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Protein molecules in cells function as miniature antennas

Credit: Credit: Petr Pachl / IOCB Prague Researchers led by Josef Lazar of the Institute of Organic Chemistry and Biochemistry

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Researchers led by Josef Lazar of the Institute of Organic Chemistry and Biochemistry of the Czech Academy of Sciences (IOCB Prague) have demonstrated that molecules of fluorescent proteins act as antennas with optical properties (i.e. the ability to absorb and emit light) dependent on their spatial orientation. First discovered in jellyfish, fluorescent proteins are nowadays widely used in studies of molecular processes in living cells and organisms. The newly described properties of these molecules will find applications in basic biological research as well as in novel drug discovery. A team of researchers from IOCB Prague, the Institute of Microbiology, and the Institute of Molecular Genetics of the Czech Academy of Sciences has published its findings in the journal Proceedings of the National Academy of Sciences of the United States of America.

To achieve these results, the researchers produced sufficient amounts of fluorescent proteins by using genetically modified bacteria, identified the conditions under which the proteins form crystals, and determined the atomic structure of the crystals. Employing a unique microscope developed within the group, they then measured how these crystals absorb and emit light, and from the data they calculated the directional properties of the individual molecules. This allowed them to verify that the fluorescent protein molecules do not behave as tiny luminescent dots, as they are often mistakenly assumed, but rather as miniature antennas. Much like antennas for radio, WiFi, and television transmission, these molecules only absorb light from certain directions. Likewise, they only emit light in certain directions. The researchers also succeeded in precisely establishing these directions.

The possibility of fluorescent protein molecules behaving as antennas capable of absorbing extraneous light had been assumed, but it long proved difficult to confirm, and that limited its applications. The obstacles have been overcome by Josef Lazar of IOCB Prague and his team, which specializes in the development and use of advanced optical microscopy methods.

“Based on the findings of other laboratories and our own, we suspected that fluorescent protein molecules likely behaved as antennas. Nonetheless, we were surprised to see just how true that analogy is and how accurately we were able to establish the directions from which these molecules absorb light and emit it,” says Josef Lazar.

The fact that fluorescent protein molecules function as miniature antennas is interesting not only as a curiosity of physics – it can also have important practical applications. Attaching a fluorescent protein to some other protein of interest means attaching a miniature antenna to it that can then be used to establish, in detail, changes in the shape of the molecules of the protein of interest, directly in a living cell. Such changes in molecular shape can be induced by a drug, for instance. The present discovery will thus find applications in the study of important physiological processes at the molecular level as well as in novel drug discovery.

“The significance of our finding lies in the fact that even though fluorescent protein molecules are widely used in biological research, their ability to behave like antennas isn’t fully appreciated yet, nor is it really being put to use. Knowledge of the directional properties of fluorescent proteins can lead to new ways of using these useful molecules,” explains Lazar.

In collaboration with other groups at IOCB Prague, Josef Lazar’s team is already attempting to apply the present findings in, for example, the study of the physiological effects of insulin and the development of insulin substitutes for peroral use. Another example of a possible application of the present discovery is the tracing of electrical signals in nerve cells, which could prove beneficial in the study of the brain and neurological diseases.

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The Institute of Organic Chemistry and Biochemistry of the Czech Academy of Sciences / IOCB Prague (http://www.uochb.cz) is a leading internationally recognized scientific institution whose primary mission is the pursuit of basic research in chemical biology and medicinal chemistry, organic and materials chemistry, chemistry of natural substances, biochemistry and molecular biology, physical chemistry, theoretical chemistry, and analytical chemistry. An integral part of the IOCB Prague’s mission is the implementation of the results of basic research in practice. Emphasis on interdisciplinary research gives rise to a wide range of applications in medicine, pharmacy, and other fields.

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https://www.uochb.cz/en/news/207/protein-molecules-in-cells-function-as-miniature-antennas

“Based on the findings of other laboratories and our own, we suspected that fluorescent protein molecules likely behaved as antennas. Nonetheless, we were surprised to see just how true that analogy is and how accurately we were able to establish the directions from which these molecules absorb light and emit it,” says Josef Lazar.

Source: https://bioengineer.org/protein-molecules-in-cells-function-as-miniature-antennas/

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What factors put Philippine birds at risk of extinction?

Credit: Ça?an ?ekercio?lu The lush forests and more than 7,000 islands of the Philippines hold a rich diversity of life,

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The lush forests and more than 7,000 islands of the Philippines hold a rich diversity of life, with 258 bird species who live nowhere but the Philippine archipelago. A new study from University of Utah researchers suggests that, due to deforestation and habitat degradation, more bird species may be endangered that previously thought – including species that may not have been discovered yet. The study is published in Frontiers in Ecology and Evolution.

“Our study provides a roadmap for not only which species may warrant heightened conservation attention,” says Kyle Kittelberger, a doctoral student in the University of Utah School of Biological Sciences, “but which traits a species may have that can help inform if it may likely be more at risk of extinction.”

Birds of the Philippines

Located in Southeast Asia, the Philippines is considered a global biodiversity hotspot and one of the most biodiverse countries in the world, hosting nearly 600 bird species. A high proportion of the wildlife is endemic to the country, meaning that it is found nowhere else. The Philippines also hosts some of the highest richness of species recently identified as distinct from other closely related species, showing that scientists still have much to learn about the Philippine ecosystems.

Within the last decade the number of endemic species has risen from 172 to 258. This increase of 86 endemic species is more than all the endemic bird species in China (67) or India (75) and more than any country in South America or Africa.

Çağan Şekercioğlu, an associate professor in the School of Biological Sciences who has done ornithological field work in over 90 countries on all continents cannot forget his first visit to the islands.

“When I first visited the Philippines in 2008, I was awestruck by the diversity and especially the endemism of its avifauna but also greatly depressed by the rapid loss of habitat,” he says. Excursions into the field took hours due to extensive deforestation. “While looking for rare forest birds in the lowlands of Mindanao, we were literally trying to keep ahead of the loggers that were cutting down century-old rainforest trees within a couple hundred meters of us,” he adds. Despite that, in 13 days he saw 161 bird species he had never seen before- and still has 163 bird species to go.

Deforestation, habitat degradation and wildlife exploitation, however, threatens that biodiversity. Southeast Asia, the authors write, is forecast to lose over a third of its biodiversity over the next century. The Philippines in particular ranks 8th in the world for the number of globally threatened bird species.

“There is a pressing need to assess what traits make some species more at risk of extinction than others,” Kittelberger says, and use this understanding to help inform conservation efforts.”

Traits of threatened birds

To understand the status of Philippine birds, the researchers first determined the bird traits most predictive of extinction risk by correlating bird species’ ecological and life history traits, including body mass, diet, elevation range, and clutch size (the number of eggs laid in a nesting season) with their conservation status. A species endemic to the Philippines was significantly more likely to face an extinction risk, they found. Narrow elevation ranges, dependence on forests and high body mass also put birds at risk for extinction.

Then the researchers turned around and evaluated Philippine birds’ expected conservation status using those traits, comparing predicted conservation status with the IUCN Red List conservation designations. They found that 84 species were predicted to be in worse shape than their Red List designation, with 14 species predicted to be globally threatened (i.e. vulnerable, endangered, or critically endangered) that aren’t currently classified as such.

“We predicted that the Philippine Serpent-eagle and Writhed Hornbill, two species that are not currently recognized as being globally threatened, are respectively endangered and critically endangered,” Kittelberger says. “We also predicted that the Palawan Peacock-pheasant, Calayan Rail and Philippine Eagle-owl, three species currently recognized internationally as being vulnerable, are likely endangered species. All these birds therefore warrant heightened conservation attention as they may be more threatened than currently believed.”

Lost before they’re found

Among the 84 species predicted to be more threatened, 12 were recently recognized as separate species, and three of those were predicted to be “vulnerable.”

“The Philippines have a very high level of endemism and it is currently estimated that there are twice as many bird species in the Philippines that have not yet been split and officially recognized, so there is a real risk of losing species before they are described,” Kittelberger says.

Kittelberger says that their research can be applied broadly to assess the conservation status of birds throughout the region.

“The most important thing that the Philippines can do to protect birds,” Kittelberger says, “is to address the high levels of deforestation, habitat degradation, and wildlife exploitation, and to increase land protection for wildlife and increase funding for conservation efforts.”

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Find the full study here.

Co-authors also include Montague H. C. Neate-Clegg, J. David Blount and Çağan Şekercioğlu of the U’s School of Biological Sciences, Mary Rose C. Posa of the California Botanic Garden and John McLaughlin of the University of California, Santa Barbara. The study was supported by the Christensen Fund.

Within the last decade the number of endemic species has risen from 172 to 258. This increase of 86 endemic species is more than all the endemic bird species in China (67) or India (75) and more than any country in South America or Africa.

Source: https://bioengineer.org/what-factors-put-philippine-birds-at-risk-of-extinction/

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Stem cells may hold a key to developing new vaccines against COVID-19

Coronavirus activates a stem cell-mediated defense mechanism that reactivates dormant TB in a mouse model and has implications for developing

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Coronavirus activates a stem cell-mediated defense mechanism that reactivates dormant TB in a mouse model and has implications for developing new vaccines and avoiding a global TB pandemic, report investigators in The American Journal of Pathology

Philadelphia, June 16, 2021 – The SARS-CoV-2 virus that causes COVID-19 may have the ability to reactivate dormant tuberculosis (TB). In a novel study scientists report in The American Journal of Pathology that infection with a specific coronavirus strain reactivated dormant Mycobacterium tuberculosis (MTB) in mice. This knowledge may help to develop new vaccines for COVID-19 and avoid a potential global tuberculosis epidemic.

The COVID-19 pandemic caused by the SARS-CoV-2 virus demonstrates the ability of an emerging virus to affect masses and strain and disrupt the workings of modern healthcare systems around the world. A significant number of infected COVID-19 individuals have recovered. However, a possible host defense or antiviral mechanism against the virus is yet to be identified. There are concerns that in the long-term, the virus might activate dormant bacterial infections such as TB in select infected individuals, as alarmingly, TB is already present in one quarter of the world population. Viral infections such as the influenza virus or SARS-CoV-1 are known to cause transient immune suppression that leads to reactivation of dormant bacterial infection. The highest death rate during the Spanish flu pandemic of 1918 was in patients with TB, and patients with TB or multidrug-resistant TB had a worse prognosis than others during the influenza A (H1N1) pandemic in 2009.

“There is an urgent need to study the association of COVID-19 with dormant TB reactivation to avoid a potential global TB pandemic,” explained lead investigator Bikul Das, MD, PhD, Department of Stem Cell and Infectious Diseases, KaviKrishna Laboratory, Guwahati Biotech Park, Indian Institute of Technology, Guwahati, India; and Department of Stem Cell and Infection, Thoreau Lab for Global Health, University of Massachusetts, Lowell, MA, USA. “It is important to understand the host defense mechanism against this disease to develop a better vaccine and/or treatment. We therefore postulated that, similar to bacteria, adult stem cells may also exhibit an altruistic defense mechanism to protect their niche against external threat.”

Investigators studied the coronavirus strain murine hepatitis virus-1 (MHV-1) infection in the lung in a mouse model (dMtb) of mesenchymal stem cell (MSC)-mediated MTB dormancy. This showed 20-fold lower viral loads than the dMtb-free control mice by the third week of viral infection and a six-fold increase of altruistic stem cells (ASCs), thereby enhancing the defense. Tuberculosis was reactivated in the dMtb mice, suggesting that dormant TB bacteria hijack these ASCs to replicate in the lung to cause pulmonary TB. Results suggest that these ASCs are transient (they expand for two weeks and then undergo apoptosis or cellular suicide) and exhibit antiviral activities against MHV-1 by secreting soluble factors.

“These findings are important because they reveal a novel ASC defense mechanism against mouse coronavirus infection, which could be used to develop novel therapeutic approaches against COVID-19,” noted Bikul Das. “The finding of TB reactivation in a stem cell-mediated Mtb dormancy mouse model during MHV-1 coronavirus infection indicates that in the long-term, post-pandemic, the SARS-CoV-2 virus might activate dormant bacterial infections. This is a significant finding considering the current coronavirus pandemic, where many individuals in India and other developing countries with dormant TB infection may see an increase in active TB cases post COVID-19. The ASC-mediated defense mechanism may be targeted to develop vaccines against viral infections and avoid a potential global TB pandemic.”

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Background notes

This study of stem cell altruism was inspired by the Indian Vedantic Philosophical theory of altruistic behavior, which was referred to in the poem “Fire of Golden Nail” written by Vedic philosopher and poet Krishna Ram Das of Kamrupa, India, noted the study’s authors. Poet Krishna Ram Das conceptualized the idea while undergoing surgery for throat cancer and initiated the KaviKrishna Foundation to test his idea through vigorous scientific research.

“Proving altruism in mammalian cell biology is a challenging task, as we faced years of resistance from colleagues,” commented Bikul Das. “Altruism is about group selection, which is very challenging to demonstrate at the molecular level. However, the idea of altruism that we are describing here is the philosophical view of Vedic Jiva Upakarvada (Vedic altruism), a part of Vedantic thought that states that during stress, the living organism acquires a higher state, known as ‘Avatar.’ The mandate of the KaviKrishna laboratory is to take this philosophical view forward to modern biology, specifically to develop a philosophical and social theory on global health.

First author Lekhika Pathak, PhD student at the KaviKrishna Lab, GBP, IIT-Guwahati, India, commented: “I joined the laboratory hoping to further ASC research exploiting the model of MHV-1-infected stem cell-mediated Mtb dormancy. Our research findings now may provide a novel approach to understand the interaction between two pathogens, coronavirus and M. tuberculosis, both of which are major threats to global health.”

Co-investigator Herman Yeger, PhD, of the Department of Pediatric Laboratory Medicine, Hospital for Sick Children, Toronto, Ontario, Canada, added: “I commend Bikul Das for being innovative in transforming a piece of Indian philosophy into a testable biological experiment on altruism. Now that we have obtained convincing data on the identification of ASC and their defense against coronavirus, we hope to develop a novel approach to tackle this growing pandemic.”

https://www.elsevier.com/about/press-releases/research-and-journals/stem-cells-may-hold-a-key-to-developing-new-vaccines-against-covid-19

Source: https://bioengineer.org/stem-cells-may-hold-a-key-to-developing-new-vaccines-against-covid-19/

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$1 million grant to address cold storage logistics in vaccine delivery

Credit: Penn State College of Engineering COVID-19 vaccines have been tested, validated and administered to millions of people around the

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COVID-19 vaccines have been tested, validated and administered to millions of people around the world. But in some countries, the vaccines have yet to arrive in great enough numbers.

One significant hurdle is that the vaccines must be stored between 36 and 46 degrees Fahrenheit to retain their full efficacy, according to the Centers for Disease Control. To ensure the proper temperature, the vaccines need a refrigerated supply chain, also known as a cold chain, as they are distributed across the globe.

“If they are in warm temperatures, COVID vaccines and other medications are susceptible to degradation, which means they lose potency,” said Medina, who heads the Medina Group Precision Therapeutics and Bioresponsive Materials Lab at Penn State. “And the cold storage supply chain is expensive to maintain, with several transport steps necessary from the manufacturer to the distributer to the provider facility.”

To address that challenge, Medina and his team plan to develop fluorochemical dispersants, known as “FTags,” which coat the proteins within the vaccine liquids to stabilize them thermally.

“The FTags dissolve the proteins in a fluorine-based liquid, which yields proteins that we believe may be stable at elevated temperatures, without compromising their structure or function,” Medina said. “When dissolved in the fluorine-based liquid, the proteins also are immune to contamination by microorganisms and enzymes.”

Fluorochemicals are used in a range of applications, such as in making surfaces resistant to scratches and chemical degradation, as in the case of non-stick cookware.

Eventually, Medina plans to study the use of fluorochemical coatings in other biological products, with the goal of eliminating the need to move any pharmaceutical via a cold chain.

“This will allow access to medications in places where currently there is not,” Medina said. “For example, a soldier at war could be exposed to a harmful chemical agent. A fluorochemical-coated protein, which can be carried without refrigeration, could neutralize that agent immediately. This is part of DARPA’s interest in supplying this grant.”

The grant is part of DARPA’s Young Faculty Award program, which provides funding, mentoring and networking opportunities to faculty early in their careers who plan to focus their research on Department of Defense and national security interests.

In 2020, Medina published a study in ACS Nano on delivering therapeutic medications directly to a precise area of the body through an acoustically sensitive carrier, guided by ultrasound. The proposed DARPA-funded study is a spin-off of that study’s findings.

“Janna Sloand, my former grad student who recently defended her doctoral research, came up with the coating technology in our last study,” Medina said. “It dovetails nicely with our new study, which will use those same coatings to take on the limitations of the cold chain.”

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Source: https://bioengineer.org/1-million-grant-to-address-cold-storage-logistics-in-vaccine-delivery/

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