Culture

Understanding the effect of aging on the genome

Time may be our worst enemy, and aging its most powerful weapon. Our hair turns grey, our strength wanes, and a slew of age-related diseases represent what is happening at the cellular and molecular levels. Aging affects all the cells in our body's different tissues, and understanding its impact would be of great value in fighting this eternal enemy of all ephemeral life forms.

The key is to first observe and measure. In a paper published in Cell Reports, scientists led by Johan Auwerx at EPFL started by asking a simple question: how do the tissues of aging mice differ from those of mice that are mere adults?

To answer the question, the researchers used the multiple techniques to measure the expression of everyone one of the thousands of mouse's genes, and to identify any underlying epigenetic differences. The researchers not only measured different layers of information, but they did it across three different tissues: liver, heart, and muscle.

The data collectively allowed them to define an aging "footprint" that can serve as a field for investigation. But while many of the known aging manifestations were recovered, different tissues behaved differently.

"We will never have a thorough understanding of aging by studying a single tissue, and this applies to many other processes and diseases," says lead author Maroun Bou Sleiman. "Data, whether freshly produced or reused, is the key to understanding complex systems, and we are just scratching the surface."

Through multiple bioinformatics analyses, the scientists identified certain genes and proteins that may be controlling the complex aging process. By including human population data, they also showed that many of the "players" they identified in the mouse genome may be also relevant in human aging.

Finally, the researchers used human genetic data to show that some of the "players" may also explain why some humans live longer than others. "Our final goal is not to stop ageing, but to age better and disease-free, and to do that, we will need to characterize this system," says Johan Auwerx. "This is a perfect example of cross-species integration starting from the laboratory mouse and ending in human population data that takes us one step closer to understanding one of the most complex processes in biology."

Credit: 
Ecole Polytechnique Fédérale de Lausanne

Microwaves are useful to combine amino acids with hetero-steroids

Steroid hybrid molecules have recently attracted great attention from researchers in recent years owing to their bioactive properties. Earlier a team of researchers led by Dr. Bumal Banik and colleagues, reported the synthesis of several steroid-peptide conjugates of a potential biologically important class of steroid hybrid molecules. During the course of this study, the researchers have come to realize the diverse and interesting biological activities of hetero-steroids. The team recently performed microwave-induced synthesis of steroid-peptide conjugates based on some hetero-steroids containing N, O and S coupling with N-(tert-butoxycarbonyl)-L-phenylalanine as the amino acid residue following Ugi-4-component reaction (Ugi-4-CR). Hetero-steroids are first synthesized from available steroids. These are subjected to Ugi-4-CR to obtain a number of hetero-steroid-peptide conjugates - a new class of steroid-peptide conjugate. Their research findings have been published in a in Current Organic Synthesis.

The synthesis of hetero-steroid-amino acid conjugate starting from epiendrosterone to incorporate a heterocyclic ring fused to its D-ring is described in the article. To synthesize the Hetero-steroid-amino acid conjugate starting from easily available progesterone, a different approach is adopted. The Heterosteroid-amino acid conjugate is also prepared starting from 3β-acetoxy-19-formyloxy-7-iodo-6-nor-5,7-seco-pregnan-5,20-dione.

The team believes that this method will undoubtedly find a significant place in organic synthesis processes. "Microwave-promoted Ugi-4CR towards the synthesis of a new class of hybrid molecules, viz., Hetero-steroid-amino acid conjugates based on hetero-steroidal amines is a useful addition to synthetic organic chemistry." Says Dr Banik. "Additionally, hetero-steroid-amino acid conjugates may have diverse biological properties, which adds to their value.", he concludes. Under classical conditions, synthesis of many of these compounds as described here proves to be problematic due to the occurrence of undesirable side reactions. In contrast, the microwave method is proved to be excellent in terms of the yields of the products and rapidity of the reactions.

Credit: 
Bentham Science Publishers

Covert tobacco industry marketing tactics exposed by former employees

To circumvent current tobacco advertising, promotion and sponsorship (TAPS) laws in Australia, tobacco companies are incentivising retailers with cash payments, all-expenses paid holidays, exclusive parties and tickets to sporting events to drive tobacco sales.

Published today in Global Public Health, this is the first study to use interviews with former tobacco industry employees as key informants to understand the tactics that tobacco companies use to exploit gaps in the Australian legislation.

"Direct advertising of tobacco to consumers has long been banned, however this study exposes that tobacco companies continue to market their products through thousands of tobacco retailers," said lead author Christina Watts from University of Sydney and Tobacco Control Policy at Cancer Council NSW.

"Tobacco companies have focused their marketing budget on retailers as they are one of the only remaining avenues to communicate directly with consumers.

Under Australian legislation, incentives and benefits connected to the sale of tobacco cannot be provided to consumers, however, such laws do not explicitly apply to tobacco retailers. A recent sample survey of Australian tobacco retailers found that one-third had received a benefit or incentive from a tobacco company in return for doing something for the company.

In the study, former tobacco industry employees described covert tobacco marketing and promotion strategies to retailers including:

- Providing financial incentives such as price promotions, cash payments and rebates

- Providing experiential incentives such as all-expenses paid holidays, exclusive parties and events, tickets to international sporting events (with events used to indirectly promote products)

- Incentivising retail staff to reach sales targets and upskilling them to be effective tobacco brand ambassadors.

These strategies had the ultimate objective of increasing market share and driving sales through increased retailer loyalty and rapport.

"Despite the tobacco industry's repeated argument that such promotional activities are only to increase their individual market share, rather than drive new sales, our research shows that incentives were provided to encourage retailers to reach or exceed sales targets and to push products directly to consumers," said Ms Watts.

Study supervisor Dr Becky Freeman from the University of Sydney's Faculty of Medicine and Health said that changes to the current tobacco advertising, promotion and sponsorship laws are urgently needed in Australia.

"The tobacco industry continues to market its deadly products, while pretending to be a "reformed" company that supports public health.

"Tobacco companies appear to be exploiting current laws by using the retail environment as an indirect channel to reach consumers.

"By only restricting tobacco marketing practices aimed directly at consumers, Australian legislation has failed to respond to the importance of retail marketing in the promotion of tobacco. This has enabled tobacco companies to funnel resources into this 'last line of marketing' of their products.

"We're calling for Australian laws to be strengthened to prohibit all marketing of tobacco products - with no contributions allowed of any kind to any event, activity, or individual.

"Restrictions must address direct product advertising to tobacco retailers, in order to prevent any ongoing and future covert promotion of tobacco," she said.

Australia is considered to be a global leader in tobacco control with a suite of measures to restrict tobacco marketing activities such as:

- bans on tobacco advertising, promotion and sponsorship

- plain packaging with graphic health warnings

- removal of visible displays of tobacco products at point-of-sale.

These measures have contributed to daily smoking rates declining in Australia from 24 percent of adults in 1991 to 11 percent in 2019.

Credit: 
Taylor & Francis Group

Unknowns and uncertainties raise ethical concerns for UK egg freezing

The Nuffield Council on Bioethics has today published a 'bioethics briefing note' which highlights a pressing need for data on egg freezing success rates to be presented more clearly, accessibly, and transparently. At present, research suggests that women find these data difficult to navigate.

Frances Flinter, Nuffield Council member and Emeritus Professor of Clinical Genetics at Guy's and St Thomas' NHS Foundation Trust, said:

"It's vital for women thinking about freezing their eggs to be able to make informed choices. To do this, they need easy access to data on their chances of success across various stages of the process - from freezing and thawing eggs, to having a live birth. But they also need clinics to be frank about the process, and about what is known and unknown about egg freezing. This is especially important given egg freezing's increasing popularity."

Egg freezing as an employment benefit

One area where clear information and research are likely to be important in the future is where egg freezing is offered as part of an employment benefits package. Although this isn't common in the UK at present, it is beginning to be offered by some companies.

For some women, being offered egg freezing as an employment benefit could feel empowering and give a sense of being in more control over their reproductive future. For others, the offer might make them feel pressured to delay motherhood. If more employers consider providing this benefit, research needs to focus on women's needs and their experiences of using such schemes.

The Nuffield Council also highlights that offering egg freezing as part of a benefits package is not the only option for employers to support employees' reproductive choices. Improvements to family-friendly work environments, childcare subsidies, and family leave also have a key role to play.

Other conclusions

The briefing note also reports that:

The way social egg freezing is presented and marketed is potentially of concern and should be the focus of closer attention. Concerns raised on this issue include the trivialisation of egg freezing in media coverage, the role of social media influencers' promotion of the technology, the use of algorithms that target women with egg freezing adverts, and irresponsible marketing strategies, including events where egg freezing is discussed over prosecco. Research also suggests that women can feel pressure to freeze to avoid blaming themselves later. It is important that marketing strategies consider such research so that women's anxieties are not exploited.

There appear to be few arguments against increasing the storage limit for social egg freezing from its current limit of ten years. Changes to this limit are currently being considered by the Government.

Credit: 
Nuffield Council on Bioethics

Forgetting past misdeeds to justify future ones

Proven fact: we remember our altruistic behaviour more easily than selfish actions or misdeeds that go against our own moral sense. Described as 'unethical amnesia' by scientists, it is generally explained by self-image maintenance. But could these selective oversights, not necessarily conscious, have a more strategic aim? To find out, a team of behavioural economists from the CNRS (1) recruited 1322 volunteers in an online experiment which took place over two sessions. The first session involved 20 repetitions of a lottery task, the results of which determined the participants' monetary payoff; however, as the participants had to self-report the outcomes they had the opportunity to cheat (2). During the second session, three weeks later, the same participants were monetarily incentivised to recall as accurately as possible the outcomes they had reported in the previous session. Half of the volunteers were informed that they would then have the opportunity to voluntarily return some of the money if they had overreported their outcomes in the first session. It was within this configuration that the participants were most prone to amnesia, as reported by scientists in PNAS on 28th September 2020. In other words, they remembered their cheating behaviour less accurately when they knew they would have to make a moral decision again, even though they could earn more money by remembering the reported outcomes. It was as if forgetting this incident would allow them to restore their reputation, making it more acceptable for a future breach of morality.

Credit: 
CNRS

'Cool' sampling sites more likely to show false trends

image: Flower-rich meadow at a park in Leipzig, Germany.

Image: 
Gabriele Rada / iDiv

To manage and conserve natural ecosystems, it is essential to know how biodiversity changes. As one of those questions, it is important to know whether we are we gaining or loosing species. However, getting reliable measurements to study this is a complex task. Data can be collected by researchers during field trips, but a vast amount of data is also provided by different initiatives such as citizen science programs. However, to ensure measurements are reliable, samples need to be representative of the real world. If samples are not representative, they are biased.

In their study, scientists from iDiv, UL and MLU showed that a bias can dramatically change the measurements of biodiversity change. They focused on the so-called site-selection bias, where sampling sites are not selected representatively. For example, if a person wanted to find out how the number of butterfly species is changing in the area over the next ten years, this person will likely not choose a typical and average spot, such as a little meadow behind a supermarket. Instead, a place such as a clearing in the park may seem well suited. Thus, the sampling site is biased towards where many butterfly species can be found. This is the site-selection bias.

Site-selection bias may amplify or even revers trends

Using a computer simulation, the scientists showed that this bias can lead to false conclusions about how biodiversity changes. "If we measure biodiversity at places that have unusually many species, statistical principles suggest that we will more likely observe a drop in species numbers over time," said first author Dr Andrea Mentges from iDiv and UL. The biased choice of where to take samples may manipulate the collected data and even lead to wrong conclusions. "We found that site-selection bias can even make our measurements point into the wrong direction: while for example in reality we are gaining species, our measurements would falsely suggest that the number of species goes down. This makes clear how important it is to choose representative sampling sites."

The scientists analysed how wide-spread such site-selection biases are, and found that they can potentially occur in many data sources, such as data collected by museums, national parks, citizen scientists and academic researchers. Whether the site-selection bias affects the measurements depends on the purpose of the collection. The data on the butterflies counted in the local park may still be informative, said Andrea Mentges: "Such data can be used to find out if a certain butterfly species can still be found in the area or if new species are immigrating. But if we use it to find out whether butterfly numbers are increasing or decreasing in the surrounding landscape, we might be wrong."

Citizen scientists more likely to choose 'cool' spots

For their study, the scientists also looked at 44 citizen science initiatives. In many programmes, participants were allowed to choose sites themselves. This free site selection can potentially lead to a bias - depending strongly on the training participants received. Andrea Mentges said: "We assume that if people are not explicitly told that it is important to choose a 'normal' site they will always tend to choose a 'cool' spot. That's why we think such programmes can potentially be problematic when there is no in-person training or instructions available online that also focus on site selection."

In Germany, such training is not very common in citizen science initiatives. Although information material is available to interested participants this may not always prevent a site-selection bias - for example, when participants are encouraged to look for meadows and flower-rich wayside for their observations. "These are great initiatives that collect a lot of useful data," said Andrea Mentges. "But it may not be suitable for some research questions - for example, whether the number of a certain butterfly species such as the small tortoiseshell is going up or down in general." However, such site-selection biases can easily be prevented. Prof Dr Jonathan Chase, head of the Biodiversity Synthesis group at iDiv and professor at MLU, said: "The most objective way would be to use systematic, computer-based site-selection schemes, these are also applied more and more often. But it's always a fine line between scientific accuracy and practical feasibility. And, of course, citizen science programmes owe their existence to the motivation of the many volunteers contributing with their data."

Credit: 
German Centre for Integrative Biodiversity Research (iDiv) Halle-Jena-Leipzig

Identified the cellular process by which Cisplatin chemotherapy causes neuronal damage

image: Cisplatin induces senescence of peripheral neurons through overexpression of the p21 protein, which would explain the neuropathy.

Image: 
Bellvitge Biomedical Research Institute (IDIBELL)

Despite the great advances in cancer research in recent years, treatments that can cause very severe adverse effects are still used. This is the case of neuropathy caused by chemotherapy with platinum derivatives, such as Cisplatin and Oxaliplatin. These are widely used drugs that can damage the peripheral nervous system causing a progressive and increasing loss of sensitivity, which may even affect the mobility. The appearance of these adverse effects may force to reduce the dose or change the treatment for a less effective second-line treatment.

To design drugs that alleviate or avoid the adverse effects of Cisplatin, it is important to know the mechanism by which it causes neuropathy. And this is precisely the focus of the study carried out by a team from the Bellvitge Biomedical Research Institute (IDIBELL), the Catalan Institute of Oncology (ICO), the Bellvitge University Hospital (HUB) and the Autonomous University of Barcelona (UAB), which has shown that Cisplatin induces senescence of peripheral neurons through overexpression of the p21 protein, which would explain the neuropathy.

"This discovery represents a paradigm shift in the field, because until now it was believed that oxidative stress and apoptosis cell death caused Cisplatin neuropathy", says Dr. Jordi Bruna, project leader. The study, published in the Neuro-Oncology journal, shows that neurons respond to Cisplatin damage by generating a series of metabolic changes. These changes induce them to enter in a kind of permanent hibernation, called senescence, which would be causing neuropathic symptoms, and not the direct death of neurons as previously believed.

The study shows the overexpression of the p21 protein induced by the administration of Cisplatin. This is a protein that in response to injury can regulate both, senescence and cellular apoptosis processes. However, the study shows that the pathways involved in apoptosis are not activated. Furthermore, both electron microscopy studies and molecular markers of cellular senescence have confirmed that neurons show morphological characteristics of senescence after treatment with Cisplatin.

"Neurons are the paradigm of a highly differentiated cell that cannot replicate, and senescense processes, classically described in replicative cells, are more controversial in non-replicative cells. Therefore, our work contributes to other recent studies that point that senescence processes can be relevant in different neurological pathologies" says Dr. Esther Udina, researcher at the Institut de Neurociències of the UAB (INc-UAB) and co-author of this research.

Until now, clinical trials of neuroprotective treatments aimed to alleviate platinum neuropathy have failed. Dr. Bruna concludes that "this could be because the treatments were focused on preventing neuronal apoptosis," and adds, "this study provides new targets to alleviate platinum neuropathy. These neuroprotective treatments, administrated with chemotherapy, could prevent the onset of neuropathy, and are less likely to interfere with antitumor efficacy than those aimed to prevent apoptosis". " In this way, chemotherapy with Cisplatin would not be limited depending on the appearance of this common adverse effect."

These studies used a mouse model that perfectly mimics the clinical characteristics of the patients. By a cell separation method, each neuron of the dorsal spinal ganglion was individualized and, the genes that were expressed at each moment were studied, with the subsequent validation with protein expression. It is an innovative method that has never been used in this field of research.

Credit: 
IDIBELL-Bellvitge Biomedical Research Institute

Astrophysicist probes cosmic "dark matter detector"

A University of Colorado Boulder astrophysicist is searching the light coming from a distant, and extremely powerful celestial object, for what may be the most elusive substance in the universe: dark matter.

In two recent studies, Jeremy Darling, a professor in the Department of Astrophysical and Planetary Sciences, has taken a deep look at PSR J1745-2900. This body is a magnetar, or a type of collapsed star that generates an incredibly strong magnetic field.

"It's the best natural dark matter detector we know about," said Darling, also of the Center for Astrophysics and Space Astronomy (CASA) at CU Boulder.

He explained that dark matter is a sort of cosmic glue--an as-of-yet unidentified particle that makes up roughly 27% of the mass of the universe and helps to bind together galaxies like our own Milky Way. To date, scientists have mostly led the hunt for this invisible matter using laboratory equipment.

Darling has taken a different approach in his latest research: Drawing on telescope data, he's peering at PSR J1745-2900 to see if he can detect the faint signals of one candidate for dark matter--a particle called the axion--transforming into light. So far, the scientist's search has come up empty. But his results could help physicists working in labs around the world to narrow down their own hunts for the axion.

The new studies are also a reminder that researchers can still look to the skies to solve some of the toughest questions in science, Darling said. He published his first round of results this month in the Astrophysical Journal Letters and Physical Review Letters.

"In astrophysics, we find all of these interesting problems like dark matter and dark energy, then we step back and let physicists solve them," he said. "It's a shame."

Natural experiment

Darling wants to change that--in this case, with a little help from PSR J1745-2900.

This magnetar orbits the supermassive black hole at the center of the Milky Way Galaxy from a distance of less than a light-year away. And it's a force of nature: PSR J1745-2900 generates a magnetic field that is roughly a billion times more powerful than the most powerful magnet on Earth.

"Magnetars have all of the magnetic field that a star has, but it's been crunched down into an area about 20 kilometers across," Darling said.

And it's where Darling has gone fishing for dark matter.

He explained that scientists have yet to locate a single axion, a theoretical particle first proposed in the 1970s. Physicists, however, predict that these ephemeral bits of matter may have been created in monumental numbers during the early life of the universe--and in large enough quantities to explain the cosmos' extra mass from dark matter. According to theory, axions are billions or even trillions of times lighter than electrons and would interact only rarely with their surroundings.

That makes them almost impossible to observe, with one big exception: If an axion passes through a strong magnetic field, it can transform into light that researchers could, theoretically, detect.

Scientists, including a team at JILA on the CU Boulder campus, have used lab-generated magnetic fields to try to capture that transition in action. Darling and other scientists had a different idea: Why not try the same search but on a much bigger scale?

"Magnetars are the most magnetic objects we know of in the universe," he said. "There's no way we could get close to that strength in the lab."

Narrowing in

To make use of that natural magnetic field, Darling drew on observations of PSR J1745-2900 taken by the Karl G. Jansky Very Large Array, an observatory in New Mexico. If the magnetar was, indeed, transforming axions into light, that metamorphosis might show up in the radiation emerging from the collapsed star.

The effort is a bit like looking for a single needle in a really, really big haystack. Darling said that while theorists have put limits on how heavy axions might be, these particles could still have a wide range of possible masses. Each of those masses, in turn, would produce light with a specific wavelength, almost like a fingerprint left behind by dark matter.

Darling hasn't yet spotted any of those distinct wavelengths in the light coming from the magnetar. But he has been able to use the observations to probe the possible existence of axions across the widest range of masses yet--not bad for his first attempt. He added that such surveys can complement the work happening in Earth-based experiments.

Konrad Lehnert agreed. He's part of an experiment led by Yale University--called, not surprisingly, HAYSTAC--that is seeking out axions using magnetic fields created in labs across the country.

Lehnert explained that astrophysical studies like Darling's could act as a sort of scout in the hunt for axions--identifying interesting signals in the light of magnetars, which laboratory researchers could then dig into with much greater precision.

"These well-controlled experiments would be able to sort out which of the astrophysical signals might have a dark matter origin," said Lehnert, a fellow at JILA, a joint research institute between CU Boulder and the National Institute of Standards and Technology (NIST).

Darling plans to continue his own search, which means looking even closer at the magnetar at the center of our galaxy: "We need to fill in those gaps and go even deeper."

Credit: 
University of Colorado at Boulder

New genetic knowledge on the causes of severe COVID-19

Worldwide, otherwise healthy adolescents and young people without underlying conditions are sometimes severely affected by COVID-19, with the viral infection in the worst cases quickly becoming life-threatening. But why is this happening?

A world-wide consortium of researchers is determined to investigate this - and they have now made so much progress that Science has just published two scientific articles describing some of their results.

Professor Trine Mogensen from the Department of Biomedicine at Aarhus University is co-author on the two research articles in Science. She conducts research into rare immunodeficiencies that lead to increased susceptibility to viral infections and, together with her research group, participates in the steering committee of the research consortium Covid human genetic effort (covidhge) as the only Danish representativ.

She explains that in the vast majority of people, infection with the COVID-19 causing coronavirus leads to an anti-viral response in which interferon plays a crucial role. Interferon is an importantimmune signaling hormone that slows the division of the virus and prevents it from penetrating the surrounding cells. In the event of a viral infection, the body normally quickly begins producing interferon, and the virus can be brought under control withing a few hours. In popular terms, interferon is our first safeguard against an infection.

"However, if there are defects in the interferon signalling pathways, there is nothing to inhibit the virus dividing, and while the coronavirus usually remains in the cells in the throat, it can in this case also infect other parts of the body such as the lungs, kidneys and perhaps even the brain," explains Trine Mogensen, who also is Medical Specialist at the Department of Infectious Diseases, Aarhus University Hospital, Denmark

Genetic and immunological analyses of blood samples from 650 patients from all over the world with severe COVID-19 show that some of these patients have an inherited immunodeficiency which leads to the anti-viral interferon either not being produced or not working on the body's cells. Blood samples from 1,226 healthy individuals have functioned as a control group - with all of the samples being taken prior to the COVID-19 pandemic.

The researchers have obtained consent to collect blood samples and carry out a genetic analysis from hospitalized and severely ill COVID-19 patients. From the blood samples, the researchers have purified immune cells from the 650 patients and subsequently infected these immune cells with coronavirus, which enabled them to ascertain that the immune system was not properly activated. In addition, a genetic sequencing of DNA from the 650 patients has been carried out, with some of this work being carried out at Aarhus University Hospital.

"Our DNA consists of approximately 20,000 genes, and we have found defects in thirteen different genes. This means that the proteins which the genes encode become defective and therefore cannot perform their role in the immune system. We're already aware of some of these genetic defects from patients affected by severe influenza, but some are new and specific to COVID-19," says Trine Mogensen.

The next task for the international research consortium is to translate - i.e. transfer - the basic immunological findings to the treatment of patients, and the first clinical trials are on the way. Medical doctors will be able to measure whether the patients have autoantibodies in their blood as these are relatively easy to measure, and if they are, they can be filtered from the blood. It will also be possible to screen for the thirteen critical genes identified and in this way have the ability to identify particularly vulnerable individuals. This group will then be able to receive preventative medical treatment and a vaccine once this is available.

"The goal is to prevent the very severe cases of COVID-19 with high mortality rates," summarizes Trine Mogensen, who is optimistic and hopes that the clinical trials will demonstrate positive results - perhaps already within a year.

She does not only base her optimism on the unique international collaboration which exists in the COVID Human Genetic Effort, as the international research consortium is named.

"I've never experienced anything like it before in my field of immunology and infectious diseases. We share knowledge and work together in a very altruistic spirit," she adds. The consortium comprises more than 250 researchers under the overall leadership of Professor Jean-Laurent Casanova from The Rockefeller University in the United States - with the professor also serving as an Honorary Skou professor at Aarhus University since 2019.

Credit: 
Aarhus University

Planet collision simulations give clues to atmospheric loss from Moon's origin

video: Cross-section animation of the early stages of a 3D simulation of a head-on, slow giant impact using 30 to 100 million particles, coloured by its material or its internal energy, related to its temperature.

Image: 
Jacob Kegerreis, Durham University.

Earth could have lost anywhere between ten and 60 per cent of its atmosphere in the collision that is thought to have formed the Moon.

New research led by Durham University, UK, shows how the extent of atmospheric loss depends upon the type of giant impact with the Earth.

Researchers ran more than 300 supercomputer simulations to study the consequences that different huge collisions have on rocky planets with thin atmospheres.

Their findings have led to the development of a new way to predict the atmospheric loss from any collision across a wide range of rocky planet impacts that could be used by scientists who are investigating the Moon's origins or other giant impacts.

They also found that slow giant impacts between young planets and massive objects could add significant atmosphere to a planet if the impactor also has a lot of atmosphere.

The findings are published in the Astrophysical Journal Letters.

The Moon is believed to have formed about 4.5 billion years ago following a collision between the early Earth and a giant impactor possibly the size of Mars.

Research lead author Dr Jacob Kegerreis, in the Institute for Computational Cosmology, Durham University, said: "The puzzle about how the Moon formed and the other consequences of a giant collision with the early Earth is something that scientists are working hard to unravel.

"We ran hundreds of different scenarios for many different colliding planets, showing the varying impacts and effects on a planet's atmosphere depending upon a number of factors such as the angle, speed of impact or the sizes of the planets.

"While these computer simulations don't directly tell us how the Moon came to be, the effects on the Earth's atmosphere could be used to narrow down the different ways it might have been formed and lead us closer to understanding the origin of our nearest celestial neighbour."

Earlier this year, an initial study by Durham University reported that giant impacts which dominate the late stages of planet formation can have a wide range of consequences for young planets and their atmospheres.

That study examined the ways that thin atmospheres could be removed by objects impacting at different angles and speeds.

The researchers' latest paper looks at the effects across a much wider variety of impacts adjusting for size, mass, speed and angle of the impacting object. They also changed the density of the impactor and if it was made of iron, rock or both.

The simulations revealed the different outcomes when one or more of these variables are changed, leading to atmospheric loss or gain, or sometimes the complete obliteration of the impacted planet.

The research team also included scientists at the BAERI/NASA Ames Research Centre and the University of Washington, USA, and the University of Glasgow, UK.

Co-author Dr Luis Teodoro, in the School of Physics and Astronomy, University of Glasgow, and the BAERI/NASA Ames Research Centre, said: "This major suite of planetary simulations also sheds light on the role of impacts in the evolution earth like exoplanets."

Credit: 
Durham University

Nasal calcium rich salts show reduction of exhaled aerosol particles up to 99%

image: FEND is available from October 5 at hellofend.com

Image: 
Raphael Edwards Photography (left) and Tom Devlin Designs (right)

In a paper published in Molecular Frontiers Journal, researchers from Cambridge, Massachusetts have discovered a more effective way of eliminating airborne particles from airways using nasal calcium-rich salts called FEND, which have potential applications in the fight against Covid-19.

Sensory Cloud, creators of FEND and a Boston-based technology startup that designs solutions to problems of human wellbeing and healthcare through pioneering discoveries at the frontiers of olfaction and respiratory biology, studied the effectiveness of nasal administration of physiological salts at reducing airborne particles from exhaled breath including the sub-micron aerosolized particles that are ineffectively filtered by cloth face masks. Lead authors of the paper are Dr. David Edwards (John A. Paulson School of Engineering, Harvard University) and Dr. Robert Langer (Department of Chemical Engineering, MIT),

Ninety-two men, women and children were observed in three separate studies showcasing the use of FEND in various situations: in the workplace, quarantining at home, and in comparison to cloth face masks. The studies assessed how FEND, a drug-free calcium-enriched nasal salt, would interact with airway lining mucus to cleanse the airways of bioaerosols. The results showed a reduction of exhaled aerosol particles of up to 99%, with an overall reduction of exhaled particles in the largest cohort of human subjects (76 workers) of around 75%.

"The findings, which build on an earlier study this summer, suggest that we can provide what is, in effect, a nasal filter to protect at-risk populations from viral carrying aerosols," said Sensory Cloud founder Edwards. "Access to a new hygiene protocol for reducing the spread of these smallest particles, which can otherwise be dispersed into indoor air and enter deep into our lungs, can be an important intervention as we head back to work and school, as winter approaches, and as troubling data about rates of infection continue to emerge."

In the first study, 76 COVID-negative volunteers (including 74 workers and two children) from No Evil Foods in Asheville, NC, ages 15-66, were recruited. Prior to the nasal hygiene intervention, exhaled aerosol from the 76 workers followed a classical "super spreading" distribution, with 20% of participants accounting for 80% of the overall exhaled aerosol. Within the "super spreader" group, half of the individuals (or the top 10% of exhaled particle producers) were found to be responsible for 80% of the super spreader production - or 64% of the overall production. The 76 volunteers then received FEND, a drug-free nasal saline hygiene formulation comprised of calcium chloride and sodium chloride in distilled water and administered via a mist of 9-10 micron diameter droplets by a hand-held mister. The FEND intervention suppressed 84% of exhaled aerosols for the highest producing super-spreaders and 78% overall for all super-spreaders. Overall, exhaled aerosols among all participants did not change after a nasal saline control intervention, Simply Saline from Arm & Hammer, a nasal spray of isotonic sodium chloride.

"Health and safety is a huge priority at No Evil Foods," said Sadrah Schadel, co-founder and Chief Creative Officer of No Evil Foods. "Having the chance to actually see FEND work, clearing particles from our exhaled breath, was an overwhelmingly positive experience for our team."

The second study evaluated the exhaled aerosols of a volunteer family of four in quarantine with one COVID-positive mother. The study followed the family for five days starting at eight days post-symptoms for the mother. The mother's exhaled aerosols showed extremely high output on days eight and nine. After receiving the FEND intervention, her levels decreased to average baseline levels for a COVID-negative patient, with suppression lasting several hours following the intervention.

The final study compared the use of FEND to surgical mask use in 12 children and adults. The surgical masks reduced overall exhaled particles by around 34% for the group, while FEND reduced overall exhaled particles by 46% -- with one individual showing no statistical difference on using the mask or FEND, possibly for failure to administer properly. Excluding the outlier subject, exhaled aerosols were reduced by 59% when wearing masks and 87% following the FEND intervention. The differential benefit of FEND was due to its more effective reduction in sub-micron aerosol particles, given that most exhaled aerosol particles for all individuals are sub-micron.

The paper concludes that FEND can be an important addition to current COVID-19 hygiene protocols of mask wearing, hand washing, and social distancing. FEND adds to the efficacy of masks at reducing the penetration of respiratory droplets into the lungs or back into the environment and provides an added layer of defense for when mask wearing is not a possibility.

"We continue to support human volunteer studies in the USA and overseas, exploring unique hygiene protocols for collaborative teams, and deepening our understanding of nasal salt hygiene among those infected with COVID-19," said Edwards. "As FEND comes to market in coming weeks, we will prioritize distribution to healthcare professionals, and other essential workers in the USA and in countries around the world that are hardest hit by the COVID-19 pandemic. As we scale up production, we hope also to be helpful to clearing the air for children and teachers in public schools around the world."

Credit: 
World Scientific

Discovery of cells that heal cardiac damage after infarction

image: From left to right: Dr Adrián Ruiz-Villalba and Dr Felipe Própser, Regenerative Medicine and Cell Therapy researchers at Cima and Clinica

Image: 
Cima Universidad de Navarra

Pamplona (Spain), September 29th, 2020. Researchers at Cima and the Clinica Universidad de Navarra (Spain) have led an international study identifying the cardiac cells responsible for repairing the damage to this organ after infarction. These "restorative" cells are a subpopulation of cardiac fibroblasts that play a fundamental role in the creation of the collagen scar needed to avoid the rupture of the ventricular wall. The research also reveals the molecular mechanisms involved in the activation of these cells and the regulation of their function.

This finding, in which basic and clinical researchers have participated, will permit the identification of new therapeutic targets and the development of targeted therapies which will control the healing process of the heart after infarction.

The study has been published in the latest issue of the journal Circulation, the leading scientific journal of the American Heart Association.

Characterization of the reparative cardiac fibroblasts

Cardiac fibroblasts are one of the fundamental components of the heart. These cells play an essential role in maintaining the structure and mechanism of this vital organ. "Recent studies have shown that fibroblasts do not respond homogeneously to heart injury. Therefore the object of our study was to determine their heterogeneity during the remodeling of the injured ventricle and to understand the mechanisms that regulate the function of these cells", said Dr Felipe Prósper, a researcher at Cima and the Clinica Universidad de Navarra, the leader of the study.

"Using single-cell transcription analysis techniques (single-cell RNA-seq), we identified a subpopulation within the cardiac fibroblasts, which we have named Reparative Cardiac Fibroblasts (RCF) due to their role after the cardiac injury. We have found that, when a patient has a heart attack, these RCF are activated and offer a fibrotic response due to which a collagen scar is generated to avoid the rupture of the cardiac tissue", stated Dr Prósper, who is also a member of the Red de Terapia Celular (TerCel) and the Instituto de Investigación Sanitaria de Navarra (IdiSNA).

CTHRC1, a protein related to collagen and essential for the regenerative process

In the detailed molecular study, the researchers have found that the RCF have a unique transcriptional profile, that is to say, a specific information pattern for the expression of the genes involved in their cardiac function. "Among the main differential markers of the transcriptome of these cells, we have identified the CTHRC1 protein (Collagen Triple Helix Repeat Containing 1), a molecule with a fundamental role in the fibrotic response after myocardial infarction. Specifically, this protein participates in the collagen synthesis of the extracellular cardiac matrix and is crucial for the process of ventricular remodeling", in the words of Adrián Ruiz-Villalba, a researcher on the Regenerative Medicine Program at Cima and first author of the article.

These results "suggest that the RCF activates the healing scar process of the cardiac lesion by secreting the CTHRC1 protein. Thus, this molecule may be considered as a biomarker associated with the physiological condition of the injured heart and a potential therapeutic target for patients who have suffered a heart attack or have dilated cardiomyopathy", stated Ruiz-Villalba, who is also a researcher at IdiSNA. In addition to Cima and the Clinica Universidad de Navarra, basic and clinical researchers from the United States, Belgium and Austria have taken part in this research.

This work falls within the framework of the Cell Therapy and Regenerative Medicine research line being carried out at Cima and the Clinica Universidad de Navarra, aimed at understanding the regenerative potential of stem cells and their therapeutic application in different diseases such as cardiovascular ones. Specifically, this study is linked to the BRAV? project, an international research project combining bioengineering and cardiac stem cells to restore the function of an infarcted heart. BRAV? is an H2020 funded program by the European Union (H2020-SC1-BHC-07-2019-874827).

Credit: 
Universidad de Navarra

Prototype graft, designed to replace damaged heart vessels, shows promise in cell study

In a proof-of-concept study, North Carolina State University researchers reported promising preclinical findings for a prototype of a vascular graft designed as a replacement for a damaged or blocked coronary artery, which supplies blood to the heart.

The findings, which were made in partnership with researchers from Case Western Reserve University, are part of an effort to develop a synthetic graft that could replace a damaged or blocked coronary artery when a patient's own vessels are not available as viable replacements after a heart attack. Ultimately, the graft is designed as a scaffold to aid in regeneration of the patient's own blood vessels. And while their work is still in early stages, the researchers said their design will help to move the field forward.

In the journal Materials Science and Engineering: C, researchers reported they made their prototype vascular graft by knitting a collagen material with a synthetic yarn. They found their design showed improved strength compared to a model that used the collagen material alone, and flexibility that compared to the human coronary artery. Also, in studies with human endothelial cells, they saw increased growth and adhesion of cells on the graft, indicating it could aid in the regeneration of the coronary artery lining.

"We see this as a new direction for research into coronary artery replacement grafts," said the study's senior author Martin King, professor of biotextiles and textile technology at NC State. "The use of collagen yarns is very new. We relied not just on one material, but we mixed the materials together and showed the two yarns can provide both mechanical strength and the biological response that we're looking for."

Currently, researchers said the "gold standard" is to use a patient's own blood vessel, such as a vein from the leg or the mammary artery, to replace the coronary artery, but some patients do not have viable blood vessels that can be harvested and used.

"There is a need to find an alternative solution for this kind of patient," said Fan Zhang, the study's first author and graduate student at NC State. "That's why we're looking to use tissue-engineered vascular grafts."

There are multiple challenges to designing a synthetic vascular graft that could replace a coronary artery, the researchers said. Some models have failed due to problems with clotting and narrowing of the arteries. Meanwhile, other models aren't able to stretch and relax with the beating heart.

"The coronary artery is only about three to four millimeters in diameter so it's a very fine artery, and it's very easy for it to get blocked," King said. "The question is: Do we have materials that will serve as a conduit without provoking this clotting on the arterial wall? That is one of the challenges. The other is that the heart is continually expanding and contracting, so we need a structure that can stretch and relax with every heart beat."

To develop their design, the NC State investigators collaborated with researchers at Case Western Reserve who have designed a biological yarn made of collagen. They combined that collagen yarn with a synthetic fiber made of polylactic acid, which is "biocompatible." When it degrades, it forms lactic acid, researchers said, which is easily tolerated because the muscles in our bodies continuously generate lactic acid.

Researchers said their model is designed to form a temporary scaffold that can regenerate a cell lining similar to the patient's own blood vessels.

"We're not designing a prototype that is a 'final product,' we're putting in the ingredients that will allow the patient to heal, and use this construct to heal and function as a coronary artery," King said. "The fibers would eventually degrade and be absorbed into the body."

Researchers found that by knitting the collagen fibers together with the synthetic PLA yarn, human endothelial cells stuck to the scaffold 10 times as much as to the synthetic yarn alone. The experiment also showed three times greater cell growth after adhesion.

Also, they found it had "excellent" bursting strength and compliance, which are the properties that will allow it to expand and contract with each heart beat - similar to a healthy coronary artery.

"We were able to mimic the compliance of the coronary artery," Zhang said. "This is the most important finding. In addition, with the addition of the collagen yarn component, we were able to promote endothelial cells to grow faster within this structure. That is very important for recovery of the endothelium."

Their work is still at a preclinical stage and has yet to be tested in a living animal. They still have work to improve their prototype to overcome additional design challenges, including how to reduce the porous nature of the hybrid graft.

However, they believe their findings show it is possible to combine both biological and synthetic materials in the design of a synthetic coronary artery graft. They are working on solutions to prevent blood leakage.

"With this combination of materials, we have been able to balance the mechanical performance with the biological response," King said. "We were also able to manufacture the prototype graft using high speed textile production machinery, which will facilitate future manufacturing scale-up and translation to a commercial graft and the clinic."

Credit: 
North Carolina State University

Study highlights lack of evidence for plasticity-led evolution in lizards

image: A micro computed tomography scan of an Anolis lizard

Image: 
Nathalie Feiner (CC BY 4.0)

Scientists have challenged a popular theory behind the evolution of similar traits in island lizards, in a study published recently in eLife.

The findings in Greater Antillean Anolis lizards provide insights on why creatures often evolve similar physical features independently when living in similar habitats. They suggest that the role of developmental plasticity in shaping adaptive evolution may be less important than commonly thought.

Developmental plasticity refers to how development responds to the environment, in particular the way that an organism's genetic constitution (or genotype) interacts with its environment during development to produce a particular set of characteristics (or phenotype).

"Anolis lizards that live on all four of the Greater Antillean islands have independently and repeatedly evolved six different body types for maneuvering through their given habitat," says lead author Nathalie Feiner, Researcher at the Department of Biology, Lund University, Sweden. "As a result, they make a great model for studying why evolution often repeats itself."

To address this question, Feiner and the team used micro computed tomography scans to measure the shoulder, hip and leg bones of 95 species of anoles that live on the Greater Antillean islands. Their work revealed that several of the species' body shapes evolved along similar trajectories.

"These body shapes are adapted by natural selection, but several different shapes could in principle perform equally well in a given habitat," says senior author Tobias Uller, Professor of Evolutionary Biology at the Department of Biology, Lund University. "As a result, repeated evolution is more likely to occur when species share a developmental biology that makes some characteristics appear readily, while others are rare or even impossible."

One source of these developmental biases can be found in how individuals respond to different environments, a hypothesis known as plasticity-led evolution. The researchers tested how the anoles' bones responded to stresses induced by climbing and running to see if these changes directly matched the skeletal structure (or morphology) of those specialised to a given habitat.

To do this, they raised two groups of anoles - some that typically perch on narrow twigs, and others that typically run and climb on tree trunks - on two different types of surfaces, which changed the way the animals moved or perched, as well as their morphology. However, these changes were poorly matched to the evolutionary divergence between habitat specialists that evolved repeatedly on different islands.

"The responsiveness of bone to mechanical stress is a good candidate for plasticity-led evolution," Feiner explains. "But this responsiveness does not seem to have channelled the evolution of the locomotor skeleton in Anolis lizards. Instead, our findings suggest that the morphologies that evolved again and again in these lizards are likely due to simple genetic changes."

Credit: 
eLife

Study suggests link between unexplained miscarriages and how women perceive men's body odor

Women who have suffered unexplained repeated pregnancy loss (uRPL) have altered perceptions and brain responses to male body odours, in comparison to those with no history of uRPL, suggests a new study published today in eLife.

The results could lead to urgently needed answers for many women who experience repeat miscarriage with no clear underlying explanation.

Around 50% of human conceptions and 15% of human pregnancies result in miscarriage, but only a limited number of these can be explained. Body odour has been linked to many aspects of healthy human reproduction - such as synchrony of menstruation between women who live together, and the influence of body odours of breast-feeding women on the timing of ovulation and menstruation in others.

"Given that sense of smell is associated with human reproduction, we hypothesised that it may also be related to disorders of human reproduction," explains lead author Liron Rozenkrantz, who was a graduate student at the Azrieli National Institute for Human Brain Imaging and Research, and the Weizmann Institute of Science, Israel, and is now a Postdoctoral Fellow at the Massachusetts Institute of Technology (MIT), Cambridge, US. "We set out to test the hypothesis that perception of smell - known as olfaction - is altered in unexplained pregnancy loss, specifically the smell of body odours."

The team started by testing a key olfactory function important in reproduction: the ability to identify mates by smell. They offered 33 women with uRPL and the same number of women with no history of uRPL (controls) three body odour sniff jars, containing body odour from their spouse, a non-spouse male and one with no odor. They found that the women with a history of uRPL were twice as likely to correctly identify their spouse than the control women.

To see whether this was because the women with a history of uRPL had a better sense of smell, the team compared their ability to smell a range of different odours, such as peanuts and soap. The women with experience of uRPL were also better at discriminating between the smells, but only marginally.

The researchers next asked whether it was the characteristics of the men's body odours that made the women who have had uRPL better at identifying their spouse by smell. They asked 36 women (18 who have experienced uRPL) to rate men's body odours based on intensity, pleasantness, sexual attraction and fertility. Based on these criteria, the uRPL group rated non-spouse body odours lower when compared with the control group.

To look at how these perceptions might be controlled, the team used MRI scans to look at brain structure and function. They found that women with a history of uRPL had smaller olfactory bulbs, which was surprising given their apparent greater ability to perceive and discriminate between different smells. When they measured brain activity while the women watched an emotional film clip, with or without the subliminal presence of a non-spouse male body odour, they found a remarkable response in the hypothalamus region: while body odour increased the hypothalamus activity in women with history of uRPL, it decreased this activity in the control group.

"We have found that women who experience unexplained pregnancy loss are much more likely to recognise their spouse by smell and rate men's body odour differently than other women," concludes senior author Noam Sobel, Professor in Neurobiology at the Azrieli National Institute for Human Brain Imaging and Research, and the Weizmann Institute of Science. "We have also found differences in structural and functional brain patterns, which have not been previously associated with unexplained repeat pregnancy loss. We hope our findings will help direct further thinking and research on this condition, which is currently not well understood or managed."

Credit: 
eLife