDonough's new model shows that during the early formation of our solar system, when the young sun was surrounded by a swirling cloud of dust and gas, grains of iron were drawn toward the center by the sun's magnetic field. When the planets began to form from clumps of that dust and gas, planets closer to the sun incorporated more iron into their cores than those farther away.

The researchers found that the density and proportion of iron in a rocky planet's core correlates with the strength of the magnetic field around the sun during planetary formation. Their new study suggests that magnetism should be factored into future attempts to describe the composition of rocky planets, including those outside our solar system.

The composition of a planet's core is important for its potential to support life. On Earth, for instance, a molten iron core creates a magnetosphere that protects the planet from cancer-causing cosmic rays. The core also contains the majority of the planet's phosphorus, which is an important nutrient for sustaining carbon-based life.

Using existing models of planetary formation, McDonough determined the speed at which gas and dust was pulled into the center of our solar system during its formation. He factored in the magnetic field that would have been generated by the sun as it burst into being and calculated how that magnetic field would draw iron through the dust and gas cloud.

As the early solar system began to cool, dust and gas that were not drawn into the sun began to clump together. The clumps closer to the sun would have been exposed to a stronger magnetic field and thus would contain more iron than those farther away from the sun. As the clumps coalesced and cooled into spinning planets, gravitational forces drew the iron into their core.

When McDonough incorporated this model into calculations of planetary formation, it revealed a gradient in metal content and density that corresponds perfectly with what scientists know about the planets in our solar system. Mercury has a metallic core that makes up about three-quarters of its mass. The cores of Earth and Venus are only about one-third of their mass, and Mars, the outermost of the rocky planets, has a small core that is only about one-quarter of its mass.

This new understanding of the role magnetism plays in planetary formation creates a kink in the study of exoplanets, because there is currently no method to determine the magnetic properties of a star from Earth-based observations. Scientists infer the composition of an exoplanet based on the spectrum of light radiated from its sun. Different elements in a star emit radiation in different wavelengths, so measuring those wavelengths reveals what the star, and presumably the planets around it, are made of.

"You can no longer just say, 'Oh, the composition of a star looks like this, so the planets around it must look like this,'" McDonough said. "Now you have to say, 'Each planet could have more or less iron based on the magnetic properties of the star in the early growth of the solar system.'"

The next steps in this work will be for scientists to find another planetary system like ours--one with rocky planets spread over wide distances from their central sun. If the density of the planets drops as they radiate out from the sun the way it does in our solar system, researchers could confirm this new theory and infer that a magnetic field influenced planetary formation.

July 2, 2021 - For health care organizations looking to improve performance and patient experiences, implementing data-driven solutions can be effective when focusing on addressing health equity and reducing patient length of stay. These topics are explored in selected member-submitted abstracts from the 2020 Vizient® Connections Education Summit that appear in a special supplement to the July/August 2021 issue of the American Journal of Medical Quality, the official journal of the American College of Medical Quality (ACMQ).

Interventions for addressing health equity

To help health care organizations address health equity, Andrew S. Resnick, MD, MBA, Brigham and Women's Hospital, Karthik Sivashanker, MD, MPH, CPPS, Brigham and Women's Hospital, and Tam Duong, MS, Institute for Healthcare Improvement, developed an intervention framework that "provides a road map for organizations to advance equitable and safe care to all patients by using current patient safety reporting mechanisms to identify events pertaining to explicit, implicit, individual, group, and structural biases." The events identified are then analyzed to identify effective solutions and track their implementation. The authors tested the framework at Brigham and Women's Hospital and saw an "80-fold increase in actions taken from root cause analysis to addressing inequities." Learn more in the abstract "Equity Is a Patient Safety Emergency."

Using data to reduce length of stay

Over the last four years, the Vizient length of stay (LOS) index at Memorial Hermann Texas Medical Center has had a downward trend that plateaued in the past year. The stall in the LOS index has led to nursing units reaching capacity and to an increase in patient wait times for beds. To ensure that resources are allocated appropriately, Stephen W. Simington, MS, MPH, Memorial Hermann Texas Medical Center, and Bela Patel, MD, Memorial Hermann Texas Medical Center/UT Health, developed a statistical dashboard using the Vizient Clinical Data Base to help the health system "identify data-driven opportunities that focus on maximizing resources in the greatest areas of opportunity." The authors expect that the use of the tool and subsequent interventions will show a reduction in the LOS index over time. Learn more in the abstract "Four Clicks from Vizient Data to Actional Information."

GAINESVILLE, Fla. --- Archaeologists have unearthed a rare trove of more than 80 metal objects in Mississippi thought to be from Hernando de Soto's 16th-century expedition through the Southeast. Many of the objects were repurposed by the resident Chickasaws as household tools and ornaments, an unusual practice at a time when European goods in North America were few and often reserved for leaders.

The researchers believe Spaniards left the objects behind while fleeing a Chickasaw attack that followed frayed relations between the two groups in 1541. The victors took advantage of the windfall of spoils - axe heads, blades, nails and other items made of iron, lead and copper alloy - modifying many of them to suit local uses and tastes. Chickasaw craftspeople turned pieces of Spanish horseshoes into scrapers, barrel bands into cutting tools and bits of copper into jingling pendants.

The sheer abundance of objects from the site, an area of northeastern Mississippi known as Stark Farms, is one of the factors that makes the find unique, said Charles Cobb, the study's lead author and Florida Museum of Natural History Lockwood Chair in Historical Archaeology.

"Typically, we might find a handful of European objects in connection with a high-status person or some other special context," Cobb said. "But this must have been more of an open season - a pulse of goods that became widely available for a short period of time."

If the researchers' diagnosis is correct, Stark Farms is only the second place to yield convincing archaeological evidence of direct contact with de Soto's expedition, after the historic site of the Apalachee capital of Anhaica in present-day Tallahassee, Cobb said.

'Unconquered and unconquerable'

By the time de Soto arrived in Mississippi in 1540, the conquistador had trekked through the Southeast for more than a year with about 600 people, hundreds of horses and pigs and heavy equipment in tow. A shrewd man with a reputation for bloodshed, de Soto was previously a key figure in the Spanish destruction of the Inca Empire in South America and came to Florida with an eye to further increase his wealth. Finding little gold, he pressed deeper into the interior, alternately befriending and warring with the Native Americans he encountered.

The Spaniards began on a friendly, if aloof, footing with the Chickasaws, whose leader, known as Chikasha Minko, gave them a modest village in which to spend the winter. But tensions rose as the months dragged on: De Soto executed two Chickasaws and cut off the hands of another accused of stealing pigs. The Chickasaws, who farmed maize in the region's rich prairie soil, also must have grown tired of providing food and shelter for such a large encampment of uninvited guests, Cobb said.

With spring drawing near, de Soto demanded that Chikasha Minko provide him with hundreds of Chickasaws to carry the Spaniards' equipment to their next destination. According to Spanish accounts of the expedition, the conversation did not go well.

Shortly afterwards, the Chickasaws launched a surprise attack under the cover of night, torching the Spanish camp and killing at least a dozen men, as well as many horses and pigs. The retreating Spaniards set up another camp about a mile away, where they were assaulted a second time. Better prepared, they fought back, but soon picked up and headed north, having lost much of their livestock, clothing and goods.

Meanwhile, the Chickasaws collected from the battlefield dozens of prized metal objects, usually reserved by the Europeans for strategic trades or as gifts to smooth relationships with local leaders.

"It's kind of like inflation," Cobb said. "You don't want too much stuff to get out or that gift will be devalued. That's what makes this site unusual."

After the Chickasaws sent the Spanish packing, the region remained largely free of European presence for nearly 150 years.

"This research shows how Chickasaws adapted to invasion by alien intruders and secured their reputation as unconquered and unconquerable," said study co-author Brad Lieb, director of Chickasaw archaeology for the Chickasaw Nation's Heritage Preservation Division. "The findings are remarkable in their success in addressing a baseline event in Chickasaw cultural history - the first encounter with Hernando de Soto and the Spanish invaders."

History confirmed by metal detectors

When Cobb, Lieb and their colleagues first arrived at Stark Farms in 2015, they weren't just looking for traces of de Soto. The Chickasaw Nation, removed from its traditional homeland to Oklahoma by the U.S. Department of War in 1837, had commissioned the team to identify and preserve ancestral sites and provide Chickasaw university students the opportunity to reconnect with their heritage through an archaeology fieldwork program.

The team focused on studying the environmental factors in the movements of Native Americans across the landscape, where radiocarbon dates showed people had lived since the 14th or 15th century. Curious about early residents' potential interactions with outsiders, the researchers brought metal detectors, a speedy way of finding objects of European origin. The first day they deployed the detectors, the machines began pinging. Soon, the team was uncovering dozens of items, including a small cannon ball, a mouth harp and what could be a Spanish bridle bit, emblazoned with a golden cross.

"We couldn't believe it," Cobb said. "There was a lot of serendipity for sure."

The style and type of objects, as well as their location, aligned with Spanish accounts of the de Soto expedition and the 1541 battle at Chikasha, the main Chickasaw town. But the researchers found no evidence of a burned village or the remains of horses and pigs. Cobb said the site was likely a village near Chikasha, whose inhabitants visited the site of the conflict and brought items back to their households. They may also have acquired some of the objects during the previous winter through under-the-table trading with Spanish soldiers.

The Chickasaws generally relied on bone, cane or stone as raw materials for their cutting and scraping tools, making the haul of metal a particular boon. While some of the objects retain their original form, the Chickasaws painstakingly reworked others into more familiar shapes. They bent metal back and forth until it broke and ground down and smoothed edges, modifying tools to mimic the design of their traditional Chickasaw counterparts.

"One of the most stunning things we've found is an exact iron replica of a Native American stone celt, or axe head," Cobb said. "I've never seen anything like this in the Southeast before."

Among the more sobering finds were chain links, pulled apart with sharpened edges. "The Spanish brought reams of chain with them to shackle Native Americans as captives and porters," Cobb said. "This is evidence of some of the first examples of European enslavement of people in what is now the U.S."

The refashioned items from Stark Farms represent a stage of Native American experimentation and improvisation with foreign items that largely faded by the late 1700s and 1800s, as they folded European materials and technology more completely into their own.

"In the 1500s, a thimble might be turned into a bangle. By the late 1700s, a thimble is a thimble," Cobb said. "You tend to see a more regular adoption of goods over time."

Spanish survivors did their own repurposing

De Soto failed to establish any permanent settlements in the Southeast, joining a line of ill-fated expeditions that demonstrated the precariousness of Europeans' early attempts to dominate the region. He succumbed to a fever on the banks of the Mississippi River in 1542, and his remaining band of men made rafts and floated south to Mexico where they found passage back to Spain.

There, they undertook a repurposing effort of their own: Having failed to find fame and fortune in the Americas, they sold their stories, many of which became bestselling books, Cobb said.

"There was a thriving industry in explorer and survival tales, which is probably one of the reasons why some of these individuals provided their accounts. From that perspective, it was very modern."

The objects will be repatriated to the Chickasaw Nation for permanent curation and exhibits.

MANHATTAN, KANSAS -- A recent study by Kansas State University virologists demonstrates successful postinfection treatment for SARS-CoV-2, the virus that causes COVID-19.

College of Veterinary Medicine researchers Yunjeong Kim and Kyeong-Ok "KC" Chang published the study in the prestigious journal Proceedings of the National Academy of Sciences of the United States of America, or PNAS. They found that animal models infected with SARS-CoV-2 and treated with a deuterated protease inhibitor had significantly increased survival and decreased lung viral load.

The results suggest that postinfection treatment with inhibitors of proteases that are essential for viral replication may be an effective treatment against SARS-CoV-2. These protease inhibitors are a class of antiviral drugs that prevent viral replication by selectively binding to viral proteases and blocking the activation of proteins that are necessary for the production of infectious viral particles.

"We developed the protease inhibitor GC376 for treating a fatal coronavirus infection in cats, which is now under commercial development as an investigational new animal drug," said Kim, associate professor of diagnostic medicine and pathobiology. "After COVID-19 emerged, many research groups reported that this inhibitor is also effective against the coronavirus that causes COVID-19, and many are currently pursuing the development of protease inhibitors as a treatment."

Kim and Chang modified GC376 using a tool called deuteration to test its efficacy against SARS-CoV-2.

"Treating SARS-CoV-2-infected mice with deuterated GC376 significantly improved survival, viral replication in lungs and weight losses, which shows the efficacy of the antiviral compound," said Chang, professor of diagnostic medicine and pathobiology. "The results suggest deuterated GC376 has a potential for further development, and this deuteration method can be utilized to other antiviral compounds to generate potent inhibitors."

The virologists are continuing to develop improved inhibitors using various methods. Deuterated GC376 is currently being evaluated for further potential development.

It is the membrane of cancer cells that is at the focus of the new research now showing a completely new way in which cancer cells can repair the damage that can otherwise kill them.

In both normal cells and cancer cells, the cell membrane acts as the skin of the cells. And damage to the membrane can be life threatening. The interior of cells is fluid, and if a hole is made in the membrane, the cell simply floats out and dies - a bit like a hole in a water balloon.

Therefore, damage to the cell membrane must be repaired quickly, and now research from a team of Danish researchers shows that cancer cells use a technique called macropinocytosis. The technique, which is already a known tool for cells in other contexts, consists in the cancer cells pulling the intact cell membrane in over the damaged area and sealing the hole in a matter of minutes. Next, the damaged part of the cell membrane is separated into small spheres and transported to the cells' 'stomach' - the so-called lysosomes, where they are broken down.

In the laboratory, the researchers damaged the membrane of the cancer cells using a laser that shoots small holes in the membrane and triggers macropinocytosis. Here they can see that if the process is inhibited with substances blocking the formation of the small membrane spheres, the cancer cell can no longer repair the damage and dies.

- Our research provides very basic knowledge about how cancer cells survive. In our experiments, we have also shown that cancer cells die if the process is inhibited, and this points towards macropinocytosis as a target for future treatment. It is a long-term perspective, but it is interesting, says group leader Jesper Nylandsted from the Danish Cancer Society's Research Center and the University of Copenhagen, who has headed the new research and who for many years has investigated how cancer cells repair their membranes.

Possibility of recycling

One of the most dangerous properties of cancer is when the disease spreads in the body. If tumors occur in new parts of the body, the disease becomes more difficult to treat and typically requires more extensive forms of treatment. It is also when cancer cells spread through the body's tissues that they are particularly prone to damage to their membrane.

Researchers at the Danish Cancer Society have previously shown how cancer cells can use another technique to repair the membrane, namely by tying off the damaged part, rather like when a lizard throws its tail.

However, the experiments in the laboratory could indicate that especially the aggressive cancer cells use macropinocytosis. This may be due to the fact that the cancer cell has the opportunity to reuse the damaged membrane when it is degraded in the lysosomes. This type of recycling will be useful for cancer cells because they divide frequently, requiring large amounts of energy and material for the new cells.

And although the researchers have now published the new results, their work is not over. This is explained by another member of the research team, postdoc Stine Lauritzen Sønder:

- We continue to work and investigate how cancer cells protect their membranes. In connection with macropinocytosis in particular, it is also interesting to see what happens after the membrane is closed. We believe that the first patching is a bit rough and that a more thorough repair of the membrane is needed afterwards. It can be another weak point in the cancer cells, and is something we want to examine closer, she says.

(Boston)--Would you be more willing to get vaccinated against the COVID-19 virus if you could participate in a lottery for cash and prizes? The answer was surprisingly no, according to Boston University School of Medicine (BUSM) researchers who found that Ohio's "Vax-a-Million" lottery-based incentive system, intended to increase COVID-19 vaccination rates, was not associated with an increase in COVD-19 vaccinations.

Prior reports in the media had suggested that the Ohio lottery increased COVID-19 vaccinations, leading other states to use COVID-19 vaccine incentive lotteries in an attempt to increase slowing vaccination rates. "However, prior evaluations of the Ohio vaccine incentive lottery did not account for other changes in COVID-19 vaccination rates in the United States, such as those that may have been due to expansion of vaccination to ages 12-15," explained corresponding author Allan J. Walkey, MD, MSc, professor of medicine at BUSM.

Using data from the U.S. Centers of Disease Control to evaluate trends in vaccination rates among adults 18 and older, the researchers compared vaccination rates before and after the Ohio lottery versus other states in the U.S. that did not yet have vaccine incentive lottery programs. Vaccination rates in other states served as a "control" for vaccination trends measured in Ohio, allowing the researchers to account for factors besides the Ohio lottery (such expanding vaccine eligibility to adolescents) throughout the country.

"Our results suggest that state-based lotteries are of limited value in increasing vaccine uptake. Therefore, the resources devoted to vaccine lotteries may be more successfully invested in programs that target underlying reasons for vaccine hesitancy and low vaccine uptake," said Walkey, a physician at Boston Medical Center.

The researchers believe identifying interventions that can successfully increase COVID-19 vaccination rates is a critical public health issue necessary to curb the pandemic. "It is important to rigorously evaluate strategies designed to increase vaccine uptake, rapidly deploy successful strategies, and phase out those that do not work," Walkey said.

Although Walkey and his colleagues were sorry to see that state lottery incentives were not associated with an increase COVID-19 vaccinations, they hope their findings will lead to a shift in focus away from ineffective and expensive lotteries, and on to further study of other programs that may more successfully increase vaccine uptake.

Some three quarters of the biomass in hop plants used in beer-making ends up in landfills. But a group of Japanese researchers has developed a technique that 'upcycles' that waste hop into cellulose nanofibers (CNFs). A paper describing the technique was published in the journal ACS Agricultural Science & Technology on June 11.

In the past few years, craft beer-making has exploded in popularity around the world, including many beer styles that make use of many more and different types of hops than conventional commercial beers. A traditional preservative in beer, hops also add a rich bitterness and impart floral or citrus aromas and flavors. As a result, hop production hit a record high in 2019.

However, only the flower of the hop plant is used in beer making. The stems and leaves, which make up about 75 percent of the biomass produced in hop cultivation, are typically burned or tossed in a landfill after harvest. As some 75% of hop plants end up in landfills, the technique should reduce the beer industry's growing waste and land footprint while also cutting back on petroleum feedstocks.

A group of researchers have developed a technique that 'upcycles' these waste products by using hop stems as raw material to extract CNFs. Since the 2000s, there has been increasing interest in CNFs due to their outstanding properties, including low weight and high strength and stabilization. Thanks to those advantages, CNFs are expected to be used as excellent plant-derived materials for reducing the amount of petroleum based plastics in various industrial applications such as automotive and housing industries as well as food and cosmetic fields.

"This really would deserve a hearty 'cheers' if we managed to reduce dependence on petroleum while also radically reducing the agricultural waste from the beer industry," said Izuru Kawamura, associate professor in the Graduate School of Engineering Science at Yokohama National University and the lead researcher on the project.

CNFs had been extracted successfully from wood and from agro-industrial wastes such as pineapple leaves, banana stems, grapefruit peels, and even spent coffee grounds from cafes.

"But until now, no attempt had been made to isolate CNFs from hop stems," Kawamura added.

Plant cell walls are made of cellulose microfibrils, or very small and slender fibers, in a matrix composed of lignin and hemicellulose. The particular chemical compositions of cellulose, hemicellulose, and lignin vary widely depending on the source of the fibers.

Generally, CNFs are extracted from wood pulp via a series of purification steps followed by refinement via treatment with chemicals or enzymes. Previously, a technique involving application of 2,2,6,6-tetramethylpiperidine-1-oxyl radical (described more simply as 'TEMPO) to pretreated cellulose from wood followed by a gentle mechanical disintegration in water had obtained CNFs of 3-4 nanometers in width.

The researchers used the TEMPO technique, but also reduced the pretreatment processes for removing lignin and hemicellulose in hop stems which is considered as lignocellulose fibers prior to the TEMPO step. Even without the pretreatments, they could obtain CNFs with a median of about 2 nanometers. Using the chemical composition analysis, they were able to conclude that the hop stems contained a proportion of cellulose that is almost equal in proportion to that of wood.

This means that not only could this technique replace petroleum, but in a third environmental win, hop waste could also be used instead of wood as an alternative source for CNFs.

"You might even say 'three cheers' for CNFs from hops."

As a next step, the team wants to actually prepare some emulsions stabilized by hop stem-derived CNFs and demonstrate to industry their feasibility. If successful, they should lead to a significant reduction in the amount of conventional synthetic surfactants used.

Wander around a desert most anywhere in the world, and eventually you'll notice dark-stained rocks, especially where the sun shines most brightly and water trickles down or dew gathers. In some spots, if you're lucky, you might stumble upon ancient art - petroglyphs - carved into the stain. For years, however, researchers have understood more about the petroglyphs than the mysterious dark stain, called rock varnish, in which they were drawn.

In particular, science has yet to come to a conclusion about where rock varnish, which is unusually rich in manganese, comes from.

Now, scientists at the California Institute of Technology, the Department of Energy's SLAC National Accelerator Laboratory and elsewhere think they have an answer. According to a recent paper in Proceedings of the National Academy of Sciences, rock varnish is left behind by microbial communities that use manganese to defend against the punishing desert sun.

The mystery of rock varnish is old, said Usha Lingappa, a graduate student at Caltech and the study's lead author. "Charles Darwin wrote about it, Alexander von Humboldt wrote about it," she said, and there is a long-standing debate about whether it has a biological or inorganic origin.

But, Lingappa said, she and her colleagues didn't actually set out to understand where rock varnish comes from. Instead, they were interested in how microbial ecosystems in the desert interact with rock varnish. To do so, they deployed as many techniques as they could come up with: DNA sequencing, mineralogical analyses, electron microscopy, and - aided by Stanford Synchroton Radiation Lightsource (SSRL) scientist Samuel Webb - advanced X-ray spectroscopy methods that could map different kinds of manganese and other elements within samples of rock varnish.

"By combining these different perspectives, maybe we could draw a picture of this ecosystem and understand it in new ways," Lingappa said. "That's where we started, and then we just stumbled into this hypothesis" for rock varnish formation.

Among the team's key observations was that, while manganese in desert dust is usually in particle form, it was deposited in more continuous layers in varnish, a fact revealed by X-ray spectroscopy methods at SSRL that can tell not only what chemical compounds make up a sample but also how they are distributed, on a microscopic scale, throughout the sample.

That same analysis showed that the kinds of manganese compounds in varnish were the result of ongoing chemical cycles, rather than being left out in the sun for millennia. That information, combined with the prevalence of bacteria called Chroococcidiopsis that use manganese to combat the oxidative effects of the harsh desert sun, led Lingappa and her team to conclude that rock varnish was left behind by those bacteria.

For his part, Webb said that he always enjoys a manganese project - "I've been a mangaphile for a while now" - and that this project arrived at the perfect time, given advances in X-ray spectroscopy at SSRL. Improvements in X-ray beam size allowed the researchers to get a finer-grained picture of rock varnish, he said, and other improvements ensured that they could get a good look at their samples without the risk of damaging them. "We're always tinkering and fine-tuning things, and I think it was the right time for a project that maybe 5 or 10 years ago wouldn't really have been feasible."