Thursday, March 11, 2021

Study suggests healthy ecosystems are vital in reducing risk of future deadly pandemics

Practices recommended to reduce the risk of future pandemics through 'protected and conserved area management'

CABI

IMAGE: INVASIVE ALIEN PLANTS HAVE REDUCED THE HABITAT QUALITY OF THE MAURITIAN FLYING FOX, RESULTING IN INCREASED FORAGING IN AGRICULTURAL LANDS AND URBAN ENVIRONMENTS. view more
CREDIT: PIXABAY

CABI scientist Dr Arne Witt has shared his expertise on invasive alien plant species as part of a new paper which argues that healthy ecosystems are vital in reducing the risk of future pandemics - such as coronaviruses (including COVID-19) - that threaten human health.

The paper - 'Land use-induced spillover: priority actions for protected and conserved area managers' - is published as part of a special issue by the journal PARKS entitled 'COVID-19 and Protected Areas: Essential Reading for a World Haunted by a Pandemic.'

Lead author Dr Jamie K. Reaser - along with a team of researchers from institutions including the African Wildlife Foundation, the University of Oklahoma and the IUCN World Commission on Protected Areas - recommend practices to reduce the risk of future pandemics through 'protected and conserved area management.'

They rightly state that pandemic prevention 'requires that human health be regarded as an ecological service' and call upon multi-lateral conservation frameworks to recognise that 'protected area managers are in the frontline of public health safety.'

The scientists highlight that land use change 'drives the emergence and spread of micro-organisms (pathogens) that infest wildlife and humans with severe consequences for environmental, animal and human health.'

The authors underscore the fact that "The COVID-19 pandemic, caused by the SARS-CoV-2 virus, demonstrates society's inability to respond it a timely manner to novel pathogens. The result is mass human suffering and mortality, bringing substantial moral, ethical and economic dilemmas."

"A protected and conserved areas are the most widely used approaches to securing species and ecological integrity, they have a crucial role to play in safeguarding public health."

"From our perspective, a 'healthy' ecosystem is one in which wildlife-pathogen interactions are in balance, wildlife are not overly stressed or concentrated together by land use-induced changes."

The scientists say that the strategic removal of invasive alien plants, that support populations of zoonotic pathogens, vectors or hosts, can function as an ecological countermeasure.

Dr Witt said, "In Mauritius, for example, invasive alien plants have reduced the habitat quality of the Mauritian flying fox (Pteropus niger), resulting in increased foraging in agricultural lands and urban environments."

"Krivek et al. (2020) showed that non-native plant invasions reduced native fruit production and that weeded forests provide a better habitat for flying foxes. They conclude that their study lends support to invasive alien plant control as a management strategy in mitigating human-wildlife conflicts."

Dr Reaser and the team of researchers put forward a series of proposals that reinforce existing conservation strategies while 'elevating biodiversity conservation as a priority health measure.'

The proposals include conducting surveillance about the occurrence of pathogens, or their clinical diseases, in animal or human populations as well as fostering 'landscape immunity' in conserved and protected areas. The latter of which can be achieved, the scientists suggest, by measures including not disturbing landscapes and 'retaining a full complement of native species and their inter-relationships.'

Dr Reaser and her colleagues conclude by arguing that, "Nations can no longer treat conservation as a second order priority. COVID-19 shows that we should now recognise that protected areas are at the frontline of public health infrastructure and that their managers are vital to disease prevention."

"Looking ahead, we have to conserve nature as if our lives depended on it."

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Full paper reference

Reaser, J. K., G. M. Tabor, D. J. Becker, P. Muruthi, A. Witt, S. J. Woodley, M. Ruiz-Aravena, J. A. Patz, V. Hickey, P. J. Hudson, H. Locke, and R. K. Plowright. 'Land use-induced spillover: priority actions for protected and conserved area managers', 11 March 2021, PARKS, 27, Special Issue, 161-178. DOI: 10.2305/IUCN.CH.2021.PARKS-27-SUKR.en

The paper can be read as part of the special issue of the journal PARKS - 'COVID-19 and Protected Areas: Essential Reading for a World Haunted by a Pandemic' here: https://parksjournal.com/

CAPTION

The authors state that human activities that destroy and degrade ecological systems can trigger land use-induced spillover--the infect-shed-spill-spread cascade. Wildlife stressed by the environmental conditions associated with land use change can decline in immune function, thus becoming more susceptible to zoonotic pathogen infection. Stress can also increase the likelihood that wildlife will release (shed) pathogens in ways and locations that lead to the infection of other animals of the same or different species, including humans (spillover). When land use change increases interaction between infected animals and people, it is more likely that zoonotic pathogens will be transmitted into human populations. The rate and scale of pathogen spread in human populations is largely driven by patterns of human contact (social behaviour) and pathogen biology.

CREDIT

PARKS

Rare earths outside China: FAU researchers identify new deposits

UNIVERSITY OF ERLANGEN-NUREMBERG

Research News

Rare earth elements are the gold of the 21st century: rare and highly prized all over the world. Most known and economically viable sources of rare earths are located in China, where more than 80 percent of them are refined. This has resulted in a near monopoly situation, with China dominating international trade, particularly in heavy rare earths. Geologists and materials scientists at FAU have now discovered a new way of finding new and previously unknown deposits of rare earths, or rare earth metals, worldwide. They have published the findings of their study in the journal Geology.

Rare earth metals are irreplaceable for manufacturing advanced high-tech industrial products due to their luminescent and catalytic properties. They are used to make permanent magnets that are a vital part of modern electronics in televisions, smartphones, notebooks, jet engines, and rocket guidance systems as well as in solar and wind power plants, electric motors and in medical engineering.

Contrary to what their name might suggest, sources of rare earth elements or rare earth metals are distributed fairly equally all over the world. However, there are only very few sources that are economically viable. FAU geologists Dr. Sönke Brandt, Prof. Dr. Reiner Klemd, Marc Fassbender and Prof. Dr. Karsten Haase have now discovered an indicator that can identify such deposits.

They inspected rock samples from the Vergenoeg fluorite mine in South Africa and discovered that fayalite crystals in the sediment of granite-like magma can contain large amounts of heavy rare earth elements. The mineral, which is reddish brown to black in colour, is mainly mined for use as a gemstone and is also used for sand blasting. Fayalite can be found worldwide in igneous rock and abyssal rocks.

'Since heavy rare earth elements are becoming increasingly scarce on the world market, the discovery of fayalite as a new potential source for locating new deposits of rare earths is extremely important for the economy,' says Prof. Dr. Reiner Klemd from Geozentrum Nordbayern at FAU, who led the study.

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New report reveals how the U.S. can renew its leadership in global health R&D

Analysis from the Global Health Technologies Coalition provides blueprint for capitalizing on opportunities revealed by COVID-19 to defeat a range of health threats

BURNESS

Research News

"The same core capabilities instrumental to defeating COVID-19 can also defeat diseases that have plagued humanity for generations--such as AIDS, tuberculosis, malaria and Ebola--while targeting emerging pathogens of pandemic potential," said GHTC Director Jamie Bay Nishi. "Developing vaccines in such record-breaking time is, in reality, the product of decades of R&D investments. With smart funding and policy decisions, this foundation can generate a new era of innovations that will protect the health of millions of Americans and billions of people around the world."

The report breaks down the individual and often less-appreciated engines of the U.S. global health R&D enterprise--including critical initiatives within the U.S. Agency for International Development (USAID)--to identify specific actions across the government that can channel President Biden's promise to lead with science and international cooperation, to realize the promise of R&D for global health.

It notes that such investments produce more than just health benefits. They also have a strong track record of creating hundreds of thousands of jobs across the United States and tens of billions of dollars in economic benefits. Meanwhile, the assessment reveals how the rapid development of COVID-19 vaccines is directly connected to work on other global health threats: the Johnson & Johnson vaccine uses a similar approach as the company's Ebola vaccine; the Moderna platform was previously being developed for candidates against other respiratory viruses and chikungunya; and the Oxford University-AstraZeneca vaccine is based on technology from malaria vaccine research.

But the report warns that today, global health R&D hangs in the balance between "broad setback and inspiring possibility." It notes how the demands of fighting the COVID-19 pandemic revealed the enormous value of investing in global heath innovations, while at the same time it has diverted resources and personnel from the battle against many other threats.

GHTC's prescription for rejuvenating global health R&D includes:

Doubling support for global health programs at USAID and setting minimum funding targets for R&D within these increases, establishing a new position--chief science and product development officer--within the agency, and funding a new $200 million USAID Grand Challenge for global health security. The report notes that USAID is the "only U.S. agency with a mandate to focus on global health and development." Yet despite USAID's strong track record in delivering high-impact health innovations and an extensive network of partnerships, GHTC found that the agency's unique capabilities have been underutilized and underfunded as part of the U.S. government's COVID-19 response.
Increasing funding for the U.S. Centers for Disease Control and Prevention (CDC), particularly for its Center for Global Health, the National Center for Emerging and Zoonotic Infectious Diseases, and the Division of Tuberculosis Elimination and its Tuberculosis Trials Consortium. The report notes these programs have been "operating on tight and relatively stagnant budgets" and that the fight against COVID-19 compounded the problem by diverting resources and expertise. Meanwhile, the analysis points to the need to revitalize CDC's global health work as part of the broader effort to rebuild an agency that was "politicized and undermined" during the COVID-19 response.
New, targeted funding at the National Institutes of Health (NIH), including more support for product development and translational research for areas lacking commercial interest and steady funding increases for the Fogarty International Center alongside sustained growth for the National Institute of Allergy and Infectious Diseases and the Office of AIDS Research. The report points out that NIH's high-profile work in confronting COVID-19 has highlighted the importance of past investments that have provided the "building blocks of future drugs, vaccines and diagnostics." But it also warns that the pandemic has stymied non-COVID-19 work, "leading to urgent requests for relief."
Establishing a permanent funding line at the Biomedical Advanced Research and Development Authority (BARDA), supported by at least $300 million annually, to support work on emerging infectious diseases, antimicrobial resistance (including drug-resistant tuberculosis or TB), and pandemic influenza. The report finds that, despite its proven value in dealing with a range of threats, BARDA has been overly reliant on "one-off" emergency supplemental appropriations in response to epidemic crises, leading to gaps in its portfolio. For example, BARDA is not involved in research on drug-resistant TB, even though experts have warned that it's a major health security threat to the United States.
Working with the executive office of the president to create much tighter coordination for US-funded global health work. The report calls on the White House to elevate the importance of global health R&D in achieving social justice priorities and to ensure USAID is involved in high-level advisory bodies on the pandemic response. The report found that USAID, despite its significant global footprint, was largely excluded from White House pandemic response efforts in 2020. But GHTC notes that USAID's expertise and partnerships around the world will be essential for achieving the global pandemic response envisioned by the Biden-Harris administration.
Protecting malaria and other parasitic disease work along with TB and antimicrobial research supported by the Department of Defense (DoD). The report pushes back against recent DoD moves to eliminate malaria research programs, noting that such cuts would scuttle decades of progress achieved via research at the Walter Reed Army Institute of Research and the Naval Medical Research Center. GHTC calls on Congress to consider protecting DoD work on malaria--which it notes remains a considerable threat to U.S. troops deployed abroad--with a dedicated funding line. Meanwhile, the report views increased funding for DoD's efforts to develop new treatments for antimicrobial-resistant pathogens as essential to "strengthening global health security by preventing a post-antibiotic era."
Increasing support for key multilateral initiatives, such as the Coalition for Epidemic Preparedness Innovations (CEPI). GHTC believes joining CEPI and committing at least $200 million annually would provide a much-needed boost to an initiative dedicated to developing vaccines against epidemic threats and making them globally accessible. GHTC also seeks a greater role for the U.S. Food and Drug Administration (FDA) in working alongside the World Health Organization (WHO) to provide technical support to under-resourced regulatory authorities that would accelerate access to a range of biomedical advances.

GHTC's analysis finds that by embracing a strong action plan for global health R&D, decisionmakers in Congress and the Biden-Harris administration can seize on the possibilities revealed by the work to defeat COVID-19 to launch a new, stronger era of research for neglected and emerging infectious diseases.

"Never has a single disease demonstrated what can be accomplished in so little time with the full resources and focus of the U.S. government," it concludes. "Scientific milestones to defeat many of our world's toughest global health challenges are within sight, and with strong funding and smart policy, these milestones can be reached."

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The Global Health Technologies Coalition (GHTC) works to save and improve lives by encouraging the research and development of essential health technologies. We bring together more than 30 nonprofit organizations, academic institutions, and aligned businesses to advance policies to accelerate the creation of new drugs, vaccines, diagnostics, and other tools that bring healthy lives within reach for all people.

Wing tags severely impair flight in African Cape Vultures

Study urges the use of leg bands for marking individuals instead of wing tags

MAX-PLANCK-GESELLSCHAFT

Research News

IMAGE: CAPE VULTURE WITH PATAGIAL (WING) TAG FITTED CORRECTLY TO THE PATAGIUM view more
CREDIT: VULPRO

Conservationists who apply wing tags for identifying Cape Vultures--a species of African vulture that is vulnerable to extinction--are putting the birds' lives further at risk, a new movement ecology study has shown. Researchers from the Max Planck Institute of Animal Behavior in Germany and VulPro NPC in South Africa have demonstrated that Cape Vultures fitted with tags on their wings travelled shorter distances and flew slower than those fitted with bands around their legs. The research emphasises the importance of investigating the effects that tagging methods can have on the behaviour and conservation of species, prompting a shift towards the less invasive method of leg bands in the future study of Cape Vultures.

For over a decade, many conservationists and NGOs have been marking vultures by placing a tag on the wing area known as the patagium. Patagial tags have the advantage that they are large and conspicuous enough for individuals to be identified from far away. Leg bands are smaller in size, fitted around the tarsus of the vultures leg and thus, harder to notice and record the unique number.

"After receiving many grounded and injured vultures from incorrect placement of wing tags, we felt there was an immediate need to find out exactly what these tags were doing to the flight of birds and whether this technique was, in fact, hindering the species rather than protecting them," says senior author Kerri Wolter, CEO of VulPro NPC, a vulture conservation organisation in South Africa.

The study was motivated by recent VulPro NPC research, which highlighted how an incorrect patagial tag could cause injuries and result in the grounding of vultures. To find out how patagial tags affected the birds' flights, researchers from the Max Planck Institute used GPS devices to track 27 Cape Vultures (Gyps coprotheres) marked with either patagial tags or leg bands.

The GPS devices, which were mounted to the birds' backs, recorded the birds' positions as often as every minute for 24 hours a day. These recordings allowed researchers to investigate the birds' flight performance, including occurrence of flight, proportion of time spent flying in a day, daily distance travelled and ground speed.

Individuals equipped with patagial tags covered a much smaller area in comparison to the leg band group. They were less likely to take flight and, when doing so, flew at lower ground speed compared to individuals wearing leg bands.

"Although we did not measure the effects of patagial tags on body condition or survival, our results strongly suggest that patagial tags have severe adverse effects on vultures' flight performance," says first author Teja Curk, a PhD student at the Max Planck Institute of Animal Behavior.

Vultures are scavengers. By feeding on dead animals, they play an important role in the ecosystem due to the services they provide, such as preventing the spread of infectious diseases, recycling organic material into nutrients and stabilising food webs.

"Therefore, restricted flight potential and a reduction in the area covered by these birds, caused by improper tag attachment, can have far-reaching consequences at the ecosystem level," says co-author Kamran Safi, a group leader at the Max Planck Institute of Animal Behavior.

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Original publication Teja Curk, Martina Scacco, Kamran Safi, Martin Wikelski, Wolfgang Fiedler, Ryno Kemp and Kerri Wolter Wing tags severely impair movement in African Cape Vultures Animal Biotelemetry 9(11) 09 March 2021

CAPTION

Cape Vulture with a coloured leg band. By feeding on dead animals, vultures play an important role in the ecosystem due to the services they provide, such as preventing the spread of infectious diseases, recycling organic material into nutrients and stabilising food webs.

CREDIT

VulPro

Female snowy plovers are no bad mothers

However, their parental care depends on the survival prospects of the chicks

MAX-PLANCK-GESELLSCHAFT

Research News

IMAGE: IN SNOWY PLOVERS, MALES MOSTLY CARE FOR THE YOUNG ALONE UNTIL THEY ARE FLEDGED. view more
CREDIT: CLEMENS KÜPPER

In snowy plovers, females have overcome traditional family stereotypes. They often abandon the family to begin a clutch with a new partner whereas the males continue to care for their young until they are independent. An international team led by scientists from the Max Planck Institute for Ornithology in Seewiesen, Germany, has now investigated the decision-making process that determines the duration of parental care by females. They found that offspring desertion often occurs either under poor environmental conditions, when chicks die despite being cared for by both parents, or when chicks have a good chance of survival even without the female.

It seems cruel and somewhat senseless when bird parents desert their vulnerable young to mate again. However, theoretical and experimental studies show that this is often beneficial for the parents, even if they have already invested energy and time in the brood. After all, re-mating after deserting an unsuccessful brood can improve their overall reproductive success.

A team of scientists led by researchers of the Max Planck Institute for Ornithology in Seewiesen, Germany, has now investigated in more detail which factors cause female parents to desert their broods. They studied snowy plovers (Charadrius nivosus) that often breed on salt flats or at brackish inland lakes. This barren environment puts great pressure on parents, as temporary salt ponds often dry up and many chicks die of thirst or starvation. "Males have survival advantages at all life stages", says Clemens Küpper, research group leader at Seewiesen. "Although equal numbers of females and males hatch from eggs, adult population therefore show a surplus of males

CAPTION

Snowy plovers (Charadrius nivosus) often breed on salt flats or at brackish inland lakes. This barren environment puts great pressure on parents, as temporary salt ponds often dry up and many chicks die of thirst or starvation.

CREDIT

Clemens Küpper

Reversed parental roles

As females are less abundant in the population, they have an advantage in finding mates. Therefore, the parental roles are reversed in this species: males care for the young until they are fledged, while females often leave the family and pair up with another partner for a new breeding attempt.

The research team analyzed the parental behaviour and survival of more than 260 broods over a seven-year period. Of these, more than 70 percent were deserted by the females. Although one parent is often sufficient for parental care, as the chicks are precocial and find the food on their own. However, the study shows that chicks from an abandoned brood actually survive less often than in other broods where females stay longer.

So, are snowy plover mothers making the wrong decisions here? The scientists found that broods were more likely to be deserted at the beginning of the breeding season. This makes sense because there are more opportunities for the female to mate again. The current number of chicks is also important: females are especially likely to abandon broods on days when a chick dies. "This suggests that females who initially decided to care, suddenly abandon their broods when their chicks start to die", says Krisztina Kupán, first author of the study. These females try then to rescue their reproductive success by starting over with a new male.

CAPTION

Females often desert their offspring either under poor environmental conditions, when chicks die despite being cared for by both parents - or if in contrast, the chicks have a good chance of survival even without the female.

CREDIT

Clemens Küpper

Females are sensitive to environmental conditions

The researchers concluded that there are two main reasons for females to desert their brood and remate. First, the chicks have a good chance of survival with their fathers alone, so the female can leave and continue to reproduce. Second, the chicks begin to die despite both parents are caring for the brood. This means that conditions for chick rearing are so poor that additional parental care does little for the chick survival. Instead, the female tries to increase her reproductive success frequently starting to breed elsewhere. "Females are flexible and make sensible decisions," says Krisztina Kupán. "They are sensitive to environmental conditions and stay with the chicks if they can contribute substantially to their survival."

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Original publication

Krisztina Kupán, Tamás Székely, Medardo Cruz-López, Keeley Seymour, Clemens Küpper Offspring desertion with care? Chick mortality and plastic female desertion in Snowy Plovers Behavioral Ecology, araa141 08 March 2021

Electricity could help speed wound healing, new study shows

Electrical impulses may help vessels more quickly get healing agents to injuries

OHIO STATE UNIVERSITY

Research News

COLUMBUS, Ohio - Electric stimulation may be able to help blood vessels carry white blood cells and oxygen to wounds, speeding healing, a new study suggests.

The study, published in the Royal Society of Chemistry journal Lab on a Chip, found that steady electrical stimulation generates increased permeability across blood vessels, providing new insight into the ways new blood vessels might grow.

The electrical stimulation provided a constant voltage with an accompanying electric current in the presence of fluid flow. The findings indicate that stimulation increases permeability of the blood vessel - an important characteristic that can help wound-healing substances in the blood reach injuries more efficiently.

"There was this speculation that blood vessels could grow better if you stimulated them electrically," said Shaurya Prakash, senior author of the study and associate professor of mechanical and aerospace engineering at The Ohio State University. "And we found that the response of the cells in our blood vessel models shows significant promise towards changing the permeability of the vessels that can have positive outcomes for our ongoing work in wound healing."

Blood vessels are crucial for wound healing: They thread throughout your body, carrying nutrients, cells and chemicals that can help control inflammation caused by an injury. Oxygen and white blood cells - which protect the body from foreign invaders - are two key components delivered by blood vessels.

But when there is an injury - for example, a cut on your finger - the architecture of the blood vessels at the wound site are disrupted. That also interrupts the vessels' ability to help the wound heal. Blood vessels regrow on their own, almost like the branches of trees, without external sources of electricity, as part of the healing process.

"And as the blood vessels begin to grow, they replenish the skin and cells and establish a healing barrier again," Prakash said. "But our question was: How do you make this process better and faster, and is there any benefit to doing that?"

What they found, in laboratory tests performed using human cells, is that stimulating blood vessels with electricity showed a marked increase in blood vessel permeability, which is a physical marker suggestive of possible new vessel growth.

"These initial findings are exciting, and the next phase of the work will require us to study if and how we can actually grow new vessels," Prakash said.

Jon Song, co-author of the paper and associate professor of mechanical and aerospace engineering at Ohio State, said the results imply that one of the primary ways blood vessels work to heal injuries is by allowing molecules and cells to move across the vessels' walls.

"And now we have better understanding for how electric stimulation can change the permeability across the vessel walls," Song said. "Let's say you have a cutaneous wound, like a paper cut, and your blood vessels are severed and that's why you have blood leaking out. What you need is a bunch of bloodborne cells to come to that place and exit out the blood vessel to initiate the wound repair."

The study suggested that changes in blood vessel permeability could get those bloodborne cells to a wound site more quickly, though it did not explain the reasons why that happened. The study seemed to indicate that electricity affected the proteins that hold blood vessel cells together, but those results were not conclusive.

The study is an extension of work by a broader team, led by Prakash, that previously showed electric bandages could help stimulate healing in wounded dogs. That work indicated that electrical stimulation might also help manage infections at wound sites - a phenomenon the researchers also hope to research further.

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Other Ohio State researchers who worked on this study include Prashanth Mohana Sundaram, Kaushik K. Rangharajan, Tanner J. Hadick and Ehsan Akbari. This work was funded by the National Heart, Lung and Blood Institute, the American Heart Association and the National Cancer Institute.

CONTACTS: Shaurya Prakash, prakash.31@osu.edu

Jon Song, song.1069@osu.edu

Written by Laura Arenschield, arens

New study provides detailed view of how hepatitis B virus establishes chronic infection

The research offers potential strategies for development of new treatments

PRINCETON UNIVERSITY

Research News

IMAGE: HUMAN LIVER CELL LINES (GREEN, WITH BLUE NUCLEI) INFECTED WITH HBV EXPRESS AN HBV PROTEIN (IN RED) IN THIS IMAGE CAPTURED BY IMMUNOFLUORESCENCE MICROSCOPY. view more
CREDIT: IMAGE BY STEPHANIE MAYA, PRINCETON UNIVERSITY

Researchers at Princeton have determined how five cellular proteins contribute to an essential step in the life cycle of hepatitis B virus (HBV). The article describing these findings appeared March 11, 2021 in the journal Nature Communications.

Viruses have been with us, shaping our lives, societies and economies for millennia. While some viruses rapidly explode onto the world stage, others smolder in our communities for decades, shattering lives but making few headlines. Hepatitis B virus hasn't caused any nationwide lockdowns or stock market crashes because it is slow to spread from person to person and is rarely immediately fatal. It is nonetheless incredibly damaging because it can establish lifelong chronic infection with profound consequences for its victims.

"An estimated two billion people have been exposed to HBV, of whom 250-400 million are chronically infected," said Alexander Ploss, associate professor of molecular biology at Princeton University, and senior author on the study. "Currently, there is no cure for chronic HBV infection, and patients need to be on a lifelong antiviral regimen. Approximately 887,000 individuals die each year from HBV-related liver diseases or liver cancer."

Ploss and his team are striving to understand HBV's life cycle in hopes of finding a way to prevent the virus from establishing damaging chronic infections.

"Central to HBV replication is the formation of covalently closed circular DNA (cccDNA) from relaxed circular DNA (rcDNA) which is carried into the host cell by the virus during the initial infection," Ploss said. "We have recently demonstrated that HBV relies on five host proteins - namely PCNA, RFC complex, POLδ, FEN-1, and LIG1 - that are necessary and sufficient for this conversion step."

As its name implies, rcDNA is a loop of DNA. DNA is a molecule made up of nucleotides arranged in linear fashion along paired, complementary strands. The sequence of nucleotides on one strand encodes the instructions for making a protein while the other strand is its mirror image. Whereas human cellular DNA contains over 20,000 genes, HBV's DNA genome only contains four. None of the viral proteins made from these genes is required for the conversion of rcDNA to cccDNA. Instead, the virus coopts cellular proteins to accomplish this and other steps of viral replication.

A key feature of HBV rcDNA is that each of its two strands contains a gap in its nucleotide sequence. One strand, called the plus strand, has a gap that is considerably larger than and offset from the gap on the other, minus strand. Cells perceive gaps in DNA as damage that needs to be filled in and repaired. The cellular proteins that carry out DNA repair can't tell the difference between viral DNA and cellular DNA, so they set to work "repairing" rcDNA as soon as it arrives in the nucleus. This repair process converts rcDNA into an intact circle of double-stranded DNA (that is, cccDNA) that can be maintained in the cell's nucleus.

Postdoctoral fellow Lei Wei wanted to understand how this repair process takes place in detail. To investigate this, he developed a method to monitor the process of repair taking place on rcDNA. He then identified what steps are involved in repair of each individual strand, tracked the order in which they are completed, and determined which cellular proteins are needed for each step.

The experiments showed that conversion of the plus strand into a continuous circle happens rapidly and requires all five of the cellular proteins working in concert. In contrast, repair of the minus strand requires only two of the five proteins (FEN-1 and LIG1) but is slower because there is a viral protein attached to one end of the minus strand that must be removed before the nucleotide gap can be sealed.

"In this paper, Wei and Ploss provide a compelling story in elucidating the cellular machinery that is essential for converting the incoming HBV genome into the cccDNA," said Dr. T. Jake Liang, a National Institutes of Health Distinguished Investigator in the Liver Diseases Branch who is an expert on HBV and related viruses. "This work offers not only important insights into the biochemical pathway of cccDNA biogenesis but also potential strategies to target cccDNA for therapeutic development."

Furthering that goal, the Princeton researchers showed that two compounds targeting cellular proteins could disrupt rcDNA conversion to cccDNA in test tubes. Wei and Ploss are hopeful that future studies will identify drugs that work in the human body.

"Our findings, biochemical approaches, and the novel reagents that we generated and engineered, open the door to providing an in depth understanding how this major human virus establishes persistence in host cells," Ploss said.

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This work was supported in part by grants from the National Institutes of Health, the American Cancer Society, the Burroughs Wellcome Fund, the New Jersey Commission on Cancer Research, and Princeton University.

Read to succeed -- in math; study shows how reading skill shapes more than just reading

University at Buffalo psychologist identifies a connectivity fingerprint suggesting that the brain's reading network is at work across cognitive domains; 'reading affects everything,' he says

UNIVERSITY AT BUFFALO

Research News

BUFFALO, N.Y. - A University at Buffalo researcher's recent work on dyslexia has unexpectedly produced a startling discovery which clearly demonstrates how the cooperative areas of the brain responsible for reading skill are also at work during apparently unrelated activities, such as multiplication.

Though the division between literacy and math is commonly reflected in the division between the arts and sciences, the findings suggest that reading, writing and arithmetic, the foundational skills informally identified as the three Rs, might actually overlap in ways not previously imagined, let alone experimentally validated.

"These findings floored me," said Christopher McNorgan, PhD, the paper's author and an assistant professor in UB's Department of Psychology. "They elevate the value and importance of literacy by showing how reading proficiency reaches across domains, guiding how we approach other tasks and solve other problems.

"Reading is everything, and saying so is more than an inspirational slogan. It's now a definitive research conclusion."

And it's a conclusion that was not originally part of McNorgan's design. He planned to exclusively explore if it was possible to identify children with dyslexia on the basis of how the brain was wired for reading.

"It seemed plausible given the work I had recently finished, which identified a biomarker for ADHD," said McNorgan, an expert in neuroimaging and computational modeling.

Like that previous study, a novel deep learning approach that makes multiple simultaneous classifications is at the core of McNorgan's current paper, which appears in the journal Frontiers in Computational Neuroscience.

Deep learning networks are ideal for uncovering conditional, non-linear relationships.

Where linear relationships involve one variable directly influencing another, a non-linear relationship can be slippery because changes in one area do not necessarily proportionally influence another area. But what's challenging for traditional methods is easily handled through deep learning.

McNorgan identified dyslexia with 94% accuracy when he finished with his first data set, consisting of functional connectivity from 14 good readers and 14 poor readers engaged in a language task.

But he needed another data set to determine if his findings could be generalized. So McNorgan chose a math study, which relied on a mental multiplication task, and measured functional connectivity from the fMRI information in that second data set.

Functional connectivity, unlike what the name might imply, is a dynamic description of how the brain is virtually wired from moment to moment. Don't think in terms of the physical wires used in a network, but instead of how those wires are used throughout the day. When you're working, your laptop is sending a document to your printer. Later in the day, your laptop might be streaming a movie to your television. How those wires are used depends on whether you're working or relaxing. Functional connectivity changes according to the immediate task.

The brain dynamically rewires itself according to the task all the time. Imagine reading a list of restaurant specials while standing only a few steps away from the menu board nailed to the wall. The visual cortex is working whenever you're looking at something, but because you're reading, the visual cortex works with, or is wired to, at least for the moment, the auditory cortex.

Pointing to one of the items on the board, you accidentally knock it from the wall. When you reach out to catch it, your brain wiring changes. You're no longer reading, but trying to catch a falling object, and your visual cortex now works with the pre-motor cortex to guide your hand.

Different tasks, different wiring; or, as McNorgan explains, different functional networks.

In the two data sets McNorgan used, participants were engaged in different tasks: language and math. Yet in each case, the connectivity fingerprint was the same, and he was able to identify dyslexia with 94% accuracy whether testing against the reading group or the math group.

It was a whim, he said, to see how well his model distinguished good readers from poor readers - or from participants who weren't reading at all. Seeing the accuracy, and the similarity, changed the direction of the paper McNorgan intended.

Yes, he could identify dyslexia. But it became obvious that the brain's wiring for reading was also present for math.

Different task. Same functional networks.

"The brain should be dynamically wiring itself in a way that's specifically relevant to doing math because of the multiplication problem in the second data set, but there's clear evidence of the dynamic configuration of the reading network showing up in the math task," McNorgan says.

He says it's the sort of finding that strengthens the already strong case for supporting literacy.

"These results show that the way our brain is wired for reading is actually influencing how the brain functions for math," he said. "That says your reading skill is going to affect how you tackle problems in other domains, and helps us better understand children with learning difficulties in both reading and math."

As the line between cognitive domains becomes more blurred, McNorgan wonders what other domains the reading network is actually guiding.

"I've looked at two domains which couldn't be farther afield," he said. "If the brain is showing that its wiring for reading is showing up in mental multiplication, what else might it be contributing toward?"

That's an open question, for now, according to McNorgan.

"What I do know because of this research is that an educational emphasis on reading means much more than improving reading skill," he said. "These findings suggest that learning how to read shapes so much more."

What is Godel's Theorem?

January 25, 1999

Melvin Henriksen--Professor of Mathematics Emeritus at Harvey Mudd College--offers this explanation:

KURT GODEL achieved fame in 1931 with the publication of his Incompleteness Theorem.

Giving a mathematically precise statement of Godel's Incompleteness Theorem would only obscure its important intuitive content from almost anyone who is not a specialist in mathematical logic. So instead, I will rephrase and simplify it in the language of computers.

Imagine that we have access to a very powerful computer called Oracle. As do the computers with which we are familiar, Oracle asks that the user "inputs" instructions that follow precise rules and it supplies the "output" or answer in a way that also follows these rules. The same input will always produce the same output. The input and output are written as integers (or whole numbers) and Oracle performs only the usual operations of addition, subtraction, multiplication and division (when possible). Unlike ordinary computers, there are no concerns regarding efficiency or time. Oracle will carry out properly given instructions no matter how long it takes and it will stop only when they are executed--even if it takes more than a million year

Let's consider a simple example. Remember that a positive integer (let's call it N) that is bigger than 1 is called a prime number if it is not divisible by any positive integer besides 1 and N. How would you ask Oracle to decide if N is prime? Tell it to divide N by every integer between 1 and N-1 and to stop when the division comes out evenly or it reaches N-1. (Actually, you can stop if it reaches the square root of N. If there have been no even divisions of N at that point, then N is prime.)

What Godel's theorem says is that there are properly posed questions involving only the arithmetic of integers that Oracle cannot answer. In other words, there are statements that--although inputted properly--Oracle cannot evaluate to decide if they are true or false. Such assertions are called undecidable, and are very complicated. And if you were to bring one to Dr. Godel, he would explain to you that such assertions will always exist.

Even if you were given an "improved" model of Oracle, call it OracleT, in which a particular undecidable statement, UD, is decreed true, another undecidable statement would be generated to take its place. More puzzling yet, you might also be given another "improved" model of Oracle, call it OracleF, in which UD would be decreed false. Regardless, this model too would generate other undecidable statements, and might yield results that differed from OracleT's, but were equally valid.

Do you find this shocking and close to paradoxical? It was even more shocking to the mathematical world in 1931, when Godel unveiled his incompleteness theorem. Godel did not phrase his result in the language of computers. He worked in a definite logical system and mathematicians hoped that his result depended on the peculiarities of that system. But in the next decade or so, a number of mathematicians--including Stephen C. Kleene, Emil Post, J.B. Rosser and Alan Turing--showed that it did not.

Research on the consequences of this great theorem continues to this day. Anyone with Internet access using a search engine like Alta Vista can find several hundred articles of highly varying quality on Godel's Theorem. Among the best things to read, though, is Godel's Proof by Ernest Nagel and James R. Newman, published in 1958 and released in paperback by New York University Press in 1983.

LA REVUE GAUCHE - Left Comment: Godel, Cantor, Wiener and Schrodinger's Cat

LA REVUE GAUCHE - Left Comment: Search results for MATH

Dry eye disease negatively affects physical and mental health as well as vision

UNIVERSITY OF SOUTHAMPTON

Research News

Patients suffering from dry eye disease symptoms have a lower quality of life compared to those without symptoms, a new study reports. The findings showed that patients with the condition reported negative effects on visual function, their ability to carry out daily activities and their work productivity.

Dry eye disease is a common condition and a frequent reason for patients to seek medical care. It can affect people of any age but is most prevalent in women and in older people. Symptoms include irritation and redness in the eyes, blurred vision, and a sensation of grittiness or a foreign body in the eye. It has been reported that up to a third of adults over 65 years old have the condition, although the actual number is likely to be higher as there is no established diagnostic test and people with mild symptoms are less likely to report them to their doctor.

Treatment often involves prescriptions of artificial tears, ocular lubricants and astringents, which come at a cost to the NHS; in 2014, 6.4 million items were prescribed at a cost of over £27 million.

This new study, led by the University of Southampton, set out to explore how dry eye disease affects the lives of adults in the UK through an online survey of one thousand patients with the condition and further one thousand without. Participants undertook a questionnaire from the National Eye Institute about their visual function and a EuroQol questionnaire on health-related quality of life. Those who declared that they experienced dry eye disease also answered further questions to assess the severity of their symptoms.

The results, published in the journal BMJ Open, showed that a higher proportion of participants with dry eye disease had problems with mobility and experienced more difficulties in their day-to-day activities than patients without the condition. The surveys also revealed they were more likely to suffer from anxiety and depression.

Those with the most severe symptoms we more likely to experience a negative impact on their social and emotional functioning as well work productivity, including missing more time from work as a result of their symptoms.

Dr Parwez Hossain, Associate Professor in Ophthalmology at the University of Southampton, led the study. He said: "This study provided some very useful information on the burden that dry eye disease places on patients. As well as confirming the impact on work and social lives we also discovered showed that the extent of the effects are consistent with the severity of symptoms. We also found that participants with dry eye disease symptoms were a lot more likely to suffer from other comorbidities, twice as many suffered from arthritis, hearing loss or irritable bowel disease compared to the cohort without symptoms.

"Whilst we cannot draw causal associations through this study, the presence of dry eye disease does appear to impact on an individual's health and vision related quality of life."

Although both groups reported similar levels of digital screen use and reading, the cohort with symptoms reported more exposure to environmental factors such as air conditioning, forced heating or air pollution. The research team believe that these factors could either contribute to dry eye disease, or be noticed more by sufferers.

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