Culture

BOSTON - Significant amounts of atherosclerotic plaque have been found in the coronary arteries of people with HIV, even in those considered by traditional measures to be at low-to-moderate risk of future heart disease, according to a study published in JAMA Network Open.

This finding emerged from the global REPRIEVE (Randomized Trial to Prevent Vascular Events in HIV) study, in which Massachusetts General Hospital (MGH) is playing a key coordinating role. Researchers found that the higher-than-expected levels of plaque could not be attributed simply to traditional cardiovascular disease risk factors like smoking, hypertension, and lipids in the blood, but were independently related to increased arterial inflammation and immune system activation.

"While we know that people living with HIV who are receiving antiretroviral therapy are at increased risk of coronary artery disease, our understanding of the mechanisms behind this phenomenon have been very limited," says Steven Grinspoon, MD, chief of the MGH Metabolism Unit and co-principal investigator of REPRIEVE. "The latest findings from REPRIEVE expand our knowledge and provide important insights that set the stage for further studies to identify effective plaque reduction or prevention strategies, such as the possible use of statin medicines."

REPRIEVE is the largest study of cardiovascular disease among people living with HIV, having enrolled 7,700 participants at more than 100 sites in 12 countries around the world, in collaboration with the AIDS Clinical Trials Group (ACTG). The newly published results are from a subset of the overall trial, consisting of 755 individuals between the ages of 40 and 75 enrolled in 31 sites across the United States. This is the largest study to assess plaque levels in the arteries of people with HIV who have no known heart disease and are eligible for primary cardiovascular prevention. The study used coronary CT angiography to assess plaque and then correlate results with blood samples that measured inflammation and immune activation.

The MGH-led study found that 49 percent of participants had plaque in their coronary arteries. While significant narrowing of the arteries was rare, nearly a quarter had plaque which the researchers considered "vulnerable," that is, at risk for potential future cardiovascular problems. "The prevalence of plaque found in people with HIV was striking, though the number of lesions was limited in most people and only a portion could be explained by traditional risk factors," says co-author Michael Lu, MD, MPH, co-director of the MGH Cardiovascular Imaging Research Center. "We learned that the plaque burden was also associated with higher levels of arterial inflammation and immune system activation independent of traditional risk scores."

Enabling researchers to assess these nontraditional cardiovascular risk factors were two biomarkers which they hypothesized could reflect premature cardiovascular disease among people with HIV. They are interleukin 6 (IL-6), associated with immune system activation, and LpPLA2, associated with arterial inflammation. "It was particularly notable to observe the increased levels of IL-6 in relationship to plaque among relatively healthy people with HIV, inasmuch as immune system activation may have damaging effects on the vessels of the heart over time," notes Grinspoon.

In addition to helping researchers better understand the mechanisms of cardiovascular risk in people with HIV, the two biomarkers will be evaluated in the next phase of REPRIEVE for their ability to predict major events, such as heart attacks and strokes. That ongoing research will also investigate the potential of statin therapy to reduce lipid levels - its primary therapeutic target -- as well as plaque and markers of inflammation.

"We know that cardiovascular disease is occurring among people with HIV at approximately twice the rate of people without the disease," says Grinspoon, "which is why REPRIEVE is so critical in terms of discovering new ways to mitigate those risks so that people with HIV can be assured healthy and full lives."

In Brazil, researchers at the University of São Paulo’s Medical School (FM-USP) have discovered that SARS-CoV-2 infects and replicates in the salivary glands.

Analysis of samples from three types of salivary gland obtained during a minimally invasive autopsy procedure performed on patients who died from complications of COVID-19 at Hospital das Clínicas, FM-USP’s hospital complex, showed that tissues specializing in producing and secreting saliva serve as reservoirs for the novel coronavirus.

The study was supported by FAPESP and reported in an article published in the Journal of Pathology.

The researchers said the discovery helps explain why the virus is so abundant in saliva and has enabled scientists to develop saliva-based diagnostic tests for COVID-19.

“This is the first report of a respiratory virus’s capacity to infect and replicate in salivary glands. Until now it was thought that only viruses that cause highly prevalent diseases such as herpes used salivary glands as reservoirs. The discovery may help explain why SARS-CoV-2 is so infectious,” Bruno Fernandes Matuck, a PhD candidate at USP’s Dental School and first author of the article, told Agência FAPESP.

A previous study by the same group had already demonstrated the presence of RNA from SARS-CoV-2 in the periodontal tissue of patients who died from COVID-19 (more at: agencia.fapesp.br/35675/).

Because SARS-CoV-2 is highly infectious compared with other respiratory viruses, they raised the hypothesis that it may replicate in cells of the salivary glands and hence be present in saliva without coming into contact with nasal and lung secretions. Prior research detected ACE2 receptors in salivary gland ducts. The spike protein in SARS-CoV-2 binds to ACE2 in order to invade and infect cells. More recently, other research groups have conducted studies in animals showing that other receptors besides ACE2, such as transmembrane serine protease 2 (TMPRSS2) and furin, both of which are present in salivary glands, are targets of SARS-CoV-2.

To test this hypothesis in humans, ultrasound-guided autopsies were performed on 24 patients who died from COVID-19, with a mean age of 53, to extract tissue samples from the parotid, submandibular and minor salivary glands.

The tissue samples were submitted to molecular analysis (RT-PCR), which detected the presence of the virus in more than two-thirds. Immunohistochemistry – a form of immunostaining in which antibodies bind to the antigen in the tissue sample, a dye is activated, and the antigen can then be seen under a microscope – also demonstrated the presence of the virus in the tissue. Finally, examination under an electron microscope detected not just the presence of the virus but also its replication in cells and the type of organelle it uses to replicate.

“We observed several viruses clustering in salivary gland cells, which showed that they were replicating there. They weren’t in these cells passively,” Matuck said.

The mouth as direct point of entry

The researchers now plan to see whether the mouth can be a direct point of entry for SARS-CoV-2, given that ACE2 and TMPRSS2 are found in various parts of the cavity, as well as in gum tissue and oral mucosa. In addition, the mouth has a larger contact area than the nasal cavity, which is widely considered the main way in for the virus.

“We’re going to partner with researchers at the University of North Carolina in the United States to map the distribution of these receptors in the mouth and quantify viral replication in oral tissues,” said Luiz Fernando Ferraz da Silva, a professor at FM-USP and principal investigator for the project.

“The mouth could be a viable medium for the virus to enter the body directly,” Matuck said.

Another idea is to find out whether older people have more ACE2 receptors in their mouths than younger people, given the decrease in salivary secretion with age. Nevertheless, the researchers found a high viral load even in older patients, who have less salivary tissue.

“These patients had almost no salivary tissue, almost only fatty tissue. Even so, viral load was relatively high,” Matuck said.

The article “Salivary glands are a target for SARS-CoV-2: a source for saliva contamination” (doi: 10.1002/path.5679) by Bruno Fernandes Matuck, Marisa Dolhnikoff, Amaro Nunes Duarte-Neto, Gilvan Maia, Sara Costa Gomes, Daniel Isaac Sendyk, Amanda Zarpellon, Nathalia Paiva de Andrade, Renata Aparecida Monteiro, João Renato Rebello Pinho, Michele Soares Gomes-Gouvêa, Suzana C.O.M. Souza, Cristina Kanamura, Thais Mauad, Paulo Hilário Nascimento Saldiva, Paulo H. Braz-Silva, Elia Garcia Caldini and Luiz Fernando Ferraz da Silva is at: onlinelibrary.wiley.com/doi/10.1002/path.5679.

Journal

The Journal of Pathology

DOI

10.1002/path.5679

Five Simon Fraser University scholars are among international scientists sounding an alarm over the "pervasive social and ecological consequences" of the destruction and suppression of the knowledge systems of Indigenous Peoples and local communities.

Their paper, published today in the Journal of Ethnobiology, draws on the knowledge of 30 international Indigenous and non-Indigenous co-authors, and highlights 15 strategic actions to support the efforts of Indigenous Peoples and local communities in sustaining their knowledge systems and ties to lands.

Study co-lead, SFU archaeology professor Dana Lepofsky, says, "We worked hard to find a balance between discussing the threats to Indigenous and local knowledge and highlighting how Indigenous Peoples and local communities are taking action to turn around these threats. Around the world, Indigenous Peoples and local communities are celebrating, protecting, and revitalizing their knowledge systems and practices.

"As scientists, policymakers, and global citizens, we need to support these efforts in our professional activities, in the policies of our governmental agencies, and in our personal choices."

The authors summarize how the knowledge systems and practices of Indigenous Peoples and local communities play fundamental roles in safeguarding the biological and cultural diversity of our planet. They also document how this knowledge is being lost at alarming rates, with dramatic social and ecological consequences.

"Although Indigenous and local knowledge systems are inherently adaptive and remarkably resilient, their foundations have been and continue to be compromised by colonial settlement, land dispossession, and resource extraction," says study co-lead Álvaro Fernández-Llamazares, a post-doctoral researcher from the University of Helsinki, Finland. "The ecological and social impacts of these pressures are profound and widespread."

The paper is part of the "Scientists' Warning to Humanity" series, which highlights threats to humanity caused by climate change, biodiversity loss and other global changes.

People who receive mRNA COVID-19 vaccines are up to 91 percent less likely to develop the disease than those who are unvaccinated, according to a new nationwide study of eight sites, including Salt Lake City. For those few vaccinated people who do still get an infection, or "breakthrough" cases, the study suggests that vaccines reduce the severity of COVID-19 symptoms and shorten its duration.

Researchers say these results are among the first to show that mRNA vaccination benefits even those individuals who experience breakthrough infections.

"One of the unique things about this study is that it measured the secondary benefits of the vaccine," says Sarang Yoon, D.O., a study co-author, assistant professor at the University of Utah Rocky Mountain Center for Occupational and Environmental Health (RMCOEH), and principal investigator of the RECOVER (Research on the Epidemiology of SARS-CoV-2 in Essential Response Personnel) study in Utah.

The study, published online in the New England Journal of Medicine, builds on preliminary data released by the Centers for Disease Control and Prevention (CDC) in March.

The study was designed to measure the risks and rates of infection among those on the front lines of the pandemic.

"We gave these vaccines to some of the highest risk groups in this country--doctors, nurses, and first responders," Yoon says. "These are the people who are getting exposure to the virus day in and day out, and the vaccine protected them against getting the disease. Those who unfortunately got COVID-19 despite being vaccinated were still better off than those who didn't."

The study found that mRNA COVID-19 vaccines were:

91% effective in reducing risk for infection once participants were "fully" vaccinated, two weeks after the second dose.

81% effective in reducing risk for infection after "partial" vaccination, two weeks after the first dose but before the second dose was given.

The HEROES-RECOVER network recruited 3,975 participants at eight sites. In addition to Salt Lake City, sites included Miami, Florida; Temple, Texas; Portland, Oregon; Duluth, Minnesota; and Phoenix and Tucson, as well as other areas in Arizona. Participants submitted samples for COVID-19 testing on a weekly basis for 17 weeks between Dec. 13, 2020 and April 10, 2021. Participants also reported weekly whether they had COVID-19-like symptoms, including fever, shortness of breath, and loss of taste and smell.

Only 204 (5%) of the participants eventually tested positive for SARS-CoV-2, the virus that causes COVID-19. Of these, 156 were unvaccinated, 32 had an indeterminate vaccine status, and 16 were fully or partially vaccinated. The fully or partially vaccinated participants who developed breakthrough had milder symptoms than those who were unvaccinated:

Presence of fever was reduced 58% percent among those vaccinated with a breakthrough infection.

Days spent sick in bed were reduced by 60% among those who developed a breakthrough infection.

Detection of the virus was reduced by 70% percent among those with breakthrough infections, from 8.9 days to 2.7 days.

The three people who were hospitalized were not immunized, meaning that no one who developed a breakthrough infection was hospitalized.

These findings also suggest that fully or partially vaccinated individuals who get COVID-19 might be less likely to spread the virus to others. The researchers found that infected study participants who had been fully or partially vaccinated when infected had 40% less detectable virus in the nose and did so for six fewer days compared to those who were unvaccinated.

Overall, the researchers conclude the study's findings support the CDC's recommendation to get fully vaccinated as soon as possible.

"I hope these findings reassure the public that mRNA COVID-19 vaccines are safe and protect us from this severe disease," Yoon says.

The RECOVER study is ongoing, and results from future phases will help determine how long COVID-19 vaccines protect against infection and the real-world effectiveness of newer vaccines. A new study will test the same questions in children 12 and older who are now eligible to receive the COVID-19 vaccination. The research will also investigate how well COVID-19 vaccines protect against new variants now circulating in the U.S., including the highly transmissible Delta variant of SARS-CoV-2.

When traffic is clogged at a downtown intersection, there may be a way to reduce some of the congestion: Eliminate a few left turns.

According to Vikash Gayah, associate professor of civil engineering at Penn State, well-placed left-turn restrictions in certain busy intersections could loosen many of the bottlenecks that hamper traffic efficiency. He recently created a new method that could help cities identify where to restrict these turns to improve overall traffic flow.

"We have all experienced that feeling of getting stuck waiting to make a left turn," Gayah said. "And if you allow these turns to have their own green arrow, you have to stop all other vehicles, making the intersection less productive. Left turns are also where you find the most severe crashes, especially with pedestrians. Our idea is to get rid of these turns when we can to create safer and more efficient intersections."

By selectively restricting left turns, but not banning them entirely, drivers may simply need to find alternate routes to their destinations in certain areas, Gayah said. Some may be required to travel a few extra blocks, but Gayah believes more efficient traffic flow through busy intersections offsets the additional distance.

For urban planners, he added, determining where to place the restrictions is a balancing act between intersection productivity and increased travel lengths. With so many restriction possibilities to consider, finding the most efficient layout may prove difficult.

"For example, if you just have 16 intersections to consider, each with a choice to allow or not allow left turns, that is already 65,000 different configurations," Gayah said. "It gets even more complicated when you consider that traffic flows from one intersection to the next, so decisions depend on one another. There ends up being so many possible answers that we can never find the best one."

Gayah's new method relies on heuristic algorithms, which use shortcuts to find solutions that nearly approach, but are not guaranteed to be, an optimal outcome.

"We make a guess, we learn from that guess, and then we make better guesses," he said. "Over time, we can get really, really close to the best answer."

In a study published in Transportation Research Record, Gayah combined two existing heuristic algorithms to create a new hybrid approach. The first, a population-based incremental learning (PBIL) algorithm, randomly sampled potential configurations and recognized the patterns of high-performing options. Next, a Bayesian optimization algorithm analyzed this new set of high performers to identify how restrictions were affecting traffic at adjacent intersections. Bayesian optimization combines initial information about the problem and updates it over time as new information is learned to attain a solution which is close to, but not necessarily perfect. The algorithm then applied this knowledge of traffic dynamics to find more efficient solutions.

"Instead of starting the Bayesian optimization with a random guess, we fed it with the best guesses from the PBIL," Gayah said. "The first method creates the starting point, and the second refines it."

Gayah tested the hybrid method through a simulated, square network in a variety of scenarios, finding that all three methods -- PBIL, Bayesian optimization and hybrid -- identified configurations that led to more efficient traffic patterns than a layout with zero restrictions. However, in simulations with more realistic settings, the hybrid method proved to be the most effective.

According to Gayah, the most efficient configurations tended to ban left turns in the middle of the city and allowed them more often on the periphery. While the method was applied to a generalized network, the results can be used as a starting point for real-world traffic patterns with the algorithms being customizable on a city-by-city basis.

"The grid network is the most generalizable and not specific to any city," Gayah said. "I cannot take the best configuration for New York and apply it to San Francisco, but this generalized approach could be configured for any network with a little bit of coding."

Using artificial intelligence, UT Southwestern scientists have identified thousands of genetic mutations likely to affect the immune system in mice. The work is part of one Nobel laureate's quest to find virtually all such variations in mammals.

"This study identifies 101 novel gene candidates with greater than 95% chance of being required for immunity," says Bruce Beutler, M.D., director of the Center for the Genetics of Host Defense (CGHD) and corresponding author of the study published this week in the Proceedings of the National Academy of Sciences. "Many of these candidates we have already verified by re-creating the mutations or knocking out the genes." Lead author Darui Xu, a computational biologist at CGHD, wrote the software.

"We've developed software called Candidate Explorer (CE) that uses a machine-learning algorithm to identify chemically induced mutations likely to cause traits related to immunity. The software determines the probability that any mutation we've induced will be verified as causative after further testing," Beutler says. His discovery of an important family of receptors that allow mammals to quickly sense infection and trigger an inflammatory response led to the 2011 Nobel Prize in Physiology or Medicine.

"The purpose of CE is to help researchers predict whether a mutation associated with a phenotype (trait or function) is a truly causative mutation. CE has already helped us to identify hundreds of genes with novel functions in immunity. This will improve our understanding of the immune system so that we can find new ways to keep it robust, and also know the reason it sometimes falters," says Beutler, Regental Professor, and professor of immunology and internal medicine at UT Southwestern.

"CE provides a score that tells us the likelihood that a particular mutation-phenotype association will be verified for cause and effect if we re-create the mutation or knock out the gene," he says.

CE examines 67 features of the primary genetic mapping data to arrive at an estimate of the likelihood of causation. For some mutations, causation is very clear; for others, less so. Over time, the program "learns" from experiments in which researchers re-create the mutation in a fresh pedigree and verify or exclude the hypothesis of causation. All mutations are made available to the scientific community through a public repository, and the data supporting causation are viewable within the Candidate Explorer program on the CGHD website, Mutagenetix.

The team used CE to evaluate about 87,000 mutation/trait associations that passed the initial statistical threshold for candidacy. The traits examined were flow cytometry data collected on circulating immune cells of third-generation mutant mice. In this screen, Candidate Explorer ranked a total of 2,336 mutations in 1,279 genes as good or excellent candidates for causation of traits, the team reports.

Beutler adds that this work is part of a research program he set out on nearly a decade ago to identify every mutation that may affect the mouse immune system.

"We've now worked through about 60% of the genome and have identified thousands of genes - hundreds of them novel - that participate in immunity in the mouse," he says. "The vast majority of these also contribute to human immunity."

Beutler adds that the mouse and human genome are very similar in size and content of genes. "Almost all mouse genes have a human counterpart, and vice versa," he says.

Scientists have taken the first steps in developing a new method of identifying the movements of criminals using chemical analysis of soil and dust found on equipment, clothing and cars. The locating system allows police or security services to match soil remnants found on personal items to regional soil samples, to either implicate or eliminate presence at a crime scene. The work is presented as a Keynote Lecture at the Goldschmidt Geochemistry Conference, after recent publication.

Dr Patrice de Caritat, Principal Research Scientist at Geoscience Australia, Australia's public sector geoscience organisation, said:

"We've done the first trials to see if geochemical analysis could narrow down a search area. We took a 260 km2 area of North Canberra and divided it into cells (squares) of 1 km x 1 km, and sampled the soil in each cell. We were then given 3 samples from within the survey area, and asked to identify which grid cells they came from. This was a 'blind' experiment, in other words we did not know where the samples came from until the end of the experiment. For comparison, Manhattan Island is around 60 km2, so that shows that we looked at a pretty big area".

Using these methods, they were able to eliminate 60% of the territory under investigation.

Dr de Caritat said "Much of forensics is about elimination, so being able to rule out 60% of an area is a substantial contribution toward successfully locating a sample. You can reduce the time, risk and investment of the ongoing investigation. The more parameters we look at, the more accurate the system is. We have reached 90% detection in some cases, although we think that would involve too many factors for real-world crime detection".

The team used a range of analytical instrumentation - Fourier Transform InfraRed Spectroscopy, X-Ray Fluorescence, Magnetic Susceptibility and Mass Spectrometry to compare the 3 blind samples to the previously collected samples.

Dr de Caritat, who is also Adjunct Professor at the National Centre for Forensic Studies at the University of Canberra, said:

"This shows that our systems work, and that we have a potential new tool for criminal and intelligence investigations. It's the next stage which is potentially most interesting. Most developed countries have existing soil databases*, used for such things as mineral exploration or land use decision support. We're plugging our methods into these databases to see if we can locate samples from the database information, rather than needing to collect samples specifically for each investigation.

Conventional soil analysis has already been used in Australia to identify and prosecute criminals. For example, soil analysis was used to identify the movements of a man who carried out a sexual assault on a young girl in Adelaide. There are several such examples. We now want to take this further".

Dr de Caritat worked with the Australian Federal Police in 2017-18, where he helped them develop their capability to analyse soils for forensic location. He said:

"Geoscience Australia is now working with the Australian Federal Police, the University of Adelaide, Flinders University and the University of Canberra on a Defence Department project to incorporate environmental DNA (e.g. from local plants) and X-Ray Diffraction mineralogy into the soil and dust location system**".

Commenting, Professor Jennifer McKinley (Queen's University, Belfast) said 'The breakthrough in Dr de Caritat's work is that it integrates robust compositional data analysis of the multivariate geochemical data into forensic geoscience and applies this in an innovative way to forensic soil provenance'.

In the movie "A Fish Called Wanda", the villain Otto effortlessly gobbles up all the occupants of Ken`s fish tank. Reality, however, is more daunting. At least one unfortunate fan who re-enacted this scene was hospitalized with a fish stuck in the throat. At the same time this also was a painful lesson in ichthyology (the scientific study of fishes), namely that the defense of some fishes consists of needle-sharp fin spines.

Two types of fin elements

Indeed, many fish species possess two types of fin elements, "ordinary" soft fin rays, which are blunt and flexible and primarily serve locomotion, and fin spines, which are sharp and heavily ossified. As fin spines serve the purpose to make the fish less edible, they offer a strong evolutionary advantage. With over 18.000 members, the spiny-rayed fish are the most species-rich fish lineage. These fishes even evolved separate "spiny fins" consisting of spines only. Therefore, the evolution of fin spines is considered a major factor in determining diversity and evolutionary success amongst fishes.

In the study published in PNAS, researchers at the University of Konstanz from a team led by Dr Joost Woltering, who - together with his PhD student and first author of the study Rebekka Höch - works in the laboratory of Professor Axel Meyer, show how fin spines arise during embryonic development. They also explain how the spines could evolve out of ancestral soft-rays independently in different lineages of fish. The study focuses on a model species for the spiny-rayed fish, the cichlid Astatotilapia burtoni, which possesses well-developed soft-rayed and spiny fin parts.

Different developmental genes for spines and soft-rays

As a first step, the team determined the genetic profiles of soft-ray and spiny fins during embryonic development. "What became clear from these first experiments was that a set of genes that we already knew from fin and limb development becomes differently activated in spines and soft-rays," says Rebekka Höch. These genes correspond to so-called master regulator genes and are known to determine morphology in the axial and the limb skeleton. In the fish fins, these genes appear to provide a genetic code that determines whether the emerging fin elements will develop looking like a spine or like a soft-ray.

Soft-rays can change into spines and vice versa

Next, the team identified genetic pathways that switch on these master regulator genes and that determine their activity at different positions across the fins. "Importantly, we were able to address the roles of these pathways using chemical tools, so-called inhibitors and activators, as well as the 'gene scissors' CRISPR/Cas9 and thereby test how spiny and soft-rayed fin domains are established during development," says Joost Woltering, assistant professor in the Department of Biology at the University of Konstanz and senior author of the study.

In their experiments, the scientists were able to alter the number of spines or soft-rays in the fins. This effect was most striking when the so-called BMP (bone morphogenetic protein) signaling was modulated. "We did not only see changes in the activation of the master regulatory genes, but we also observed so-called homeotic transformations, in which soft-rays had become spines, or the other way around, spines had turned into soft-rays," Joost Woltering explains.

An additional observation was that in these fish not only the morphology of the fin elements changed, but also the accompanying fin coloration. "Male cichlids have bright yellow spots on their fins, but these are restricted to the soft-rayed part. What we observed was that when a soft-ray changed into a spine, the fin also lost the yellow spots at this position," says Joost Woltering. This observation shows that in spiny-rayed fish, spines and soft-rays are integrated parts of a larger developmental module that determines a number of the visible features of the fins.

The same principle in different fish lineages

As the puzzle was put together, the team came to realize that a deeply conserved patterning system had become redeployed during evolution of the spiny fin. "In fact, the genetic code that determines the fin domain where spines will appear is also active in fins that do not have spines. This indicates that an ancestral genetic pattern was redeployed for making spines," says Rebekka Höch.

With this newly gained insight in mind the authors set out to investigate fin patterning in catfish, a group of fish of which members have independently evolved spines in the fins. Indeed, the genetic code identified for spines in the cichlid matched the one of the catfish spines. Although some differences exist between the different spiny fish species, it altogether suggests the existence of a deeply conserved fin pattern that is relied on to make spines when this is favored by evolutionary selection.

The next steps

For its future research the team will focus on the genes that act downstream of the identified spine and soft-ray control genes to find out how exactly they alter fin morphology by controlling ossification and cellular growth pathways. "In the end we want to gain a better understanding of how new anatomical structures arise that make some species more successful than others, and how this contributed to the incredible evolutionary diversity of the fish lineages," concludes Joost Woltering.

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."