Aphrodite And The Comet (Planetary Science)

On December 19, 2021, the planet Venus will pass approximately 50,000 km from the orbit of Comet Leonard (C / 2021 A1), in the region where meteoroids larger than a millimeter should be present. This could cause a meteor storm in the planet’s atmosphere which – if observed – would help astronomers determine the activity of the comet’s core when it was far away from the Sun, beyond 30 astronomical units.

2021 began with the discovery of comet C / 2021 A1 (Leonard) when it was about 5 astronomical units from the Sun (equal to 750 million km). It is a comet that travels in a heliocentric orbit with great eccentricity at the limit of the hyperbolic: the orbit is retrogradewith an inclination of 133 ° on the ecliptic plane. The Leonard will pass into perihelion on January 3, 2022 – exactly one year after its discovery – reaching up to 91 million km from the Sun: a not too short distance, so it is very likely that the core will survive the heat of our star and return towards the boundaries of the solar system. Instead, from the geocentric point of view, the Leonard will reach the minimum distance of about 34 million km from the Earth on December 12, 2021, when it should show itself with an apparent magnitude of +5.5 in the sky of sunrise and sunset: no respect. to the show offered by the brilliant comet Neowise (C / 2020 F3) in July 2020. As far as we are concerned, a comet like there are many, but the orbit that the Leonard travels through is such thaton December 18, 2021 at 02:09 UT will bring it only 4.3 million km from Venus , the planet that in these months is clearly visible in the west immediately after the sunset.

Venus is a planet with an orbit internal to that of the Earth, so it can be observed at dawn before the sun rises, or after sunset as happens in these months: from the sky of the Earth Venus can never be seen in the middle of the night , as it happens instead for the planets with the orbit external to ours, for example Jupiter and Saturn, clearly visible in these months in the night sky. On October 29, 2021, Venus will be at its maximum elongation from the Sun – i.e. it will be at its maximum angular distance from our star (about 47 °) – after which it will move towards the lower conjunction, which will take place at the beginning of January 2022. As Galileo discovered in 1610, Venus shows the phases like our Moon, and in the passage from the maximum west elongation to the lower conjunction it passes, in practice, from the first quarter phase to that of extremely illuminated sickle subtle. At the lower conjunction Venus lies roughly between the Sun and the Earth, and we can only see its hemisphere in shadow.

We know that comets, following the sublimation of the volatile materials of the nucleus, emit gas and dust into space. Leonard is no exception, on the contrary: having discovered it when it was 5 astronomical units from the Sun is an indication of a good activity of the nucleus even at great distances from our star. Telescopic observations show that the emission is dominated by dust, with diameters between 0.1 and 1 mm, while the gas is scarce. Once emitted from the nucleus with a very low relative speed, the dusts undergo the action of the pressure of solar radiation, which tends to move them away from the nucleus. Smaller dust grains have a higher surface / mass ratio, are more subject to radiation pressure and tend to be pushed towards the sun,

On 19 December 2021 at 21 UT, the Leonard will already be about 12.5 million km from Venus, which however will pass only 50 thousand km from the orbit of the comet that is behind the nucleus. With this very short distance, Aphrodite might encounter a cloud of dust grains larger than 1mm. The conditional is a must: Leonard’s activity is known only approximately, while the largest specks of dust – emitted when Leonard was over 30 astronomical units from the Sun – are the best candidates for intercepting Venus. In fact, it is these grains that should have moved far enough away from the core to be in the right position to collide with the planet. We do not know what the comet’s activity was at those great distances (more or less at the height of Neptune’s orbit) nor how quickly the macroscopic grains were ejected from the nucleus, but it is reasonable to assume that the sublimation of super ices – birds has made their contribution.

Map for the potential meteors observable on Venus on December 19, 2021 at 9:00 PM UT. The white lines indicate the curves of the same zenith angle of the radian and surround the point of the sub-radian (marked by +). The dark lines indicate the equator and the axis of rotation of Venus, while the white crescent represents the portion of the planet illuminated by the Sun and visible from the Earth. Meteors are potentially observable anywhere on the disk where the zenith angle is less than 90 °, but are more likely near the sub-radiant point. Credits: Zhang et al., 2021

When it passes through the Leonard dust trail, Venus will be about 28 ° from the Sun and subtend an apparent diameter of over 50 arc seconds. The planet will appear to the telescope as a large sickle being illuminated only 12 percent of the disk facing the Earth. The Leonard meteoroids will enter the atmosphere of Venus with a speed of 78 km / s and could give rise to brilliant fireballs , quite similar to those we see in our sky. A rough comparison can be made between the Venusian Leonard swarm and that of the Leonids. Leonid meteoroids strike the Earth’s atmosphere at speeds of about 71 km / s and often generate fireballs of magnitude -12. If the Leonard meteoroids behave in the same way, a -12 meteoroid on Venus becomes +16 when viewed from Earth, still within range of 0.5-0.6 meter diameter telescopes equipped with Ccd / Cmos cameras in capable of shooting burst images with exposure times on the order of one second. Fortunately for us, most of the shadowed hemisphere of Venus with the sub-radiant point will be observable from Earth, and to have a non-zero probability of capturing some Venusian fireballit will be necessary to film the dark side of the planet from the sunset, at 15:37 UT, until the sunset of Venus, at 17:50 UT. To decrease the contribution of the illuminated crescent of Venus and enhance the radiation of the meteors in its atmosphere, it can be observed using an interference filter centered on the emission lines of the neutral sodium doublet (589.0-589.6 nm), a light that meteors emit in abundance. Even the use of a coronograph , which screens the brilliant Venusian sickle, can be of help in the observation of this elusive phenomenon.

The close encounter that will take place between the orbit of Leonard and Venus is among the closest ever between a planet and a long-term comet and is surpassed, in recent history, only by the flyby of comet C / 2013 A1 (Siding Spring) with Mars, which on 18 October 2014 passed only 140 thousand km from the planetary center, while a few hours later the planet passed only 30 thousand km from the comet’s orbit. This close passage has produced a meteor shower that has been indirectly observed by several spacecraft orbiting the Red Planet, and the same thing is expected to happen for Venus. The observation of any fireballs in the atmosphere of Venus will allow to haveinformation on the activity of the comet’s nucleus when it was over 30 astronomical units from the Sun : get your telescopes ready!

Featured image: False color image of comet Leonard (indicated by the arrow) taken on 7 April 2021 with the “GD Cassini” telescope of the Loiano Astronomical Station. Credits: A. Carbognani / Inaf Oas Bologna


To know more:


Provided by INAF

Why Lockdown Is Making It Hard For You to Concentrate? (Psychology)

Studies show the way we remember and process information is greatly affected when we are in isolation.

Scientists have found the ‘Groundhog Day’ effect of lockdown affects our memory and cognitive ability.

While there’s a lack of data on the Australian lockdown experience, a study on Italians who were locked down for about two months last year found an increase in distractions and mind wandering was common.

Professor Brett Hayes from UNSW’s School of Psychology says that a study of 4000 respondents found 30 per cent had experienced some degree of change in their everyday cognition.

Some of the common everyday problems were memory problems, such as where you left your mobile phone, trouble in focusing your attention, and losing focus when trying to read a book or watching something online.

“Literally starting one job and without thinking about it, going off and starting a second job without finishing the first one,” the cognitive psychologist says.

“It was also worst for people who had emotional issues, who were feeling depressed, or stressed and anxious, they had more of these symptoms.

“But even for those without those issues, these cognitive issues were very common.”

How the brain lays down memories

The study suggests the reason why our everyday memory gets worse in lockdown is because we are living through a sort of Groundhog Day, which in turn makes it harder for our brain to lay down memories and retrieve them later on.

“What we know about human memory is that the context is really important. You might be doing a job at home, chatting to a friend, or watching a movie,” Prof. Hayes says.

“When we have those experiences, we might be focused on the main part of the experience, but our brain is actually encoding a lot of other things just incidentally, like where that’s happening, the location, where and when it’s taking place.”

He says our brain is sensitive to this background context, which helps us lay down our memories in a way that it’s easy for us to retrieve those experiences later on.

“So when the context is changing, which is does normally in everyday life when we are moving around and visiting different places in different times of the day, then it’s easy to lay down memories and recall them,” Prof. Hayes says.

“But when you are in lockdown, your opportunities to move around in the environment and engage in different activities are very limited.

“And when you do get into that Groundhog Day cycle, just variations on the same thing each day, that’s when the days do tend to start blurring into each other, because we have the same context for each day.”

This makes it harder for our brain to separate those experiences and that’s one of the reasons why we experience memory fog during lockdown, he says.

Recovery is quick when restrictions ease

study on a two-month lockdown in Scotland last year tasked recipients with online tasks to test their memory, decision making and selective attention.

They found performance was poorer during lockdown, but once restrictions were eased, particularly the social isolation, they recovered quite quickly.

Levels of social interaction during lockdown were also correlated with cognitive performance.

“People who were able to maintain their online interaction more during lockdown did better at these tasks,” he says.

“So complete isolation is really very bad for our cognitive functioning, but if we can keep up that level of interaction to some degree with whoever is in our house or online, that seems to be good for our cognitive functioning.”

Researchers have also found that people who had conversations within the last three days were a bit more protected from cognitive issues during long lockdown.

Other studies are looking at how people’s options are limited in COVID and have pointed to the importance of having a bit of variation and exercise every day.

“From a memory point of view, if you are able to exercise outside the house, vary those exercise paths from day to day to just to allow a different context for your brain to encode those different days, if you want to be able to remember what you did from day to day a bit better,” Prof. Hayes says.

Change your exercise routine

Variations on exercises and activities in your house or apartment will also help you avoid the memory fog.

Prof. Hayes says there’s a close connection between good cognitive ability and physical activity.

“So keeping up regular exercise is good to try and keeping our memory and decision making in shape as much as you can during lockdown.

“There’s some evidence that even if you are really restricted – even doing something like playing Exergames (online exercise games) where you watch a screen and jump around, that does show some benefits.

“The nice thing is that you can play with your family and so there’s a social dimension as well.”

Online yoga and dancing were things that people reported as part of their activity which he says seemed to have a beneficial effect on cognition.

“While there hasn’t been time to conduct research on the long term effects of lockdowns on memory, the evidence so far shows that as restrictions are eased, these cognitive issues should improve,” he says.

Featured image: Overseas studies have shown it’s common to have a lack of concentration and to have problems remembering when in lockdown. Photo: Shutterstock.


Reference: Gabriella Santangelo et al, Subjective cognitive failures and their psychological correlates in a large Italian sample during quarantine/self-isolation for COVID-19, Neurological Sciences (2021). DOI: 10.1007/s10072-021-05268-1


Provided by UNSW

Fine Aerosols Emitted During Talking and Singing May Play A Crucial Role in COVID-19 Transmission (Medicine)

Landmark findings underscore the importance of reducing exposure to fine respiratory aerosols, especially in indoor environments

The coronavirus disease 2019 (COVID-19) has been thought to spread primarily when an infected person coughs or sneezes, but little is known about its transmissibility through activities such as breathing, talking and singing.

A new study led by researchers from the National University of Singapore (NUS), and conducted at the National Centre for Infectious Diseases (NCID), revealed that severe acute respiratory syndrome coronavirus (SARS-CoV-2) particles can be aerosolised by an infected person during talking and singing. They also found that fine aerosols (less than 5 micrometres, or μm) generated from these two types of activities contain more viral particles than coarse aerosols (more than 5 μm). The researchers concluded that fine respiratory aerosols may play a significant role in SARS-CoV-2 transmission, especially in an indoor environment, and hence, should be taken into consideration when planning infection prevention measures.

“While previous studies have established the relative amount of aerosols (or the amount of particles) produced through similar activities, they did not measure the amount of SARS-CoV-2 virus particles generated. To our knowledge, this is the first study to quantify and compare SARS-CoV-2 particles in aerosols generated through breathing, talking and singing. Therefore, our team’s work provides a foundation for estimating the risk of transmission of infection,” said project leader Associate Professor Tham Kwok Wai, who is from the Department of the Built Environment at the NUS School of Design and Environment.

The study was first published online in the journal Clinical Infectious Diseases on 6 August 2021. Within a day of its publication, the paper was ranked among the top 5 per cent of all research outputs scored by data science company Altmetric, and was given one of the highest attention score after different factors, like the relative reach from social media sites, blogs, policy documents, and more, were taken into account.

Measuring SARS-CoV-2 particles in respiratory aerosols

The study involved 22 COVID-19 positive patients who were admitted to the NCID from February to April 2021. The NCID was the research site that selected and recruited the patients, and performed whole genome sequencing to determine their viral strains of infection.

The participants had to perform three separate expiratory activities on the same day. These activities involved 30 minutes of breathing, 15 minutes of talking in the form of reading aloud passages from a children’s book, and 15 minutes of singing different songs, with rest between activities.

The participants had to carry out these three activities using a specially designed exhalation collection equipment known as the Gesundheit-II. This equipment was made available for this research by its inventor Professor Donald Milton from the University of Maryland, who is one of the co-authors of the paper and a collaborator on the project. In the studies, participants were required to place their head at the cone-shaped inlet of the equipment. This cone served as a ventilation hood where air is continuously drawn around the participant’s head, allowing the collection of expiratory particles into the connecting sampler.

Aerosols were collected in two size fractions, namely coarse (more than 5 μm) and fine (less or equal to 5 μm). The sample viral load was quantified by using a method known as reverse transcription-quantitative polymerase chain reaction.

“We observed that COVID-19 patients who are early in the course of illness are likely to shed detectable levels of SARS-CoV-2 RNA in respiratory aerosols. However, person-to-person variation in virus emission was high. Some patients surprisingly released more virus from talking than singing,” shared project co-leader Dr Kristen Coleman from Duke-NUS Medical School.

“It has thus far been difficult to directly show how SARS-CoV-2 can be transmitted. Through the coordinating efforts of one of our resident doctors, Dr Sean Ong, and the support of our nursing team and patients, we were able to study key high risk activities like talking and singing while ensuring the safety of the patients and staff involved. The end result provides direct measurements to show that besides respiratory droplets, virus particles emitted in exhaled breath and vocalisation activities are likely important mechanisms for transmitting SARS-CoV-2,” said Dr Mark Chen, Head, NCID Research Office, National Centre for Infectious Diseases.

The research also involved collaborators from the NUS Yong Loo Lin School of Medicine’s Departments of Microbiology and ImmunologyOtolaryngology, and Medicine, Tan Tock Seng Hospital, National University Health System, as well as the Institute of Molecular and Cell Biology at the Agency for Science, Technology and Research (A*STAR). It was supported by the Singapore National Medical Research Council and NUS.

Multi-layered approach for infection control

The findings of this study demonstrated that exposure to fine-particle aerosols needs to be mitigated, especially in indoor environments where airborne transmission of SARS-CoV-2 is most likely to occur. Reducing exposure to fine respiratory aerosols can be achieved through non-pharmaceutical interventions, such as universal masking, physical distancing, increased room ventilation, more efficient filtration and appropriately applied air-cleaning technologies.

In particular, the research team recommended a multi-layered approach of control measures to decrease the risk of airborne SARS-CoV-2 transmission.

“Although our attempts to grow infectious virus in cell culture were unsuccessful, our studies can provide an important baseline to guide infection prevention activities,” explained Professor Paul Tambyah from the NUS Yong Loo Lin School of Medicine, who is one of the co-authors of the research paper.

“In situations involving singing, safe distancing among singers, as well as the averting and filtering of airflow from choir to audience, such as by deploying air curtains, are important considerations. For situations involving talking, determining airflow patterns and minimising exposure through seating and furniture configurations, distancing, and air movement alteration, such as fans, including desk fans are practical options that can be taken to lower the risk of SARS-CoV-2 transmission,” commented Assoc Prof Tham.

Further studies

In view of more recent variants of the coronavirus, especially the Delta variant which has been reported to be more infectious, the researchers plan to use the same methods to determine if the aerosol viral load associated with the new variants, especially the Delta variant, is higher than previous strains.

As talking is the predominant community activity, the research team is also looking to establish the infectiousness of airborne aerosols, or live virus, emitted through talking by infected persons.

Featured image: NUS researcher Mr Douglas Tay in a hospital room at the NCID demonstrating how the Gesundheit II exhalation collection equipment is used. © NUS


Reference: Kristen K Coleman, Douglas Jie Wen Tay, Kai Sen Tan, Sean Wei Xiang Ong, Than The Son, Ming Hui Koh, Yi Qing Chin, Haziq Nasir, Tze Minn Mak, Justin Jang Hann Chu, Donald K Milton, Vincent T K Chow, Paul Anantharajah Tambyah, Mark Chen, Tham Kwok Wai, Viral Load of SARS-CoV-2 in Respiratory Aerosols Emitted by COVID-19 Patients while Breathing, Talking, and Singing, Clinical Infectious Diseases, 2021;, ciab691, https://doi.org/10.1093/cid/ciab691


Provided by National University of Singapore

How 3D Space is Represented in the Mammalian Cortex by the Brain’s “GPS” System? (Neuroscience)

A new study on bats reveals an unexpected representation of three-dimensional space in the brain

In a new study published in Nature today, Weizmann Institute of Science researchers, in collaboration with colleagues from the Hebrew University of Jerusalem, unveiled for the first time how three-dimensional space is represented in the mammalian cortex by the brain’s “GPS” system. The team of researchers, led by Prof. Nachum Ulanovsky of Weizmann’s Neurobiology Department, were surprised to find that this representation is very different from the way in which two-dimensional space is represented, turning several long-standing hypotheses on their heads.

Mammals, including humans, know their position in space, owing to several types of specialized neurons in the hippocampus and its next-door neighbor the entorhinal cortex – regions located deep inside the brain. Head-direction cells, the internal compasses of the brain, indicate to the animal the direction in which its head is turned. Place cells, thought to construct a mental map of the environment, are activated when an animal crosses a specific location. Grid cells, by contrast, respond not to one, but to multiple such locations, and they are thought to provide the brain with a GPS system of sorts.

The study of grid cells and the brain’s GPS was awarded the Nobel Prize in 2014. However, these and other studies focused solely on how two dimensions are represented and said very little about the representation of three-dimensional space. To bridge this gap, Ulanovsky and colleagues set out to elucidate how grid cells act in three dimensions in freely behaving bats.

In the past, when grid cells were studied in rodents running on two-dimensional surfaces, they were found to be activated in multiple circular areas, known as firing fields, which are arranged in a symmetrical hexagonal pattern – resembling millimeter graph paper – that tiles the surface. This unparalleled symmetry and periodicity suggest that these cells may be involved in geometric spatial computations that form the core of the cerebral GPS. The entorhinal cortex, where grid cells are located, is the brain area that is first affected in Alzheimer’s disease, and it is possible that spatial disorientation, one of the early manifestations of Alzheimer’s, is due to the grid cells’ dysfunction – and the loss of the hexagonal “millimeter paper” of grid cells.

“The well-ordered global grid that is the hallmark of their two-dimensional activity was altogether gone”

Mathematically, the optimal way to pack circles in two dimensions is in a hexagonal pattern, like a honeycomb: This is possibly the reason why the circular firing fields of grid cells are represented in the brain in a hexagonal lattice when animals walk over two-dimensional surfaces. Therefore, the researchers expected the activity pattern in three dimensions to be similarly symmetrical and hexagonal. “We and many other researchers hypothesized that we’d see hexagonally stacked balls, like oranges in a grocery store neatly stacked in a pyramid, or any other extremely ordered three-dimensional arrangement,” Ulanovsky says.

To test this hypothesis, the researchers, led by doctoral student Gily Ginosar, together with Staff Scientist Dr. Liora Las, recorded the activity of grid cells in bats that had small mobile devices mounted on their heads, as the bats were flying around a room the size of a large living room. Feeding stations at different heights ensured that each bat covered most of the room’s volume in every run. Once the data started coming in, the researchers saw that grid cells did not behave as expected when responding to three-dimensional coordinates. “The well-ordered global grid that is the hallmark of their two-dimensional activity was altogether gone,” explains Ulanovsky.

Local order and global disorder. Previous work showed both local and global order in the representation of two-dimensional space, and the same was predicted for three dimensions. However, the new study found that three-dimensional space has no global lattice but does maintain local order © Weizmann Institute of Science

Instead, the three-dimensional firing fields of the grid cells, shaped in this case as spheres rather than circles, were packed like a box full of marbles. They were not completely disordered, but were certainly less organized than the three-dimensional equivalent of a hexagonal lattice – as the new arrangement allowed the “marbles” some extra degrees of freedom. Whereas any noticeable global order was lacking, the spheres did commit to a local order wherein the distance between one sphere and its nearest neighbors remained constant.

Compared to other longstanding theories, the new theoreitcal model was the most loyal to the experimental data

To offer a mechanistic explanation of this phenomenon of local rather than global order, the experimental team – Ginosar, Las and Ulanovsky – collaborated with theoreticians Dr. Johnatan Aljadeff, a former postdoctoral fellow at Weizmann and now a professor at the University of California in San Diego, and Prof. Haim Sompolinsky and Prof. Yoram Burak from the Hebrew University of Jerusalem. Together they constructed a model that uses principles, borrowed from statistical physics, that describe the interaction between particles. The model revealed that the spherical firing fields of grid cells seem to interact in almost the same way as particles do – they are “attracted” to one another when at a distance and are “repelled” once they get too close. In particular, the balance of forces acting on particles could explain the local order that kept the spheres at constant local distances from one another, while avoiding any global lattice. Compared to other models that were used in the past to predict the three-dimensional organization of grid cells’ firing fields, the new model was the most loyal to the experimental data.

Taken together, the surprising experimental data and theoretical model offer a new way of looking at the neural basis of three-dimensional navigation and the role that grid cells play in this cognitive process. While previous models extrapolated a similar three-dimensional arrangement from the two-dimensional grid, the work of Ulanovsky and colleagues and their “box of marbles” model show that things are much more complex. Since no periodic lattice is formed in three-dimensional space, the classical theories for understanding the intriguing behavior of grid cells will need to be revised.

Featured image: The Egyptian fruit bat: The representation of three dimensional space in the mammalian cortex resembles a box of marbles. Photo: Steve Gettle; Design: Maayan Visuals


Reference: Ginosar, G., Aljadeff, J., Burak, Y. et al. Locally ordered representation of 3D space in the entorhinal cortex. Nature (2021). https://doi.org/10.1038/s41586-021-03783-x


Provided by Weizmann Institute of Science

A COVID-19 Vaccine Strategy To Give the Body ‘Border Protection’ (Medicine)

Study in animals shows a way to promote immune response in nose, mouth and blood

A simple addition to injected COVID-19 vaccines could enhance their effectiveness and provide “border protection” immunity in areas like the nose and mouth to supplement antibodies in the bloodstream, new research suggests.

The strategy involves dampening the activity of an enzyme produced by some white blood cells when they’re responding to the vaccine challenge. When highly active, this enzyme breaks down not just the pathogen – its job – but also degrades pieces of cells that participate in the immune response.

Prosper Boyaka © OSU

Research in mice showed that an experimental COVID-19 vaccine containing a compound to inhibit the enzyme stimulated a robust antibody response that included immunity in the nose and mouth, ultimately providing extra protection for airways and the gastrointestinal tract.

“Our approach is to improve ‘border control.’ The benefits are broad because in addition to providing protection in the bloodstream like most vaccines do, we also have excellent protection in the doors and windows of the body that communicate with the outside,” said senior study author Prosper Boyaka, professor and chair of the Department of Veterinary Biosciences at The Ohio State University.

“If we protect the mucosal area where the pathogen enters, then even if you don’t reach total immunity there, you limit the amount of pathogen that enters the body so the antibodies inside are more efficient at clearing the infection.”

The experimental vaccine was produced by packaging a segment of the SARS-CoV-2 (the virus that causes COVID-19) spike protein as an antigen with the common vaccine ingredient aluminum salts and an enzyme inhibitor. The findings suggest this affordable design could be particularly helpful in developing countries, where cold storage needed for existing vaccines is a challenge, said Boyaka, also an investigator and program director in Ohio State’s Infectious Diseases Institute.

The study was published online Aug. 5 in Proceedings of the National Academy of Sciences.

There is an irony to the use of aluminum salts (also known as alum) in about 70% of the world’s vaccines: While alum’s presence actually enhances the immune response, it also recruits the white blood cells that secrete the enzyme, called elastase.

Alum is inexpensive to obtain or produce and can be stored at room temperature, and is effective at promoting development of a bloodstream-based antibody response to vaccination. But it doesn’t do much for cell-mediated immunity that improves protection against viruses and bacteria that use cells to reproduce, and can’t generate a useful number of antibodies in the body’s portals of entry for most pathogens: the nose, mouth and genitourinary tract.

The researchers found that suppressing elastase in a vaccine containing alum had the dual benefits of broadening and speeding up the antibody response in the bloodstream and triggering the specific types of antibodies needed for immune protection of mucous membranes.

“We found a way to have the cells come and help the immune response to develop and the enzyme to break down the pathogen, but we don’t want that response to be so high that it goes out of control. So we’re just putting a brake on the activity those enzymes would have,” Boyaka said. “And we found if you apply that strategy, you can induce a response in the airways even if the vaccine is not given through the airway.”

The experimental vaccine enhanced the magnitude of mouse antibodies, which reacted to the same section of the spike protein in the vaccine that antibodies in plasma from COVID-19 patients attach to, as well as generating antibodies in mucosal areas. Immunized mice lacking the gene for the enzyme developed high-affinity antibodies as well.

To further test the concept, the researchers found the enzyme-suppressing compound used in the study triggered production of specialized inflammation-regulating cells in cultures of human immune cells and pig spleen cells, showing that this strategy could improve vaccine immune responses in other species – including people.

Boyaka’s team envisions that a future injected vaccine containing an elastase inhibitor could expand SARS-CoV-2 vaccination availability across the world and even be used to boost existing vaccines.

“COVID will stay with us for some time, unfortunately, with the new variants,” he said. “What we need to do is have a portfolio of options that we could use depending on the health environment.

“Reprogramming the immune response induced by an injected vaccine containing alum is a way to make the vaccine more efficient for what we need. This could be a cheap and simple approach that can benefit people in developing countries.”

This work was supported by grants from the National Institutes of Health and an Ohio State Office of Research COVID-19 seed grant. A patent application has been filed spanning this research; the overall patent portfolio includes an additional U.S. issued patent.

Co-authors, all from Ohio State, include Eunsoo Kim, Zayed Attia, Rachel Woodfint, Cong Zeng, Sun Hee Kim, Haley Steiner, Rajni Kant Shukla, Namal Liyanage, Shristi Ghimire, Jianrong Li, Gourapura Renukaradhya, Abhay Satoskar, Amal Amer, Shan-Lu Liu and Estelle Cormet-Boyaka.

Featured image: Researchers envision that a future injected vaccine containing an elastase inhibitor could expand SARS-CoV-2 vaccination availability across the world and even be used to boost existing vaccines. Photo: Shutterstock.com


Reference: Eunsoo Kim et al, Inhibition of elastase enhances the adjuvanticity of alum and promotes anti–SARS-CoV-2 systemic and mucosal immunity, Proceedings of the National Academy of Sciences (2021). DOI: 10.1073/pnas.2102435118


Provided by Ohio State news

Inhibition Of Key Pathway Promotes Iron-dependent Cell Death in Pancreatic Cancer Cells (Medicine)

Cell culture study maps mechanisms underlying a new potential strategy for killing pancreatic cancer cells through a type of cell death known as ferroptosis.

One of the reasons pancreatic cancer remains the most deadly of the major cancers is that it craftily rewires normal cell survival mechanisms to keep itself supplied with nutrients to fuel its expansion.

A new study led by the University of Michigan Rogel Cancer Center demonstrates how inhibiting a key enzyme known as GOT1 can flip a switch in the cancer cells — causing them to shift from using nutrients to fuel growth toward conserving them to maintain energy levels.

In this state, the cancer cells release their iron stores and become vulnerable to a form of programmed, iron-dependent cell death known as ferroptosis, according to findings in cell cultures that appear in Nature Communications.

“If pancreatic cancer’s success comes from approaching nutrient metabolism differently than other cancers, our goal is to target aspects of that metabolism for therapeutic benefit,” said study senior author Costas Lyssiotis, Ph.D., an associate professor of molecular and integrative physiology and of internal medicine at U-M.

The study was led by first author Daniel Kremer, Ph.D., a recent graduate of U-M Program in Chemical Biology and former member of the Lyssiotis lab.

The GOT1 pathway helps the cancer cells maintain their energy balance, Kremer explained.

“When we inhibit the enzyme, it doesn’t kill the cell, but it puts it into a state of energetic stress, so it has to use those nutrients to maintain the cell rather than for growth,” he said. “This study describes the mechanisms of that process and how we might be able to exploit it to trigger cell death through ferroptosis.”

Key collaborators on the project include Yatrik Shah, Ph.D., of the Rogel Cancer Center and Kenneth Olive, Ph.D., of Columbia University and the Herbert Irving Comprehensive Cancer Center.

Featured image: Pancreatic cancer cells grown in culture, SEM / Anne Weston, Francis Crick Institute (CC BY-NC 4.0)


Paper cited: “GOT1 inhibition promotes pancreatic cancer cell death by ferroptosis,” Nature Communications. DOI: 10.1038/s41467-021-24859-2


Provided by Michigan Health Lab

UVA Discovery Suggests Potential New Treatment for Deadly Blood Cancer (Medicine)

A drug used to treat certain advanced breast cancers may offer a new treatment option for a deadly blood cancer known as myelofibrosis, new research from UVA Cancer Center suggests.

The drug, palbociclib, may be able to prevent the scarring of bone marrow that existing treatments for myelofibrosis cannot. This scarring disrupts the marrow’s production of blood cells and causes severe anemia that leaves patients weak and fatigued. The scarring also reduces the number of platelets in the blood, making clotting difficult, and often causes an enlarged spleen.

“Current therapies only provide symptomatic relief without offering significant improvement of bone marrow fibrosis. So, there is a critical need to develop more effective therapy for myelofibrosis,” said senior researcher Golam Mohi, PhD, of the University of Virginia School of Medicine’s Department of Biochemistry and Molecular Genetics. “We have identified CDK6, a regulator of cell cycle, as a new therapeutic target in myelofibrosis. We demonstrate that CDK4/6 inhibitor palbociclib in combination with ruxolitinib markedly inhibits myelofibrosis, suggesting this drug combination could be an effective therapeutic strategy against this devastating blood disorder.”

MYELOFIBROSIS: A DANGEROUS CANCER 

Myelofibrosis is a form of leukemia. It occurs in approximately 1 to 1.5 of every 100,000 people, primarily those who are middle-aged or older. Patients with intermediate or high-risk cases typically survive only 16 to 35 months.

Existing treatments for myelofibrosis do not address the bone marrow scarring that is a hallmark of the disease. The drug ruxolitinib is used to relieve patients’ symptoms, but Mohi’s new research suggests that pairing the drug with palbociclib may make a far superior treatment.

Palbociclib, by itself, reduced bone marrow scarring in two different mouse models of myelofibrosis. It also decreased the abnormally high levels of white blood cells seen in myelofibrosis and shrank the mice’s enlarged spleens.

Combining the drug with ruxolitinib offered even more benefits, restoring the bone marrow and white blood cell counts to normal and dramatically reducing the size of the mice’s enlarged spleens.

Additional research is needed to determine if the findings will hold true in human patients. But Mohi and his team are hopeful. They note that palbociclib is known to quiet the activity of bone marrow in patients with metastatic breast cancer (cancer that has spread to other parts of the body), and they hope there will be beneficial effects in patients with myelofibrosis.

“A combinatorial therapeutic approach involving palbociclib and ruxolitinib will enable lowering the doses of each of the inhibitors and thus reducing toxicities while enhancing the therapeutic efficacy,” they write in a new scientific paper outlining their findings.

New treatments for myelofibrosis are particularly needed because ruxolitinib treatment does not offer significant reduction in bone marrow fibrosis and often loses its effectiveness with prolonged use, the researchers note. 

“The findings from this study are very exciting, and they support the clinical investigation of palbociclib and ruxolitinib combination in patients with myelofibrosis,” Mohi said. 

FINDINGS PUBLISHED

Mohi and his team have published their findings in the journal Cancer Research. The research team consisted of Avik Dutta, Dipmoy Nath, Yue Yang, Bao T. Le and Golam Mohi. 

The work was supported by the National Institutes of Health grants R01 HL095685, R01 HL149893 and R21 CA235472.To keep up with the latest medical research news from UVA, subscribe to the Making of Medicine blog.

Featured image: A discovery by UVA School of Medicine researcher Golam Mohi, PhD, shows that a drug used to treat certain advanced breast cancers may offer a new treatment option for a deadly blood cancer known as myelofibrosis. © UVA Health


Reference: Avik Dutta et al, CDK6 is a therapeutic target in myelofibrosis, Cancer Research (2021). DOI: 10.1158/0008-5472.CAN-21-0590


Provided by University of Virginia

Researchers Discovered A Type of Blood Vessel Cell in Muscles That Multiplies Rapidly Upon Exercise (Physiology)

ETH Zurich Professor Katrien De Bock and her team have discovered a certain type of blood vessel cell in muscles that multiplies rapidly upon exercise, thereby forming new blood vessels. Researchers can use this to find novel therapies for vascular disorders of the muscle.

“In industrialised countries, the leading cause of surgeons having to amputate a foot or leg is impaired vascular supply to the muscles of diabetic patients,” Katrien De Bock says. As Professor for Exercise and Health at ETH Zurich, she and her team study how to treat vascular disorders of the muscles and how new blood vessels form. It’s common knowledge that exercise and sport stimulate the formation of blood vessels. By contrast, very little is known about the underlying molecular and cellular mechanisms. “Once we understand these mechanisms, we can work towards systematically improving the blood supply of patients’ muscles,” De Bock says.

In mice and using cultured human cells, De Bock and her colleagues have now investigated how exercise promotes the formation of thin blood capillaries in the muscle in healthy subjects. Turning the spotlight onto the cells of the vascular wall (known as endothelial cells), they discovered that there are two capillary endothelial cell types, which can be distinguished by the molecular marker ATF4. It turns out that cells with very little ATF4 are mainly found in the capillaries supplying the white muscle fibres, while cells with high levels of ATF4 primarily form part of the blood vessels close to red muscle fibres.

Ready to go

Moreover, the scientists demonstrated that exercise predominantly stimulates cell division of endothelial cells with high levels of ATF4 (those near red muscle fibres), leading to the formation of new capillaries. By contrast, exercise does not elicit a direct response in cells with very little ATF4. “Endothelial cells with high levels of ATF4 are on ‘metabolic standby mode’, always ready to start forming new vessels,” De Bock says. ATF4 is a regulatory protein inside the cell. Cells with this protein are primed to quickly respond to the appropriate stimulus. As soon as a person – or, in this case, a mouse – starts exercising, these cells increase their amino acid intake and accelerate the formation of DNA and proteins, encouraging rapid cell proliferation. This ultimately leads to the formation of new blood vessels.

Why these ‘ready to go’ endothelial cells are mainly found near red muscle fibres is not yet known. The researchers intend to unravel this mystery next. In addition, the scientists hope to use these findings to develop therapies that stimulate the growth of muscular blood vessels in patients suffering from diabetes or arterial occlusions and in organ transplant recipients.

Featured image: Microscopically fine blood capillaries carry oxygen and nutrients to the muscles. The picture shows several fascicles, composed of numerous muscle fibres. (Visualisations: Science Photo Library / Mikkel Juul Jensen)


Reference

Fan Z, Turiel G, Ardicoglu R, Ghobrial M, Masschelein E, Kocijan T, Zhang J, Tan G, Fitzgerald G, Gorski T, Alvarado-Diaz A, Gilardoni P, Adams CM, Ghesquière B, De Bock K: Exercise-induced angiogenesis is dependent on metabolically primed ATF3/4+ endothelial cells. Cell Metabolism, 5 August 2021, doi: 10.1016/j.cmet.2021.07.015


Provided by ETH Zurich

Alginic Acid Improves Artificial Bones, Study Shows (Material Science)

Osaka City University study shows how alginic acid improves artificial bones in 3 ways

New research shows that mixing low viscosity alginic acid with calcium phosphate cement (CPC), a material commonly used as a bone replacement, confers 3 functional improvements: shorter setting time, increased compressive strength, and acquisition of porosity.

One reason for the increased use of CPC in recent years is its self-setting nature, allowing it to be injected into a patient for a more non-invasive approach. However, CPCs have a dense microstructure that make it difficult for cells to enter. This lack of pores limits the potential for new bone growth. This study, published in the Journal of Materials Science: Materials in Medicine, explores the effect the naturally derived biopolymer alginic acid has on this issue.

Previous research has studied other biopolymers, including gelatin, collagen, and chitosan, but this joint study between the Osaka City University (OCU), Graduate School of Medicine and Graduate School of Engineering, has confirmed the positive effects of mixing alginic acid with CPC. In vitro studies showed alginic acid shorten setting time and increase compressive strength of CPC. In addition, in vivo studies showed the biopolymer increase porosity of CPC, allowing cells to enter and new bone to grow.

Alginic acid has been widely used in the medical field for procedures such as, cell immobilization, drug delivery, and wound dressing. However, there have been limited studies in conjunction with CPC. The degradability and cross-linking characteristics of alginic acid make it a promising additive to improve on the dense and generally poor mechanical properties of CPC.

This new study evaluated a series of CPC-alginate (the salt form of alginic acid) compounds with increasing amounts of alginic acid. In vitro, a pH meter showed a decrease in pH levels as alginic acid amounts increased, speeding up setting time. Scanning electron microscopy revealed that compounds with increased alginic acid had more pores and less density. In vivo, X-ray and micro-CT analysis showed that femurs injected with CPC compounds of increased amounts of alginic acid had, after 6 weeks, more degradation and bone formation than the control group.

“Artificial bones can support broken bones, but they do not replace our own bones and remain in the body as a foreign object” said Graduate Student Akiyoshi Shimatani, and first author of the study. Associate Professor Hiromitsu Toyoda of the OCU Dept. of Orthopedic Surgery continued: “To solve this problem, we have developed an artificial bone in collaboration Professor Yoshiyuki Yokogawa and his team from the OCU Faculty of Engineering, which is sticky, hard to break, and replaces the body’s own bone. We hope this becomes a new option for artificial bones.”

Featured image: Cross sectional microstructures in the set CPC samples (a) without and (b) with alginate (20 wt%). Little porosity was detected in CPC sample without alginate (a1). Adding alginate resulted in the formation of macropores within the bulk materials (b1) © Akiyoshi Shimatani、Hiromitsu Toyoda、Kumi Orita、Yuta Ibara、Yoshiyuki Yokogawa、Hiroaki Nakamura


Reference: Shimatani, A., Toyoda, H., Orita, K. et al. A bone replacement-type calcium phosphate cement that becomes more porous in vivo by incorporating a degradable polymer. J Mater Sci: Mater Med 32, 77 (2021). https://doi.org/10.1007/s10856-021-06555-1


Provided by Osaka University