Earth

Predicting the impact of DNA sequence variants is important for sorting disease-associated variants (DVs) from neutral variants. Korean researchers at Pohang University of science and technology (POSTECH) report the development of a method to predict the impact of DVs. The study appears in the journal Nucleic Acids Research in June.

Current methods to predict the mutational impacts depend on evolutionary conservation at the mutation site, which is determined using homologous sequences and based on the assumption that variants at well-conserved sites have high impacts. However, many DVs at less-conserved but functionally important sites cannot be predicted by the current methods.

The researchers present a method to find DVs at less-conserved sites by predicting the mutational impacts using evolutionary coupling analysis. Functionally important and evolutionarily coupled sites often have compensatory variants on cooperative sites to avoid loss of function. They identified DVs at less-conserved sites that were not identified using current conservation-based methods.

Prof. Kim said that "This study can be applied to a variety of precision medicine approaches such as prognosis of patient's diseases and finding personalized medicine." "Based on a large scale sequence analysis, the developed method is useful to find more disease associated variants which help to find biomarkers and therapeutic targets of various human diseases."

Pharmaceutical companies' payments to doctors may be influencing them to prescribe more expensive, brand-name versions of the pain drug gabapentin, a team of researchers report in the July 8 issue of JAMA Internal Medicine, and the increasing use of the drug suggests it may be being abused. 

"We found that the more physicians receive industry money, the more likely they were to prescribe gabapentin. But more research is needed to understand how much of that gabapentin goes to drug abuse," says lead author Greg Rhee, an assistant professor of medicine and public health at UConn Health. 

Gabapentin is a fairly old drug, normally prescribed to control seizures and treat nerve pain. But use of the drug has increased 3-fold in the US between 2002 and 2015, and Rhee and his colleagues wanted to understand why. It is chemically similar to the brain chemical gamma-aminobutyric acid, known as GABA. Gabapentin seems to work similarly to GABA by calming overexcited brain cells, which is why it is sometimes used to treat epilepsy. The way it relieves nerve pain is less well understood. But because it doesn't interact dangerously with other drugs nor cause euphoria when taken at therapeutic doses, it is frequently prescribed for chronic pain. And its use has been increasing: prescriptions of gabapentin and analogs of it rose from 1.2% of US adults in 2002 to 3.9% of US adults in 2015.

Rhee and colleagues from Yale University wondered whether payments from the pharmaceutical industry to doctors might be influencing prescribing. They looked at the Open Payments and Medicare Part D Prescriber databases for 2014-2016. Both databases are made available through the Centers for Medicare and Medicaid Services. Open Payments is a national program that obligates drug manufacturers to disclose payments made to physicians. Medicare Part D Prescriber database shows all the prescriptions made to people in Medicare Part D plans, and is searchable by doctor and by drug.

Gabapentin manufacturers paid physicians $11.5 million between 2014 and 2016, Rhee and his colleagues found. The payments went to about 14% of the doctors who prescribed any kind of gabapentin in those years, mostly pain doctors and general practitioners, most of whom were located in the southern and eastern parts of the country.

The researchers found that doctors who received payments from industry were more likely to prescribe a brand name version of gabapentin such as Lyrica, Gralise or Horizant. These brand name drugs cost several hundred dollars for a one month supply, compared to less than $20 for a one month supply of the generic. Besides cost, the rise in prescriptions is concerning because gabapentin has the potential to be abused. Although it is not reported to be intoxicating when used as directed, searching for gabapentin on drug experience websites such as erowid shows that taking it in larger quantities can cause a long lasting high. Some long-term users who took gabapentin at therapeutic doses for legitimate medical reasons also report it can be addictive. Rhee and his colleagues are concerned that the three-fold increase in prescriptions over the last decade and a half indicate some gabapentin is being diverted for recreational purposes, but caution that more research needs to be done before that can be determined.

Researchers in Japan have edited plant mitochondrial DNA for the first time, which could lead to a more secure food supply.

Nuclear DNA was first edited in the early 1970s, chloroplast DNA was first edited in 1988, and animal mitochondrial DNA was edited in 2008. However, no tool previously successfully edited plant mitochondrial DNA.

Researchers used their technique to create four new lines of rice and three new lines of rapeseed (canola).

"We knew we were successful when we saw that the rice plant was more polite - it had a deep bow," said Associate Professor Shin-ichi Arimura, joking about how a fertile rice plant bends under the weight of heavy seeds.

Arimura is an expert in plant molecular genetics at the University of Tokyo and led the research team, whose results were published in Nature Plants. Collaborators at Tohoku University and Tamagawa University also contributed to the research.

Genetic diversity for the food supply

Researchers hope to use the technique to address the current lack of mitochondrial genetic diversity in crops, a potentially devastating weak point in our food supply.

In 1970, a fungal infection arrived on Texas corn farms and was exacerbated by a gene in the corn's mitochondria. All corn on the farms had the same gene, so none were resistant to the infection. Fifteen percent of the entire American corn crop was killed that year. Corn with that specific mitochondrial gene has not been planted since.

"We still have a big risk now because there are so few plant mitochondrial genomes used in the world. I would like to use our ability to manipulate plant mitochondrial DNA to add diversity," said Arimura.

Plants without pollen

Most farmers do not save seeds from their harvest to replant next year. Hybrid plants, the first-generation offspring of two genetically different parent subspecies, are usually hardier and more productive.

To ensure farmers have fresh, first-generation hybrid seeds each season, agricultural supply companies produce seeds through a separate breeding process using two different parent subspecies. One of those parents is male infertile - it cannot make pollen.

Researchers refer to a common type of plant male infertility as cytoplasmic male sterility (CMS). CMS is a rare but naturally occurring phenomenon caused primarily by genes not in the nucleus of the cells, but rather the mitochondria.

Green beans, beets, carrots, corn, onions, petunia, rapeseed (canola) oil, rice, rye, sorghum, and sunflowers can be grown commercially using parent subspecies with CMS-type male infertility.

Beyond green

Plants use sunlight to produce most of their energy, through photosynthesis in green-pigmented chloroplasts. However, chloroplasts' fame is overrated, according to Arimura.

"Most of a plant isn't green, only the leaves above the ground. And many plants don't have leaves for half the year," said Arimura.

Plants get a significant portion of their energy through the same "powerhouse of the cell" that produces energy in animal cells: the mitochondria.

"No plant mitochondria, no life," said Arimura.

Mitochondria contain DNA completely separate from the cell's main DNA, which is stored in the nucleus. Nuclear DNA is the long double-helix genetic material inherited from both parents. The mitochondrial genome is circular, contains far fewer genes, and is primarily inherited only from mothers.

The animal mitochondrial genome is a relatively small molecule contained in a single circular structure with remarkable conservation between species.

"Even a fish's mitochondrial genome is similar to a human's," said Arimura.

Plant mitochondrial genomes are a different story.

"The plant mitochondrial genome is huge in comparison, the structure is much more complicated, the genes are sometimes duplicated, the gene expression mechanisms are not well-understood, and some mitochondria have no genomes at all - in our previous studies, we observed that they fuse with other mitochondria to exchange protein products and then separate again," said Arimura.

Manipulating plant mitochondrial DNA

To find a way to manipulate the complex plant mitochondrial genome, Arimura turned to collaborators familiar with the CMS systems in rice and rapeseed (canola). Prior research strongly suggested that in both plants, the cause of CMS was a single, evolutionarily unrelated mitochondrial gene in rice and in rapeseed (canola): clear targets in the perplexing maze of plant mitochondrial genomes.

Arimura's team adapted a technique that had previously edited mitochondrial genomes of animal cells growing in a dish. The technique, called mitoTALENs, uses a single protein to locate the mitochondrial genome, cut the DNA at the desired gene, and delete it.

"While deleting most genes creates problems, deleting a CMS gene solves a problem for plants. Without the CMS gene, plants are fertile again," said Arimura.

The fully fertile four new lines of rice and three new lines of rapeseed (canola) that researchers created are a proof of concept that the mitoTALENs system can successfully manipulate even the complex plant mitochondrial genome.

"This is an important first step for plant mitochondrial research," said Arimura.

Researchers will study the mitochondrial genes responsible for plant male infertility in more detail and identify potential mutations that could add much-needed diversity.

Boston, MA - Two new studies developed algorithms that can identify patients who are at risk of acquiring HIV and may benefit from preventive care. Both studies appear in the July 5 issue of The Lancet HIV.

Preexposure prophylaxis (PrEP) is an antiretroviral pill that is over 90% effective in preventing HIV acquisition when taken as prescribed. PrEP was recently given a Grade A recommendation from the U.S. Preventive Services Task Force but is vastly underutilized. There are nearly 40,000 new HIV infections annually in the United States, yet the Centers for Disease Control and Prevention estimates that only 7% of the 1.1 million individuals at substantial risk for HIV infection used the antiretroviral pill in 2016.

One barrier to use is the difficulty for providers in identifying patients who are at high risk of HIV acquisition. Providers often have limited time, may have limited knowledge about PrEP, and may lack training in how to talk to patients about sex or substance use. Risk prediction tools, a form of electronic clinical decision support using the data in patients' electronic health records (EHRs), are often used in other areas of medicine. Researchers from both studies, one using a patient population in California and the other in Massachusetts, built HIV risk prediction models that could be used in EHRs as automated screening tools for PrEP.

The two studies looked back at the medical records of millions of patients who were HIV-uninfected and had not yet used PrEP. Researchers extracted demographic and clinical data from these patients' EHRs on numerous potential predictors of HIV risk. A machine-learning algorithm automatically selected important HIV risk-related variables for the final models.

In the California-based study, which used medical record data of 3.7 million patients at Kaiser Permanente Northern California, the final risk prediction model included such variables as sex, race, living in a neighborhood with high HIV incidence, use of medications for erectile dysfunction, and sexually-transmitted infection (STI) testing and positivity. The model flagged 2% of the general patient population as potential PrEP candidates and identified 46% of male HIV cases, but none among females.

"Although risk prediction tools are imperfect and cannot replace the clinical judgement of skilled providers, our algorithms can help prompt discussions about PrEP with the patients who are most likely to benefit from it," said Julia Marcus, PhD, MPH, lead author of the California-based study and Assistant Professor of Population Medicine at the Harvard Pilgrim Health Care Institute and Harvard Medical School.

The Massachusetts-based study used a patient population of 1.1 million patients at Atrius Health as well as the population of Fenway Health, an independent community health center in Boston specializing in sexual health care, to test performance in a new setting with higher rates of new HIV infection. The final risk prediction model included sex, race, primary language, as well as diagnoses, tests, or prescriptions for STIs. The model flagged 1.8% of the general patient population at Atrius Health and 15.3% of the population at Fenway Health as potential PrEP candidates. The model also identified 37.5% of new HIV cases at Atrius Health and 46.3% at Fenway Health.

According to Douglas Krakower, MD, lead author of the Massachusetts-based study and Assistant Professor at Beth Israel Deaconess Medical Center, the Harvard Pilgrim Health Care Institute, and Harvard Medical School, "integrating these prediction models into primary care with routine, comprehensive HIV risk assessments by clinicians could play an important role in increasing the prescription of PrEP and preventing new HIV infections."

Jonathan Volk, MD, senior author of the California-based study and an infectious disease physician at Kaiser Permanente San Francisco Medical Center added that "a recent publication by the U.S. Preventive Services Task Force in JAMA cites the lack of effective prediction models as a major gap in research that is critical to improving PrEP delivery. Our model helps fill that gap."

If scientists could find a way to control the process for making semiconductor components on a nanometric scale, they could give those components unique electronic and optical properties - opening the door to a host of useful applications.

Researchers at the Laboratory of Microsystems, in EPFL's School of Engineering, have taken an important step towards that goal with their discovery of semiconducting nanotubes that assemble automatically in solutions of metallic nanocrystals and certain ligands. The tubes have between three and six walls that are perfectly uniform and just a few atoms thick - making them the first such nanostructures of their kind.

What's more, the nanotubes possess photoluminescent properties: they can absorb light of a specific wavelength and then send out intense light waves of a different color, much like quantum dots and quantum wells. That means they can be used as fluorescent markers in medical research, for example, or as catalysts in photoreduction reactions, as evidenced by the removal of the colors of some organic dyes, based on the results of initial experiments. The researchers' findings have made the cover of ACS Central Science.

An accidental discovery

But the unique feature of these semiconducting nanotubes is how they are formed. "Our discovery happened almost by chance. We had set out to study the role that certain ligands play in making 2D semiconducting nanometric crystals," says Xiaopeng Huang, the study's lead author. But the research team found that some ligands caused molecules to spontaneously come together in precise cylindrical structures which until then had been impossible to create.

Investigating new properties

The researchers will now investigate the other physical and electrical properties of their nanotubes and look into methods for making nanotubes with just a single wall.

The general public knows the chemical compound of carbon dioxide as a greenhouse gas in the atmosphere and because of its global-warming effect. However, carbon dioxide can also be a useful raw material for chemical reactions. A working group at Karlsruhe Institute of Technology (KIT) has now reported on this unusual application in the ChemSusChem journal. They are using carbon dioxide as a raw material to produce graphene, a technological material which is currently the subject of intense study. (DOI: 10.1002/cssc.201901404)

The combustion of fossil fuels such as coal and oil produces energy for electricity, heat and mobility, but it also leads to an increase of the amount of carbon dioxide in the atmosphere and therefore to global warming. Cutting this causal chain is what motivates scientists to search for alternative energy sources but also for alternative uses of carbon dioxide. One possibility could be to see carbon dioxide as an inexpensive raw material for the synthesis of valuable materials, feeding it back into the reusability cycle - maybe even in a profitable way.

An example can be found in nature. During photosynthesis in the leaves of plants, the combination of light, water and carbon dioxide creates biomass, closing the natural material cycle. In this process, it is the job of the metal-based enzyme RuBisCo to absorb the carbon dioxide from the air and make it usable for the further chemical reactions in the plant. Inspired by this metal enzyme-based natural conversion, researchers at KIT are now presenting a process in which the greenhouse gas carbon dioxide together with hydrogen gas is converted directly into graphene at temperatures of up to 1000 degrees Celsius with the help of specially prepared, catalytically active metal surfaces.

Graphene is the two-dimensional form of the chemical element carbon, which has interesting electrical properties and is therefore an option for new future electronic components. Its discovery and workability in 2004 led to worldwide, intensive research and earned the discoverers, Andre Geim and Konstanin Novoselov, the Nobel Prize for Physics in 2010. The two removed the graphene manually from a block of graphite using tape.

Several working groups at KIT have collaborated to present a method in the ChemSusChem journal for separating graphene from carbon dioxide and hydrogen by means of a metal catalyst. "If the metal surface exhibits the correct ratio of copper and palladium, the conversion of carbon dioxide to graphene will take place directly in a simple one-step process," explains the head of the study, Professor Mario Ruben, from the Molekulare Materialien working group at the Institute of Nanotechnology (INT) and the Institute for Inorganic Chemistry (AOC) at KIT. In further experiments the researchers were even able to produce graphene several layers thick, which could be interesting for possible applications in batteries, electronic components or filter materials. The working group's next research goal is to form functioning electronic components from the graphene thus obtained. Carbon materials such as graphene and magnetic molecules could be the building blocks for future quantum computers, which enable ultra-fast and energy-efficient calculations but are not based on the binary logic of today's computers.

An expert panel convened by the Council of Canadian Academies (CCA) has identified Canada's top climate change risks and determined that many costs and damages could be avoided with prompt and thoughtful adaptation.

Canada's climate is changing, with recent research showing that temperatures are rising twice as fast as the global average. Over the next 20 years, Canada can expect more frequent and severe hot extremes, thawing of permafrost, and increases in extreme precipitation.

"Climate change is increasingly leading to costly and disruptive impacts, and current projections suggest the warming in Canada and globally will continue, regardless of the trajectory of global emissions," said L. John Leggat, PhD, FCAE, Chair of the Expert Panel. "Understanding our top climate change risks and the role of adaptation in reducing these risks can help to support an effective response."

The Treasury Board of Canada Secretariat asked the CCA to examine the top climate change risks for Canada and their relative significance. Other studies have examined climate change risks at the sectoral and departmental level, but few have taken government-wide approach designed to help prioritize government responses.

Canada's Top Climate Change Risks identifies the top risk areas based on the extent and likelihood of the potential damage, and rates the risk areas according to society's ability to adapt and reduce negative outcomes. These 12 major areas of risk are: agriculture and food, coastal communities, ecosystems, fisheries, forestry, geopolitical dynamics, governance and capacity, human health and wellness, Indigenous ways of life, northern communities, physical infrastructure, and water.

The report describes an approach to inform federal risk prioritization and adaptation responses. The Panel outlines a multi-layered method of prioritizing adaptation measures based on an understanding of the risk, adaptation potential, and federal roles and responsibilities.

"Canada's unique geographic, environmental, and social identity shapes the hazards that it faces and its exposure to climate-related risks," said Eric M. Meslin, PhD, FCAHS, President and CEO of the CCA. "This report represents a high-level approach to prioritizing those risks, which we hope will help inform decision making about adaptation approaches."

Research by scientists into why some bacteria have different shapes has found that a curved shape can make it easier to find food.

The findings pose questions around whether disease-causing bacteria have different shapes.

Life Sciences researchers at the University of Lincoln conducted computer simulations to compare the swimming of differently shaped bacteria. Results showed that a curved shape can be beneficial for efficient swimming and for finding food through the use of chemical trails (known as chemotaxis) - but at the expense of higher cell construction costs.

This indicates that some bacteria species may balance the cost and benefits of their shape, depending on their environment and activity levels.

Before now it has not been understood what determines the different shapes of bacteria. While the shape of large creatures is driven by the effects of gravity and streamlining, for microscopic organisms these do not have such an impact.

Prof. Stuart Humphries, Professor of Evolutionary Biophysics at the University of Lincoln, said: "This work opens the door to asking a number of questions, for instance whether disease-causing bacteria have different shapes, or if different cell shapes improve the abilities of microbes we harness for industrial purposes".

Prof. David Smith, Professor of Applied Mathematics at the University of Birmingham said: "This research shows how state of the art maths and supercomputing simulation, used alongside extensive survey of a wealth of microscopy data, enables us to explore and explain aspects of the immense diversity of the living world which have hitherto been impossible."

Gas hydrate plugs not only obstruct flow but also speed up metal deformation. Resulting accidents are both a financial and an environmental burden. Previously, such plugs were removed mechanically, but today this method is being replaced by inhibitors.

Thermodynamic inhibitors (based mostly on methanol) obstruct the gas hydrate formation reactions, but methanol is quite detrimental to the environment. Kinetic inhibitors create physical obstacles for the gas flow so that gas hydrates form significantly slower; however, they are relatively expensive and not biodegradable.

"In this work, we tried to solve the existing problems by using castor oil," says co-author, project head Mikhail Varfolomeev. "We tested the substance together with the Federal Center for Toxicological Safety, and we found out that the inhibitor can be used both on land and in sea. The reagent slows down hydrate formation and hinders aggregation."

The castor-based waterborne polyurea/urethanes (CWPUUs) were synthesized on the basis of the waterborne technique. The high-pressure autoclave cell and high-pressure micro-differential scanning calorimeter using methane gas were applied to evaluate the inhibition performance of CWPUUs as an inhibitor for methane gas hydrate formation. The results of gas uptake tests confirm that the CWPUUs show high efficiency as kinetic hydrate inhibitors.

The method may lead to creating fully water-soluble materials. Tests show that a hybrid thermodynamic-kinetic technology may be proposed with much higher biodegradability and environmental safety.

The near-surface southerly wind is a key feature of East Asian summer monsoon (EASM) circulation, and a stronger EASM circulation leads to a northward shift of East Asian rainfall. Almost all climate models show an enhanced EASM circulation in a warmer climate, and previous studies attributed the enhanced EASM to the enhanced zonal land-sea thermal contrast.

"However, the land-sea thermal contrast cannot explain the seasonality of the change in East Asian circulation." said Dr. Chao He from Jinan University, China, "What's more, the enhanced EASM circulation is associated with a large-scale cyclone anomaly around Tibetan Plateau (TP), motivating us to hypothesize that TP may play a certain role".

In a recent study published in Journal of Climate, Chao He and Tianjun Zhou from Institute of Atmospheric Physics (IAP), Chinese Academy of Sciences, in cooperation with Ziqian Wang from Sun Yat-sen University andTim Li from Nanjing University of Information Science and Technology, confirmed this hypothesis. The study shows that the TP plays an essential role in enhancing the EASM circulation under global warming through enhanced latent heating over the TP.

The team compared the global warming scenarios with the present-day climate in 30 coupled models from phase 5 of the Coupled Model Intercomparison Project (CMIP5). Indeed, the latent heating over TP and its southern slope is substantially enhanced, due to the increased atmospheric water vapor content and enhanced local hydrological recycling. As confirmed by Linear Baroclinic Model, the enhanced latent heating over TP stimulates a cyclone anomaly around TP, enhancing the southerly wind in East Asia. In addition, the latent heating over TP also explains the inter-model spread of the projected changes in EASM circulation among CMIP5 models.

This study cleared up the role of the TP on the response of EASM circulation to global warming. "As the TP plays a key role in the response of EASM to global warming in future climate projections, attention should be paid to the accurate simulation of physical processes over TP." said Zhou.

Marine algae in the world's oceans store huge quantities of CO2, i.e. they bind approximately as much CO2 per year as the entire land vegetation. In this process, algae produce large amounts of carbohydrates, which can be broken down by marine bacteria and provide an important energy source for the marine food web. The research team has now elucidated the complex degradation pathway of the polysaccharide Ulvan. Ulvan is a complex sugar produced by algae of the genus Ulva and is degraded by the marine bacterium Formosa agariphila. The extensive study revealed the biochemical function of 12 enzymes. These findings are of considerable importance not only for basic research. For the first time, they enable the biotechnological exploitation of algal biomass that has never been used previously as a raw material for fermentations and for the isolation of valuable sugars.

"In our study we can show, for the first time, how marine bacteria completely decompose the highly complex polymer Ulvan from marine algae into its building blocks. These insights not only enhance our understanding of how microorganisms gain access to their food source. Using the newly decoded biocatalysts, the complex marine polysaccharide Ulvan can now also be used as a raw material for fermentations; and high-quality sugar components such as iduronic acid or rhamnose sulfate can be produced from the previously inaccessible resource provided by marine algae", explains Prof. Dr. Uwe Bornscheuer (Institute of Biochemistry, University of Greifswald).

Dr. Jan-Hendrik Hehemann, Emmy Noether Group Leader at the Max Planck Institute for Marine Microbiology and the MARUM - Center for Marine Environmental Sciences at the University of Bremen, adds: "Polysaccharides from marine algae are chemically different from those of terrestrial plants. It is largely unknown how marine bacteria degrade algal polysaccharides. Elucidating the enzymes involved in Ulvan degradation is not only of great value for future biotechnological applications, but also answers central ecological questions regarding the marine carbon cycle."

"Our results also show how important it is to conduct research in a diverse team of microbiologists, biotechnologists, biochemists and organic chemists. The DFG-funded research group POMPU provides a cross-disciplinary combination of these competencies, which has significantly contributed to the success of this project", adds Prof. Dr. Thomas Schweder (Institute of Pharmacy, University of Greifswald). The research group POMPU aims to elucidate important ecological functions of marine bacteria during algal blooms to improve the understanding of the oceans' biological pump function in view of global warming. Exploring key marine bacteria and enzymes can open up new perspectives for exploiting the promising potential of sugars from marine algae.

Media consumption by schoolchildren in the 3rd year (8-9 year-olds) and 6th year (11-12 year-olds) of Primary Education, their narrative skills and the perceptions they have about the values/countervalues of the cartoons was explored by the Department of Evolutionary Psychology and Education of the UPV/EHU's Faculty of Education, Philosophy and Anthropology. The research was conducted in various phases divided into two subcategories.

Firstly, the use that schoolchildren make of various devices, the Internet in particular, as well as the support and control strategies used by their parents, the positive and negative conceptions parents have about the use, difficulties and challenges they face when mediating in their use were identified. The aim of this section was to adapt the mediation programmes on the basis of the actual situation of families, schools and society.

Secondly, various tests were conducted to delve further into the interpretation and decoding that the schoolchildren carry out on the messages transmitted by the fictional content of the cartoons. These tests revealed that the type of narrative or non-narrative structure that characterises the cartoons affects the reception, processing, comprehension, memory and what the messages conjure up, in terms of narrative skills and perception of values/countervalues, of 8-12-year-old children. "The narrative cartoons we analysed have the same structure as classical stories (introduction, core and denouement). The thread can be easily followed. In the non-narrative cartoons we analysed, the events do not take place in the same context, the characters jump continually from an everyday atmosphere to another virtual one, and the individual watching has difficulty understanding the reasons and outcomes of the events. What is more, in the latter, clinchers are used continually," explained the UPV/EHU researcher Eider Oregui.

Didactic proposals

To conduct the study two types of cartoons were selected on the basis of high audience rates in the age groups being targeted by the study: Doraemon, with a narrative structure, and Code Lyoko, with a non-narrative structure. After displaying the cartoons, "we asked the schoolchildren to tell us what they remembered from what they had seen, and that way we analysed their narrative skills as well as the values and countervalues they had perceived," added Oregui, who was responsible for the research. The accounts by the schoolchildren who had watched the cartoons with a narrative structure were much longer and more detailed and the values and countervalues were perceived effortlessly. In the case of the non-narrative ones, however, the accounts were very short, they had been altered, and focus was placed almost exclusively on the sequences of the action; the children also experienced greater difficulty perceiving the values and countervalues of the subject matter".

The researchers also measured the schoolchildren's attention capacity while they were watching the cartoons, and they noticed that the cartoons with a narrative structure provided the children with attention breaks. By contrast, during the non-narrative cartoons the schoolchildren maintained continuous eye contact with the screen. In the narrative cartoons, "each one chooses, as a viewer, what to pay attention to or not, in other words, it involves voluntary attention, whereas in the non-narrative ones attention is not voluntary because of the ongoing effect of the clinchers," she explained. The viewers do not control their attention, which may mean that they do not properly understand the events when processing the information".

In any case, the researcher regards both types of cartoons as valid. "The same values/countervalues always appear in the narrative cartoons analysed but in different situations, and this aids the children's comprehension and processing; yet it is possible to find more types of values and countervalues in non-narrative cartoons and which could be perceived with the right mediation or various pedagogical activities; and that way, the effect exerted by the type of structure on the age groups included in the study would be prevented," pointed out Oregui. So this study has given rise to some didactic proposals targeting schoolchildren, family members and professionals in the sphere of psycho-education and communication, and which are designed to encourage the development of children's narrative skills and education in values and countervalues through their favourite fictional content.

The researcher also referred to the importance of furthering the classification of cartoons; she proposes that they be classified not only on the basis of their content, but also on the basis of their narrative level or their structure and the values they deal with. Oregui said that in the end "cartoons may be used both at school and at home to train children in values and countervalues, to deal with moral reasoning and to develop narrative skills as long as suitable resources are used and are adapted on the basis of age".

Scientists at The University of Toledo investigating improvements to a commonly used chemotherapy drug have discovered an entirely new class of cancer-killing agents that show promise in eradicating cancer stem cells.

Their findings could prove to be a breakthrough in not only treating tumors, but ensuring cancer doesn't return years later -- giving peace of mind to patients that their illness is truly gone.

"Not all cancer cells are the same, even in the same tumor," said Dr. William Taylor, a professor in the Department of Biological Sciences in the UToledo College of Natural Sciences and Mathematics. "There is a lot of variability and some of the cells, like cancer stem cells, are much nastier. Everyone is trying to figure out how to kill them, and this may be one way to do it."

Taylor and Dr. L.M. Viranga Tillekeratne, a professor in the Department of Medicinal and Biological Chemistry in the UToledo College of Pharmacy and Pharmaceutical Sciences, reported their findings in a paper recently published in the journal Scientific Reports.

Cancer stem cells are an intriguing target for researchers because of their potential to re-seed tumors.

When doctors remove a tumor surgically or target it with chemotherapy drugs or radiation therapy, the cancer may appear to be gone. However, evidence suggests that a tiny subpopulation of adaptable cancer cells can remain and circulate through the body to seed new metastasis in far-off locations.

Those cancer stem cells, Taylor said, are similar to dandelions in a well-manicured lawn.

"You could chop the plant off, but it will drop a seed. You know the seeds are there, but they're hiding," he said. "You pull one weed out and another comes up right after it. Cancers can be like this as well."

The small molecule they have isolated appears to lock on to those stem cells and kill them by blocking their absorption of an amino acid called cystine.

UToledo was awarded a patent for the discovery late last year.

For Tillekeratne and Taylor, uncovering a new class of therapeutic molecules could prove to be an even larger contribution to cancer research than the project they initially envisioned.

"At present, there are no drugs that can kill cancer stem cells, but people are looking for them," Tillekeratne said. "A lot of drugs are discovered by serendipity. Sometimes in research if you get unexpected results, you welcome that because it opens up a new line of research. This also shows the beauty of collaboration. I wouldn't have been able to do this on my own, and [Taylor] wouldn't have been able to do it on his own."

Tillekeratne has received a three-year, $449,000 grant from the National Institutes of Health National Cancer Institute to continue testing the effectiveness of the newly identified therapy.

Because the molecules so selectively target cancer stem cells, it's possible they could ultimately be paired with other chemotherapy drugs to deliver a more comprehensive treatment.

However, the researchers have found their agents show stand-alone promise in treating sarcomas and a subtype of breast cancer known as claudin-low breast cancer, which represents up to 14 percent of all breast cancers and can be particularly difficult to treat.

COLUMBUS, Ohio - In an era of concern over "fake news," a new study finds that people draw a distinction between information sources that are dishonest and those that are biased.

Researchers found that a source seen as biased may lose credibility with people, even if they believe the source is scrupulously honest.

That means untruthful - or "fake" - news isn't the only issue for consumers.

"If you want to be seen as a credible source, you have to be objective, as well as honest and knowledgeable," said Laura Wallace, lead author of the study and postdoctoral researcher in psychology at The Ohio State University.

The findings are significant because most research has suggested that source credibility is a combination of trustworthiness and expertise, Wallace said. Bias had not been considered, or was viewed as part of trustworthiness.

"I use the example of grandparents," Wallace said.

"Most everyone agrees that grandparents are honest. But if Grandma says that her grandson Johnny is the best soccer player around, most people will smile politely but not believe her. She's obviously biased."

Wallace conducted the research with Duane Wegener and Richard Petty, both professors of psychology at Ohio State. The study was published online today (June 8, 2019) in the journal Personality and Social Psychology Bulletin.

The researchers conducted several related experiments.

In one study, 169 undergraduate students read a fictitious conversation between aid workers trying to decide how to allocate resources at the beginning of an Ebola outbreak in the Congo. They had to decide whether to allocate limited resources to Rutu, a rural area where the outbreak started, or Poko, a nearby city where the disease had spread.

The aid workers were all described as "highly trained." One worker, Roger, advocated for sending aid to Rutu and for some participants was described as having worked in that area as a Peace Corps volunteer, which might indicate that he is biased. For other participants, this information was omitted, leaving no indication of bias.

After reading the conversation, participants completed a questionnaire in which they evaluated the aid workers' proposals.

Results showed that when Roger was described as having a previous connection to Rutu, participants thought Roger was biased in his recommendation to send aid to Rutu, - even though they also thought he was trustworthy, an expert in the field, and likable.

As a result, study participants thought his suggestion to send aid to Rutu was less credible, but only when they were told he had previously worked there.

"The guys in this scenario are all trying their best to contain this Ebola outbreak, they all know what they're doing, and they are all seen as very honest," Wallace said.

"But people believe that Roger's experience in one of these regions is affecting his judgment and that he just can't see things objectively."

This result shows that bias may damage credibility, just as untrustworthiness does. But that doesn't mean that bias and untrustworthiness always have the same consequences.

"In the case of biased, but honest sources, the information they present might only support one side of the issue, but at least people can treat the information as useful for understanding that side," Wallace said.

"Untrustworthy sources may never be that useful."

In addition, the difference between a biased source and an untrustworthy source has a big impact if the source changes positions. In a separate study that has not yet been published, the same researchers found that when untrustworthy sources change their position, it does not make them any more or less persuasive.

"Untrustworthy sources are seen as unpredictable. You can't tell what position they are going to take and it is not seen as meaning anything if they flip-flop," she said.

But the study found that it was quite surprising when biased sources changed their positions on an issue. This surprise had a positive effect on persuasion.

"People believe there must be new evidence that is really compelling to get a biased source to change positions and take the opposite side," Wallace said.

"So there are sometimes differences in how effective biased sources are compared to untrustworthy ones."

Wallace noted that the researchers used novel topics in the studies so that participants couldn't have pre-existing beliefs about them. As a result, the study can't say how people with their own biases would react to sources with similar or opposing biases.

But, she said, previous studies suggest that people tend to believe that those who agree with them are less biased than those who disagree with them.

Background

Most unnecessary or dangerous cells such as virus-infected cells commit suicide by activating an in-built suicide program. This type of cell death is referred to as "programmed cell death". Until about year 2000, it was considered that apoptosis*1 is almost the sole mode of programmed cell death at least in mammals. However, in recent years, various modes of "non-apoptotic" programmed cell death such as pyroptosis*2 and necroptosis have been defined based on the molecular mechanisms and morphological characteristics. In the process of apoptosis, the group of proteases called caspases, about 10 species of which are found in humans, function as suicide enzymes. Caspase-1*3, the first caspase found in mammals, has been reported to induce apoptosis in neurons in animal models of neurological disorders such as cerebral infarction, Alzheimer's disease and amyotrophic lateral sclerosis (ALS). On the other hand, subsequent studies revealed that in macrophages*4 infected by bacteria, caspase-1 induces necrosis*5-like and inflammatory programmed cell death, which was thereafter named pyroptosis. Thus, caspase-1 has been reported to induce apoptosis or pyroptosis depending on the biological context (Figure 1). The reason for this apparent discrepancy has not been clarified.

Recently, it was revealed that pyroptosis is induced by proteolysis of a protein called gasdermin D (GSDMD)*6 by caspase-1. Nonetheless, macrophages whose GSDMD gene was destroyed exhibited cell death upon activation of caspase-1, although more slowly than wild-type macrophages. Therefore, it seemed that there should be a mechanism of caspase-1-mediated cell death independent of GSDMD. However, the form and molecular mechanism of such cell death remained unknown.

Results

The present research team led by scientists of Kanazawa University together with scientists from Hokkaido University, the University of Tokyo and National Institute of Genetics, Japan, investigated the caspase-1-mediated programmed cell death of macrophages. First, they found that GMDSD-deficient macrophages underwent apoptosis when they were infected with Salmonella, although wild-type macrophages underwent pyroptosis under the same conditions. Since caspase-1-deficient macrophages exhibited little cell death under the same conditions, it was clear that both modes of programmed cell death, pyroptosis and apoptosis, were mediated by caspase-1.

Next, the team investigated caspase family members required for caspase-1-mediated apoptosis in GSDMD-deficient cells. As a result, caspase-3 and caspase-9 were found to be involved; caspase-3 is known to be necessary for induction of a broad spectrum of apoptosis, while caspase-9 is activated in response to cytochrome c release from mitochondria. Then, Bid*7, a pro-apoptotic cytoplasmic protein, emerged as a candidate for a mediator of caspase-1-induced apoptosis because of the following reasons. Bid is a well-known substrate of caspase-8, and its cleaved product, tBid induces cytochrome c release from mitochondria and subsequent caspase-9 activation. Furthermore, it has been reported that Bid can also be cleaved by caspase-1. Thus, the team generated GSDMD/Bid double deficient cells; on activation of caspase-1, it was found that apoptosis was suppressed in these cells compared to the GSDMD-deficient cells. Furthermore, GSDMD/Bid double deficient macrophages were found to be more resistant to Salmonella infection than GSDMD deficient macrophages. These results indicated that in GSDMD-deficient cells, caspase-1 activated Bid instead, which induced apoptosis.

In previous studies, caspase-1 was reported to be involved in the apoptosis of spinal cord neurons in mouse models of familial amyotrophic lateral sclerosis and of cortical neurons after oxygen/glucose deprivation. It was also demonstrated that such apoptosis was accompanied by Bid cleavage (activation) in a caspase-1-dependent manner. However, it was not clear whether Bid was necessary for the programmed death of those neurons or whether cortical and spinal cord neurons expressed GSDMD. Thus, the team investigated the expression of GSDMD mRNA and protein in the cerebral cortex and the spinal cord, and found that little GSDMD is expressed in these tissues. Moreover, cultured cortical neurons from caspase-1-deficient mice and those from Bid-deficient mice under oxygen/glucose deprivation were less susceptible to apoptosis in comparison with wild-type neurons. In addition, by consulting BioGPS (http://biogps.org/, a public database of protein expression), mast cells, a kind of immune cell, were found to express caspase-1 and Bid, but little GSDMD. Accordingly, when mast cells were stimulated by nigericin, a bacterial toxin, which is known to induce pyroptosis in macrophages, mast cells exhibited caspase-1- and Bid-dependent apoptosis.

The results of the present study revealed that apoptosis was induced even with neurons and mast cells that express little GSDMD by activation of Bid through caspase-1 action.

Future prospects

Caspase-1 is expressed in various cell-types and tissues besides macrophages and neurons, and has been suggested to be involved in myocardial infarction and renal disorders in addition to neurodegenerative diseases. It is necessary to elucidate whether in these cases, caspase-1-dependent cell death is GSDMD-dependent pyroptosis or Bid-dependent apoptosis or even due to other programmed cell death mechanisms.

In the future, by developing selective inhibitors for individual modes of programmed cell death in specific cells based on their underlying mechanisms, improvements may be expected in the prevention and treatment of diseases caused by programmed cell death.