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For 400 million years, shark-like fishes have prowled the oceans as predators, but now humans kill 100 million sharks per year, radically disrupting ocean food chains. Based on microscopic shark scales found on fossil- and modern coral reefs in Caribbean Panama, Smithsonian scientists reveal the changing roles of sharks during the last 7000 years, both before and after sharks in this region were hunted. They hope this new use for dermal denticles will provide context for innovative reef conservation strategies.

Microscopic scales covering a shark's body--dermal denticles--reduce drag as sharks swim and protect from abrasion with hard substrates and ectoparasite attachment.

"If you have ever petted a shark in an aquarium touch tank," said Erin Dillon, who began this study as an intern at the Smithsonian Tropical Research Institute (STRI) and is now wrapping up her doctoral work at the University of California, Santa Barbara, "denticles are the reason why shark skin is rough like sandpaper if you rub it in one direction yet smooth in the other direction. Sharks are essentially covered by millions of tiny teeth."

Just as humans shed dry skin and dandruff, sharks shed their denticles, which accumulate in marine sediments. The oldest denticles found so far, in the Harding Sandstone of Colorado, are about 455 million years old.

STRI paleobiologist, Aaron O'Dea, pieces together clues from fossil- and modern coral reefs to reconstruct baseline conditions before human colonization, and to understand how ecological and evolutionary processes change through time.

"Placoderms in the Paleozoic, and then marine reptiles in the Mesozoic, were larger and ate sharks." O'Dea explained. "Placoderms ruled the oceans for around 70 million years and marine reptiles of the Mesozoic ruled for more than 100 million years. Sharks are only top predators now because extinction events preferentially took out other groups but allowed sharks to survive. Sharks seem to have remarkable evolutionary resilience and I was fascinated to work on a technique that would help us explore how sharks have fared more recently when humans step into the picture."

His team sampled material from a 7000-year-old fossilized reef in Bocas del Toro, Panama and nearby modern Caribbean reefs. O'Dea asked Erin Dillon to see if she could find shark denticles in the samples.

"What started as a three-month-long internship turned into a two-year stay in Panama and then expanded into part of my PhD thesis," Dillon said. "I've grown with this project as my role shifted from first exploring and processing the samples as an intern to leading the project, analyzing and interpreting the data, and spearheading the writing."

For each week or so of collecting samples from fossil reefs and modern coral rubble, it took about a year of lab work to recover and identify the denticles. In total, Dillon and colleagues had to sift through around 300 kilograms of reef sediments, enough to fill two bathtubs, to find the denticles they needed to know how many and what kind of sharks were in Bocas del Toro in the past. First, they used acetic acid to dissolve away the chalky sediments and then they sorted the residue under a microscope using a paintbrush to isolate the denticles.

"Finding the first denticles was thrilling," exclaimed Dillon. "They were beautifully preserved and abundant enough to provide insights into millennia-old shark communities."

But before using these fossils to uncover past shark communities, Dillon wanted to better understand the relationship between shark numbers and denticle abundances, how denticles fossilize in reef sediments, and which sharks possess which types of denticles. After publishing these studies, she could finally return to the fossil record.

She found that denticle accumulation rates, and therefore, shark abundances, were over three times higher before humans began using marine resources in the region. All denticle types declined over time, but those found on commercially valuable, fished species declined the most. The oldest samples contained a higher proportion of denticles from fast swimming, pelagic sharks like hammerheads and requiem sharks. In contrast, Dillon found that nurse shark denticles are relatively more common today than they were in the past.

To complement this evidence from the fossil record, Dillon combed through archaeological studies and historical narratives to better understand the forces that might have caused these declines. She found that the steepest decline in shark abundance occurred in the late 20th century according to these historical records. This timing coincided with the development of a shark fishery in Panama, which selectively targeted pelagic sharks. Yet, the decline in denticles belonging to nurse sharks, which are infrequently harvested both today and historically, suggested that indirect factors like the loss of coral reef habitat or prey items were also to blame.

"When the Spanish arrived in the Americas, they wrote fantastic accounts of seas swarming with sharks," Dillon said. "But these days we see very few sharks: we are lucky to see the occasional nurse shark. Our data show that sharks in Bocas del Toro have been depleted both by long-term harvesting, which accelerated in the second half of the 20th century, and by habitat degradation, which began even earlier with the expansion of banana cultivation and coastal development. There is so much land-based runoff from the coast today that in some locations it's like swimming through limeade."

"Taken together, Erin's body of work shows that denticle assemblages can be used with care to help reconstruct past shark communities through time," O'Dea said. "Sharks are an integral part of ocean health and play important roles in the great diversity and functioning of coral reefs. Having empirical estimates of past shark abundances and community composition helps us frame our understanding of what is natural in the seas."

"We hope to extend this method to other locations to examine broader geographic patterns of change in reef shark communities over long ecological timescales," Dillon said. "For example, we're currently reconstructing trends in denticle accumulation along Panama's Pacific coast over the last several thousand years using sediment cores. These baseline data will help us explore the causes and consequences of changes in shark abundance and functional diversity. Our work can also help tailor shark management goals to this local region."

Scientists recently made news by using fossil shark scales to reconstruct shark communities from millions of years ago. At the same time, an international team of researchers led by UC Santa Barbara ecologist Erin Dillon applied the technique to the more recent past.

Human activities have caused shark populations to plummet worldwide since records began in the mid-20th century. However, the scientists were concerned that these baseline data may, themselves, reflect shark communities that had already experienced significant declines. Dillon compared the abundance and variety of shark scales from a Panamanian coral reef 7,000 years ago to those in reef sediments today to discern how reef-associated shark communities have changed since humans began using marine resources in the area.

The results, published in the Proceedings of the National Academy of Sciences(link is external), indicate that shark abundance in the region declined roughly three-fold since prehistoric times, with swifter-swimming species taking a harder hit. Much of this decrease is echoed in historical records, suggesting that sharks in Caribbean Panama were most heavily impacted within the past century.

"These results give us new insight into what a 'healthy' shark community might look like on a coral reef before human exploitation," said Dillon, a doctoral student in the Department of Ecology, Evolution, and Marine Biology. "And they can help us set more appropriate and location-specific baselines for management and conservation."

With their cartilaginous skeletons, sharks don't readily fossilize. Often seemingly all that remains of an ancient shark is its hard teeth. But under the right conditions, a closer look at the surrounding sediments will reveal hundreds of microscopic shark scales only a few times thicker than a human hair. Just like the animal's teeth, shark scales are composed of dentin with a hard enamel surface. Researchers call them dermal denticles, meaning "skin teeth," and believe the two are essentially the same structures -- just in different parts of the body.

Scientists often rely on microfossils to reconstruct ancient ecosystems. Items like scales, pollen grains and plankton shells can provide a wealth of information about the conditions and denizens of past ecosystems that aren't preserved in large fossils. What's more, sharks shed a lot more scales in their lifetime than teeth, so dermal denticles can offer paleo-ecologists much more material to analyze than teeth do.

Dillon and her team were fortunate to have access to a fossil reef in Bocas del Toro, on Panama's Caribbean coast. Normally, ancient reefs are entombed under the living coral, but construction had exposed the site, enabling the scientists to collect samples over several years before it was filled in.

They collected sediments that had accumulated within the fossil reef. Debris that settled between the fingers of branching coral was protected from extensive mixing with sediments of different ages. This essentially preserved a time capsule of material from the ancient reef as it accreted.

The team used radiometric dating to estimate the age of the reef. Corals incorporate trace amounts of uranium, but not thorium, into their skeletons as they grow. Scientists can use the predictable rate at which uranium decays into thorium to determine the age of a coral sample. Using this method, the authors dated corals on the fossil reef to around 7,000 years ago.

Next came the arduous process of separating the denticles from the sediments. Using a solution of acetic acid, what Dillon referred to as "glorified vinegar," she tediously dissolved around 300 kg of carbonate sand -- enough to fill two bath tubs -- to a manageable 400 g of residual material, which she then sorted through under a microscope to find the scales.

Different denticle shapes correspond with different functions. For example, thin scales with points and ridges reduce drag, and are found on sharks like great hammerheads and silky sharks that swim fast. Ridge spacing also matters, with animals that reach fast burst speeds tending to sport narrower ridges. Meanwhile, animals like nurse and zebra sharks, which spend their time near tough substrates, tend to have thick, plate-like scales that offer abrasion protection. "They're sort of like armor," Dillon explained. Accounting for the form and abundance of different scales provided the team with a sense of what types of sharks inhabited the ancient reef as well as their relative numbers.

That said, just as different parts of the mouth sport differently shaped teeth, scale morphology also varies across a shark's body. Given this variability, it's nearly impossible to match an isolated scale to a specific species, as can often be done with teeth. That's why Dillon and her colleagues stuck to broad ecological categories of sharks in their paper.

The team's painstaking analysis ultimately paid off.

"We showed that tiny shark scales can be well-preserved and found in high enough abundances to reconstruct shark baselines over long ecological timescales," Dillon said, "and we found about a 71% decrease in total shark abundance between the mid-Holocene -- before major human impact in our study region -- and now." These prehistorical reefs would have had similar environmental conditions to those of today, she added, with the primary difference being that they predate the earliest evidence of human occupation in this part of Panama.

The authors also discovered that the types of sharks found on these reefs shifted between prehistoric times and today. Midwater swimmers, like requiem and hammerheads, declined more than demersal species, like the nurse shark. "If you went snorkeling on these reefs a couple thousand years ago, not only would sharks have been a more common sight but there would have been relatively more fast-swimming pelagic sharks," she said.

Yet, Dillon was struck by the fact that sharks of all types declined over this time period. "If fishing were the only driver, then we wouldn't expect to see such a big drop in nurse sharks over time because they have low commercial value and are rarely targeted by fisheries in the region," she said. "But we did." This suggests that the observed shark declines weren't simply the result of direct impacts on the animals, like overfishing, but might also have stemmed from indirect factors like the loss of reef habitat or available prey.

Dillon and her co-authors also looked at historical accounts of shark abundance through time. "We found that the biggest decline in shark abundance, according to these records, occurred in the latter half of the 20th century," she said. Between these accounts and the results from the fossil record, the evidence suggests that most of the shark declines in this location happened within the past 100 years.

The study's findings provide insight into shark ecology as well as important context for the numbers of sharks observed on reefs today. Most modern time-series data of shark abundance come from places with well-studied commercial fisheries, and often data collection starts well after fishing had commenced. This makes it difficult to be certain how many sharks were present before human activities began impacting the ocean, as well as the long-term ecological consequences of shark declines.

Dillon plans to continue investigating dermal denticles. She is currently studying variation in the rates at which different shark species shed their scales at the Aquarium of the Pacific. If one species sheds much faster than another, that species will leave behind more scales even if there the two populations are the same size.

She and her colleagues are also collecting sediment cores from regions with different human and ecological histories to track high-resolution trends in scale types and abundances over the last several millennia.

Using shark scales to reconstruct past abundances and diversity is a relatively new methodology, and this is the first time it's been applied to questions related to shark management and conservation. "Before this, we didn't really know just how to answer the question of how abundant sharks were on intact coral reefs before human impact," Dillon said, adding that she hopes other researchers take advantage of this powerful technique and apply it to other locations around the world.

Like female voles, connections between oxytocin neurons in the hypothalamus and dopamine neurons in reward areas drive parental behaviors in male voles, according to new research published in JNeurosci.

Motherhood receives most of the attention in the research world, yet in 5% of mammals -- including humans -- fathers provide care, too. The "love hormone" oxytocin plays a role in paternal care, but the exact neural pathways underlying the behavior were not known.

He et al. measured the neural activity of vole fathers while they interacted with their offspring. Oxytocin neurons connecting the hypothalamus to a reward area fired when the fathers cared for their offspring. Stimulating the oxytocin neurons increased paternal behaviors, while inhibiting them reduced paternal behaviors. Inhibiting the pathway led to decreased dopamine release in the reward area when the fathers cared for their pups. These pathways are the same ones involved in promoting maternal behavior in female animals. Understanding the pathways driving paternal care could lead to interventions for paternal postpartum depression or paternal abuse.

MADISON, Wis. -- About 100 additional wolves died over the winter in Wisconsin as a result of the delisting of grey wolves under the Endangered Species Act, alongside the 218 wolves killed by licensed hunters during Wisconsin's first public wolf hunt, according to new research.

The combined loss of 313 to 323 wolves represents a decline in the state's wolf population of between 27% and 33% between April 2020 and April 2021. Researchers estimate that a majority of these additional, uncounted deaths are due to something called cryptic poaching, where poachers hide evidence of illegal killings.

The findings are the first estimate of Wisconsin's wolf population since the public hunt in February, which ended early after hunters exceeded the quota of 119 wolves within a few days. These population estimates can help the Wisconsin Department of Natural Resources (DNR) prepare for the next legally mandated wolf hunt this fall.

They also provide guidance to other states planning wolf hunts following the removal of federal protections announced in November 2020 and effective January 2021.

University of Wisconsin-Madison environmental studies scientists Adrian Treves, Francisco Santiago-Ávila and Karann Putrevu performed the research, which was published July 5 in the journal PeerJ.

Under a variety of population growth scenarios, the researchers estimate that Wisconsin now hosts between 695 and 751 wolves, compared with at least 1,034 wolves last year. The scientists say this likely represents the maximum current wolf population, because they incorporated optimistic assumptions about population growth and low poaching rates into their models.

This decline is despite the hunting quota of 119 wolves for non-native hunters, set with the goal of helping maintain but not reduce the state's wolf population. Ojibwe Tribes were granted a quota of 81 wolves, but they did not conduct a hunt.

"Although the DNR is aiming for a stable population, we estimate the population actually dropped significantly," says Treves, a professor in the Nelson Institute for Environmental Studies and director of the Carnivore Coexistence Lab at UW-Madison.

The new study suggests that about one-third of the population decline is due to hidden deaths in the wolf population, resulting from relaxed legal protections.

Previous research by the Treves lab showed that wolf population growth declined in Wisconsin and Michigan when legal protections were relaxed, regardless of the number of wolves legally killed. And Santiago-Ávila led research that found that Wisconsin's wolves and the heavily monitored Mexican wolves of the American Southwest disappeared at greater rates when lethal control methods were allowed.

Other studies by the lab of attitudes toward wolves suggest that when governments allow lethal management, would-be poachers are inclined to kill more wolves because the relaxed policies signal that predators are less valued.

Those previous findings helped Santiago-Ávila, Putrevu and Treves model the uncounted deaths in Wisconsin since last November.

"During these periods, we see an effect on poaching, both reported and cryptic. Those wolves disappear and you never find them again," says Santiago-Ávila, a postdoctoral researcher in the lab. "Additional deaths are caused simply by the policy signal, and the wolf hunt adds to that."

Treves and his team estimate that the population could recover in one to two years without hunting. Wisconsin law requires a wolf hunt between November and February when hunting is not prohibited by federal protections.

Following the federal delisting of wolves that became effective in January 2021, the DNR initially planned to conduct the first hunt in November 2021. But after a lawsuit, the DNR immediately implemented a wolf hunt at the end of February.

The research team hopes that the Wisconsin DNR and other states' natural resource agencies take advantage of their methods to develop a more complete assessment of the effect of new policies on predator populations.

"These methods and models are freely available to these agencies," says Putrevu, a doctoral student who also researches tiger populations in the Russian Far East. "They should take advantage of the best available science to meet their stated goals."

Flies have discriminating taste. Like a gourmet perusing a menu, they spend much of their time seeking sweet nutritious calories and avoiding bitter, potentially toxic food. But what happens in their brains when they make these food choices?

Yale researchers discovered an interesting way to find out. They tricked them.

In a study that could also help illuminate how people make food choices, the researchers gave hungry fruit flies the choice between sweet, nutritious food laced with bitter quinine and a less sweet, but not bitter, food containing fewer calories. Then, using neuroimaging, they tracked neural activity in their brains as they made these tough choices.

So which won? Calories or better taste?

"It depends on how hungry they are," said Michael Nitabach, professor of cellular and molecular physiology, genetics, and neuroscience at Yale School of Medicine and senior author of the study. "The hungrier they are, the more likely they will tolerate bitter taste to obtain more calories."

But the real answer to how flies make these decisions is a little more complex, according to the study published July 5 in the journal Nature Communications.

According to the research team, led by Preeti Sareen, associate research scientist at Yale, flies relay sensory information to a portion of their brain called the fan-shaped body, where signals are integrated, triggering what amounts to the insect version of an executive decision. The researchers found that patterns of neuronal activity in the fan-shaped body change adaptively when novel food choices are introduced, which dictates the fly's decision over what food to eat.

But researchers went a step further. And things got even stranger. They found they could change a fly's choice by manipulating neurons in areas of the brain that feed into the fan-shaped body. For example, when they caused a decrease in activity in the neurons involved in metabolism, the found that it made hungry flies choose the lower calorie food.

"It is one big feedback loop, not just top-down decision making," Nitabach said.

And this is where there are connections to food choices of humans, he said. Neural activity in both a fly's brain and a human's brain are regulated by the secretion of neuropeptides and the neurotransmitter dopamine, which in humans helps regulate sensations of reward. Changes in this network may alter how the brain responds to different types of food. In other words, neurochemistry may sometimes dictate food choices we think we are making consciously.

"The study provides a template to understand how it is that things like hunger and internal emotional states influence our behavior," Nitabach said.

Sareen and Li Yan McCurdy, a graduate student at Yale School of Medicine, are co-authors of the paper.

"The number of black holes is roughly three times larger than expected from the number of stars in the cluster, and it means that more than 20% of the total cluster mass is made up of black holes. They each have a mass of about 20 times the mass of the Sun, and they formed in supernova explosions at the end of the lives of massive stars, when the cluster was still very young" says Prof Mark Gieles, from the Institute of Cosmos Sciences of the University of Barcelona (ICCUB) and lead author of the paper.

Tidal streams are streams of stars that were ejected from disrupting star clusters or dwarf galaxies. In the last few years, nearly thirty thin streams have been discovered in the Milky Way halo. "We do not know how these streams form, but one idea is that they are disrupted star clusters. However, none of the recently discovered streams have a star cluster associated with them, hence we can not be sure. So, to understand how these streams formed, we need to study one with a stellar system associated with it. Palomar 5 is the only case, making it a Rosetta Stone for understanding stream formation and that is why we studied it in detail" explains Gieles.

The authors simulate the orbits and the evolution of each star from the formation of the cluster until the final dissolution. They varied the initial properties of the cluster until a good match with observations of the stream and the cluster was found. The team finds that Palomar 5 formed with a lower black hole fraction, but stars escaped more efficiently than black holes, such that the black hole fraction gradually increased. The black holes dynamically puffed up the cluster in gravitational slingshot interactions with stars, which led to even more escaping stars and the formation of the stream. Just before it completely dissolves - roughly a billion years from now - the cluster will consist entirely of black holes. "This work has helped us understand that even though the fluffy Palomar 5 cluster has the brightest and longest tails of any cluster in the Milky Way, it is not unique. Instead, we believe that many similarly puffed up, black hole-dominated clusters have already disintegrated in the Milky Way tides to form the recently discovered thin stellar streams" says co-author Dr. Denis Erkal at the University of Surrey.

Gieles points out that in this paper "we have shown that the presence of a large black hole population may have been common in all the clusters that formed the streams". This is important for our understanding of globular cluster formation, the initial masses of stars and the evolution of massive stars. This work also has important implications for gravitational waves. "It is believed that a large fraction of binary black hole mergers form in star clusters. A big unknown in this scenario is how many black holes there are in clusters, which is hard to constrain observationally because we can not see black holes. Our method gives us a way to learn how many BHs there are in a star cluster by looking at the stars they eject.'', says Dr. Fabio Antonini from Cardiff University, a co-author of the paper.

Palomar 5 is a globular cluster discovered in 1950 by Walter Baade. It is in the Serpens constellation at a distance of about 80,000 light-years, and it is one of the roughly 150 globular clusters that orbit around the Milky Way. It is older than 10 billion years, like most other globular clusters, meaning that it formed in the earliest phases of galaxy formation. It is about 10 times less massive and 5 times more extended than a typical globular cluster and in the final stages of dissolution.

The theory that modern society is too clean, leading to defective immune systems in children, should be swept under the carpet, according to a new study by researchers at UCL and the London School of Hygiene & Tropical Medicine.

In medicine, the 'hygiene hypothesis' states that early childhood exposure to particular microorganisms protects against allergic diseases by contributing to the development of the immune system.

However, there is a pervading view (public narrative) that Western 21st century society is too hygienic, which means toddlers and children are likely to be less exposed to germs in early life and so become less resistant to allergies.

In this paper, published in the Journal of Allergy and Clinical Immunology, researchers point to four significant reasons which, they say, disprove this theory and conclude we are not "too clean for our own good".

Lead author, Emeritus Professor of Medical Microbiology Graham Rook (UCL Infection & Immunity), said: "Exposure to microorganisms in early life is essential for the 'education' of the immune and metabolic systems.

"Organisms that populate our guts, skin and airways also play an important role in maintaining our health right into old age: so throughout life we need exposure to these beneficial microorganisms, derived mostly from our mothers, other family members and the natural environment.

"But for more than 20 years there has been a public narrative that hand and domestic hygiene practices, that are essential for stopping exposure to disease-causing pathogens, are also blocking exposure to the beneficial organisms.

"In this paper, we set out to reconcile the apparent conflict between the need for cleaning and hygiene to keep us free of pathogens, and the need for microbial inputs to populate our guts and set up our immune and metabolic systems."

In a review of evidence, the researchers point to four factors.

Firstly, the microorganisms found in a modern home are, to a significant degree, not the ones that we need for immunity.

Secondly, vaccines, in addition to protecting us from the infection that they target, do a lot more to strengthen our immune systems*, so we now know that we do not need to risk death by being exposed to the pathogens.

Thirdly, we now have concrete evidence that the microorganisms of the natural green environment are particularly important for our health; domestic cleaning and hygiene have no bearing on our exposure to the natural environment.

Finally, recent research** demonstrates that when epidemiologists find an association between cleaning the home and health problems such as allergies, this is often not caused by the removal of organisms, but rather by exposure of the lungs to cleaning products that cause a type of damage that encourages the development of allergic responses.

Professor Rook added: "So cleaning the home is good, and personal cleanliness is good, but, as explained in some detail in the paper, to prevent spread of infection it needs to be targeted to hands and surfaces most often involved in infection transmission. By targeting our cleaning practices, we also limit direct exposure of children to cleaning agents

"Exposure to our mothers, family members, the natural environment, and vaccines can provide all the microbial inputs that we need. These exposures are not in conflict with intelligently targeted hygiene or cleaning."

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.