The (un)social network: The emergence of digital thought clones and what to do about them

Digital thought clones that prey on and manipulate real-time online behavior can be tackled with tough legislation, say experts

QATAR UNIVERSITY, COLLEGE OF LAW

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VIDEO: RESEARCHERS SUGGEST THAT THERE IS AN URGENT NEED FOR STRINGENT DOMESTIC REGULATIONS TO PROTECT CITIZENS AGAINST MISUSE OF DIGITAL THOUGHT CLONES view more 

CREDIT: CENTRE FOR LAW AND DEVELOPMENT, COLLEGE OF LAW, QATAR UNIVERSITY

In The Social Dilemma, the Netflix documentary that has been in the news recently for its radical revelations, former executives at major technology companies like Facebook, Twitter, and Instagram, among others, share how their ex-employers have developed sophisticated algorithms that not only predict users' actions but also know which content will keep them hooked on their platforms. The knowledge that technology companies are preying on their users' digital activities without their consent and awareness is well-known. But Associate Professor Jon Truby and Clinical Assistant Professor Rafael Brown at the Centre for Law and Development at Qatar University have pulled the curtain on another element that technology companies are pursuing to the detriment of people's lives, and investigated what we can do about it. "We had been working on the digital thought clone paper a year before the Netflix documentary aired. So, we were not surprised to see the story revealed by the documentary, which affirm what our research has found," says Prof Brown, one of the co-authors.

Published in Information & Communications Technology Law, their paper identifies "digital thought clones," which act as digital twins that constantly collect personal data in real-time, and then predict and analyze the data to manipulate people's decisions. Activity from apps, social media accounts, gadgets, GPS tracking, online and offline behavior and activities, and public records are all used to formulate what they call a "digital thought clone". The paper defines digital thought clone as "a personalized digital twin consisting of a replica of all known data and behavior on a specific living person, recording in real-time their choices, preferences, behavioral trends, and decision making processes."

"Currently existing or future artificial intelligence (AI) algorithms can then process this personalized data to test strategies in real-time to predict, influence, and manipulate a person's consumer or online decisions using extremely precise behavioral patterns, and determine which factors are necessary for a different decision to emerge and run all kinds of simulations before testing it in the real world," says Prof Truby, a co-author of the study.

An example is predicting whether a person will make the effort to compare online prices for a purchase, and if they do not, charging a premium for their chosen purchase. This digital manipulation reduces a person's ability to make choices freely. Outside of consumer marketing, imagine if financial institutions use digital thought clones to make financial decisions, such as whether a person would repay a loan. What if insurance companies judged medical insurance applications by predicting the likelihood of future illnesses based on diet, gym membership, the distance applicants walk in a day--based on their phone's location history--and their social circle, as generated by their phone contacts and social media groups, and other variables?

The authors suggest that the current views on privacy, where information is treated either as a public or private matter or viewed in contextual relationships of who the information concerns and impacts, are outmoded. A human-centered framework is needed, where a person can decide from the very beginning of their relationship with digital services if their data should be protected forever or until they freely waive it. This rests on two principles: the ownership principle that data belongs to the person, and that certain data is inherently protected; and the control principle, which requires that individuals be allowed to make changes to the type of data collected and if it should be stored. In this framework, people are asked beforehand if data can be shared with an unauthorized entity.

The European Union's landmark General Data Protection Regulation and the California Consumer Privacy Act of 2018 can serve as a foundation for governments everywhere to legislate on digital thought clones and all that they entail. But the authors also raise critical moral and legal questions over the status of these digital thought clones. "Does privacy for humans mean their digital clones are protected as well? Are users giving informed consent to companies if their terms and conditions are couched in misleading language?" asks Prof Truby.

A legal distinction must be made between the digital clone and the biological source. Whether the digital clone can be said to have attained consciousness will be relevant to the inquiry but far more important would be to determine whether the digital clone's consciousness is the same as that of the biological source.

The world is at a crossroads: should it continue to do nothing and allow for total manipulation by the technology industry or take control through much-needed legislation to ensure that people are in charge of their digital data? It's not quite a social dilemma.

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Authors

Jon Truby, Rafael Brown

Title of original paper

Human Digital Thought Clones: The Holy Grail of Artificial Intelligence for Big Data

Journal

Information & Communications Technology Law

DOI

https://doi.org/10.1080/13600834.2020.1850174 10.1080/13600834.2020.1850174

Affiliations

Centre for Law & Development, College of Law, Qatar University

About Associate Professor Jon Truby

Jon Truby is an Associate Professor of Law and directs the Centre for Law and Development at Qatar University. His research interests include technology law and sustainability, particularly artificial intelligence and financial technology. Prof Truby has secured major research grants and he recently spoke on a panel at the United Nations General Assembly on blockchain law and policy. He directs the undergraduate and graduate Environmental Law programs, and runs a continuing legal education program for the community. He was the founding editor-in-chief of the International Review of Law, an internationally peer reviewed bilingual law journal.

About Clinical Assistant Professor Rafael Brown

Rafael Brown received his Juris Doctor from Case Western Reserve University School of Law. He has been serving as a Clinical Assistant Professor at the Legal Skills Department of Qatar University College of Law since 2015, where he teaches legal skills and legal writing. He is a Vice Chair of Faculty Affairs in the Faculty Senate, and an Affiliate Member of the Centre for Law and Development. He previously taught LL.M at the Case Western Reserve University Law School, U.S. and the Global Legal Studies Program. His research interests encompass the intersection of law and technology, focusing specifically on artificial intelligence and cybersecurity.

Disclaimer: AAAS an

The new generation solar, developed by TalTech, cells contribute to the green revolution

ESTONIAN RESEARCH COUNCIL

Research News

 

IMAGE: RESEARCHERS AT TALTECH LABORATORY OF PHOTOVOLTAIC MATERIALS view more 

CREDIT: TALTECH

The European Union is determined to undertake a major reform known as the European Green Deal with an aim of making Europe the first climate neutral continent in 2050. The biggest changes will take place in the energy production sector, which stands on the brink of a complete transition to renewable energy sources, including solar energy. To boost the power output of solar cells to a terawatt-scale, technologies that leave a smaller ecological footprint, are more efficient and offer a wider range of applications need to be developed alongside with the first-generation silicon-based solar cells currently dominating in the solar cell market.

TalTech's photovoltaic materials and optoelectronic materials physics research groups published an article in the journal Solar Energy titled "The effect of S/Se ratio on the properties of Cu2CdGe(SxSe1?x)4 microcrystalline powders for photovoltaic applications", which focused on the development of the new generation monograin layer solar cells.

One of the authors of the article, Head of the TalTech Laboratory of Photovoltaic Materials, Senior Researcher Marit Kauk-Kuusik says, "Unlike the widespread silicon-based solar panels, the next-generation solar cells are made of very thin layers of material. To build such solar cells, semiconductors with very good light-absorbing properties must be used. As is known, light absorption in silicon is rather poor, thus requiring relatively thick absorber layers, which make solar cells heavy and rigid. Our research focused on the analysis of the potential applications of the Cu2CdGe(SxSe1?x)4 semiconductor in the production of solar energy. In this study, we focused on the effect of sulfur/selenium (S/Se) ratio on the optoelectronic properties of the absorber material in order to maximise the spectral sensitivity range."

Solar cell works on the principle of photovoltaic effect, i.e. energy can be produced directly by light. A solar cell absorber should be able to absorb light as efficiently as possible, in particular to harness the full spectrum of wavelengths in solar radiation. In addition, the absorption coefficient of the absorber material must be as high as possible, which means that already a very thin layer of the absorber should absorb all the incident light. This in turn means that less material is required to produce an absorber than in case of a lower absorption coefficient. Therefore, while absorbers made of silicon, which is a material with a low absorption coefficient, are 150-200 μm thick, the layers of modern absorber materials based on monograin powders can be 5-10 times thinner (i.e. 10-30 μm thick). It also automatically reduces the weight of the solar cell.

Lower weight of solar sells also means a decrease in material consumption, which is of course not of minor importance in our current era of increase in environmental awareness and green revolution. "It is important to consistently search new alternatives to the existing silicon-based solar cells used for decades," Marit Kauk-Kuusik says. The trend is towards environmental friendliness and overall sustainability. In addition to reduced material consumption and weight, the new solutions are also much more innovative. The keywords are still high-performance, lightness, flexibility and durability.

While conventionally costly vacuum evaporation or sputtering technologies have been widely used to produce solar cells, the unique monograin powder technology applied by TalTech material researchers does not require any high vacuum equipment. Microcrystalline powder is synthesized by molten salt method in quartz ampoules in a special chamber furnace. The mass obtained is washed and sieved into narrow size fractions by a special sieving system and the synthesized high-quality microcrystalline powder, monograin powder, is used for the production of solar cells.

Marit Kauk-Kuusik says, "The monograin powder produced by our powder technology consists of microcrystals that form miniature solar cells in a large module. This provides major advantages over silicon-based solar panels: the material is lightweight, flexible, can be semi-transparent, while being environmentally friendly and significantly less expensive."

Environmentally friendly energy production has become vital in the light of the green revolution and sustainable consumption. Renewable energy, where solar energy plays an increasingly significant role, is an important keyword here.

"The power conversion efficiency of the solar cell developed as a result of our research is 6.4%, which is world highest published performance for Cu2CdGe(SxSe1?x)4 based solar cells and slightly higher than that of the world's first, silicon-based cell developed decades ago. Thus, it is a promising result," Kauk-Kuusik says. She is also convinced that, unlike with this invention, it will no longer take 30 to 40 years to achieve higher power conversion efficiency, as was the case with the silicon, but results in science will be achieved in a much shorter period of time.

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Source: Solar Energy "The effect of S/Se ratio on the properties of Cu2CdGe(SxSe1?x)4 microcrystalline powders for photovoltaic applications", 10.2020 https://www.sciencedirect.com/science/article/pii/S0038092X2030997X

Additional information: Researcher at TalTech Laboratory of Photovoltaic Materials Marit Kauk-Kuusik, marit.kauk-kuusik@taltech.ee

Kersti Vähi, TalTech Research Administration Office

Curtin collision models impact the future of energy

CURTIN UNIVERSITY

Research News

 

A new Curtin University-created database of electron-molecule reactions is a major step forward in making nuclear fusion power a reality, by allowing researchers to accurately model plasmas containing molecular hydrogen.

The Curtin study, published in the Atomic Data and Nuclear Data Tables journal, is supplying data to the International Thermonuclear Experimental Reactor (ITER) - one of the largest scientific projects in the world aimed at developing fusion technology for electricity production on Earth.

Lead researcher, PhD candidate and Forrest Scholar Liam Scarlett from the Theoretical Physics Group in Curtin's School of Electrical Engineering, Computing and Mathematical Sciences said his calculations and the resulting collision database will play a crucial role in the development of fusion technology.

"Our electron-molecule collision modelling is an exciting step in the global push to develop fusion power - a new, clean electricity source. Fusion is the nuclear reaction which occurs when atoms collide and fuse together, releasing huge amounts of energy. This process is what powers the Sun, and recreating it on Earth requires detailed knowledge of the different types of collisions which take place in the fusion plasma - that's where my research comes in," Mr Scarlett said.

"We developed mathematical models and computer codes, and utilised the Perth-based Pawsey Supercomputing Centre to calculate the probabilities of different reactions taking place during collisions with molecules. The molecules we looked at here are those which are formed from atoms of hydrogen and its isotopes, as they play an important role in fusion reactors.

"Until now the available data was incomplete, however our molecular collision modelling has produced an accurate and comprehensive database of more than 60,000 electron-molecule reaction probabilities which, for the first time, has allowed a team in Germany to create an accurate model for molecular hydrogen in the ITER plasma.

"This is significant because their model will be used to predict how the plasma will radiate, leading to a better understanding of the plasma physics, and the development of diagnostic tools which are vital for controlling the fusion reaction."

The research project was funded by the United States Air Force Office of Scientific Research as part of an international research endeavour to harness fusion power as a future energy source.

Research supervisor and co-author Professor Dmitry Fursa, from Curtin's School of Electrical Engineering, Computing and Mathematical Sciences, said fusion power is attractive due to its virtually unlimited fuel supply (hydrogen) and the lack of long-lived radioactive waste or carbon emissions.

"Fusion is one of the biggest projects in the world right now. You can harness an enormous amount of energy from the reaction that occurs when you take hydrogen atoms and fuse them together," Professor Fursa said.

"This new and comprehensive electron-molecule collision modelling has provided a solid basis for other researchers to continue their work into developing an efficient reactor to re-create the Sun's fusion process here on Earth."

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The full research paper, Complete collision data set for electrons scattering on molecular hydrogen and its isotopologues, published in Atomic Data and Nuclear Data Tables, is available online here.

The paper was written in collaboration with researchers at Los Alamos National Laboratory and the National Institute of Standards and Technology in the US

Drug reverses age-related cognitive decline within days

Rapid mental rejuvenation in old mice suggests age-related losses may be broadly reversible 

UNIVERSITY OF CALIFORNIA - SAN FRANCISCO

Research News

 

Just a few doses of an experimental drug can reverse age-related declines in memory and mental flexibility in mice, according to a new study by UC San Francisco scientists. The drug, called ISRIB, has already been shown in laboratory studies to restore memory function months after traumatic brain injury (TBI), reverse cognitive impairments in Down Syndrome , prevent noise-related hearing loss, fight certain types of prostate cancer , and even enhance cognition in healthy animals.

In the new study, published December 1, 2020 in the open-access journal eLife , researchers showed rapid restoration of youthful cognitive abilities in aged mice, accompanied by a rejuvenation of brain and immune cells that could help explain improvements in brain function.

"ISRIB's extremely rapid effects show for the first time that a significant component of age-related cognitive losses may be caused by a kind of reversible physiological "blockage" rather than more permanent degradation," said Susanna Rosi , PhD, Lewis and Ruth Cozen Chair II and professor in the departments of Neurological Surgery and of Physical Therapy and Rehabilitation Science (http://ptrehab.ucsf.edu/) .

"The data suggest that the aged brain has not permanently lost essential cognitive capacities, as was commonly assumed, but rather that these cognitive resources are still there but have been somehow blocked, trapped by a vicious cycle of cellular stress," added Peter Walter , PhD, a professor in the UCSF Department of Biochemistry and Biophysics and a Howard Hughes Medical Institute investigator. "Our work with ISRIB demonstrates a way to break that cycle and restore cognitive abilities that had become walled off over time."

Could Rebooting Cellular Protein Production Hold the Key to Aging and Other Diseases?

Walter has won numerous scientific awards, including the Breakthrough , Lasker  and Shaw  prizes, for his decades-long studies of cellular stress responses. ISRIB, discovered in 2013 in Walter's lab, works by rebooting cells' protein production machinery after it gets throttled by one of these stress responses -- a cellular quality control mechanism called the integrated stress response (ISR; ISRIB stands for ISR InhiBitor).

The ISR normally detects problems with protein production in a cell -- a potential sign of viral infection or cancer-promoting gene mutations -- and responds by putting the brakes on cell's protein-synthesis machinery. This safety mechanism is critical for weeding out misbehaving cells, but if stuck in the on position in a tissue like the brain, it can lead to serious problems, as cells lose the ability to perform their normal activities, Walter and colleagues have found.

In particular, recent animal studies by Walter and Rosi, made possible by early philanthropic support from The Rogers Family Foundation, have implicated chronic ISR activation in the persistent cognitive and behavioral deficits seen in patients after TBI, by showing that, in mice, brief ISRIB treatment can reboot the ISR and restore normal brain function almost overnight.

The cognitive deficits in TBI patients are often likened to premature aging, which led Rosi and Walter to wonder if the ISR could also underlie purely age-related cognitive decline. Aging is well known to compromise cellular protein production across the body, as life's many insults pile up and stressors like chronic inflammation wear away at cells, potentially leading to widespread activation of the ISR.

"We've seen how ISRIB restores cognition in animals with traumatic brain injury, which in many ways is like a sped-up version of age-related cognitive decline," said Rosi, who is director of neurocognitive research in the UCSF Brain and Spinal Injury Center and a member of the UCSF Weill Institute for Neurosciences. "It may seem like a crazy idea, but asking whether the drug could reverse symptoms of aging itself was just a logical next step."

ISRIB Improves Cognition, Boosts Neuron and Immune Cell Function

In the new study, researchers led by Rosi lab postdoc Karen Krukowski , PhD, trained aged animals to escape from a watery maze by finding a hidden platform, a task that is typically hard for older animals to learn. But animals who received small daily doses of ISRIB during the three-day training process were able to accomplish the task as well as youthful mice, much better than animals of the same age who didn't receive the drug.

The researchers then tested how long this cognitive rejuvenation lasted and whether it could generalize to other cognitive skills. Several weeks after the initial ISRIB treatment, they trained the same mice to find their way out of a maze whose exit changed daily -- a test of mental flexibility for aged mice who, like humans, tend to get increasingly stuck in their ways. The mice who had received brief ISRIB treatment three weeks before still performed at youthful levels, while untreated mice continued to struggle.

To understand how ISRIB might be improving brain function, the researchers studied the activity and anatomy of cells in the hippocampus, a brain region with a key role in learning and memory, just one day after giving animals a single dose of ISRIB. They found that common signatures of neuronal aging disappeared literally overnight: neurons' electrical activity became more sprightly and responsive to stimulation, and cells showed more robust connectivity with cells around them while also showing an ability to form stable connections with one another usually only seen in younger mice.

The researchers are continuing to study exactly how the ISR disrupts cognition in aging and other conditions and to understand how long ISRIB's cognitive benefits may last. Among other puzzles raised by the new findings is the discovery that ISRIB also alters the function of the immune system's T cells, which also are prone to age-related dysfunction. The findings suggest another path by which the drug could be improving cognition in aged animals, and could have implications for diseases from Alzheimer's to diabetes that have been linked to heightened inflammation caused by an aging immune system.

"This was very exciting to me because we know that aging has a profound and persistent effect on T cells and that these changes can affect brain function in the hippocampus," said Rosi. "At the moment, this is just an interesting observation, but it gives us a very exciting set of biological puzzles to solve.

ISRIB May Have Wide-Ranging Implications for Neurological Disease

It turns out that chronic ISR activation and resulting blockage of cellular protein production may play a role in a surprisingly wide array of neurological conditions. Below is a partial list of these conditions, based on a recent review by Walter and colleague Mauro Costa-Mattioli of Baylor College of Medicine, which could potentially be treated with an ISR-resetting agent like ISRIB: 

• Frontotemporal Dementia
• Alzheimer's Disease
• Amyotrophic Lateral Sclerosis (ALS)
• Age-related Cognitive Decline
• Multiple Sclerosis
• Traumatic Brain Injury
• Parkinson's Disease
• Down Syndrome
• Vanishing White Matter Disorder
• Prion Disease

ISRIB has been licensed by Calico, a South San Francisco, Calif. company exploring the biology of aging, and the idea of targeting the ISR to treat disease has been picked up by other pharmaceutical companies, Walter says.

One might think that interfering with the ISR, a critical cellular safety mechanism, would be sure to have serious side effects, but so far in all their studies, the researchers have observed none. This is likely due to two factors, Walter says. First, it takes just a few doses of ISRIB to reset unhealthy, chronic ISR activation back to a healthier state, after which it can still respond normally to problems in individual cells. Second, ISRIB has virtually no effect when applied to cells actively employing the ISR in its most powerful form -- against an aggressive viral infection, for example.

Naturally, both of these factors make the molecule much less likely to have negative side effects -- and more attractive as a potential therapeutic. According to Walter: "It almost seems too good to be true, but with ISRIB we seem to have hit a sweet spot for manipulating the ISR with an ideal therapeutic window.

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Authors: Other authors on the study were Amber Nolan, Elma S. Frias, Morgane Boone, Katherine Grue, Maria-Serena Paladini, and Edward Elizarraras of UCSF; and Gonzalo Ureta, Luz Delgado and Sebastian Bernales of Fundación Ciencia & Vida in Santiago, Chile; Fundación Ciencia & Vida. Bernales is also an employee of Praxis Biotech, LLC.

Funding: The study was supported by continued generous support of the Rogers Family Foundation, as well as the UCSF Weill Innovation Award, the U.S. National Institutes of Health (NIH R01AG056770), National Institute on Aging (NIA F32AG054126); National Center for Advancing Translational Sciences (NCATS TL1 TR001871); National Institute of Neurological Disorders and Stroke (NINDS K08NS114170) and the Howard Hughes Medical Institute (HHMI).

Disclosures: Gonzalo Ureta works at Fundacion Ciencia & Vida and receives partial funding from Praxis Biotech. Sebastian Bernales is an employee of Praxis Biotech. Peter Walter is an inventor on U.S. Patent 9708247 held by the Regents of the University of California that describes ISRIB and its analogs. Rights to the invention have been licensed by UCSF to Calico.

About UCSF: The University of California, San Francisco (UCSF) is exclusively focused on the health sciences and is dedicated to promoting health worldwide through advanced biomedical research, graduate-level education in the life sciences and health professions, and excellence in patient care. UCSF Health, which serves as UCSF's primary academic medical center, includes top-ranked specialty hospitals and other clinical programs, and has affiliations throughout the Bay Area. Learn more at ucsf.edu, or see our Fact Sheet .

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Genomic analysis of mako shark reveals genes relating to tumor suppression in humans

Genetic mapping of the shark's liver and eye tissue showed overexpression of nine genes known for action in tumor suppression, wound healing, and probable monochrome vision

FUNDAÇÃO DE AMPARO À PESQUISA DO ESTADO DE SÃO PAULO

Research News

 

IMAGE: SCHEMATIC OF THE STUDY'S PIPELINE: COLLECTION OF MAKO SHARK'S EYE AND LIVER TISSUE, MRNA EXTRACTION AND ITS DNA CONVERSION (CDNA), COMPARISON BETWEEN THIS GENE SEQUENCE AND THOSE DEPOSITED IN DATA... view more 

CREDIT: RODRIGO DOMINGUES / IMAR-UNIFESP

Anecdotal reports claim that the incidence of cancer in sharks is very low, but there is not enough data to confirm this estimate categorically. A study published in the journal Genomics, however, presents strong evidence of anti-tumor activity in the genome of the Shortfin mako shark, Isurus oxyrinchus.

This large pelagic species, which can be as long as 4 meters, inhabits temperate and tropical seas worldwide. It is classified as endangered by IUCN, owing mainly to non-selective longline fishing with hundreds of hooks by factory ships that capture many animals in a single pass. They spend up to two months at sea, bringing back hundreds or even thousands of tons of fish.

Fishery observers with the Portuguese Institute for Sea and Atmosphere (IPMA) collected tissue samples of various organs from four mako sharks on one of these ships. Brazilian researchers genetically sequenced eye and liver tissue samples, finding that nine out of the ten most overexpressed genes in the animal's liver relate to tumor suppression in humans.

"Because these fishing cruises stay out at sea for such a long time, few of the tissue samples had well-conserved RNA. We managed to retrieve genetic material only from four livers and three eyes, but even so they produced surprising results," said Rodrigo Domingues, first author of the paper. The study was conducted while Domingues was on a postdoctoral internship at the Federal University of São Paulo (UNIFESP) in its Department of Marine Sciences in Santos, Brazil, under the supervision of Fernando Mendonça.

Domingues performed part of the analysis while he was an intern at the Interdisciplinary Center of Marine and Environmental Research (CIIMAR) in Portugal, also with a scholarship from FAPESP (São Paulo Research Foundation). The research is part of a project involving Brazil-Portugal collaboration, funded by FAPESP and Portugal's Foundation for Science and Technology (FCT).

The analysis revealed 3,774 differentially expressed genes in the two organs - 1,612 in the eye and 2,162 in the liver. Most of the genes that were overexpressed in the eye related to the structure of the organ and visual signaling to the brain. Few genes relating to light reception were found, suggesting that the mako probably has monochrome vision and can see only shades of the same color, like all other sharks known to science.

The recently completed genome sequencing of the Great white shark (Carcharodon carcharias), the largest sequencing of any shark species, revealed two positively selected genes with anti-tumor activity. Hence the Brazilian researchers' surprise on finding that out of the top ten overexpressed genes in the mako's genome, no fewer than nine are cancer-related.

From colon cancer to glioma

Among the genes with above-normal activity in the liver, HABP2 is known to reduce colony formation and cellular migration in thyroid tumors, while PON3 encodes an enzyme that can act as a cellular antioxidant, protecting cells from oxidative stress, which is a significant factor in cancer.

NIT2, RMC1 and FGFRK1 are expressed in various tissues and are potential tumor suppressants. The first two relate to suppression of colon cancer cells, while the third has a negative effect on cell proliferation in the initiation and progression of prostate cancer.

ITIH3 is involved in inflammatory diseases, schizophrenia, depression, heart attack, and stomach cancer. CBS and A1CF are involved in the progression of colon, ovarian, and breast cancer, although CBS has tumor-suppressant effects in glioma, a common type of brain cancer. SERPIND1 plays a role in rapid wound healing in sharks, and in inflammation, blood clotting, and cancer metastasis in humans.

"To find out if any compounds from shark livers could act on human cells, we would need to make an extract from the organ and test it on tumor cells. If such bioactive compounds were found to produce a significant benefit, other groups could synthesize them and possibly use them to produce a new drug for therapeutic use," Domingues said.

The authors note that the mako is already being overfished by commercial fleets, which sell its fins to Asian markets and its meat in Brazil. "We, therefore, discourage increased fishing of the species and a further population decline for this additional purpose. On the other hand, it might be possible to combine research activities in order to optimize the sampling of this endangered shark species, especially when scientific observers are on commercial vessels and can continue to take samples from specimens that are already dead when captured," they write.

To contribute to the conservation of the species, the researchers are now looking for single nucleotide polymorphisms (SNPs), which can act as biological markers to locate mutations and help explain whether there are several population groups in this or that ocean, for example. If differences are found in certain regions of the genome in 200 samples from the Atlantic and Indian Oceans, it may be possible to use them to identify oceanographic factors (water temperature and salinity, chlorophyll levels etc.) that contribute to this separation into groups. If so, the information can be used to formulate fishery policy, including a ban on shark fishing in certain areas.

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About São Paulo Research Foundation (FAPESP)

The São Paulo Research Foundation (FAPESP) is a public institution with the mission of supporting scientific research in all fields of knowledge by awarding scholarships, fellowships and grants to investigators linked with higher education and research institutions in the State of São Paulo, Brazil. FAPESP is aware that the very best research can only be done by working with the best researchers internationally. Therefore, it has established partnerships with funding agencies, higher education, private companies, and research organizations in other countries known for the quality of their research and has been encouraging scientists funded by its grants to further develop their international collaboration. You can learn more about FAPESP at http://www.fapesp.br/en and visit FAPESP news agency at http://www.agencia.fapesp.br/en to keep updated with the latest scientific breakthroughs FAPESP helps achieve through its many programs, awards and research centers. You may also subscribe to FAPESP news agency at http://agencia.fapesp.br/subscribe.

'Anti-antibiotic' allows for use of antibiotics without driving resistance

PENN STATE

Research News

 

IMAGE: RESEARCHERS HAVE FOUND THAT AN INEXPENSIVE, FDA-APPROVED DRUG FOR TREATING CHOLESTEROL -- CHOLESTYRAMINE -- TAKEN IN CONJUNCTION WITH AN ANTIBIOTIC PREVENTS THE ANTIBIOTIC FROM DRIVING ANTIMICROBIAL RESISTANCE IN THE GUT. view more 

CREDIT: ANDREW CHESHIRE, PENN STATE

UNIVERSITY PARK, Pa. -- An inexpensive, FDA-approved drug -- cholestyramine -- taken in conjunction with an antibiotic prevents the antibiotic from driving antimicrobial resistance, according to new research by scientists at Penn State and the University of Michigan. The team's findings appear today (Dec. 1) in the journal eLife.

"Antimicrobial resistance is a serious problem that has led to people dying from common bacterial infections," said Andrew Read, Evan Pugh Professor of Biology and Entomology and director of the Huck Institutes of the Life Sciences, Penn State. "Many of our most important antibiotics are failing, and we are beginning to run out of options. We have created a therapy that may help in the fight against antimicrobial resistance, an 'anti-antibiotic' that allows antibiotic treatment without driving the evolution and onward transmission of resistance."

According to Valerie Morley, postdoctoral scholar in the Huck Institutes of the Life Sciences, Penn State, an important cause of antibiotic-resistant infections in healthcare settings is vancomycin-resistant [VR] Enterococcus faecium.

"E. faecium is an opportunistic pathogen that colonizes the human gastrointestinal tract and spreads via fecal-oral transmission," she said. "The bacterium is asymptomatic in the gut but can cause serious infections, such as sepsis and endocarditis, when introduced to sites like the bloodstream or the spinal cord."

Morley noted that daptomycin is one of the few remaining antibiotics to treat VR E. faecium infection, yet VR E. faecium is quickly becoming resistant to daptomycin as well. Daptomycin is administered intravenously to treat infections caused by VR E. faecium. The antibiotic is mostly eliminated by the kidneys, but 5-10% of the dose enters the intestines, where it can drive the evolution of resistance.

To investigate whether systemic daptomycin treatment does, indeed, drive an increase in daptomycin-resistant VR E. faecium, the team inoculated mice orally with different strains of daptomycin-susceptible VR E. faecium. Beginning one day after inoculation, the researchers gave the mice daily doses of either subcutaneous daptomycin, oral daptomycin or a control mock injection for five days. The team used a range of doses and routes of administration, including those that would be similar to clinical human doses, to maximize the likelihood of observing resistance emergence. Next, they collected fecal samples from the mice to measure the extent of VR E. faecium shedding into the environment and to determine daptomycin susceptibility of the E. faecium bacteria that were present in the feces.

The researchers found that only the highest doses of daptomycin consistently reduced fecal VR E. faecium below the level of detection, whereas lower doses resulted in VR E. faecium shedding. From the bacteria that were shed, the team found that one strain acquired a mutation in a gene that had previously been described in association with daptomycin resistance, while another acquired several mutations that had not previously been associated with daptomycin resistance.

"Our experiments show that daptomycin resistance can emerge in E. faecium that has colonized the GI tract, and that this resistance can arise through a variety of genetic mutations," said Morley.

The team also observed that daptomycin-resistant bacteria were shed even when the daptomycin was administered subcutaneously.

Finally, the team investigated whether the orally administered adjuvant cholestyramine -- an FDA-approved bile-acid sequestrant -- could reduce daptomycin activity in the GI tract and prevent the emergence of daptomycin-resistant E. faecium in the gut. They found that cholestyramine reduced fecal shedding of daptomycin-resistant VR E. faecium in daptomycin-treated mice by up to 80-fold.

"We have shown that cholestyramine binds the antibiotic daptomycin and can function as an 'anti-antibiotic' to prevent systemically administered daptomycin from reaching the gut," said Read.

Amit Pai, professor and chair of the Department of Clinical Pharmacy, University of Michigan, noted that no new strategies have been developed to reduce antimicrobial resistance beyond the use of combination therapy, the development of vaccines for upper and lower respiratory tract infections and simply reducing the unnecessary use of antibiotics.

"These are blunt instruments for antimicrobial resistance reduction at the population level but do not readily translate to an intervention that can be used in individuals," said Pai. "Reducing selective antibiotic pressure on bacteria that reside in the colon is a potential individual-level strategy that deserves greater attention."

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Other Penn State authors on the paper include Derek Sim, senior research assistant; Samantha Olson, undergraduate student; Lindsey Jackson, undergraduate student; Elsa Hansen, assistant research professor; Grace Usher, graduate student; and Scott Showalter, professor of chemistry. Authors from the University of Michigan include Clare Kinnear, postdoctoral research fellow, and Robert Woods, assistant professor of internal medicine.

The Penn State Eberly College of Science and the Eberly Family Trust supported this research.