Culture

The future of hazelnuts: the economic value of subseasonal forecasts

A weather forecast may not allow time to make decisions that minimize the economic impacts of an extreme event, while a seasonal forecast is not precise enough to predict it. Thus, a spring frost - an event that can affect a small area and that can occur in a very short time - can lead to significant economic damages for the agribusiness players.

Predicting a cold spell a few weeks in advance can allow sector players to optimize their economic choices, changing the purchase times of raw materials in the case of a buyer or adopting adaptation strategies in the case of a farm.

The paper "Multi-model subseasonal forecasts of spring cold spells: potential value for the hazelnut agribusiness" (Materia et al. 2020 - https://journals.ametsoc.org/doi/abs/10.1175/WAF-D-19-0086.1), just released on the journal Weather and Forecasting, is the result of a research on the topic led by CMCC Foundation.

"Our case study focuses on the production of hazelnuts in the coastal areas of Turkey facing the Black Sea, home of about 70% of global hazelnut production: since this area is exposed to cold spells, being able to anticipate the extreme events that can compromise the production in the region can have an effect on a global scale" explains Stefano Materia, main author of the paper and researcher at the Climate Simulation and Prediction Division of the CMCC Foundation. The research assesses the reliability of the sub-seasonal forecasts in this area and their consequent economic value for some actors in the sector.

"Today we have data that allow us to make sub-seasonal forecasts on a time scale that is longer than that of the weather (which has a time horizon of 10 days), although not as far from the event as that of the seasonal forecasts. We can make predictions up to 5-6 weeks in advance", clarifies Dr. Materia.

We are seeing today the first applications of a new dataset made available to the international community from 2017, allowing to make predictions of impacts on civil society in a time scale of 30-45 days, which is of great interest to end-users.

The analysis, in addition to studying - thanks to a multi-model approach - the reliability of sub-seasonal forecasts for predicting frosts in advance, calculates their potential economic value for agribusiness players. "Predicting a cold spell a few weeks in advance can allow sector players that use hazelnuts as the main raw material of their products to change the time of purchase. In practical terms, they may start trading on nut price in advance, when the kernel is not even formed yet, on the basis of the forecast outcome. In the event of a predicted cold spell, they can fix the price beforehand, guaranteeing a net gain in case the cold spell occurs. In the same way, a farm will have the time to make adaptation interventions such as covering plants or install anti-frost turbine", continues Stefano Materia. "As shown by our research, the potential forecast economic value is large for many users, who may benefit from the use of sub seasonal predictions compared to a no action strategy. The economic value of forecasts supplied two weeks before the expected event is around 60%, but even forecasts supplied 3 to 6 weeks in advance - that have poorer prediction skills - may result in up to 20% economic gain for agribusiness operators".

Credit: 
CMCC Foundation - Euro-Mediterranean Center on Climate Change

Major Asia gene study to help doctors battle disease

image: "Under-representation of Asian populations in genetic studies has meant that medical relevance for more than half of the human population is reduced," said researcher Aakrosh Ratan, PhD, of the University of Virginia School of Medicine's Department of Public Health Sciences and the Center for Public Health Genomics.

Image: 
Dan Addison | UVA Communications

An ambitious new study of genes in Asian populations is filling in big gaps in our understanding of human genetics, shedding light on the history of human migration and ultimately aiming to improve our ability to treat disease.

Researchers from dozens of institutions around the world, including the University of Virginia School of Medicine, are seeking to address the under-representation of Asian populations in genetic research. Working as the GenomeAsia100K Consortium, they have examined the genomes of 1,739 people from 219 different population groups in 64 countries across Asia. The ultimate goal, as the group's name suggests, is to sequence the genomes of 100,000 people across Asia. This will produce a treasure trove of genetic information to help medical researchers and doctors better understand and treat genetic diseases, identify those at risk and even determine how patients will respond to drugs.

"Under-representation of Asian populations in genetic studies has meant that medical relevance for more than half of the human population is reduced," said researcher Aakrosh Ratan, PhD, of UVA's Department of Public Health Sciences and the Center for Public Health Genomics. "The main goal of the project is to increase the number of people included in these genetic studies, primarily to boost our knowledge about medical genetics but also to understand human migration and human origins."

Natural Gene Mutations

There are natural gene mutations among and between different populations, Ratan explained. This partly explains why certain populations of different ancestry seem to have a greater risk of certain diseases. Creating detailed reference databases for Asian populations will be a big benefit for medical genetics for all human populations, but especially for efforts to understand rare diseases in Asia.

"For example, in our new paper, we talk about MODY, which refers to maturity-onset diabetes of the young. This is a rarer type of diabetes that usually develops before the age of 25, and often you do not require insulin," Ratan said. "What we showed was that if doctors wanted to treat patients in India with the disease, they would greatly benefit from having information about genetic mutations found in Indian populations to identify the genetic differences that could be causing the disease. If you only look in databases that contain mutation data from European individuals, you are more likely to see false-positive results, and you will find it harder to pinpoint the exact gene causing the disease."

Not only does the research shed light on the cause of diseases, but it will also help doctors better care for patients. For example, some groups may be more prone to an adverse reaction to a particular drug. Identifying the genes responsible could help doctors know which patients should not get that drug, or should not get that drug in certain doses.

"We also studied the genetic differences associated with an adverse reaction to several common drugs and were able to identify Asian populations that showed large variation in their response," Ratan said. "These reference databases are vital to predict or understand why some drugs should not be dispensed in certain dosages to people of certain populations."

Findings Published

Ratan and his collaborators in the GenomeAsia100K Consortium have published their early findings in the prestigious scientific journal Nature. They expect their research will continue for several years.

"I am excited that sequences from several Asian populations will become available as a result of this project," Ratan noted. "It was my first time working in an international consortium, and it was an amazing learning experience."

Credit: 
University of Virginia Health System

Researchers foresee the ongoing use of cash

image: Researchers foresee the ongoing use of cash.

Image: 
UPV

Are the countries of the Eurozone ready to drop cash in hand? In light of a study of the UPV and UV, the answer is no. The work concludes that in these countries, there are still many years left of paying with cash. And, in Spain, this seems to be the case even more. These and other conclusions have recently been published in Cuadernos de Economía.

In their study, researchers conducted a detailed analysis of the countries in the Eurozone, based on the Global Findex survey of the World Bank: they studied the percentage of the population that has a bank account and uses it - which is known as financial inclusion - and of their use of cash, extracting data both globally and specific to each country.

"The end goal of the study was to learn whether the Eurozone is prepared, or not, to drop cash and implement new methods of payment, specifically, a digital cryptocurrency based on blockchain technology and managed by the European Central Bank," explains Nerea Gómez-Fernández, researcher for the Quality and Change Management Centre of the UPV.

Among its conclusions, the research states that the Eurozone has a higher use of cash than other similarly developed areas. However, there are significative differences among the countries studied. On one hand there are countries such as Finland, France, Germany, Austria, the Benelux countries and Estonia - a country that is clearly committed to digitisation and an economy free of cash, according to the authors - who use less cash.

On the other side of the spectrum are the Mediterranean Europe countries and the Eastern European countries - except for Estonia - in which a greater use of cash usually coincides with lower ownership of accounts. However, there is one exception that proves the rule: Spain. Being one of the countries where one of the highest percentages of population have and use a bank account, it is the second where the most wages are paid in cash, just behind Greece. The third in this ranking is Cyprus.

"This disparity can be explained by the lower relative income of these countries. However, we can't forget about factors as important as banking crises, as well as different behavioural natures and permissiveness with underground economy, which is usually linked to a greater use of cash," adds Juan Francisco Albert, from the Department of Applied Economy of the UV.

Higher income, less cash

The study also concludes that the higher the level of education and income, the higher the probability of having an account with a financial institution, as well as making payments online or with phones. Furthermore, it verifies that people with lower incomes or lower educational levels use cash more often in their daily transactions (paying bills, collecting wages or ordering transfers). Also, that women are less likely to make payments online or with their phones.

Public support

As a conclusion, the UPV and UV researchers add that, given the financial heterogeneity of the countries, legislation that aims to remove cash from the Eurozone would have to be implemented in a very gradual manner.

"And, in any case, public support is necessary, as has happened in countries such as Sweden or Denmark, to facilitate the digitisation of payment methods for people with low incomes or education levels, given their lower financial inclusion and greater use of cash. It is the only possible way to achieve total digitisation and an inclusive payment system that makes it possible to take advantage of the benefits of blockchain technology and the removal of cash that they enable," highlight the study authors.

Benefits of the global cryptocurrency

The study authors say that replacing cash with a cryptocurrency managed by the ECB would entail significant micro and macroeconomic benefits. Firstly, it would make it possible to decrease the cost of transactions and printing of cash, as well as making it more difficult to pay for illegal activities, such as corruption, money laundering, fiscal evasion or financing terrorism. Furthermore, from a macroeconomic viewpoint, this proposal would act as a solution to deal with the liquidity trap and stagnation issues that a majority of developed areas are currently suffering from, which would allow the European Central Bank to implement negative interest rates down to the level necessary to stimulate aggregate demand - the total goods and services demanded by a country, at a specific level of prices and for a specific period of time.

Credit: 
Universitat Politècnica de València

AI could deceive us as much as the human eye does in the search for extraterrestrials

image: Picture of the Vinalia Faculae region of Ceres obtained by NASA's Dawn spacecraft on July 6, 2018 at an altitude of about 58 kilometres. Can a square and/or a triangle be seen?

Image: 
NASA/JPL-Caltech/UCLA/MPS/DLR/IDA

An artificial neural network has identified a square structure within a triangular one in a crater on the dwarf planet Ceres, with several people agreeing on this perception. The result of this intriguing visual experiment, carried out by a Spanish neuropsychologist, calls into question the application of artificial intelligence to the search for extra-terrestrial intelligence (SETI).

Ceres, although the largest object in the main asteroid belt, is a dwarf planet. It became famous a few years ago for one of its craters: Occator, where some bright spots were observed, leading to all manner of speculations. The mystery was solved when NASA's Dawn probe came close enough to discover that these bright spots originated from volcanic ice and salt emissions.

Now researchers from the University of Cadiz (Spain) have looked at one of these spots, called Vinalia Faculae, and have been struck by an area where geometric shapes are ostensibly observable. This peculiarity has served them to propose a curious experiment: to compare how human beings and machines recognize planetary images. The ultimate goal was to analyse whether artificial intelligence (AI) can help discover 'technosignatures' of possible extra-terrestrial civilizations.

"We weren't alone in this, some people seemed to discern a square shape in Vinalia Faculae, so we saw it as an opportunity to confront human intelligence with artificial intelligence in a cognitive task of visual perception, not just a routine task, but a challenging one with implications bearing on the search for extraterrestrial life (SETI), no longer based solely on radio waves," explains Gabriel G. De la Torre.

The team of this neuropsychologist from the University of Cadiz, who has already studied the problem of undetected non terrestrial intelligent signals (the cosmic gorilla effect), now brought together 163 volunteers with no training in astronomy to determine what they saw in the images of Occator.

They then did the same with an artificial vision system based on convolutional neural networks (CNN), previously trained with thousands of images of squares and triangles so as to be able to identify them.

"Both people and artificial intelligence detected a square structure in the images, but the AI also identified a triangle," notes De la Torre, "and when the triangular option was shown to humans, the percentage of persons claiming to see it also increased significantly." The square seemed to be inscribed in the triangle.

These results, published in the Acta Astronautica journal, have allowed researchers to draw several conclusions: "On the one hand, despite being fashionable and having a multitude of applications, artificial intelligence could confuse us and tell us that it has detected impossible or false things," says De la Torre, "and this therefore compromises its usefulness in tasks such as the search for extra-terrestrial technosignatures in some cases. We must be careful with its implementation and use in SETI."

"On the other hand," he adds, "if AI identifies something our mind cannot understand or accept, could it in the future go beyond our level of consciousness and open doors to reality for which we are not prepared? What if the square and triangle of Vinalia Faculae in Ceres were artificial structures?"

Finally, the neuropsychologist points out that AI systems suffer from the same problems as their creators: "The implications of biases in their development should be further studied while they are being supervised by humans."

De la Torre concludes by acknowledging that, in reality, "we don't know what it is, but what artificial intelligence has detected in Vinalia Faculae is most probably just a play of light and shadow."

Credit: 
Spanish Foundation for Science and Technology

How active shooter incidents off campus lead to guns on campus

A new study finds that active shooter incidents off campus and politics are key factors that led state legislators to pass laws allowing concealed weapons on college and university campuses between 2004 and 2016.

"We assumed that campus carry legislation might be driven by active shooter incidents in educational contexts," David R. Johnson, lead author of the research, sociologist and assistant professor of higher education leadership in the College of Education at the University of Nevada, Reno, said. "Our analysis found that bill introduction is associated with active shooter incidents anywhere within a legislator's state, but not specifically those occurring at schools and universities."

"The dataset we developed tracked state legislative behaviors related to concealed weapons on campus and captured key factors that may have influenced these activities," said Liang Zhang, coauthor of the research and professor of higher education at New York University Steinhardt School of Culture, Education and Human Development. "We found that following a mass shooting, Republican legislatures tend to introduce and sometimes adopt legislation that would specifically allow people to bring concealed weapons onto college campuses, while Democrat-controlled legislatures do not."

Johnson and Zhang's academic paper, "Intrastate and interstate influences on the introduction and enactment of campus carry legislation" was published in Educational Researcher, a peer-reviewed journal of the American Educational Research Association that features the field's leading research. This is believed to be the first empirical analysis of the policy process related to campus carry legislation.

As of 2018, campus carry laws have been enacted in 11 states, 16 states ban concealed weapons and in 23 states the decision to ban or allow guns at higher education institutions is left to university systems or individual schools. The analysis showed that factors unrelated to crime on school grounds led to the introduction and enactment of these bills.

In addition to active shooter incidents, bill introduction is influenced by the percentage of Republicans in state government, conservative citizen political ideology and policy diffusion - the influence of neighboring states' policies on the issue. The analysis of bill enactment reveals that conservative citizen political ideology and contributions from anti-gun control interest groups are the driving forces behind policy adoption.

"Other research suggests that nearly 95 percent of students and faculty at large public universities are opposed to allowing guns on school grounds," Johnson continued. "There's no clear security issue, most stakeholders don't want guns on campus, and it seems that legislators push it through to please their constituents."

An active shooter incident could lead policymakers to adopt new or stronger prohibitions against concealed weapons on campus, but the chief legislative emphasis in the past two decades has been to remove prohibitions established in the 1980s and 1990s.

Zhang added that these gun bills and laws are largely unfunded mandates. The legislature doesn't include funding for the implementation of the new laws, but the schools must install signs, storage lockers and hire more police. The estimates are in the millions for a state higher education system to regulate guns on campus. When considering SB1474 in 2012, the state of Arizona estimated that allowing concealed weapons would introduce $13.3 million in one-time costs and $3.1 million annually for three state universities. The bill ultimately failed.

Zhang and Johnson focused on proposed bills aimed at permitting concealed weapons on campus to explain the policy process related to their introduction and either passage or failure to pass. Their work expands the empirical scope of higher education policy research by considering a social problem that is only indirectly related to student achievement but nevertheless a high priority for some state legislators.

While there are some areas of gun policy that draw bipartisan support, allowing concealed carry in more places is not one of them: 68% of Republicans support increased concealed carry in more places compared to only 26% of Democrats, according to the Pew Research Center. This helps explain why the prevalence of conservative leaning citizens within a state is so influential on the policy process.

In Nevada, for example, the state legislature has three times considered permitting firearms at postsecondary institutions - once in 2011 with a Democratic controlled legislature, once in 2013 with a Democratic controlled legislature and again in 2015 in a Republican controlled legislature. The 2011 and 2013 bills died without consideration. In 2015 AB148 was passed by the Assembly. The Senate never considered the bill.

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New York University

Third Reich's legacy tied to present-day xenophobia and political intolerance

HOUSTON - (Jan. 28, 2020) - Who -- or what -- is to blame for the xenophobia, political intolerance and radical political parties spreading through Germany and the rest of Europe? A new study from Rice University and Washington University in St. Louis shows a major factor is people's proximity to former Nazi concentration camps.

"Legacies of the Third Reich: Concentration Camps and Outgroup Intolerance" will appear in an upcoming edition of the journal American Political Science Review. Lead author Jonathan Homola, an assistant professor at Rice, and fellow authors Miguel Pereira and Margit Tavits of Washington University were interested in understanding why some Europeans are more xenophobic, less accepting of "outgroups" and more supportive of radical right-wing political parties.

The researchers focused closely on Germany but also examined other parts of Europe. They looked at survey responses from the European Values Study and the German General Social Survey as well as recent electoral results. They were especially interested in explaining intolerance toward Jews, Muslims and foreigners and support for radical right-wing parties. The researchers also used census data, information on the location of Third Reich concentration camps and historical election results.

The researchers found consistent evidence that present-day Germans who live closer to concentration camp sites are more xenophobic; less tolerant of Jews, Muslims and immigrants; and more likely to support extreme right-wing political parties. They also found preliminary evidence of this behavior in other parts of Europe.

"We believe that individuals living near concentration camps during World War II were more likely to conform to the beliefs system of the regime," Homola said. "And we think this was because of cognitive dissonance."

Cognitive dissonance is the process of people justifying new information and beliefs that don't necessarily align their values in order to eliminate feelings of guilt or psychological discomfort. In the case of the Holocaust, these beliefs were passed down from generation to generation, Homola and his fellow authors said.

"While the causes of the Holocaust have attracted ample scholarly attention, its long-term sociopolitical consequences are less understood," Homola said. "Our evidence proves that when it comes to political attitudes, these consequences are real and measurable even today. The prejudice that this racist and inhumane institution instilled in the local population is hard to erase even after the institution itself is long gone."

Homola said prior research in the U.S. has established a similar link between extreme political beliefs or racism and proximity to areas that once were home to a large number of slaves. These historical explanations for present-day prejudice are especially timely, he said, as political developments in the U.S. and Europe have brought intolerance toward marginalized groups back into the limelight.

"It is important to understand both contemporary factors and historical legacies that make exclusionary political appeals attractive," he said.

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Rice University

'Scrambled' cells fix themselves

Human cells have a defense mechanism that protects them from microbial attacks, a Canadian-led team of international researchers has discovered.

When microbes enter our body, they liberate toxins that can damage cells by poking holes in the external cell layer. To defend themselves from the intrusion, cells scramble their membrane fat (lipid) into a more liquid form that allows them to fix the holes, the research team found.

Those repairs prevent the cells from breaking up and dying.

Led by André Veillette, an Université de Montréal medical professor and researcher at the Montreal Clinical Research Institute (IRCM), the discovery was recently published in Cell Reports.

''Our body is very clever", said Veillette. "Some microbes cause diseases by punching holes in the external layer of cells and killing these cells. But our body has the ability to repair these holes. We have identified a molecule, known as TMEM16F, that can repair the holes and prevent the cells from dying."

The researchers hope that by stimulating the scrambling of cell fat with new drugs, they may help to protect humans from some microbes such as listeria, which causes severe diarrhea, and streptococcus, which can trigger destruction of blood cells.

Credit: 
University of Montreal

Pneumonia recovery reprograms immune cells of the lung

(Boston)--Researchers have determined that after lungs recover from infection, alveolar macrophages (immune cells that live in the lungs and help protect the lungs against infection) are different in multiple ways and those differences persist indefinitely.

How the lungs protect themselves when they are at their healthiest, like in young adult humans, is complex and only beginning to be understood. Researchers from Boston University School of Medicine (BUSM) propose that the new alveolar macrophage biology resulting from prior experiences with infections is one of the elements helping to protect the lungs of young adults against pneumonia.

"We have determined that these immune cells have a memory of their prior experiences and that memory influences how they will respond to any subsequent challenges like later infections," explained corresponding author Joseph Mizgerd, ScD, professor of medicine, microbiology and biochemistry at BUSM.

Worldwide, pneumonia remains a serious public health burden. Each year more than one million children under the age of five die from pneumonia and associated complications. In the U.S., pneumonia is the most common reason for the hospitalization of children and accounts for nearly half of the infectious disease-related hospitalizations and deaths of older adults.

In this study, experimental models were infected with a bacteria called pneumococcus, which is a normal experience for humans during childhood, and then allowed to recover. Another set of models were never infected. The researchers then compared the alveolar macrophages in the lungs of these two different groups, including the receptors on the cell surfaces, the genes being expressed by these cells and the metabolites inside of these cells. The alveolar macrophages in the models which had recovered from pneumonia had a new baseline in all these read-outs. In addition, their alveolar macrophages responded differently to subsequent infections, compared to the alveolar macrophages in lungs without a history of infections.

According to the researchers, young children are extremely susceptible to pneumonia, but multiple types of lung defense develop during childhood and protect against pneumonia, persisting through young adulthood. "The combination of aging, poor living habits and disease degrade these lung defenses so that pneumonia susceptibility increases again in later years," added Mizgerd.

By working to elucidate the naturally acquired defenses against pneumonia in young healthy adults the researchers hope to find better ways of identifying those most at risk for developing pneumonia and to devise new strategies for preventing or curing pneumonia.

Credit: 
Boston University School of Medicine

AI can jump-start radiation therapy for cancer patients

image: Dr. Mu-Han Lin, left, consults with Dr. Steve Jiang about a radiation treatment plan developed by artificial intelligence. Dr. Jiang's team trained four deep-learning models to instantly generate dosage plans and shorten the time patients must wait before starting radiation therapy.

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UTSW

DALLAS - Jan. 27, 2020 - Artificial intelligence can help cancer patients start their radiation therapy sooner - and thereby decrease the odds of the cancer spreading - by instantly translating complex clinical data into an optimal plan of attack.

Patients typically must wait several days to a week to begin therapy while doctors manually develop treatment plans. But new research from UT Southwestern shows how enhanced deep-learning models streamlined this process down to a fraction of a second.

"Some of these patients need radiation therapy immediately, but doctors often have to tell them to go home and wait," says Steve Jiang, Ph.D., who directs UT Southwestern's Medical Artificial Intelligence and Automation (MAIA) Lab. "Achieving optimal treatment plans in near real time is important and part of our broader mission to use AI to improve all aspects of cancer care."

Radiation therapy is a common form of cancer treatment that utilizes high radiation beams to destroy cancer cells and shrink tumors. Previous research shows that delaying this therapy by even a week can increase the chance of some cancers either recurring or spreading by 12-14 percent.

Such statistics motivated Jiang's team to explore methods of using AI to improve multiple facets of radiation therapy - from the initial dosage plans required before the treatment can begin to the dose recalculations that occur as the plan progresses.

Jiang says developing a sophisticated treatment plan can be a time-consuming and tedious process that involves careful review of the patient's imaging data and several phases of feedback within the medical team.

A new study from the MAIA Lab on dose prediction, published in Medical Physics, demonstrated AI's ability to produce optimal treatment plans within five-hundredths of a second after receiving clinical data for patients.

Researchers achieved this by feeding the data for 70 prostate cancer patients into four deep-learning models. Through repetition, the AI learned to develop 3D renderings of how best to distribute the radiation in each patient. Each model accurately predicted the treatment plans developed by the medical team.

The study builds upon other MAIA research published in 2019 that focused on developing treatment plans for lung and head and neck cancer.

"Our AI can cut out much of the back and forth that happens between the doctor and the dosage planner," Jiang says. "This improves the efficiency dramatically."

A second new study by Jiang, also published in Medical Physics, shows how AI can quickly and accurately recalculate dosages before each radiation session, taking into account how the patient's anatomy may have changed since the last therapy. A conventional, accurate recalculation sometimes requires patients to wait 10 minutes or more, in addition to the time needed to conduct anatomy imaging before each session.

Jiang's researchers developed an AI algorithm that combined two conventional models that had been used for dose calculation: a simple, fast model that lacked accuracy and a complex one that was accurate but required a much longer time, often about a half-hour.

The newly developed AI assessed the differences between the models - based on data from 70 prostate cancer patients - and learned how to utilize both speed and accuracy to generate calculations within one second.

UT Southwestern plans to use the new AI capabilities in clinical care after implementing a patient interface. Meanwhile, the MAIA Lab is developing deep-learning tools for several other purposes, including enhanced medical imaging and image processing, automated medical procedures, and improved disease diagnosis and treatment outcome prediction.

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UT Southwestern Medical Center

Discovery could help slow down progression of Parkinson's disease

A collaboration between scientists at Rutgers University and Scripps Research led to the discovery of a small molecule that may slow down or stop the progression of Parkinson's disease.

Parkinson's, which affects 1 million people in the United States and over 10 million worldwide according to the Parkinson's Foundation, is a neurodegenerative disorder with no cure. Symptoms develop slowly over time and can be debilitating to patients, who most recognizably develop tremor, slow movements and a shuffling gait.

A key feature of Parkinson's disease is a protein named α-synuclein, which accumulates in an abnormal form in brain cells causing them to degenerate and die. However, it has been difficult to target α-synuclein because it does not have a fixed structure and keeps changing its shape, making it very difficult for drugs to target. Because higher levels of the protein in the brain speed the degeneration of brain cells, scientists have been looking for ways to decrease the protein production as a form of treatment.

In 2014, Parkinson's disease expert and scientist M. Maral Mouradian, William Dow Lovett Professor of Neurology and director of the Rutgers Robert Wood Johnson Medical School Institute for Neurological Therapeutics, contacted Matthew D. Disney, chemistry professor at Scripps Research in Florida, to explore a novel idea for treating Parkinson's disease using a new technology developed by Disney.

Disney's method matches RNA structure with small molecules or drug-like compounds. The two collaborators believed this innovative technology could be used to find a drug that targets the messenger RNA that codes for α-synuclein, which causes the disease, in order to reduce production of the protein in the brains of Parkinson's patients. Since the protein itself can't be treated with drugs, RNA could be a more robust and reliable target.

They were right. The NIH-funded study, which was published in the Proceedings of the National Academy of Sciences on January 3, showed that by targeting messenger RNA, the team found a compound that prevents the harmful Parkinson's protein from being made. This new compound, named Synucleozid, reduces specifically α-synuclein levels and protects cells against the toxicity of the misfolded form of the protein, suggesting that it has the potential of preventing disease progression.

"We found the molecule to be very selective at both the RNA level and the protein level," Disney says.

"Currently, there is no cure for Parkinson's disease, and it is truly a devastating disease. For the first time, we discovered a drug-like compound that has the potential to slow down the disease before it advances through an entirely new approach," said Mouradian. Such a treatment would be most effective for people who are in the early stages of the disease with minimal symptoms, she said.

"Several other experimental drugs currently being tested for Parkinson's disease are antibodies that target a very late stage of α-synuclein protein aggregates. We want to prevent these protein clumps from forming in the first place before they do damage and lead to advancing disease.," she said. "This new compound has the potential to do that and could change the course of life for people with this devastating disease."

Mouradian says this discovery is 'highly promising' and is eager for the next steps in optimizing and testing the compound. Additionally, this can benefit another devasting disease that also has α-synuclein clumps, known as Dementia with Lewy Bodies. Further, this new concept of targeting RNA to reduce protein production developed in Disney's lab at Scripps Research may be applied to other challenging diseases because of their similar undruggable proteins including Alzheimer's disease.

"The reach of our study could go beyond people with Parkinson's disease to many other neurodegenerative diseases. It is a classic example of how interdisciplinary research leads to significant change," she shares.

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Rutgers University

Hundreds of UCLA students publish encyclopedia of 1,000 genes linked to organ development

image: Visible on this page are images of fruit flies' eyes (top), wings and lymph glands, showing which genes are active (red) or were previously active (green). (Download the full image to also see scans of the brain.)

Image: 
Cory Evans

A team of 245 UCLA undergraduates and 31 high school students has published an encyclopedia of more than 1,000 genes, including 421 genes whose functions were previously unknown. The research was conducted in fruit flies, and the genes the researchers describe in the analysis may be associated with the development of the brain, eye, lymph gland and wings.

The fruit fly is often the object of scientific research because its cells have similar DNA to that of human cells -- so knowledge about its genes can help researchers better understand human diseases. The UCLA study should be useful to scientists studying genes involved in sleep, vision, memory and many other processes in humans.

The research is published in the journal G3: Genes, Genomes, Genetics. The study's senior authors include researchers Cory Evans and John Olson, who taught UCLA's Biomedical Research 10H, the course in which the studies were conducted.

"I expect this will be a highly cited paper and a valuable resource to life scientists," said Tracy Johnson, director of UCLA's biomedical research minor, which offers the course the students all took. "It's inspiring to know all of this really important research came from freshmen and sophomores. It's beautiful, high-quality research."

The students studied short DNA sequences to learn how specific genes are turned on and off and understand how those genes control the functions of various cell types. Although all cells have essentially the same collection of genes, specific genes are turned on or off depending on the cells' needs, Evans said.

Each student studied several genes, ultimately producing a total of more than 50,000 microscopic images; the researchers then posted their analysis on an online database where other scientists can study the genes' roles.

"This shows not only which genes are turned on, but the history of which genes have been turned on," Johnson said.

The research was conducted as part of a UCLA life sciences course that was developed in the early 2000s by Utpal Banerjee, a UCLA distinguished professor of molecular, cell and developmental biology, a Howard Hughes Medical Institute Professor and a senior author of the paper. The course received initial funding from the HHMI.

"Research on science education says that one of the best way to teach science is by having authentic research experiences embedded in a course," said Johnson, who holds the Keith and Cecilia Terasaki Presidential Endowed Chair in the Division of Life Sciences and is an HHMI Professor. "Professor Banerjee understood years ago when he envisioned the class that students learn more by doing science. They learn how to design experiments, how to think like scientists, how to write about science and how to present their research."

Johnson said the approach is analogous to teaching a sport. "If a kid wants to play soccer, you don't say, 'Don't touch the soccer ball yet. You have to first learn all of the rules, watch other people play and read about the soccer greats, and maybe in a couple of years, we'll let you kick the ball.' No, bring out the soccer balls! So we need to get science students in the lab."

The students completed two other research projects, one of which Evans expects will be published this year. In that study, the undergraduates studied the effects of turning off specific genes in fruit flies using a scientific technique called RNA interference. They then determined which of those 4,000 genes, when turned off, affect the proper development of blood cells.

"We teach students how to do research, not fly biology," said Evans, who is now an assistant professor of biology at Loyola Marymount University. "Their science literacy is high, and they know how to evaluate evidence."

Credit: 
University of California - Los Angeles

Study examines poverty, suicide associations among US youth

What The Study Did: Associations between county-level concentrations of poverty in the United States and suicide rates among children and adolescents (ages 5 to 19) were explored in this observational study.

To access the embargoed study: Visit our For The Media website at this link https://media.jamanetwork.com/

Authors: Jennifer A. Hoffman, M.D., of the Ann & Robert H. Lurie Children's Hospital of Chicago, is the corresponding author.

(doi:10.1001/jamapediatrics.2019.5678)

Editor's Note: The article contains conflict of interest disclosures. Please see the article for additional information, including other authors, author contributions and affiliations, financial disclosures, funding and support, etc.

Credit: 
JAMA Network

Diabetes screening in barbershops to identify undiagnosed black men

What The Study Did: This research letter reports on diabetes screening in barbershops to identify undiagnosed black men.

To access the embargoed study: Visit our For The Media website at this link https://media.jamanetwork.com/

Authors: David C. Lee, M.D., of the NYU Grossman School of Medicine in New York, is the corresponding author.

(doi:10.1001/jamainternmed.2019.6867)

Editor's Note: The article includes conflict of interest and funding/support disclosures. Please see the article for additional information, including other authors, author contributions and affiliations, financial disclosures, funding and support, etc.

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JAMA Network

Unmet need for physicians, services among US adults

Bottom Line: Twenty years of survey data from the Centers for Disease Control and Prevention were used to examine the unmet need to see a physician and for services among insured and uninsured adults from 1998 to 2017, a time of change in the U.S. health care system that included passage of the Affordable Care Act (ACA). The proportion of adults who reported being unable to see a physician because of cost increased, with worsening access among insured adults whose numbers increased over time. The proportion of adults with chronic medical conditions unable to see a physician because of cost also increased for most conditions. A bigger share of adults received guideline-recommended cholesterol tests and flu shots but the proportion of women receiving mammograms decreased. A limitation of the study was the use of self-reported data.

To access the embargoed study: Visit our For The Media website at this link https://media.jamanetwork.com/

Authors: Laura Hawks, M.D., Cambridge Health Alliance, Cambridge, Massachusetts, and coauthors.

(doi:10.1001/jamainternmed.2019.6538)

Editor's Note: The article includes conflict of interest and funding/support disclosures. Please see the article for additional information, including other authors, author contributions and affiliations, financial disclosures, funding and support, etc.

Credit: 
JAMA Network

New look at odd holes involved in taste, Alzheimer's, asthma

image: Using cryo-electron microscopy, Furukawa's lab compiled a 3D image detailing the exact arrangement of the proteins that shape each CALHM pore. Pictured: CALHM1 as seen from the side, from the outside of the cell (extracellular), and from the inside of the cell (cytoplasm).

Image: 
Furukawa lab/CSHL, 2020

Many cells are covered with mysterious large holes, pores that have been associated with the sense of taste as well as Alzheimer's disease, depression, and even asthma. Knowing the structure of these varied holes will help researchers better understand this range of associations and provide a blueprint for developing new therapies.

"One of the most recently discovered of these 'large holes' are called calcium homeostasis modulators (CALHMs)," said Cold Spring Harbor Laboratory Professor Furukawa. "They're basically pores on the surface of some cells such as neurons," that let various molecules enter and exit the cell.

As described recently in Nature Structural & Molecular Biology, researchers from Furukawa's lab showcased the detailed structure of two CALHMs and how they function.

"If you have large holes in cells, you'd think the cells would burst open or shrink," said Johanna Syrjanen, a postdoctoral researcher who helped lead the research. However, she added, cells with functioning pores "remain quite happily as they are."

That suggests these pores are important for maintaining cell health. To investigate this, the researchers studied two kinds of pores. The pore CALHM1 is involved in sensing bitter or sweet tastes, and even that savory fifth taste known as umami. This pore is also involved in controlling the airways in your lungs, which implicates it in asthma. Additionally, mutations in the genes that shape CALHM1 have been associated with Alzheimer's disease. The researchers also studied another pore, CALHM2 that might be involved in depression. To their surprise, they found that CALHM2 has much larger pore size compared to CALHM1.

"Presumably the opening and closing of these pores is tightly regulated in some way," said Syrjanen. This opening and closing might be key to how the pores influence taste or are associated with disease. To make sense of this, "we first have to be able to visualize them and use that information as a guide for further experiments," she explained.

To visualize the structure of CALHM1 and CALHM2, Furukawa's lab used cryo-electron microscopy, which fires a powerful electron through a rapidly frozen specimen to obtain images. They then carefully compound the images in various orientations into a 3-D model that highlights the finite details of each pore's structure.

"We've provided science with the first blueprint of these pores to design therapeutic compounds," said Furukawa. "The hope is that such compounds could be effective in treating diseases and disorders like Alzheimer's and depression, and potentially in asthma."

Credit: 
Cold Spring Harbor Laboratory