Culture

Alzheimer's disease: Inflammation triggers fatal cycle

image: (so-called ASC specks, red) in the nucleus of an accumulation of amyloid beta peptides (blue). Furthermore, immune cells (green) are shown. Computer visualization based on microscopic image data.

Image: 
(c) Dario Tejera/Uni Bonn

An immune reaction in the brain seems to play a major role in the development of Alzheimer's disease. In a way, it "adds fuel to the fire" and apparently causes an inflammation that, in a sense, keeps kindling itself. The study has now been published in the journal Cell Reports.

Alzheimer's disease is characterized by clumps of the protein Aß (amyloid beta), which form large plaques in the brain. Aß resembles molecules on the surface of some bacteria. Over many millions of years, organisms have therefore developed defense mechanisms against such structures. These mechanisms are genetically determined and therefore belong to the so-called innate immune system. They usually result in certain scavenger cells absorbing and digesting the molecule.

In the brain, the microglia cells take over this role. In doing so, however, they trigger a devastating process that appears to be largely responsible for the development of dementia. On contact with Aß, certain molecule complexes, the inflammasomes, become active in the microglia cells. They then resemble a wheel with enzymes on the outside. These can activate immune messengers and thereby trigger an inflammation by directing additional immune cells to the site of action.

"Sometimes the microglia cells perish during this process," explains Prof. Dr. Michael Heneka, head of a research group at the German Center for Neurodegenerative Diseases (DZNE) and director of the Department of Neurodegenerative Diseases and Gerontopsychiatry at the University Hospital Bonn. "Then they release activated inflammasomes into their environment, the ASC specks."

Disastrous dual role

These released specks take on a calamitous dual role: On the one hand, they bind to the Aß proteins and make their degradation more difficult. On the other hand, they activate the inflammasomes in even more microglia cells, and much more than Aß alone would do. During this process, more and more ASC specks are released. It thus adds fuel to the fire, as it were, and thereby permanently stokes up the inflammation. "As a result, a fundamentally useful immune mechanism becomes an essential factor in the development of Alzheimer's disease," emphasizes Heneka.

It is actually desirable that ASC specks remain active after cell death: They can then be taken up and used by other immune cells. "These then do not have to produce their own inflammasomes, which means that they can react more quickly to a bacterial infection, for example," says Heneka. In the brain, however, this mechanism is of little benefit: Nerve cells constantly produce small amounts of Aß. It is possible that these deposits only become a serious threat to brain function in combination with the ASC specks.

The scientists hope that a better understanding of these processes might also lead to the development of new therapeutic approaches. This is because the accumulation of Aß probably begins decades before the first symptoms of disease appear. Early intervention may be able to slow down this fateful process. "This might make it possible to treat Alzheimer's disease preventively in the future, so that there is no impairment of mental performance in the first place," hopes Prof. Heneka.

Credit: 
University of Bonn

On the origin of massive stars

image: This image shows a region of space called LHA 120-N150. It is a substructure of the gigantic Tarantula Nebula. The latter is the largest known stellar nursery in the local Universe. The nebula is situated more than 160 000 light-years away in the Large Magellanic Cloud, a neighbouring dwarf irregular galaxy that orbits the Milky Way.

Image: 
ESA/Hubble, NASA, I. Stephens

This scene of stellar creation, captured by the NASA/ESA Hubble Space Telescope, sits near the outskirts of the famous Tarantula Nebula. This cloud of gas and dust, as well as the many young and massive stars surrounding it, is the perfect laboratory to study the origin of massive stars.

The bright pink cloud and the young stars surrounding it in this image taken with the NASA/ESA Hubble Space Telescope have the uninspiring name LHA 120-N 150. This region of space is located on the outskirts of the Tarantula Nebula, which is the largest known stellar nursery in the local Universe. The nebula is situated over 160 000 light-years away in the Large Magellanic Cloud, a neighbouring irregular dwarf galaxy that orbits the Milky Way.

The Large Magellanic Cloud has had one or more close encounters in the past, possibly with the Small Magellanic Cloud. These interactions have caused an episode of energetic star formation in our tiny neighbour -- part of which is visible as the Tarantula Nebula.

Also known as 30 Doradus or NGC 2070, the Tarantula Nebula owes its name to the arrangement of bright patches that somewhat resemble the legs of a tarantula. It measures nearly 1000 light-years across. Its proximity, the favourable inclination of the Large Magellanic Cloud, and the absence of intervening dust make the Tarantula Nebula one of the best laboratories in which to study the formation of stars, in particular massive stars. This nebula has an exceptionally high concentration of massive stars, often referred to as super star clusters.

Astronomers have studied LHA 120-N 150 to learn more about the environment in which massive stars form. Theoretical models of the formation of massive stars suggest that they should form within clusters of stars; but observations indicate that up to ten percent of them also formed in isolation. The giant Tarantula Nebula with its numerous substructures is the perfect laboratory in which to resolve this puzzle as in it massive stars can be found both as members of clusters and in isolation.

With the help of Hubble, astronomers try to find out whether the isolated stars visible in the nebula truly formed alone or just moved away from their stellar siblings. However, such a study is not an easy task; young stars, before they are fully formed -- especially massive ones -- look very similar to dense clumps of dust.

LHA 120-N 150 contains several dozen of these objects. They are a mix of unclassified sources -- some probably young stellar objects and others probably dust clumps. Only detailed analysis and observations will reveal their true nature and that will help to finally solve the unanswered question of the origin of massive stars.

Hubble has observed the Tarantula Nebula and its substructures in the past -- always being interested in the formation and evolution of stars.

Credit: 
ESA/Hubble Information Centre

Bad sleep habits can depress teens

Nagging negative thoughts - and striving for perfection - keep teenagers awake at night, raising their chance of becoming depressed and anxious, a new study shows.

An online study of almost 400 adolescents aged 14 to 20 years confirmed the link, leading sleep researchers at Flinders University to recommend alternative treatments for repetitive negative thinking and perfectionism in dealing with delayed sleep and mental health problems among teenagers.

Professor Michael Gradisar, director of the Child and Adolescent Sleep Clinic at Flinders University, says the study confirmed a link between repeated negative thinking and delayed sleep. This was exacerbated in respondents with perfectionism tendencies.

"Repetitive negative thinking is habit forming and it can significantly contribute to making sleep difficult and causing depressed mood in teenagers, who already like to stay up late at night," Professor Gradisar says.

"This study supports the need to recognise repetitive negative thinking in preventing and treating sleep problems, along with individual differences in perfectionism and mood."

The role of repetitive negative thinking and perfectionism in explaining the link between sleep onset problems and depressed mood has important clinical implications through providing possible treatment targets.

International studies indicates depression affects between 3% and 8% of adolescents. It is often recurring and may continue to develop into more severe depressive disorders during adulthood.

In teenagers, depression can cause poor concentration, a loss of interest in schoolwork, difficulties in peer relationships, and even suicide.

Clinical child psychology Professor Michael Gradisar stresses that sleep plays an important part in preventing and treating depression in teenagers.

He says parents and carers can implement better sleep health by encouraging regular bedtime routines during the school week and weekends, and encouraging mobile phones to be turned off earlier in the evening.

Professor Gradisar says busy lifestyles, stress and screen time makes self-help and accessible resources for better sleep increasingly important.

Credit: 
Flinders University

Control mechanism of force-induced cell-to-cell adhesion

image: The FGFR-KRYF mutant blocked Erk2 activation in Xenopus epithelial tissue.

Image: 
NIBB

Using the amphibian Xenopus laevis as a model, Drs. Noriyuki Kinoshita and Naoto Ueno from the National Institute for Basic Biology (NIBB), Japan and Dr. Ileana Cristea from Princeton University, USA have demonstrated that physical forces, such as centrifugal force, enhance cell-to-cell attachment and increase the stiffness of embryonic tissues as a result of force induced cell shape change. In addition, they have also elucidated a part of the signaling pathway underlying the phenomenon. This work revealing how physical forces build-up the structurally robust and stable embryonic tissue architectures during development was published on March 2020 in Cell Reports.

It is being increasingly recognized that in addition to genes and proteins, physical forces are also essential components for living organisms to proceed with normal development and maintain homeostasis.

This research has further deepened the existing collaboration between NIBB and Princeton University, which in turn has led to an article being published in 2019 (Ref: https://doi.org/10.1016/j.cels.2019.01.006), and investigated the force-dependent cellular event by clarifying detailed molecular and cellular mechanism. In the research referred to previously, the authors demonstrated that a sizable number of proteins in embryonic tissues become phosphorylated immediately after centrifugal or compression forces are applied to embryos, and that ZO-1, a tight junction component accumulates at the junction, leading to enhanced cell-to-cell contact caused by the bridging of said junctions. The authors found that Erk2, an important signaling component mediating various external stimuli, becomes phosphorylated by forces and translocated to the nucleus. It was additionally confirmed that inhibition of Erk2 phosphorylation by its chemical inhibitor attenuated the force induced enhancement of cellular junctions and stiffening of tissues, demonstrating that the response of Erk2 is essential for the force-induced cellular remodeling process. Furthermore, the group also found that the Erk2 phosphorylation is triggered by the signal through the receptor for fibroblast growth factor (FGF), FGFR and proposed an interesting mechanism that FGFR is activated by forces in the absence of FGF ligand, which is a unique mechanism opposing the conventional mechanism of FGFR activation by its ligand. These results also suggest that the activation of FGFR is triggered by force induced cell deformation (shape change). This work represents a significant step towards addressing the long-standing question of how physical forces influence cell and tissue behaviors.

Credit: 
National Institutes of Natural Sciences

Alzheimer risk genes converge on microglia

Our DNA determines a large part of our risk for Alzheimer's disease, but it remained unclear how many genetic risk factors contribute to disease. A team led by Prof. Bart De Strooper (VIB-KU Leuven) and Dr. Mark Fiers now show that many of risk factors affect brain maintenance cells called microglia, and more particularly their response to amyloid-beta, one of the proteins aggregating in the brains of Alzheimer patients. The individual effects of small genetic variations are likely small, but the combination of hundreds of such subtle alterations might tip the balance and cause disease.

Why do some people get Alzheimer's disease while others do not, even when growing very old? Despite decades of research, we still don't know the full answer to this question. Epidemiological studies show that about two-thirds of a person's risk for Alzheimer's disease is genetically determined. A few dozen risk genes have been identified, however, recent evidence shows that there could be hundreds of additional genetic variants that each contribute in a small but significant way to disease risk.

From risk gene to disease mechanism

Bart De Strooper (VIB-KU Leuven) has been studying the mechanisms of Alzheimer's disease for decades. His team tries to find out what this combined genetic risk can teach us about how the disease develops in our brain: "Two crucial questions arise from the myriad of genetic studies. First, what is the link between these Alzheimer risk genes and the amyloid-beta plaques or tau tangles we find in Alzheimer brains; and second, are they all involved in one central cellular or molecular pathway, or do they define many parallel pathways that all lead to Alzheimer's?"

The researchers set out to understand when these genes are expressed and in particular, whether they respond to tau or amyloid?beta pathology. "When it comes to risk, you always need to take the context into account," explain Mark Fiers, co-lead author of the study. "If you don't wear your seatbelt in the car, there is no problem as long as you don't have an accident."

With this in mind, the researchers aimed to understand under which circumstances genetic risk for Alzheimer's comes into play. Fiers: "Almost every person develops some degree of Alzheimer pathology in the brain, i.e. amyloid-beta plaques and tau tangles. However, some people remain cognitively healthy despite a high pathology load, while others develop Alzheimer symptoms quite rapidly."

"To gain more insight we checked gene expression in two different mouse models of Alzheimer's, one displaying amyloid-beta and the other tau pathology, at different ages," says Annerieke Sierksma, a postdoctoral researcher in De Strooper's lab. "We identified that many of the genes linked to Alzheimer's risk are particularly responsive to amyloid-beta but not to tau pathology."

Microglia activation

The team identified 11 new risk genes that are significantly upregulated when facing increased amyloid-beta levels. All these genes are expressed in microglia, cells that play a key role in brain maintenance.

Ashley Lu, a PhD student closely involved in the analysis: "We could confirm that microglia exposed to amyloid-beta drastically switch to an activated status, something that occurs to a much lesser extent in the tau mice. These new insights indicate that a large part of the genetic risk of Alzheimer's disease involves the microglial response to amyloid-beta."

Understanding genetic risk

Should we rethink the classical gene?based view, where certain mutations or genetic variants lead to disease? De Strooper thinks so: "One single genetic variant within a functional network will not lead to disease. However, multiple variants within the same network may tip the balance to a disease?causing disturbance. Such a hypothesis could also explain the conundrum that some /individuals with a lot of amyloid-beta in their brain do not develop clinical symptoms."

"While amyloid-beta might be the trigger of the disease, it is the genetic make?up of the microglia, and possibly other cell types, which determines whether a pathological response is induced," adds Fiers. "Identifying which genetic variants are crucial to such network disturbances and how they lead to altered gene expression will be the next big challenge."

Credit: 
VIB (the Flanders Institute for Biotechnology)

Sugar brings a lot of carbon dioxide into the deeper sea

image: Coscinodiscus wailesii is a microalgae belonging to the diatoms, which form algal blooms and produce substantial amounts of polysaccharides in energy stores, cell walls and as exudates. The research group Marine Glycobiology studies the turnover and role of these glycans in the carbon cycle.

Image: 
Max Planck Institute for Marine Microbiology/C. Robb

In the sunlit surface layer of the ocean, photosynthetic microalgae such as diatoms convert more carbon dioxide into biomass than Earth's tropical forests. Like land plants, diatoms sequester carbon dioxide into polymeric carbohydrates - in other words: into long-chained sugars. However, it has proven difficult to quantify how much carbon dioxide can be stored in the global oceans throughout this process.

This gap of knowledge sparked the interest of the research group Marine Glycobiology, which is located at the Max Planck Institute of Marine Microbiology and the MARUM, Center for Marine Environmental Sciences at the University of Bremen and cooperates with the Alfred Wegener Institute for Polar and Marine Research. To close this gap, the scientists utilized a recently developed enzymatic assay to dissect photosynthetic microalgae and measure concentrations of the long-chained sugar laminarin, an important energy source for microalgae including diatoms.

Laminarin fixes carbon dioxide

Based on microalgae obtained from the Arctic, Atlantic, and Pacific Oceans and the North Sea, the researchers estimated that this biomass is on average composed of 26 percent laminarin. "This amount suggests that photosynthesis in the surface ocean produces on average twelve gigatons of carbon annually in the form of algal laminarin" says Stefan Becker, first author of the study, published in the scientific journal PNAS in March 2020. "This is a large amount, considering that, according to the Global Carbon Budget 2019, humans released 11.5 gigatons of carbon during 2018." However, only a small part of the carbon bound by laminarin is permanently removed from the atmosphere - a large part is subsequently released again through natural processes. In total, the oceans permanently absorbed around 2.6 gigatons of carbon in 2018. "Yet, our findings indicate that sugars like laminarin are also important for the permanent fixation of carbon in the sea," says Becker.

Furthermore the scientists found that laminarin comprises as much as 50 percent of the organic carbon in sinking diatom-containing particles. "Thus laminarin plays a central role in carbon transfer from surface waters to the deeper ocean," says Jan-Hendrik Hehemann, leader of the research group Marine Glycobiology. "Whether laminarin is fixed in deep waters is an important further question that we will address in the future".

Variation during the day

In addition, as microalgae represent the all-important base of the marine food web, the findings show that laminarin occupies a prominent position in global ocean ecology. The researchers from Bremen found out, that the amount of sugar in microalgae is high, but not always the same. "The concentration in algal cells increased markedly during the day and decreased over the night, in analogy to the seasonal storage of energy in starchy roots and fruits of land plants", says Hehemann. "This may have a major impact on the feeding behavior of marine animals, as the time of day determines how much sugar - and therefore energy - animals get when they eat."

Collectively, these findings highlight the prominent ecological role and biochemical function of the sugar laminarin in the ocean.

Credit: 
Max Planck Institute for Marine Microbiology

Maggot analysis goes molecular for forensic cases

Maggots on a dead body or wound can help pinpoint when a person or animal died, or when maltreatment began in elder, child care or animal neglect cases. However, the current process for making this determination is time consuming and resource intensive. It also relies on species assessment by trained entomologists. Now, researchers report in ACS' Analytical Chemistry the development of a molecular maggot analysis method that's quick, easy and less subjective.

Pregnant blowflies, which can detect decomposing tissue from as far as 2 miles away, lay their eggs on remains within a few minutes or hours of death. After the eggs hatch, the emerging larvae -- known as maggots -- feed on the tissue. Forensic investigators collect the larvae, and entomologists determine their species and life stage, which can reveal when death occurred. However, this analysis can be difficult because a body might be infested with a mass of eggs and larvae from several species, all mixed together. In addition, the larvae from different species are hard to tell apart, so they are typically raised to adulthood when they can be more reliably identified. But that takes time and training that investigators might not have, and the larvae in the collected samples might not be alive at the time of examination. As a quicker and more objective alternative, researchers have tried DNA analysis to distinguish species, but genomes from many of these flies are unknown. So Rabi A. Musah and colleagues set out to develop a better method.

Building on their previous work on single-species determinations, the researchers optimized their method for multispecies analyses. They used a method called direct analysis in real time-high resolution mass spectrometry to obtain molecular information about various combinations of maggot species. Then, they developed a new hierarchical conformal predictor and applied it to the data. With this method, for the first time, maggots from mixtures of up to six species could be distinguished.

Credit: 
American Chemical Society

Beetles changed their diet during the Cretaceous period

image: Reconstruction of the beetle on a water lily in its habitat. On the "back" it carries pollen from the water plant.

Image: 
© J.A. Peñas

Like a snapshot, amber preserves bygone worlds. An international team of paleontologists from the University of Bonn has now described four new beetle species in fossilized tree resin from Myanmar, which belong to the Kateretidae family. They still exist today, with only a few species. As well as the about 99 million years old insects, the amber also includes pollen. It seems that the beetles helped the flowering plants to victory, because they contributed to their propagation. In turn, the beetles benefited from the new food source. The results have now been published in the journal "iScience".

The researchers have described the new beetle species using specimens in four amber pieces from Myanmar (previously known as Burma). The pieces are estimated to be 99 million years old and date from the Cretaceous period, when dinosaurs were a rich and diverse group. Two of the pieces are in the Museum of Natural Sciences of Barcelona (Spain), while the other two specimens are kept in the Institute of Geology and Palaeontology in Nanjing (China).

"Although Myanmar surprises us time and again with finds of great scientific importance, amber pieces containing numerous organisms are not often found there," says project leader Dr. David Peris, who comes from Spain and is a postdoc at the Institute for Geosciences at the University of Bonn with an Alexander von Humboldt Foundation's fellowship. He carried out the project with scientists from the USA, Spain, Germany, China and the Czech Republic.

Three of the examined amber pieces contained numerous beetles, while the fourth piece contained only one specimen of this family. Many pollen grains of different groups of seed plants, some of them long extinct, have been preserved with the beetles in the tree resin. Peris: "This close association suggests that the grains were distributed in the viscous lump of resin by the movement of the beetles."

The beetle family still exists today

The Kateretidae are a small family of beetles with less than 100 described modern species that today live in South America and other temperate and subtropical regions. The species of this family feed on pollen and flower parts. Due to their dietary habits, they are nowadays regarded as pollinators of flowering plants (angiosperms). But in the middle Cretaceous period their rapid development had just begun. Previously, the Earth was colonized by gymnosperms, literally meaning "naked seeds", which also includes our conifers. "The most important aspect of this study is that the pollen grains in three of the amber pieces do not belong to flowering plants," says Peris. The pollen grains on the beetle of the fourth piece of amber, however, come from a water lily, a group of very primitive angiosperms that emerged at an early stage.

Living together for mutual benefit

There are other pollinating insects in amber, but almost all of them concern gymnosperms. When flowering plants (angiosperms) began their early development, they represented a new resource that was used by the Kateretidae. The beetles adapted quickly and formed a mutually beneficial symbiosis: The flowering plants served the beetles as a food source and these animals contributed to the propagation of the new angiosperms by pollination.

In earlier studies it was speculated that the beetles might belong to the insect groups that pollinated the earliest flowers. Some of these animals had developed the ability to pollinate gymnosperms well before the appearance of angiosperms. "Our study supports this hypothesis of significant host plant relocation, as there are no Kateretidae associated with gymnosperms today," says Peris. Adapting to the new resource has proven to be an evolutionary advantage.

Credit: 
University of Bonn

New sensor could help prevent food waste

CAMBRIDGE, MA -- As flowers bloom and fruits ripen, they emit a colorless, sweet-smelling gas called ethylene. MIT chemists have now created a tiny sensor that can detect this gas in concentrations as low as 15 parts per billion, which they believe could be useful in preventing food spoilage.

The sensor, which is made from semiconducting cylinders called carbon nanotubes, could be used to monitor fruit and vegetables as they are shipped and stored, helping to reduce food waste, says Timothy Swager, the John D. MacArthur Professor of Chemistry at MIT.

"There is a persistent need for better food management and reduction of food waste," says Swager. "People who transport fruit around would like to know how it's doing during transit, and whether they need to take measures to keep ethylene down while they're transporting it."

In addition to its natural role as a plant hormone, ethylene is also the world's most widely manufactured organic compound and is used to manufacture products such as plastics and clothing. A detector for ethylene could also be useful for monitoring this kind of industrial ethylene manufacturing, the researchers say.

Swager is the senior author of the study, which appears today in the journal ACS Central. MIT postdoc Darryl Fong is the lead author of the paper, and MIT graduate student Shao-Xiong (Lennon) Luo and visiting scholar Rafaela Da Silveira Andre are also authors.

Ripe or not

Ethylene is produced by most plants, which use it as a hormone to stimulate growth, ripening, and other key stages of their life cycle. Bananas, for instance, produce increasing amounts of ethylene as they ripen and turn brown, and flowers produce it as they get ready to bloom. Produce and flowers under stress can overproduce ethylene, leading them to ripen or wilt prematurely. It is estimated that every year U.S. supermarkets lose about 12 percent of their fruits and vegetables to spoilage, according to the U.S. Department of Agriculture.

In 2012, Swager's lab developed an ethylene sensor containing arrays of tens of thousands of carbon nanotubes. These carbon cylinders allow electrons to flow along them, but the researchers added copper atoms that slow down the electron flow. When ethylene is present, it binds to the copper atoms and slows down electrons even more. Measuring this slowdown can reveal how much ethylene is present. However, this sensor can only detect ethylene levels down to 500 parts per billion, and because the sensors contain copper, they are likely to eventually become corroded by oxygen and stop working.

"There still is not a good commercial sensor for ethylene," Swager says. "To manage any kind of produce that's stored long-term, like apples or potatoes, people would like to be able to measure its ethylene to determine if it's in a stasis mode or if it's ripening."

Swager and Fong created a new kind of ethylene sensor that is also based on carbon nanotubes but works by an entirely different mechanism, known as Wacker oxidation. Instead of incorporating a metal such as copper that binds directly to ethylene, they used a metal catalyst called palladium that adds oxygen to ethylene during a process called oxidation.

As the palladium catalyst performs this oxidation, the catalyst temporarily gains electrons. Palladium then passes these extra electrons to carbon nanotubes, making them more conductive. By measuring the resulting change in current flow, the researchers can detect the presence of ethylene.

The sensor responds to ethylene within a few seconds of exposure, and once the gas is gone, the sensor returns to its baseline conductivity within a few minutes.

"You're toggling between two different states of the metal, and once ethylene is no longer there, it goes from that transient, electron-rich state back to its original state," Fong says.

In bloom

To test the sensor's capabilities, the researchers deposited the carbon nanotubes and other sensor components onto a glass slide. They then used it to monitor ethylene production in two types of flowers -- carnations and purple lisianthus. They measured ethylene production over five days, allowing them to track the relationship between ethylene levels and the plants' flowering.

In their studies of carnations, the researchers found that there was a rapid spike in ethylene concentration on the first day of the experiment, and the flowers bloomed shortly after that, all within a day or two.

Purple lisianthus flowers showed a more gradual increase in ethylene that started during the first day and lasted until the fourth day, when it started to decline. Correspondingly, the flowers' blooming was spread out over several days, and some still hadn't bloomed by the end of the experiment.

The researchers also studied whether the plant food packets that came with the flowers had any effect on ethylene production. They found that plants given the food showed slight delays in ethylene production and blooming, but the effect was not significant (only a few hours).

Credit: 
Massachusetts Institute of Technology

How does an intersex bee behave?

image: The bee's left side was male-like, with a long antenna, a delicate, pointed mandible, and a slender, naked left hindleg, all typical male characteristics. The right side was female-like, with a shorter antenna, a stout, toothed mandible and a robust hindleg with branched hairs for transporting pollen.

Image: 
Chelsey Ritner

In the neotropical forest of Barro Colorado Island in Panama, an unusual bee hatched: half male and half female. The Smithsonian Tropical Research Institute students and scientists working on nocturnal, socially flexible Megalopta bees at BCI recognized it as a gynandromorph: a rare condition that results in the expression of both male and female characteristics.

The bee's left side was male-like, with a long antenna, a delicate, pointed mandible, and a slender, naked left hindleg, all typical male characteristics. But the right side was female-like, with a shorter antenna, a stout, toothed mandible useful for digging a nest, and a robust hindleg plumose with branched hairs for transporting pollen. It also had a sting, pointing outward from the female half of the body.

The first discovery of a Megalopta gynandromorph was made in 1999. STRI staff scientist Bill Wcislo found a M. genalis that exhibited the same condition in Barro Colorado. The recent discovery is the first report of gynandromorphism in the closely related bee species Megalopta amoenae.

Given the singularity of the occurrence, the group decided to describe an aspect of the bee's behavior that hadn't been previously studied in gynandromorphs: circadian activity, an internal process that enables organisms to clock their daily activities, and for bees and other pollinators to coordinate their foraging behavior with the availability of floral resources. The observations were led by former STRI intern Erin Krichilsky, a student from Cornell University.

They found that the gynandromorph's activity started earlier in the day, compared to the male and female bees, but that its highest intensity periods most closely resembled the behavior of females. These results were recently published in the Journal of Hymenoptera Research.

"It is impressive that even though there has been intense sampling of Megalopta at STRI for nearly 30 years, only two gynandromorphs have ever been found," said Krichilsky. "This really exhibits the rarity of these creatures. Finding the M. amoena felt like striking gold or winning the Darwinian lottery."

For the research team, cases like these are intriguing, not only because they help determine the frequency and distribution of gynandromorphs globally, but also because the insects may exhibit odd or novel behaviors. Ultimately, their unusual activity patterns could potentially lead to new evolutionary paths.

Credit: 
Smithsonian Tropical Research Institute

E-cigarette use rises while new data points to heart health risks

A new study adds to mounting evidence that the use of electronic cigarettes (e-cigarettes), or vaping, has increased in recent years among U.S. adults, with nearly 1 in 20 reporting current use of e-cigarettes, according to research presented at the American College of Cardiology's Annual Scientific Session Together with World Congress of Cardiology (ACC.20/WCC). In addition, two studies examining blood samples suggest e-cigarette exposure is roughly equivalent to tobacco smoke in terms of promoting oxidative stress that can lead to blood vessel damage and heart disease.

The first study, based on a survey of more than 930,000 U.S. adults, found nearly 29,000 people identified as current e-cigarette users, which translates to about 10.8 million U.S. adults. The proportion of survey respondents reporting current e-cigarette use rose from 4.3% in 2016 to 4.8% in 2018.

"While an increase of 0.5% over three years may not sound like a large increase, that's a lot of [new] e-cigarette users once you extrapolate out to the overall population," said Mahmoud Al Rifai, MD, MPH, a cardiology fellow at Baylor College of Medicine and the study's lead author. "Based on our findings, I think the trend is only going to go upward, but we don't know yet what the long-term health effects are."

For this study, researchers analyzed data from the Behavioral Risk Factor Surveillance System, a large phone-based survey conducted annually for more than 35 years that is designed to be representative of the U.S. adult population. Survey participants who said they used e-cigarettes every day or on some days were counted as current e-cigarette users.

While vaping rates rose across the overall population from 2016-2018, the increase was particularly pronounced in certain groups. Current e-cigarette use increased from 3.3% to 4.3% among women; from 3.9% to 5.2% among adults 45-54 years old; and from 5.2% to 7.9% among former smokers. Vaping also rose dramatically among users of smokeless tobacco products, from 9.2% in 2016 to 16.2% in 2018.

Al Rifai said he believes the trends may reflect a push by e-cigarette makers to position their products for smoking cessation. He added that the findings underscore an urgent need for further research on the prevalence of vaping and to understand its potential long-term health implications for both the individual and public health.

"Because e-cigarettes have only been around for about a decade, many large cohort studies have only just recently started incorporating e-cigarette information into their questionnaires. Yet, the cumulative effects of e-cigarettes may take years to develop, especially in the context of cardiovascular disease," Al Rifai said. "It's something that we need to keep a very close eye on."

Growing evidence points to potential heart risks

Two other small studies being presented bolster emerging evidence for potential links between e-cigarette use and heart disease. For these studies, researchers compared blood samples from non-smokers, smokers and e-cigarette users to examine immune cell characteristics and markers of oxidative stress associated with plaque buildup in the heart's arteries. They found that using e-cigarettes led to many of the same characteristics as tobacco smoke at the cellular level, with both e-cigarette users and tobacco smokers showing significantly more evidence of harmful oxidative stress than non-smokers.

"Oxidative stress is one of the main instigators for many diseases that contribute to aging," said Holly Middlekauff, MD, a cardiologist at the University of California, Los Angeles, and senior author of the studies. "We found that not only do the immune cells that are circulating have greater oxidative stress in smokers and e-cigarette users than non-smokers, there are also more of these chronic inflammatory cells present. Our study suggests there is a continuum of harm, with non-users having the least amount of oxidative stress, electronic cigarette users showing an intermediate level and chronic tobacco smokers having the largest amount of oxidative stress."

Credit: 
American College of Cardiology

PTSD strongly linked with heart disease in female veterans

Female veterans suffering from post-traumatic stress disorder (PTSD) were substantially more likely to have ischemic heart disease than those without PTSD in a study presented at the American College of Cardiology's Annual Scientific Session Together with World Congress of Cardiology (ACC.20/WCC).

The new study is the largest and most comprehensive to date evaluating the association between PTSD and ischemic heart disease in women. Ischemic heart disease is a leading cause of death in the U.S. and includes heart attacks, chest pain and other problems caused by clogged or hardened arteries in the heart (a condition known as coronary heart disease) or abnormalities in smaller vessels.

"The association we found was incredibly strong," said Ramin Ebrahimi, MD, a cardiologist affiliated with the Veterans Affairs (VA) Greater Los Angeles Healthcare System, professor of medicine at the University of California in Los Angeles and the study's lead author. "We have a rising number of women veterans, and a large proportion of them--nearly 1 in 5--have PTSD. These women are at high risk for heart disease, and what's more, they appear to be getting it at a younger age--even in their 40s. This is not something we can ignore."

The researchers used a nationwide VA database to analyze health records from more than 835,000 female veterans who visited any VA facility at least twice between 2000-2017. On average, patients in the sample were just over 50 years old at the end of the study period. More than 150,000 (about 18%) had been diagnosed with PTSD.

Overall, the women with PTSD had a 20% increased risk of having ischemic heart disease than those without PTSD. This association remained extremely strong and independent when researchers accounted for a comprehensive panel of risk factors--conditions or traits that could heighten the risk of heart disease--including age, elevated blood pressure, cholesterol, diabetes, obesity, chronic kidney disease, neuroendocrine disorders, psychiatric disorders, smoking and alcohol and illicit drug dependence.

Ebrahimi said previous studies of PTSD and heart disease have typically accounted for fewer risk factors or assessed PTSD status based on symptoms rather than a documented diagnosis. The new study's unique methodology strengthens the evidence that PTSD is independently related to heart disease, rather than a relationship mediated by other health conditions or lifestyle factors.

"No matter how many variables we accounted for, PTSD still came out to be independently associated with ischemic heart disease," Ebrahimi said.

Researchers also accounted for female-specific risk factors, including those related to pregnancy such as gestational diabetes, gestational hypertension and problems with the placenta such as separation of placenta from the uterus or infarction of placenta.

Women with PTSD were about 47 years old, on average. This was five years younger than the average age of those without PTSD, suggesting the risk should be taken seriously even in younger women.

"There may be practice implications for earlier, more routine and a higher degree of screening, at least for this group of at-risk patients," Ebrahimi said.

While we don't know why PTSD might affect or influence heart health, Ebrahimi explained several possibilities have been proposed, including elevated levels of the stress hormone cortisol, inflammation, blood clotting disorders, endocrine disorders--such as thyroid and adrenal--and other disorders that may affect blood pressure, heart rate or other metabolic factors, such as glucose or lipids.

PTSD is a mental health condition that can develop after a person experiences or witnesses a traumatic event. Previous studies, mostly focused on men, have yielded mixed findings on the relationship between PTSD and heart disease. Ebrahimi and his team plan to continue their study to investigate the mechanisms through which PTSD might contribute to heart disease, as well as the timing of when each condition arises.

Ebrahimi said the study underscores the need for further research on heart disease in women, a group that has historically been understudied. Further research could also shed light on whether the relationship between PTSD and heart disease also extends to women who have not served in the armed forces.

Credit: 
American College of Cardiology

'Fatal attraction': Small carnivores drawn to kill sites, then ambushed by larger kin

image: A gray wolf in Denali National Park and Preserve, Alaska, shown on a wildlife camera. Wolves and cougars are the top predators in most western landscapes.

Image: 
Kaija Klauder/University of Washington

In many parts of the world, there is an imbalance in the food chain.

Without top predators such as wolves and grizzly bears, smaller meat-eating animals like coyotes and foxes or grazers such as deer and elk can balloon in population, unchecked. This can initiate more deer-vehicle collisions, scavenging by urban coyotes and other unnatural human-animal interactions.

University of Washington researchers have discovered that large predators play a key yet unexpected role in keeping smaller predators and deer in check. Their "fatal attraction" theory finds that smaller predators are drawn to the kill sites of large predators by the promise of leftover scraps, but the scavengers may be killed themselves if their larger kin return for seconds.

The study, published March 18 in the journal Ecology Letters, is the first to examine carnivore killing and scavenging activities in relation to each other across dozens of landscapes around the world. Patterns that emerged from their analysis could be used to make important management decisions about large carnivores worldwide, the authors said.

"I hope this paper will spur researchers to think more holistically about these killing and scavenging interactions, because currently we're not really getting a full understanding of how carnivore communities function by examining them separately," said senior author Laura Prugh, a wildlife ecologist and associate professor in the UW School of Environmental and Forest Sciences.

Large carnivores such as cougars, wolves and grizzly bears have disappeared from many regions, allowing some smaller carnivores -- coyotes, foxes and bobcats, for example -- to increase in population. The absence of large carnivores, especially on the East Coast, also has ignited populations of deer and other prey, creating an imbalance in many areas.

But in regions where top carnivores are present, such as the western U.S., their relationship with smaller predators is complex. When they kill deer and other prey, they often leave scraps for smaller predators to scavenge. But larger predators also are known to kill smaller carnivores.

With these dynamics in mind, the researchers wanted to test whether large carnivores serve as an overall net benefit to smaller predators by providing more food supply, especially when other food is scare due to drought, wildfires or particularly harsh winters.

The team analyzed more than 250 earlier papers, looking globally at patterns of killing and scavenging to quantify the positive and negative interactions among top and smaller predators. Overall, they found that large predators generally suppress smaller predators, even though they provide a significant amount of food in the form of leftover prey.

"We initially thought maybe smaller carnivores are scavenging the wolf kills and benefiting," explained Prugh, referencing one of the top predators, wolves, examined in the study. "But then we realized that at these scavenging sites, they might be running into the wolves and getting killed. The scavenging, instead of providing a benefit, could actually be functioning as a trap that's drawing in the smaller carnivores."

The researchers thus developed their fatal attraction theory, which proposes that even though large predators are helpful providers of food, their kill sites ultimately are dangerous for smaller predators, which can then become prey themselves when the top predator returns.

As populations of deer and small carnivores like coyotes have surged in areas without top predators, research has posited that humans might be able to take over the role of large carnivores through hunting activities. But though hunters sometimes leave gut piles after they kill a deer, they certainly don't return to the kill site to hunt smaller predators. The research shows this behavior, not replicated by human hunters, could be an important way that smaller carnivores' populations are kept in check.

"If scavenging increases the risk of mortality of smaller carnivores, that might explain why it appears to be very hard for humans to replace the role of large carnivores in a landscape," Prugh explained. "This link between scavenging and mortality might be one of the mechanisms that make large carnivores so effective in controlling smaller carnivores."

From their analysis, the researchers noted these additional findings:

* In areas where there were at least three larger predators, smaller predators had more than twice the mortality rates as their counterparts in areas with only two larger predators. This shows that each predator leverages its unique hunting strategy -- such as outrunning or stalking prey -- and that more predators with different ways of hunting made it much harder for their target, smaller prey, to survive. Having a diversity of larger predators is a good strategy for keeping smaller carnivore populations in check, the authors said.

* Large cats such as cougars were "equal opportunity killers," meaning they were just as likely to kill smaller animals in the cat, dog or mustelid families. But large animals in the dog family such as wolves were five times more likely to kill smaller dogs than animals in other families. Big picture, this means that large cats might have a more widespread impact on smaller carnivores, compared with large dogs that mostly target smaller dogs.

"This finding shows that it really is a dog-eat-dog world out there," Prugh said.

Credit: 
University of Washington

Music as medicine? 30 minutes a day shows benefits after heart attack

Listening to music can be enjoyable, but is it also good for your heart? Patients who suffered episodes of chest pain soon after a heart attack, known as early post-infarction angina, had significantly lower levels of anxiety and pain if they listened to music for 30 minutes a day, according to a study presented at the American College of Cardiology's Annual Scientific Session Together with World Congress of Cardiology (ACC.20/WCC).

Nearly 700,000 people survive a heart attack in the U.S. each year, and it is estimated that roughly 1 in 9 heart attack survivors experience subsequent episodes of chest pain and anxiety within the first 48 hours. The new research suggests music, combined with standard therapies such as medications, could be a simple, accessible measure that patients can do at home to potentially reduce these symptoms and help prevent subsequent cardiac events.

"There have been very few studies analyzing the effects of music on heart conditions," said Predrag Mitrovic, MD, PhD, professor of cardiology at the University of Belgrade School of Medicine and the study's lead author. "Based on our findings, we believe music therapy can help all patients after a heart attack, not only patients with early post-infarction angina. It's also very easy and inexpensive to implement."

The researchers recruited 350 patients diagnosed with heart attack and early post-infarction angina at a medical center in Serbia. Half were randomly assigned to receive standard treatment while half were assigned to regular music sessions in addition to standard treatment. For most patients, standard treatment included a variety of medications such as nitrates, aspirin, clot-preventing drugs, beta blockers, statins, calcium channel blockers, blood pressure-lowering medications and the angina-reducing drug ranolazine.

Patients receiving music therapy first underwent a test to determine which musical genre their body was likely to respond to positively. Participants listened to nine 30-second samples of music they found soothing, while researchers assessed each participant's body for automatic, involuntary responses to the music samples based on dilation or narrowing of the pupils. Researchers then fine-tuned the selection by working with the patient to determine the optimal music tempo and tonality.

Participants were asked to listen to their designated musical selection for 30 minutes each day whenever it was convenient for them to sit, ideally while resting with their eyes closed. Patients continued with these daily listening sessions for seven years, documenting their sessions in a log. They returned to the medical center for follow-up assessments every three months for the first year and annually thereafter.

At the end of seven years, music therapy was found to be more effective than standard treatment alone in terms of reducing anxiety, pain sensation and pain distress. The patients with music therapy, on average,

had anxiety scores one-third lower than those on standard treatment and reported lower angina symptoms by about one-quarter. These patients also had significantly lower rates of certain heart conditions, including an 18% reduction in the rate of heart failure; 23% lower rate of subsequent heart attack; 20% lower rate of needing coronary artery bypass graft surgery; and 16% lower rate of cardiac death.

Mitrovic said the music may work by helping to counteract the activity of the sympathetic nervous system, the part of the nervous system that drives the "fight-or-flight" response when a person faces a stressful situation. Because it increases heart rate and blood pressure, a sympathetic response can put added strain on the cardiovascular system.

"Unrelieved anxiety can produce an increase in sympathetic nervous system activity, leading to an increase in cardiac workload," Mitrovic said. He suggested regular sessions of listening to music could interrupt that cascade of events by reducing the anxiety associated with angina after a heart attack.

The researchers plan to further analyze the data to determine whether music therapy may show benefits for certain subgroups of patients, such as those in a certain age range or those with other health conditions like diabetes.

Credit: 
American College of Cardiology

To reap heart benefits of a plant-based diet, avoid junk food

Plant-based diets are becoming more popular in many areas of the world, but the health benefits of this dietary pattern may depend largely on the specific foods consumed. A new study being presented at the American College of Cardiology's Annual Scientific Session Together with World Congress of Cardiology (ACC.20/WCC) suggests that people following a plant-based diet who frequently consumed less-healthful foods like sweets, refined grains and juice showed no heart health benefit compared with those who did not eat a plant-based diet.

"Based on these results, it seems that simply following a plant-based or vegetarian diet is not enough to reduce cardiovascular disease risk," said Demosthenes Panagiotakos, PhD, professor of biostatistics, research methods and epidemiology at Harokopio University of Athens, Greece and the study's lead author. "It is also important to focus on specific, healthful plant-based food groups to see a benefit in terms of reducing cardiovascular disease."

Researchers tracked eating behavior and the development of heart disease among more than 2,000 Greek adults over a 10-year period, beginning in 2002. Participants were asked to complete a detailed food frequency survey at the time of enrollment, after five years and after 10 years.

At the end of the study period, researchers analyzed the relationship between diet and the development of cardiovascular disease using a dietary index that divided participants into three groups based on the number of animal-based foods (which included meats as well as animal-derived products such as eggs and dairy) they consumed per day. Overall, men eating fewer animal-based foods were 25% less likely to develop heart disease compared to men eating more animal-based foods. The same overall trend was seen in women, but the relationship was less strong, with an overall risk reduction of about 11% among women eating the fewest animal-based foods.

Even though the difference in cardiovascular disease risk was significant between these groups, the overall difference in consumption of animal-based foods was relatively small. Those following a more plant-based diet consumed, on average, three animal-based foods daily while those following a less plant-based diet consumed five.

"These findings highlight that even a small reduction in the daily consumption of animal-based products--principally the less healthy foods, such as processed meat products--accompanied by an increase in healthy plant-based foods may contribute to better cardiovascular health," Panagiotakos said.

Focusing in on participants who followed a more plant-based diet, researchers then categorized each participant's diet as either healthful (reflecting increased consumption of fruits, vegetables, whole grains, nuts, legumes, oils and tea or coffee) or unhealthful (reflecting increased consumption of juices,

sweetened beverages, refined grains, potatoes and sweets). Only participants following a healthful plant-based diet had a significant reduction in cardiovascular risk compared to those who ate more animal-based products.

Differences in eating patterns--and associated cardiovascular risk reduction--were also observed between women and men. In general, men ate about three times per day while women tended to snack more, eating four to five times daily. At the same time, women showed a more dramatic increase in heart disease risk when eating an unhealthful plant-based diet and a more dramatic reduction in risk when eating a healthful plant-based diet compared to men who fell into the same two categories. This suggests that snacking on healthful foods can be beneficial while snacking on unhealthful foods can bring higher risks, Panagiotakos said.

The study was limited by its reliance on questionnaires to track participants' diets. However, the findings bolster evidence for the heart health benefits of a plant-based diet and could help inform future dietary guidance for prevention of cardiovascular disease.

"In the future, I believe it will be useful if cardiovascular disease prevention guidelines offer clearer and specific nutrition suggestions, in terms of the types of foods that are recommended and the portions that should be consumed," Panagiotakos said.

This study received funding from the Hellenic Cardiology Society, Hellenic Atherosclerosis Society and the pharmaceutical industry.

Credit: 
American College of Cardiology