Showing posts with label Biology. Show all posts
Showing posts with label Biology. Show all posts

Thursday, September 23, 2021

Vampire bats may coordinate with ‘friends’ over a bite to eat

 

Photo: Sherri and Brock Fenton
Vampire bats that form bonds in captivity and continue those “friendships” in the wild also hunt together, meeting up over a meal after independent departures from the roost, according to a new study.

Researchers attached tiny “backpack” computers to 50 vampire bats – some that had previously been in captivity together and others that had lived only in the wild – to track their movement during their nightly foraging outings. By day, the bats shared a hollow tree in Panama, and at night they obtained their meals by drinking blood from wounds they made on cows in nearby pastures.

Tracking data showed that vampire bats set out to forage separately rather than as a group – and those that had established social relationships would reunite during the hunt for what the researchers speculated was some sort of coordination over food.

The findings suggest “making friends” in the roost could create more interdependence among socially bonded vampire bats – meaning they could benefit from each other’s success at obtaining blood meals and join forces when competing with other groups of bats for food resources.

“Everything we’ve been studying with vampire bats has looked at what they’re doing inside of a roost. What nobody has really known up until now is whether these social relationships serve any function outside the roost,” said study co-author Gerald Carter, assistant professor of evolution, ecology and organismal biology at The Ohio State University.

“Understanding their interactions with a completely different group of bats out on the pasture can help us understand what’s going on inside the colony. If every time they leave the roost they’re getting into battles, that can increase the amount of cooperation within the colony.”

Co-author Simon Ripperger, a former postdoctoral researcher in Carter’s lab, later supplemented the tracking data by capturing video and audio of foraging vampire bats. He observed bats clustered together on one cow and others atop separate cows, some drinking from different wounds and some fighting over food access. He also made what are likely the first audio recordings of a specific type of vampire bat vocalization associated with foraging.

Sunday, September 19, 2021

Targeting tickborne diseases

"Benedict Khoo" Source: University of Minnesota

For Benedict Khoo, making a breakthrough discovery in health-related research doesn’t mean much if it can’t be put to use bettering people’s lives.

For Benedict Khoo, making a breakthrough discovery in health-related research doesn’t mean much if it can’t be put to use bettering people’s lives.

He knows from experience. When he worked in a research lab in Ohio, he felt “divorced from having a tangible impact,” due largely to regulatory hurdles in the field.

But that all changed when he turned to public health. There, he says, however his work turns out, he learns something that could help people make their own health decisions or influence policies. 

“That’s what drove me—to have that impact on the world and feel like I’m doing something,” says Khoo, a doctoral student in the School of Public Health (SPH). 

He found his niche with Jonathan Oliver, an assistant professor of environmental health sciences in SPH, who is now his adviser. Together they study the prevalence of Lyme disease and other tickborne diseases of humans, in a study area comprising Minnesota and adjacent northern Iowa and western Wisconsin. 

Tuesday, September 14, 2021

Flipping the “genetic paradox of invasions”

A close-up look at a green crab. Image credit: Ted Grosholz

The green crab, Carcinus maenas, is considered a globally distributed invasive species, an organism introduced by humans that eventually becomes overpopulated, with increased potential to negatively alter its new environment. Traditionally, it’s been assumed that successful populations contain high genetic diversity, or a variety of characteristics allowing them to adapt and thrive. On the contrary, the green crab - like many successful invasive populations - has low genetic diversity, while still spreading rapidly in a new part of the world.

A new study led by Carolyn Tepolt, an associate scientist of biology at Woods Hole Oceanographic Institution, is investigating the adaptive mechanisms of the green crab along the west coast of North America, where it has shown extensive dispersal in the last decade despite minimal genetic diversity. The study was published recently in Molecular Ecology and is a collaboration between WHOI, the University of California at Davis, Portland State University, and the Smithsonian Environmental Research Center.

“Invasive species like these are generally unwelcome. Green crabs can compete with native species, rip up eelgrass ‘nurseries’, and eat small shellfish before they have a chance to be harvested. Green crabs can be an ecological menace and an economic burden,” Tepolt said. “In this study, we found that one of the world's most serious marine invasive species has evolved specific genetic variation that likely helps it adapt to new environments really quickly, even when it's lost a lot of genetic diversity overall.”

Genetic diversity refers to small individual-to-individual differences in DNA, and often translates into a range of different inherited traits within a species. A population with high genetic diversity is more likely to include individuals with a wide range of different traits. In order for a population to adjust to changing environments, this variation can be crucial - or so scientists have often thought. Invasive species often challenge this assumption, successfully spreading in new regions despite low genetic diversity caused by descending from a small number of initial colonists.

This study focuses on a northwest Pacific population of green crab that has spread within the last 35 years from a single source. High-profile marine invasive species, such as green crabs, often live across thousands of kilometers of ocean, spanning countless environmental differences, both small and large. Using six U.S. west coast locations spanning over 900 miles from central California to British Columbia, Tepolt and her team examined the species’ genetic structure at thousands of places across its genome. While this population has lost a large amount of overall genetic diversity relative to its European source, a piece of DNA associated with cold tolerance in a prior study appears to be under strong selection from north to south across its invasive West Coast range.

This may represent a type of genetic feature - a balanced polymorphism - that evolved to promote rapid adaptation in variable environments despite high gene flow, and which now contributes to successful invasion and spread in a novel environment. Researchers do occasionally find incredibly successful populations that have passed through severe bottlenecks, dramatically decreasing their genetic diversity relative to their source. This study is amplifying the need to consider that diversity at specific parts of the genome (rather than genome-wide diversity) may play a critical role in resilience in new or changing environments.

“This is exciting for two main reasons. First, the study tests a partial resolution to ‘the genetic paradox of invasions’, demonstrating that variation at key parts of the genome permits rapid adaptation even in a population with low overall genetic diversity. Second, it suggests that high gene flow in a widespread species’ native range may generate evolutionary mechanisms, like this one, which provide that species with the substrate for rapid adaptive change as it spreads across new environments,” Tepolt explained.

Identifying invasive species spread can also be a job for non-scientists. As the climate changes and as humans get better and better at moving stuff around the globe, there’s more potential for species to come along for the ride and expand into new environments. Tepolt says it’s important to keep an eye out for cues, changes in the environment and possible new species in places they haven’t been before. She recommends seizing the opportunity to tell officials and researchers if there is something unusual at the coastline. There may be signs at beaches and boat ramps asking people to keep a lookout for particular species and giving contact information. If there are suddenly green crabs in an area for the first time, for example, on the West Coast in the Salish Sea and in Alaska, they likely should not be there and should be reported.

Source/Credit: Woods Hole Oceanographic Institution

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Thursday, September 9, 2021

How land birds cross the open ocean

 

Terrestrial birds are capable of flying for hundreds of kilometers over the open sea. Nourani et al. show that the autumn migration trajectories of some of these birds correspond with uplift over the sea surface. Suitable uplift means less drag, making sea-crossing less energetically demanding. Moreover, strong uplift can allow the birds to soar.
© Elham Nourani / Max Planck Institute of Animal Behavior

Migrating birds choose routes with the best wind and uplift conditions, helping them to fly nonstop for hundreds of kilometers over the sea

Researchers at the Max Planck Institute of Animal Behavior and University of Konstanz in Germany have identified how large land birds fly nonstop for hundreds of kilometers over the open ocean—without taking a break for food or rest. Using GPS tracking technology, the team monitored the global migration of five species of large land birds that complete long sea crossings. They found that all birds exploited wind and uplift to reduce energy costs during flight—even adjusting their migratory routes to benefit from the best atmospheric conditions. This is the most wide-ranging study of sea-crossing behavior yet and reveals the important role of the atmosphere in facilitating migration over the open sea for many terrestrial birds.

Flying over the open sea can be dangerous for land birds. Unlike seabirds, land birds are not able to rest or feed on water, and so sea crossings must be conducted as nonstop flights. For centuries, bird-watchers assumed that large land birds only managed short sea crossings of less than 100 kilometers and completely avoided flying over the open ocean.

However, recent advances in GPS tracking technology have overturned that assumption. Data obtained by attaching small tracking devices on wild birds has shown that many land birds fly for hundreds or even thousands of kilometers over the open seas and oceans as a regular part of their migration.

But scientists are still unraveling how land birds are able to accomplish this. Flapping is an energetically costly activity, and trying to sustain nonstop flapping flight for hundreds of kilometers would not be possible for large, heavy land birds. Some studies have suggested that birds sustain such journeys using tailwind, a horizontal wind blowing in the bird’s direction of flight, which helps them save energy. Most recently, a study revealed that a single species—the osprey—used rising air thermals known as “uplift” to soar over the open sea.

Now, the new study has examined sea-crossing behavior of 65 birds across five species to gain the most wide-ranging insight yet into how land birds survive long flights over the open sea. The researchers analyzed 112 sea-crossing tracks, collected over nine years, with global atmospheric information to pinpoint the criteria that the birds use for selecting their migration routes over the open sea. A large international collaboration of scientists shared their tracking data to make this study possible.

The findings not only confirm the role of tailwind in facilitating sea-crossing behavior, but also reveal the widespread use of uplift for saving energy during these nonstop flights. Suitable uplift means less drag, making sea crossing less energetically demanding.

“Until recently, uplift was assumed to be weak or absent over the sea surface. We show that is not the case,” says first author Elham Nourani, a DAAD PRIME postdoctoral fellow at the Department of Biology at the University of Konstanz, who did the work when she was at the Max Planck Institute of Animal Behavior.

Terrestrial birds are capable of flying for hundreds of kilometers over the open sea. Nourani et al. show that the autumn migration trajectories of

some of these birds correspond with uplift over the sea surface. Suitable uplift means less drag, making sea-crossing less energetically demanding. Moreover, strong uplift can allow the birds to soar.

“Instead, we find that migratory birds adjust their flight routes to benefit from the best wind and uplift conditions when they fly over the sea. This helps them sustain flight for hundreds of kilometers,” says Nourani.

The oriental honey buzzard, for example, flies 700 kilometers over the East China Sea during its annual migration from Japan to southeast Asia. The roughly 18-hour nonstop sea crossing is conducted in autumn when the air movement conditions are optimal. “By making use of uplift, these birds can soar up to one kilometer above the sea surface,” says Nourani.

The study also raises the question of how migration will be affected by a changing climate. “Our findings show that many land birds are dependent on atmospheric support to complete their migrations over the open sea, indicating their vulnerability to any changes to the Earth’s atmospheric circulation patterns,” says Nourani. “Collaborative studies like this are important to unravel general patterns about how migratory birds depend on the weather patterns. This enables future studies to make robust predictions about how these birds will be impacted by climate change.”

Source/Credit: Max-Planck-Gesellschaft

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Newly developed software unveils relationships between RNA modifications and cancers

Researchers from CSI Singapore have developed a software called ModTect that identifies relationships between RNA modifications and the development of diseases as well as survival outcomes
 In a research breakthrough, a team of researchers from the Cancer Science Institute of Singapore (CSI Singapore) at the National University of Singapore has developed a software that can help reveal the relationships between RNA modifications and the development of diseases and disorders.

Led by Professor Daniel Tenen and Dr Henry Yang, the scientists devised ModTect – a new computational software that can identify RNA modifications using pre-existing sequencing data from clinical cohort studies. With ModTect, the team carried out their own novel pan-cancer study covering 33 different cancer types. They found associations between these RNA modifications and the different survival outcomes of cancer patients.

“This work is one of few studies demonstrating the association of mRNA modification with cancer development. We show that the epitranscriptome was dysregulated in patients across multiple cancer types and was additionally associated with cancer progression and survival outcomes,” explained Dr Henry Yang, Research Associate Professor from CSI Singapore.

"In the past decade, the ability to sequence the Human Genome has transformed the study of normal processes and diseases such as cancer. We anticipate that studies like this one, eventually leading to complete sequencing of RNA and detecting modifications directly in RNA, will also have a major impact on the characterization of disease and lead to novel therapeutic approaches," commented Prof Tenen, Senior Principal Investigator from CSI Singapore.

What are RNA modifications?

While most people are familiar with DNA, RNA plays just as much of a vital role in the human body’s cellular functions. Unlike DNA, which has the double-helix structure that most people are familiar with, RNA is a family of single-stranded molecules that perform various essential biological roles.

For example, messenger RNA (mRNA) conveys genetic information that directs the production of different proteins. Imagine DNA as an expansive library filled with books that carry instructions on how to make different proteins. Each letter in the sequences of words that make up the books’ contents are called nucleotides, which are small molecules that are used to store genetic information. To make sure these instructions are followed, mRNA makes copies of the books and carries them from a cell’s nucleus, where DNA is stored, to the ribosomes. These ribosomes are the “factories” where proteins are synthesized. Without RNA, the valuable genetic instructions stored in our cells would never be used.

Additional types of RNA perform other important functions. Some help catalyze biochemical reactions, just like enzymes, while others regulate gene expression.

Small chemical modifications to RNA can sometimes occur and alter the function and stability of the molecules. The study of these modifications and their effects is called ‘epitranscriptomics’. Research in the past has suggested a link between the development of diseases like Alzheimer’s disease and cancer with certain RNA modifications. However, despite multiple attempts to study these associations in deeper detail, the study of epitranscriptomes has proven to be difficult until this breakthrough by scientists from CSI Singapore.

In large patient cohorts, collecting and processing patient samples is challenging. Detecting RNA modifications often involves technically complex processes, such as treating the samples with chemicals that are difficult to access. These techniques often also require the use of large quantities of sample that are hard to obtain for rarer conditions. Because of this, scientists have been limited in their capacity to establish relationships between specific RNA modifications and various human diseases.

Software makes epitranscriptomics easier

The software that the CSI Singapore team created uses RNA sequences available from other large clinical cohort studies. To detect modifications in these RNA sequences, ModTect looks for mismatch signals and deletion signals. Mismatch signals arise when the experimental enzymes scientists use to turn RNA back into DNA incorporates random nucleotides during sequencing. Deletion signals, on the other hand, are when the enzymes sometimes skip a portion of the sequence. Together, these signals are referred to as misincorporation signals.

Unlike other models, ModTect does not require a database of misincorporation signal profiles corresponding to different types of RNA modifications to identify or classify them. ModTect can even identify new signal profiles that drastically differ from what has been previously recorded.

By applying the software to around 11,000 cancer patient RNA-sequencing datasets, the CSI Singapore team was able to embark on a novel study that investigated the associations between RNA modifications and clinical outcomes in patients. ModTect was able to utilize these large datasets and process them with robust statistical filtering. It unveiled that some types of epitranscriptome were associated with cancer progression and survival outcomes in patients. This finding highlighted the potential use of RNA modifications as biomarkers – molecules that can be used to test for diseases.

Unravelling the mystery of sequence differences that escape detection

As explored before, the transmission of genetic information from DNA in a cell’s nucleus to RNA molecules that carry it to a cell’s ribosomes is a critical process. However, this transmission process is not perfect and leads to differences in RNA-DNA sequences. The sites of these mismatches have been widely documented. However, it is unclear whether these observations are caused by modifications in mRNA and why these sites have escaped detection by Sanger sequencing (one of the most popular methods of DNA sequencing).

The group at CSI Singapore uncovered a potential explanation as to why these RNA modification signals have eluded detection over the years. They explained how some epitranscriptomes impede the use of standard reverse transcriptase (RT), the enzyme that is used to convert RNA into DNA. This enzyme is used by scientists in genome sequencing and its use is one of the most critical steps for experimental success. Hence, RNAs that had these impeding modifications were under-represented in Sanger sequencing techniques.

To combat this, the team used newly developed RT enzymes that have been known for their ability to bypass the effects of these modification sites. This allowed them to observe epitranscriptomes that were originally undetectable with Sanger sequencing.

The discipline of epitranscriptomics is still an emerging and rapidly developing field with around 170 RNA modifications being detected so far. By harnessing ModTect, Prof Tenen and his team were able to provide novel insights into the relationships between human diseases – like cancer – and such RNA modifications. The software will be publicly available on Github for other scientists to use.

The team is hopeful that their contribution will help further research that establishes any potential causal or mechanistic relationships between RNA modifications and tumor formation.

Source/Credit: National University of Singapore

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Tuesday, September 7, 2021

Scientists observe cross-immunity against the coronavirus

 

Researchers from Charité – Universitätsmedizin Berlin, the Berlin Institute of Health at Charité (BIH) and the Max Planck Institute for Molecular Genetics (MPIMG) have shown that certain immune cells, which are found in people previously exposed to common cold coronaviruses, enhance the body’s immune response to SARS-CoV-2, both during natural infection and following vaccination. The researchers, whose work has been published in Science, also report that this ‘cross-reactive immunity’ decreases with age. This phenomenon may help to explain why older people are more susceptible to severe disease and why their vaccine-induced immunity is often weaker than that of young people.

Last year, researchers from Charité and the MPIMG made a surprising discovery. They were the first to report that individuals with no prior exposure to SARS-CoV-2 nonetheless had immunological memory cells capable of recognizing this novel virus.

The researchers concluded that these ‘T helper cells’ must have been generated to deal with mostly harmless common cold coronaviruses and that, thanks to the structural similarities between coronaviruses (in particular the characteristic spike protein found on their outer surface), these T helper cells will also attack the novel coronavirus. This ‘cross reactivity’ hypothesis has since been confirmed by a range of studies.

Protective action by cross-reacting T helper cells

Still unclear, however – and the object of intense debate – is the question of whether these immune cells affect the course of subsequent SARS-CoV-2 infections. “Our assumption at the time was that cross-reactive T helper cells have a protective effect, and that prior exposure to endemic (i.e. long-established and widely circulating) coronaviruses therefore reduces the severity of COVID-19 symptoms,” says the study’s (and the previous study’s) first author, Dr. Lucie Loyal, a researcher based at both the Si-M (‘Der Simulierte Mensch – literally ‘The Simulated Human’, a joint research space of Charité and Technische Universität Berlin) and the BIH Center for Regenerative Therapies (BCRT).

She adds: “However, the opposite could have been true. With some viruses, a second infection involving a similar strain can lead to a misdirected immune response and a negative impact on clinical course.” In the current study, the Berlin-based research team presents evidence to support their previous assumptions regarding the existence of a protective effect. According to their data, cross-reactive immunity could be one of several reasons for the variability in disease severity seen with COVID-19 but might also explain differences in vaccine efficacy seen in different age groups.

A universal memory for coronaviruses

For the current study, the researchers recruited individuals with no prior exposure to SARS-CoV-2, testing them at regular intervals to establish whether they had contracted the infection. Out of a total of nearly 800 participants who were recruited from mid-2020 onwards, 17 persons tested positive. The researchers studied the affected individuals’ immune systems in detail. Their analyses showed that the immune response against SARS-CoV-2 also included the mobilization of T helper cells which had been generated in response to endemic common cold viruses.

The researchers also showed that the quality of the immune response against SARS-CoV-2 was linked to the quantity of cross-reactive cells which had been present in the body prior to infection. These cells were particularly effective at recognizing a certain area of the spike protein. In both the endemic viruses and the new coronavirus, this site was characterized by sequence similarities which were particularly well ‘preserved’.

“During infections with the more harmless coronaviruses, the immune system builds up a kind of protective ‘universal coronavirus’ memory,” explains the study’s corresponding author, Dr. Claudia Giesecke-Thiel, Head of the Flow Cytometry Service Group at the MPIMG. “Once exposed to SARS-CoV-2, these memory cells are reactivated and kick-start the response against the new pathogen. This could help accelerate the initial immune response to SARS-CoV-2 and limit viral propagation during the early stages of the infection and is therefore likely to have a positive effect on the course of the disease.”

Taking a more cautionary tone, the researcher adds: “This does not mean that prior exposure to common cold viruses will definitely protect an individual against SARS-CoV-2, nor does it change the course of the pandemic as of now because these underlying mechanisms have been operating all along. It in no way diminishes the importance of getting vaccinated. Our study provides one of several explanations for an observation made since the beginning of the pandemic, namely that the symptoms of SARS-CoV-2 infection can vary greatly between individuals.”

Immune-boosting effect also for vaccination

The researchers’ findings furthermore confirmed that the immunity-enhancing effects of cross-reactive T cells also occur following vaccination with the BioNTech COVID-19 vaccine. Just like natural infection, the vaccine prompts the body to produce the SARS-CoV-2 spike protein (including the well-preserved section of it) and present it to the immune system.

An analysis of the immune responses of 31 healthy individuals before and after vaccination revealed that, while the activation of normal T helper cells took place gradually over the course of two weeks, the activation of cross-reactive T helper cells was extremely rapid, taking place within one week of vaccination. Naturally, this also had a positive effect on the generation of antibodies. Even after the first dose of the vaccine, the body was able to produce antibodies against the preserved section of the spike protein at a rate normally only seen after booster vaccinations.

“Even following vaccination, the body is able to utilize at least some of its immunological memory – provided it has had previous exposure to endemic coronaviruses,” says co-corresponding author Prof. Dr. Andreas Thiel, a Charité researcher based at both the Si-M and the BCRT. He adds: “This might explain the surprisingly rapid and extremely strong protective effect we see after the initial dose of the COVID-19 vaccine, at least in younger individuals.”

Decline with age

In a second part of the study, the researchers analyzed T helper cells in approximately 570 healthy individuals. They were able to show that cross-reactive immunity declines in older adults. In fact, both the number of cross-reactive T cells and the strength of their binding interactions was shown to be lower in older participants than in younger participants. According to the authors, this decline in cross-reactive immunity is caused by normal, age-related changes. “Infection with an endemic coronavirus represents a benefit in younger people, helping them fight off SARS-CoV-2 or develop immunity following vaccination. Sadly, this benefit is less pronounced in older adults,” says Prof. Thiel. He adds: “It is likely that a third (or booster) dose would be able to compensate for this weaker immune response, ensuring that members of this high-risk group have adequate immunity.”

Source/Credit: Max-Planck-Gesellschaft

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Monday, September 6, 2021

Messengers from gut to brain

 

Thomas Korn is a professor for Experimental Neuroimmunology at TUM.
Image: Magdalena Jooss / TUM
Scientists have long been aware of a link between the gut microbiome and the central nervous system (CNS). Until now, however, the immune cells that move from the gut into the CNS and thus the brain had not been identified. A team of researchers in Munich has now succeeded in using violet light to make these migrating T cells visible for the first time. This opens up avenues for developing new treatment options for diseases such as multiple sclerosis (MS) and cancer.

The link between the gut microbiome and the CNS, known as the gut/brain axis (GBA), is believed to be responsible for many things: a person’s body weight, autoimmune diseases, depression, mental illnesses and Alzheimer’s disease. Researchers at the Technical University of Munich (TUM) and LMU University Hospital Munich have now succeeded in making this connection visible for the first time. This is cause for hope – for those suffering from MS, for example. It may offer ways to adapt treatments, and T cells could perhaps be modified before reaching the brain.

The immune system is affected by environmental factors – also in the central nervous system in case of MS patients. This autoimmune disease is subject to repeated flare-ups, experienced by patients as the improvement or worsening of their condition. T cells collect information and, in MS patients, carry it to the central nervous system (in the brain or spinal cord) where an immune response is triggered. Until now, however, it was long uncertain how and from where the T cells were traveling to the CNS.

The team working with Thomas Korn, a professor of experimental neuroimmunology at TUM, has developed a method for marking immune cells in mice using photoconvertible proteins. The T cells can then be made visible with violet light. The researchers successfully tested this method with the mouse model in lymph nodes, both in the gut and the skin. They were able to track the movement of the T cells from those locations into the central nervous systems.

T cells from the skin migrated into the gray and white matter of the CNS, while almost all T cells from the gut ended up in the white matter. For T cells in the brain, it was still possible to determine their origin. “What makes these insights so important is that they demonstrate for the first time that environmental influences impact the T cells in lymph nodes in the gut and the skin, which then carry this information into the distant organs,” says Prof. Thomas Korn. “The characteristics of the T cells are sufficiently stable for us to determine whether immune responses are influenced by skin or gut T cells,” adds LMU researcher Dr. Eduardo Beltrán, who performed the bioinformatic analyses in this study.

An important insight for MS patients: “If gut or skin cells were known to be the cause, the T cells could be treated at the source of the disease and predictions could be made on the progress of the chronic inflammation and autoimmune condition,” says first author Michael Hiltensperger. The results of the study could also mean a breakthrough for research on other autoimmune diseases or cancer.

Paper released in publication Nature Immunology

Source/Credit: Technical University of Munich

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Spread of Delta SARS-CoV-2 variant driven by combination of immune escape and increased infectivity

 

Visualization of the Covid-19 virus 
Credit: Fusion Medical Animation via Unsplash
The Delta variant of SARS-CoV-2, which has become the dominant variant in countries including India and the UK, has most likely spread through its ability to evade neutralizing antibodies and its increased infectivity, say an international team of researchers.

The findings are reported today in Nature.

As SARS-CoV-2 replicates, errors in its genetic makeup cause it to mutate. Some mutations make the virus more transmissible or more infectious, some help it evade the immune response, potentially making vaccines less effective, while others have little effect. One such variant, labelled the B.1.617.2 Delta variant, was first observed in India in late 2020. It has since spread around the globe – in the UK, it is responsible nearly all new cases of coronavirus infection.

Professor Ravi Gupta from the Cambridge Institute of Therapeutic Immunology and Infectious Disease at the University of Cambridge, one of the study’s senior authors, said: “By combining lab-based experiments and epidemiology of vaccine breakthrough infections, we’ve shown that the Delta variant is better at replicating and spreading than other commonly-observed variants. There’s also evidence that neutralizing antibodies produced as a result of previous infection or vaccination are less effective at stopping this variant.

“These factors are likely to have contributed to the devastating epidemic wave in India during the first quarter of 2021, where as many as half of the cases were individuals who had previously been infected with an earlier variant.”

To examine how well the Delta variant was able to evade the immune response, the team extracted serum from blood samples collected as part of the COVID-19 cohort of the NIHR BioResource. The samples came from individuals who had previously been infected with the coronavirus or who had been vaccinated with either the Oxford/AstraZeneca or Pfizer vaccines. Serum contains antibodies raised in response to infection or vaccination. The team found that the Delta variant virus was 5.7-fold less sensitive to the sera from previously-infected individuals, and as much as eight-fold less sensitive to vaccine sera, compared with the Alpha variant - in other words, it takes eight times as many antibodies from a vaccinated individual to block the virus.

Consistent with this, an analysis of over 100 infected healthcare workers at three Delhi hospitals, nearly all of whom had been vaccinated against SARS-CoV-2, found the Delta variant to be transmitted between vaccinated staff to a greater extent than the alpha variant.

SARS-CoV-2 is a coronavirus, so named because spike proteins on its surface give it the appearance of a crown (‘corona’). The spike proteins bind to ACE2, a protein receptor found on the surface of cells in our body. Both the spike protein and ACE2 are then cleaved, allowing genetic material from the virus to enter the host cell. The virus manipulates the host cell’s machinery to allow the virus to replicate and spread.

Using 3D airway organoids – ‘mini-organs’ grown from cells from the airway, which mimic its behaviour – the team studied what happens when the virus reaches the respiratory tract. Working under secure conditions, the team used both a live virus and a ‘pseudo typed virus’ – a synthetic form of the virus that mimicked key mutations on the Delta variant – and used this to infect the organoids. They found that the Delta variant was more efficient at breaking into the cells compared with other variants as it carried a larger number of cleaved spikes on its surface. Once inside the cells, the variant was also better able to replicate. Both of these factors give the virus a selection advantage compared to other variants, helping explain why it has become so dominant.

Dr Partha Rakshit from the National Centre for Disease Control, Delhi, India, joint senior author, said: “The Delta variant has spread widely to become the dominant variants worldwide because it is faster to spread and better at infecting individuals than most other variants we’ve seen. It is also better at getting around existing immunity – either through previous exposure to the virus or to vaccination – though the risk of moderate to severe disease is reduced in such cases.”

Professor Anurag Agrawal from the CSIR Institute of Genomics and Integrative Biology, Delhi, India , joint senior author, added: “Infection of vaccinated healthcare workers with the Delta variant is a significant problem. Although they themselves may only experience mild COVID, they risk infecting individuals who have suboptimal immune responses to vaccination due to underlying health conditions – and these patients could then be at risk of severe disease. We urgently need to consider ways of boosting vaccine responses against variants among healthcare workers. It also suggests infection control measures will need to continue in the post-vaccine era.”

The research was largely supported in India by the Ministry of Health and Family Welfare, the Council of Scientific and Industrial Research, and the Department of Biotechnology; and in the UK by Wellcome, the Medical Research Council and the National Institute of Health Research.

Credit/Source: University of Cambridge

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Blue-tongue vs red-bellied black

 

Scientists have discovered that the humble blue-tongue lizard is largely resistant to the venom of the deadly red-bellied black snake, while giant carnivorous monitor lizards which feed on Australia’s most venomous snakes are not.

The surprising finding was revealed after University of Queensland scientists compared the effects of various reptile blood plasmas when exposed to the venom.

UQ PhD candidate Nicholas Youngman said mammalian – and particularly, human – reactions had been heavily investigated, but very little was known about snake venom effects on other reptiles.

“It was a shock discovering that the eastern blue-tongue, along with the shingleback, showed resistance specifically to red black snake venom,” Mr Youngman said.

“Since their resistance was so specific to only this snake species, it seems these lizards have evolved a special plasma component – known as a serum factor – in their blood.

“This prevents specific toxins in red-bellied black snake venom from clotting the lizards’ plasma, which would lead to a rapid death in most other animals.

“This resistance doesn’t mean they’re completely immune, but it would give them a greater chance of survival, allowing them to escape or fight back.

“Much like how a COVID-19 vaccine doesn’t mean you don’t get sick at all, it just means you are less likely to die.”

The research team analyzed the effects of seven different Australian snake venoms on the plasma of two species of blue-tongued skinks and three species of monitor lizards that would interact with these snakes in the wild.

Associate Professor Bryan Fry, who heads UQ’s Venom Evolution Lab, said the results also revealed that monitor lizards – or goannas – were not resistant to the snake venoms.

“You’d think that a goanna would be significantly resistant to the venom of any snake it was hunting and eating, but that isn’t the case,” Dr Fry said.

“Snake venom can only cause harm to goannas if it’s injected into its body by the snake’s fangs, it can’t be absorbed directly through the skin.

“Goannas are heavily armored and their scales act like medieval chain mail, with each containing a piece of bone, meaning venomous snakes’ fangs struggle to pierce this armor.

“So – unlike the slow, vulnerable blue-tongue lizard – there’s no pressure for goannas to evolve resistance; natural selection has invested in their armor and it’s clearly working for them.

“These two divergent forms of resistance are fascinating examples of evolutionary novelty.”

The research has been published in Toxins

Source/Credit: University of Queensland

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Saturday, August 28, 2021

Rice lab dives deep for DNA’s secrets

 The poor bacteriophages in Yang Gao’s lab are about to have a lot of bad days.

Yang Gao

That’s all to the good for the structural biologist, who has received a prestigious Maximizing Investigators’ Research Award for New and Early Stage Investigators from the National Institutes of Health to make the lives of viruses harder so ours can be better.

The five-year grant for $1.9 million, administered by the National Institute of General Medical Sciences, will help Gao and his group detail the mechanisms of proteins that produce copies of genomic DNA, and what can go awry when they’re either subjected to stress or face other barriers.

A better understanding of the structural framework of DNA replication, stress response and repair at the atomic level could help find new ways to target processes involved in a host of diseases, including cancer.

“We’re interested in the basic question of how DNA is replicated,” said Gao, an assistant professor of biosciences who joined Rice in 2019 with the backing of a grant from the Cancer Prevention and Research Institute of Texas. “We’ve known for a long time that DNA is a fragile molecule and subject to many different assaults, environmental and physiological, like ultraviolet from sunlight and oxidative species.

“So many things damage DNA,” he said. “Despite that, DNA replication has to keep on going, even if there are errors, with an enzyme called DNA polymerase and a motor called the helicase.”

A study of stress on bacteriophage T7 will help Rice structural biologist Yang Gao and his team to reveal the atomic-scale mechanisms of DNA replication. (Credit: Yang Gao Lab/Rice University)

These are part of the replisome, a complex chain of proteins that carry out DNA replication and help repair DNA on the fly. Part of their normal function is to catch and fix coding errors. “When they see something bad they call for help, either before or after replication,” Gao said. “But how that works is still unknown, and we want to figure it out.”

The lab will start with the T7 bacteriophage, a virus whose infection mechanism in Escherichia coli bacteria is a good analog for what happens in humans.

“During my postdoc, we solved the first structure of T7 replisome to show how T7 comes together at a replication site,” he said. “We’ve continued that work at Rice, and we’re using the system to explore how it deals with different damages.”

The lab will then study the structure of mitochondria, the “power plants” inside cells, to see how DNA mutations produced there could lead to genetic diseases. “These two systems are mechanistically similar, and because we have experience with T7 and we’ve recently established a mitochondrial hub, we’re in a good position to start this investigation,” Gao said.

He noted he will continue to collaborate with Rice physicist Peter Wolynes and his group, which produces models that advance the theory of DNA replication. The lab also plans to make use of a new transmission electron microscope pegged for Rice’s BioScience Research Collaborative.

Press Release
Source / Credit: Rice University

Thursday, August 26, 2021

Plants evolved ability to actively control water-loss earlier than previously thought

 

Fern stomata Credit: University of Birmingham
New research has shed light on when plants first evolved the ability to respond to changing humidity in the air around them, and was probably a feature of a common ancestor of both flowering plants and ferns.

New research has shed light on when plants first evolved the ability to respond to changing humidity in the air around them, and was probably a feature of a common ancestor of both flowering plants and ferns.

Key to the regulation mechanism are tiny holes, or pores, on the surface of leaves, called stomata. These enable the plant to regulate the uptake of CO2 gas as fuel for photosynthesis, and the loss of water vapour – a constant balancing act that requires the pores to open and close according to changing conditions. This ability is important to agriculture because it helps crops to use less water to grow.

Plants first evolved stomata soon after they moved from water to land, some 450 million years ago, but scientists are still uncertain about the evolutionary pathway they took and the point at which plants became able to choose whether to open or close the pores in response to their environment.

In the most recently evolved plants – flowering plants – stomata closure in response to drought is actively triggered by a number of internal signals, including a hormone called abscisic acid (ABA), but scientists have been struggling to understand if this mechanism is also present in older groups of plants. In a new study, published in Current Biology, researchers at the University of Birmingham have found evidence that the fern species Ceratopteris richardii actively closes its stomata using similar signals.

This semi-aquatic tropical fern has recently become the first model for exploring genetic control of development in the fern family, and is now helping scientists to unpick the long evolutionary history between the earliest land-living plants (mosses, liverworts and hornworts) and the modern flowering plants that dominate today’s ecosystems.

The team used RNA sequencing technology to identify the genetic mechanisms behind different stomatal responses and was able to demonstrate the fern’s ability to close stomata in response to low humidity or in response to ABA involves copies of genes already known to control stomata in flowering plants.

The results suggest that both ferns and flowering plants evolved using similar stomatal closure methods. This indicates that these mechanisms were present – at least in some form – in the stomata of the last common ancestor of both groups.

Dr Andrew Plackett, of the University of Birmingham’s School of Biosciences, led the research in collaboration with groups at the University of Bristol and the University of Oxford. He said: “We know that plants have possessed stomata for most of their evolutionary history, but the point in evolution where plants became able to actively open and close them has been controversial.

“We’ve been able to show the same active closure mechanisms found in flowering plants are also present in ferns, a much older group of plants. Being able to better understand how these mechanisms have changed during plant evolution gives us useful tools to learn more about how they work. This will be important for helping our crops to adapt to future environmental changes.”

Prof Alistair Hetherington of Bristol’s School of Biological Sciences added: “This new work confirms that the earliest plants were able to actively control the water they lost through the microscopic valve like structures on the surfaces of leaves known as stomata. This is important because it shows that the intracellular machinery allowing stomata to open and close was present in the earliest land plants. The research also shows that, whether stomata respond actively or passively is dictated by the environment in which the plants lived. "

Source / Credit: University of Bristol

Farmed carnivores may become disease reservoirs posing human health risk

 Farming large numbers of carnivores, like mink, could allow the formation of undetected ‘disease reservoirs’, in which a pathogen could spread to many animals and mutate to become a risk to human health.

Research led by the University of Cambridge has discovered that carnivores have a defective immune system, which makes them likely to be asymptomatic carriers of disease-causing pathogens.

Three key genes in carnivores that are critical for gut health were found to have lost their function. If these genes were working, they would produce protein complexes called inflammasomes to activate inflammatory responses and fight off pathogens. The study is published today in the journal Cell Reports.

The researchers say that the carnivorous diet, which is high in protein, is thought to have antimicrobial properties that could compensate for the loss of these immune pathways in carnivores – any gut infection is expelled by the production of diarrhoea. But the immune deficiency means that other pathogens can reside undetected elsewhere in these animals.

“We’ve found that a whole cohort of inflammatory genes is missing in carnivores - we didn’t expect this at all,” said Professor Clare Bryant in the University of Cambridge’s Department of Veterinary Medicine, senior author of the paper. 

She added: “We think that the lack of these functioning genes contributes to the ability of pathogens to hide undetected in carnivores, to potentially mutate and be transmitted becoming a human health risk.”

Zoonotic pathogens are those that live in animal hosts before jumping to infect humans. The COVID-19 pandemic, thought to originate in a wild animal, has shown the enormous damage that can be wrought by a novel human disease. Carnivores include mink, dogs, and cats, and are the biggest carriers of zoonotic pathogens. 

Three genes appear to be in the process of being lost entirely in carnivores: the DNA is still present but it is not expressed, meaning they have become ‘pseudogenes’ and are not functioning. A third gene important for gut health has developed a unique mutation, causing two proteins called caspases to be fused together to change their function so they can no longer respond to some pathogens in the animal’s body.

“When you have a large population of farmed carnivorous animals, like mink, they can harbour a pathogen - like SARS-CoV-2 and others - and it can mutate because the immune system of the mink isn’t being activated. This could potentially spread into humans,” said Bryant.

The researchers say that the results are not a reason to be concerned about COVID-19 being spread by dogs and cats. There is no evidence that these domestic pets carry or transmit COVID-19. It is when large numbers of carnivores are kept together in close proximity that a large reservoir of the pathogen can build up amongst them, and potentially mutate.

This research was funded by Wellcome.

Source / Credit: University of Cambridge

Monday, August 23, 2021

Alex Jordan: "Fish are not stupid, they're different!"

Alex Jordan is a behavioral ecologist at the Max Planck Institute of Animal Behavior in Konstanz, Germany. His main interest: he wants to know why animals do what they do. He is especially devoted to fish, having been a hobbyist since a young age, and seeing the value of being able to study animals equally well in the wild as in captivity.

Alex, a few years ago you conducted a study that resonated strongly in the scientific community on the reaction of cleaner wrasses to their mirror image. What did you find out in the process?

We placed marks on the cleaner wrasses' bodies that they could only see in a mirror. The fish then tried to remove these marks. We performed various tests to make sure that the fish only reacted to marks that they saw on their own bodies in the mirror an nothing else.

A mirror test passed in this way is considered by researchers to be evidence of self-awareness. Only a few species score positively in this test, for example apes, corvids, dolphins - and now cleaner wrasses.

What do you conclude from this? Are the fish aware of themselves?

No, I don't think so. I suspect the wrasses have simply learned that a mirror creates an image of something - in this case, themselves. Since dark spots on fish bodies are an important signal for wrasses by nature - they usually represent parasites, which the wrasses feed on - they are naturally particularly interested in this. However, they probably do not possess self-awareness or even self-consciousness.

In any case, the test demonstrates that the fish are extremely adaptive and can exploit new opportunities for themselves. 

What can the mirror test then tell us in the first place?

In my opinion, the mirror test is not well suited for studying self-awareness in animals. We also did the test with African cichlids from Lake Tanganyika. They didn't care about the marks on their bodies at all. Also the cleaner wrasses passed the test only if the marks were brown. They didn’t care about marks of other colors. It is important to remember that other highly evolved animals, such as dogs or cats, do not pass the test either.

There are different reasons why an animal does not react to the marks, so in my opinion the test is not suitable to answer the question about self-awareness. It was developed by humans for humans. For most animals, it just doesn't fit.

How can you find out what other organisms think, feel, perceive?

That is very difficult in principle. Even you and I differ in how we perceive things. But you can at least describe your cognitive status to me. Since we can hardly or not at all communicate with animals, we can only infer what they feel, want, think. Some degree of uncertainty will always remain, because we can't help but take ourselves as the measure of all things. To leave our human world of experience and to put ourselves into the world of a fish is all but easy.

How could we nevertheless get an idea of what is going on inside a fish?

We want to try this with a completely new approach. We will measure the activity of nerve cells in the brain when zebrafish react to conspecifics or when they face their mirror image. If there are different activation patterns in the brain in the two cases, this would indicate that the fish are not seeing a conspecific, but themselves. That would be a strong hint for the fish being self-aware.

Fish are commonly regarded as primitive and not very intelligent. Is this justified?

Not at all. We need to stop seeing ourselves as the pinnacle of evolution and ranking other animals in descending order below. All organisms on earth are the result of millions of years of evolution. They and their predecessors have always managed to defy all odds and adapt. Seen in this light, even a bacterium is highly evolved.

Consequently, fish are not dumber or worse than us, they are just different!

How smart are fish?

We don't know exactly yet, but there are definitely differences between species. Fish that migrate in large anonymous schools through the ocean probably need less higher mental abilities than those that defend territories, for example. So I would expect more from a Tanganyika cichlid than from a mackerel.

It is known from other groups of animals that species with a narrow food spectrum are less capable cognitively than those that eat a variety of foods. Thus, the omnivores among fishes might generally be "smarter" than specialists.

Marine fish often exhibit more complex behaviors than freshwater species - simply because inland waters have not existed as long as the oceans, and therefore they have less time to develop such behaviors.

What can fish do?

Some fish are very sophisticated. They can play and use tools, they predict the actions of others, and they even cheat and reconciliate. Some species thus possess higher cognitive abilities than other vertebrates. They may not be that far from apes and humans.

Fish can also recognize people. They know who to expect food from and who not to expect it from, as many aquarium owners can attest. In our research area in Lake Tanganyika, for example, predatory fish from the genus Lepidiolamprologus have learned that they can prey  when my colleague and I are out diving. In doing so, they don't follow me, but her, because she flushes out most of the fish.

And not only that: some species can also distinguish conspecifics individually. Damselfish, for example, have individual color markings on their faces that are only visible in ultraviolet light, which they use to recognize each other.

Another fascinating example, which we plan to investigate ourselves, is how mullet and wrasses work together in the Mediterranean. When a mullet is foraging and scavenging on the sand, it is often accompanied by a wrasse, which preys on small critters scared up by the mullet. This alone would be nothing special, but the wrasse keeps touching the mullet - it literally caresses it. Probably the mullet knows in this way that there is no danger from above while it burrows underground. The "masseur" thus ensures that the mullet stays in its territory.

What do these findings mean for how we treat fish today?

Even if there is still a lot we don't know, one thing is clear: fish can do more than we have given them credit for up to now. They are sentient animals capable of cognitive engagement with the world around them, including social interactions, fear, suffering, and enjoyment.

Thank you for this interview!

Interview by Harald Rösch

Source / Credit: MAX-PLANCK-GESELLSCHAFT


‘Vegetarian’ giant tortoise filmed attacking and eating seabird

 The hunting tortoise was seen in July 2020 on Frégate Island, a privately owned island in the Seychelles group managed for ecotourism, where around 3,000 tortoises live. Other tortoises in the same area have been seen making similar attacks.

“This is completely unexpected behavior and has never been seen before in wild tortoises,” said Dr Justin Gerlach, Director of Studies at Peterhouse, Cambridge and Affiliated Researcher at the University of Cambridge’s Museum of Zoology, who led the study.

He added: “The giant tortoise pursued the tern chick along a log, finally killing the chick and eating it. It was a very slow encounter, with the tortoise moving at its normal, slow walking pace – the whole interaction took seven minutes and was quite horrifying.” 

The interaction was filmed by Anna Zora, conservation manager on Frégate Island and co-author of the study. 

“When I saw the tortoise moving in a strange way I sat and watched, and when I realized what it was doing I started filming,” said Zora.

The finding is published today in the journal Current Biology.

All tortoises were previously thought to be vegetarian - although they have been spotted feeding opportunistically on carrion, and they eat bones and snail shells for calcium. But no tortoise species has been seen actively pursuing prey in the wild before.

The researchers think that this entirely new hunting behavior was driven by the unusual combination of a tree-nesting tern colony and a resident giant tortoise population on the Seychelles’ Frégate island.

Extensive habitat restoration on the island has enabled sea-birds to recolonize, and there is a colony of 265,000 noddy terns, Anous tenuirostris. The ground under the colony is littered with dropped fish and chicks that have fallen from their nests.

In most places, potential prey are too fast or agile to be caught by giant tortoises. The researchers say that the way the tortoise approached the chick on the log suggests this type of interaction happens frequently.

On the Galapagos and Seychelles islands, giant tortoises are the largest herbivores and eat up to 11% of the vegetation. They also play an important role in dispersing seeds, breaking vegetation and eroding rocks.

“These days Frégate island’s combination of tree-nesting terns and giant tortoise populations is unusual, but our observation highlights that when ecosystems are restored totally unexpected interactions between species may appear; things that probably happened commonly in the past but we’ve never seen before,” said Gerlach.

This research was supported by Fregate Island Foundation.

Reference

Zora, A. & Gerlach, J.: ‘First documented observations of giant tortoises hunting and consuming birds.’ Current Biology, August 2021, DOI: 10.1016/j.cub.2021.06.088

Source / Credit: University of Cambridge 

Attribution 4.0 International (CC BY 4.0)

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