Culture

(Philadelphia, PA) - Like a failing fuel pump that causes a loss of engine power in a car, a diseased heart can take a serious toll on the body's performance. For some patients, tasks like walking up a flight of stairs or walking across a room eventually turn into exhausting endeavors. This is because, over time, regardless of the underlying cause, heart damage typically progresses, owing to a constant barrage of oxidative stress and toxic lipids that alter heart cell energetics and, ultimately, the ability of the heart to function normally.

Oxidative stress occurs when harmful oxygen-containing molecules outnumber helpful antioxidants, leading to damaging reactions with proteins, DNA, and other cell components. Now, in two new studies, researchers at the Lewis Katz School of Medicine at Temple University (LKSOM) show that in the heart, one molecule in particular, Kruppel-like factor (KLF)-5, single-handedly fuels both the generation of oxidizing molecules and the accumulation of toxic lipids known as ceramides in the heart, exacerbating heart dysfunction. The studies are the first to identify KLF5 as a common mediator of cardiac damage in animal models of different diseases that lead to abnormal heart function, including diabetes and heart attack.

"Our findings expose KLF5 as a new target for different types of cardiac disease," said Konstantinos Drosatos, PhD, Associate Professor of Pharmacology at the Center for Translational Medicine, the Center for Metabolic Disease Research, and Alzheimer's Center at Temple at LKSOM. "As a unifying factor driving oxidative stress and accumulation of toxic lipids in the heart, the implications of targeting KLF5 could be far-reaching, opening up treatment for a broad range of diseases involving heart dysfunction."

In the first study, published online December 2 in the journal Circulation Research, Dr. Drosatos and colleagues investigated the involvement of KLF5 in a mouse model of diabetic cardiomyopathy. Diabetic cardiomyopathy is a major complication of diabetes and is characterized in particular by altered heart cell metabolism and oxidative damage. The new study showed that patients with diabetes have high levels of KLF5 expression in the heart.

The researchers found that mice with diabetic cardiomyopathy similarly have high KLF5 expression, and they discovered that elevated KLF5 is linked to the build up of ceramides in the heart. Ceramides, which occur naturally in the cell membrane, are known to reach toxic levels in the presence of insulin resistance and severe heart damage, such as that inflicted by heart attack.

The Temple team showed that in mice, however, these harmful effects could be halted. "Inhibiting KLF5 with a drug, as well as with genetic interventions, not only reduced oxidative stress and prevented ceramide accumulation but also restored cardiac function," Dr. Drosatos explained.

In the second study, published online January 12 in the journal Circulation, which was driven by LKSOM MD-PhD student, Matthew Hoffman, Dr. Drosatos's team investigated the role of KLF5 in mice with heart failure induced by cardiac ischemia, a sudden, severe blockage of blood flow to the heart. Cardiac ischemia characteristically is followed by extensive increases in toxic lipids, particularly ceramides. The researchers were able to show that KLF5 is involved in causing the production of ceramides that underlies damage to the cardiac wall. Ceramide buildup was driven by KLF5-induced overexpression of a molecule known as SPT1.

"The next step is to determine whether the severity of heart disease or the way patients respond to treatment is associated with increased KLF5," Dr. Drosatos said. "We know from clinical observations, for example, that some patients with heart failure are less responsive than others to therapeutic interventions. We want to know whether KLF5 is a factor that defines how well the patients will respond to treatments."

In addition, Dr. Drosatos and colleagues plan to search for proteins that regulate KLF5, which could broaden understanding of the role and pathway of activation of KLF5 in the heart and other tissues.

The studies also mark new ground in individual and collaborative research efforts at Temple University.

A team of researchers led by the University of California, Berkeley and the University of Michigan has discovered an antibody that blocks the spread within the body of the dengue virus, a mosquito-borne pathogen that infects between 50 and 100 million people a year. The virus causes what is known as dengue fever, symptoms of which include fever, vomiting and muscle aches, and can lead to more serious illnesses, and even death.

“Protein structures determined at the APS have played a critical role in the development of drugs and vaccines for several diseases, and these new results are key to the development of a potentially effective treatment against flaviviruses.” — Bob Fischetti, group leader with Argonne’s X-ray Sciences Division and life sciences advisor to the APS director

Currently, there are no effective treatments or vaccines for the dengue virus. Since there are four different strains of the virus, building up antibodies against one strain can actually leave people more vulnerable to subsequent infection from another strain, which makes finding an effective therapeutic more difficult. Scientists using the Advanced Photon Source (APS), a U.S. Department of Energy (DOE) Office of Science User Facility located at the DOE’s Argonne National Laboratory, have reported success.

The dengue virus uses a particular protein, called Non-Structural Protein 1 (NS1), to latch onto the protective cells around organs. It weakens the protective barrier, allowing the virus to infect the cell, and may cause the rupture of blood vessels.  The research team’s antibody, called 2B7, physically blocks the NS1 protein, preventing it from attaching itself to cells and slowing the spread of the virus. Moreover, because it attacks the protein directly and not the virus particle itself, 2B7 is effective against all four strains of the dengue virus.

The research team used X-ray diffraction techniques to determine structures of the NS1 protein with a bound antibody (2B7) and showed how the antibody provides protection against the virus. These diffraction images were obtained at the General Medical Sciences and Cancer Institutes Structural Biology Facility (GM/CA) at the APS.

Researchers showed that the 2B7 antibody effectively blocks the spread of the dengue virus in live mice. They reported their results in Science. The paper suggests that this same antibody could provide new treatments for other flaviviruses like dengue, a group that includes Zika and West Nile.

“Flaviviruses infect hundreds of millions of people a year, and tens of thousands die from the associated diseases,” said Argonne’s Bob Fischetti, group leader with the X-ray Sciences Division and life sciences advisor to the APS director. “Protein structures determined at the APS have played a critical role in the development of drugs and vaccines for several diseases, and these new results are key to the development of a potentially effective treatment against flaviviruses.”

The fascinating compound eyes of insects consist of hundreds of individual eyes known as "facets". In the course of evolution, an enormous variety of eye sizes and shapes has emerged, often representing adaptations to different environmental conditions. Scientists, led by an Emmy Noether research group at the University of Göttingen, together with scientists from the Andalusian Centre for Developmental Biology (CABD) in Seville, have now shown that these differences can be caused by very different changes in the genome of fruit flies. The study was published in the journal Molecular Biology and Evolution.

Anyone who has seen hoverflies manoeuvring through the air and, quick as a flash, changing direction, has probably witnessed a mating attempt in which the male, with breath-taking accuracy, pursues a fast-moving female. To carry out this specialised visual task, the huge compound eyes of hoverflies consist of up to 6,000 individual facets. There are special individual facets directed towards the sky that show particularly high resolution. In contrast, bark beetles, which spend most of their time burrowing inside wood, rarely rely on visual information. Hence, they have developed very small eyes with a maximum of 300 facets. "This enormous diversity is particularly impressive because previous comparative studies have shown that the development of insect eyes, and for that matter our own eyes as well, is controlled by very similar processes and genes," says Dr Nico Posnien from Göttingen University, the leader of the study. "It is especially exciting to understand how, in the face of very similar genes, such a diversity of size and shape of eyes can arise." Since many of the proteins coded by genes work together in regulatory networks to control the development of complex organs, the question arises whether similar differences in eye size are caused by changes at comparable sites within the networks. As a model for their study, the researchers used several species of the genus Drosophila, some of which we would recognise as the pesky fruit flies found in everyone's kitchen.

A Drosophila species native to Mauritius has up to 250 facets more than a closely related species. Although the basic developmental processes are very similar in both studied species, numerous differences were found in their genomes that could explain the observed differences in eye size. Detailed analysis of eye development in both species suggests that changes in an important central node of the gene network lead to the formation of significantly larger eyes in the species native to Mauritius. "Interestingly, in similar work on other Drosophila species, changes in completely different nodes have been observed. Therefore, our data show that differences in the number of facets can be caused by very different mechanisms," summarises the first author of the study, Dr Elisa Buchberger from the University of Göttingen.

"The new data suggest that differences in the number of single eyes in different Drosophila species arose several times independently in evolution," says Dr Micael Reis. He is first author of a study published last year by the Göttingen research group. Overall, the work of the Göttingen group contributes to a better understanding of the evolution of complex organs. Some of the methods established in this research could also be applied to studies in animal and plant breeding, specifically looking for changes in the genome that influence complex traits, such as milk production or fruit size. "In a next step, we would like to understand whether the different eye sizes have an influence on vision, and find out whether they are related to the lifestyle of the different fly species," says Posnien.?

Egg cells are among the largest cells in the animal kingdom. If moved only by the random jostlings of water molecules, a protein could take hours or even days to drift from one side of a forming egg cell to the other. Luckily, nature has developed a faster way: cell-spanning whirlpools in the immature egg cells of animals such as mice, zebrafish and fruit flies. These vortices enable cross-cell commutes that take just a fraction of the time. But until now, scientists didn't know how these crucial flows formed.

Using mathematical modeling, researchers now have an answer. The gyres result from the collective behavior of rodlike molecular tubes called microtubules that extend inward from the cells' membranes, the researchers report on January 13 in Physical Review Letters.

"While much is not understood about the biological function of these flows, they distribute nutrients and other factors that organize the body plan and guide development," says study co-lead author David Stein, a research scientist at the Flatiron Institute's Center for Computational Biology (CCB) in New York City. Given how widely the swirling flows have been observed throughout the animal kingdom, "they are probably even in humans."

Gabriele De Canio, a researcher at the University of Cambridge, co-led the study with Stein. Their co-authors were CCB director and New York University professor Michael Shelley and Cambridge professors Eric Lauga and Raymond Goldstein.

Scientists have studied cellular flows since the late 18th century, when the Italian physicist Bonaventura Corti peered inside cells using his microscope. He saw fluids in constant motion, but scientists didn't understand the mechanisms driving these flows until the 20th century, when they identified the source of the motion: molecular motors that walk along the microtubules. Those motors haul large biological payloads such as lipids. Schlepping the cargo through a cell's relatively thick fluids is like dragging a beach ball through honey. As the payloads move through the fluid, the fluid moves too, creating a small current.

But sometimes those currents aren't so small. In certain developmental stages of a common fruit fly's egg cell, scientists spotted whirlpool-like currents that spanned the entire cell. In these cells, microtubules extend inward from the cell's membrane like stalks of wheat. Molecular motors climbing these microtubules push downward on the microtubule as they ascend. That downward force bends the microtubule, redirecting the resulting flows.

Previous studies considered this bending mechanism but applied it to isolated microtubules. Those studies predicted that the microtubules would wave around in circles, but such behavior didn't match observations.

In the new study, the researchers added a key factor to their model: the influence of neighboring microtubules. That addition showed that the fluid flows generated by the payload-ferrying motors bend nearby microtubules in the same direction. With enough motors and a sufficient density of microtubules, all the microtubules eventually lean together like a wheat field caught in a strong breeze. This collective alignment orients all the flows in the same direction, creating the cell-wide vortex seen in real fruit fly cells.

While grounded in reality, the new model is stripped down to the bare essentials to reveal the conditions responsible for the swirling flows. The researchers are now working on versions that more realistically capture the physics behind the flows to better understand the role the currents play in biological processes.

(Boston)--What percent of patients with Alzheimer's Disease (AD) currently have severe dementia? Do more people have mild disease? Or are the majority suffering with moderate dementia? A new study using data from the Framingham Heart Study (FHS) sheds light on these trends.
Boston University School of Medicine researchers have found that slightly more than half (50.4 percent) of cases are mild, just under one-third (30.3 percent) of cases are moderate and 19.3 percent are severe cases. Among all participants with mild cognitive impairment (MCI) and AD, the pooled percentage was 45.2 percent for the combined group of mild AD dementia and MCI that later progressed to AD.

"Early intervention in MCI or the mild stage of AD dementia has been the primary focus for AD research and drug development in recent years. We found that approximately 45 percent of all those who are cognitively impaired or diagnosed with AD-dementia had early AD. Our results serve to inform the design of future research studies such as clinical and observational studies and provide optimal resource allocation for policy-making," explained corresponding author Rhoda Au, PhD, professor of anatomy and neurobiology at Boston University School of Medicine.

To characterize the distribution of severity of AD dementia and MCI among prevalent cases in the population, FHS participants (aged 50-94) with prevalent MCI or AD dementia clinical syndrome were selected from three time-windows: 2004-2005, 2006-2007 and 2008-2009. Estimates of the severity distribution were achieved by pooling results across time-windows. Diagnosis and severity were assessed by consensus dementia review. MCI-progressive was determined if the participant had documented progression to AD dementia clinical syndrome using longitudinal data.

According to the researchers the finding that half of the people living with AD have mild disease underscores the need for research and interventions to slow decline or prevent progression of this burdensome disease. "It is crucial to determine risk factors or develop therapies that could alter the disease trajectory to improve individuals' quality of life and alleviate the socio-economic burden," adds Au.

The researchers believe that most people who have AD are still at a stage when there is still some preserved quality of life. "This means any drug treatment that is effective might help prevent their AD from getting worst."

In 2007, an increase in world food prices led to a global rush for land in the form of land grabs or large-scale land acquisitions. Over the last two decades, such acquisitions have resulted in millions of hectares of land changing hands in developing nations. Although such changeover can increase the cultivation of crops needed to feed the world's growing population and spark new agricultural practices and technologies, it can also lead to environmental degradation, increased carbon emissions and threats to the livelihoods of smallholder farmers.

The socioeconomic and environmental consequences of such large-scale land acquisitions have been studied, but the effect of land grabs on carbon emissions has not, at least until now.

In a newly published study in the journal Nature Food, researchers looked at what drives large-scale land acquisitions and how the implementation of large-scale land acquisitions for agricultural development affect carbon emissions, and in turn, climate change.

"Overall, the findings suggest there is a cost-effective way to produce more food while minimizing carbon emissions from this process", said Chuan Liao, assistant professor in ASU's School of Sustainability and lead author of the study.

"It's unrealistic to say that we can't convert more land given that the world's population is growing especially in developing countries, but we still must minimize carbon emissions while pursuing agricultural development," he said.

The study researchers analyzed countries that were engaged in over 1,000 transnational, large-scale land acquisitions. They identified three distinct geographic areas where land grabs take place including coastal West Africa and the East African Rift Valley; Southeast Asia; Central-South Latin America; and Eastern Europe and western Russia.

The study showed that the quest for resources, like arable land and water, drives large-scale land acquisitions. That is, countries with low or medium-low arable land availability are usually investors, whereas those with medium-high or high arable land serve as hosts, said Liao. Likewise, countries with less water scarcity often supply land, whereas those countries with higher water scarcity invest in land.

The researchers also estimated carbon emissions from nearly 1,500 cases of large-scale land acquisitions under two agricultural-development scenarios, including business as usual and enforcement of environmental regulations.

In analyzing those emissions, the researchers found that the business-as-usual scenario, that is, clearing all vegetation from 37 million hectares of land, would emit approximately 2.26 gigatons of carbon. In contrast, implementing environmental regulations to constrain land conversion and save high-carbon-value forests would reduce emissions to 0.81 gigatons.

The study also found that enforcing environmental regulation policies does not reduce the amount of land that can be used for agricultural development at the same proportion as the reduction in carbon emission.

"Instead, we allow agricultural development on lands that have lower carbon values," explained Liao. "Our strategy is to better manage these tradeoffs because food security and carbon emission mitigation are both important."

Financial responsibility means managing money in a relatively sensible way by minimizing superfluous or unnecessary spending. But according to new research from the University of Notre Dame, people think they are more financially responsible than they actually are.

Even when people consistently spend their money superfluously, they still believe that they manage their money in a responsible fashion, according to "Popping the Positive Illusion of Financial Responsibility Can Increase Personal Savings: Applications in Emerging and Western Markets," forthcoming in the Journal of Marketing from Emily Garbinsky, assistant professor of marketing at Notre Dame's Mendoza College of Business.

"People generally hold positive illusions of being financially responsible, because this enables them to feel good about themselves," said Garbinsky, who also published a recent study on financial infidelity.

Garbinsky, along with Nicole Mead from York University and Daniel Gregg from the University of New England in Australia, developed an intervention that combats this self-enhancing bias by triggering people to recognize just how often they do spend money unnecessarily. In turn, this realization motivates them to boost their self-perceptions of financial responsibility by increasing their savings.

The "superfluous-spender" intervention involved having participants answer a brief survey of five questions before making a savings decision. The questions focused on their past superfluous spending behavior such as going out to dinner instead of cooking at home. Importantly, participants responded to these five questions using a continuous scale that was anchored by either a relatively low frequency (1 equals once a year or less) or a relatively high frequency (7 equals 12+ times a year). The researchers designed the scale anchors such that most participant responses would fall in the upper range, with higher scores indicating greater frequencies of past superfluous spending.

Ensuring that the majority of responses fell in the upper range was crucial, as past research has shown that people use their placement on rating scales to make inferences about themselves (in this case, that they are not as financially responsible as they thought they were). This realization then prompts them to enhance their feelings of financial responsibility by saving.

In addition to testing the effectiveness of this intervention on students at both Notre Dame and York universities as well as on various online panels, the team conducted two studies with chronically poor coffee growers in rural Uganda -- one study examined the intervention's ability to affect savings of earned income over time, whereas the other study examined the intervention's ability to affect savings of a financial windfall. "The latter is particularly important in developing countries," Garbinsky explained, "as an emerging policy option has been to 'shock' struggling households with large monetary transfers.

"Collectively, this work shows that people view their financial responsibility through rose-colored glasses, which can undermine their financial well-being," Garbinsky said. "People around the world are not saving enough money, and we propose that one reason they under-save is because they falsely believe themselves to be financially responsible. If that is in fact the case, deflating this inflated self-view may increase saving, as people should become motivated to restore perceptions of financial responsibility."

January 13, 2021 - When there is news of a violent attack, we sometimes hear that it could be related to mental illness - which may make us ask whether the violence could have been predicted or prevented. Current research and perspectives on associations between violence and mental illness are presented in the special January/February issue of Harvard Review of Psychiatry. The journal is published in the Lippincott portfolio by Wolters Kluwer.

"[T]he articles in this Special Issue serve to summarize important facets of the complex connection between mental illness and violent behavior, and to illuminate the potential for mental health practitioners and researchers to play a more productive role in preventing violence," according to an introduction by Guest Editor Jeffrey Swanson, PhD, Professor in Psychiatry and Behavioral Sciences at Duke University School of Medicine.

Expert insights on treatment and prevention of violence related to mental illness
Violence and serious mental illness are two "top tier" public health problems in the United States. However, it's difficult to demonstrate and understand the connections between them, if any. Research suggests that only a small fraction of violent acts occurring in the community - three to five percent - are attributable to mental illness. "The large majority of the perpetrators of violent crimes do not have a diagnosable mental illness, and conversely, most people with psychiatric disorders are never violent," Dr. Swanson writes.

Representing a broad range of intellectual and clinical perspectives, the Special Issue articles "reflect both the multifaceted nature of the problem and the importance of interdisciplinary research to inform effective interventions and policies to try to solve it." Topics include:

Mental health treatments to prevent violence. Two articles review current research and practice on medications and behavioral therapies to reduce hostility and aggression, focusing on schizophrenia and autism spectrum disorders. While there's evidence that some treatments do work to reduce violent behaviors, it remains unclear how they work - especially in these two fundamentally different disorders.

Violence against family. Caregivers and other family members of people with serious mental illness are often victims of violence; evidence suggests that 1 out of 5 family members are affected. In addition to usual risk factors such as substance abuse and not taking prescribed medications, family dynamics may contribute to these events.

Violence risk assessment. Assessing the risk of violence in individual patients poses difficult challenges for mental health professionals. An expert column addresses the real-world situations in which these assessments are done, where clinicians "must balance ethical and clinical concerns at the intersection of safety with coercion and fairness."

Mass shooting events. A "Perspectives" article offers insights into the role of mental illness in mass casualty shootings. The authors propose a strategy for studying the complex causes of these tragic events, with a broader collaborative role for psychiatry in trying to prevent them. Researchers should "deliberately reject the stigmatizing assumption that psychopathology is the main driver of a mass casualty shooting."

Gun violence prevention. Dr. Swanson is lead author of an article making the case for state laws allowing psychiatrists or other professionals to petition for court orders to remove firearms from patients who pose an "imminent risk" of harm to themselves or others. A growing number of states have enacted extreme risk protection orders - sometimes called "red flag" laws - enabling law enforcement to temporarily remove guns from people with behaviors indicating imminent risk of violence. An accompanying "Disruptive Innovations" essay discusses the potential advantages and challenges of this role for mental health professionals.

Dr. Swanson voices the hope that the Special Issue articles will provide a useful guide to future research toward meeting two critical, complementary goals: "to meaningfully reduce the toll of violent injury and mortality in the population, and to safely and respectfully integrate people with mental illnesses into community life, with the acceptance and support that will allow them to thrive."

New probes allow scientists to see four-stranded DNA interacting with molecules inside living human cells, unravelling its role in cellular processes.
DNA usually forms the classic double helix shape of two strands wound around each other. While DNA can form some more exotic shapes in test tubes, few are seen in real living cells.

However, four-stranded DNA, known as G-quadruplex, has recently been seen forming naturally in human cells. Now, in new research published today in Nature Communications, a team led by Imperial College London scientists have created new probes that can see how G-quadruplexes are interacting with other molecules inside living cells.

G-quadruplexes are found in higher concentrations in cancer cells, so are thought to play a role in the disease. The probes reveal how G-quadruplexes are 'unwound' by certain proteins, and can also help identify molecules that bind to G-quadruplexes, leading to potential new drug targets that can disrupt their activity.

One of the lead authors, Ben Lewis, from the Department of Chemistry at Imperial, said: "A different DNA shape will have an enormous impact on all processes involving it - such as reading, copying, or expressing genetic information. Evidence has been mounting that G-quadruplexes play an important role in a wide variety of processes vital for life, and in a range of diseases, but the missing link has been imaging this structure directly in living cells."

G-quadruplexes are rare inside cells, meaning standard techniques for detecting such molecules have difficulty detecting them specifically. Ben Lewis describes the problem as "like finding a needle in a haystack, but the needle is also made of hay".

To solve the problem, researchers from the Vilar and Kuimova groups in the Department of Chemistry at Imperial teamed up with the Vannier group from the Medical Research Council's London Institute of Medical Sciences.

They used a chemical probe called DAOTA-M2, which fluoresces (lights up) in the presence of G-quadruplexes, but instead of monitoring the brightness of fluorescence, they monitored how long this fluorescence lasts. This signal does not depend on the concentration of the probe or of G-quadruplexes, meaning it can be used to unequivocally visualise these rare molecules.

Dr Marina Kuimova, from the Department of Chemistry at Imperial, said: "By applying this more sophisticated approach we can remove the difficulties which have prevented the development of reliable probes for this DNA structure."

The team used their probes to study the interaction of G-quadruplexes with two helicase proteins - molecules that 'unwind' DNA structures. They showed that if these helicase proteins were removed, more G-quadruplexes were present, showing that the helicases play a role in unwinding and thus breaking down G-quadruplexes.

Dr Jean-Baptiste Vannier, from the MRC London Institute of Medical Sciences and the Institute of Clinical Sciences at Imperial, said: "In the past we have had to rely on looking at indirect signs of the effect of these helicases, but now we take a look at them directly inside live cells."

They also examined the ability of other molecules to interact with G-quadruplexes in living cells. If a molecule introduced to a cell binds to this DNA structure, it will displace the DAOTA-M2 probe and reduce its lifetime; how long the fluorescence lasts.

This allows interactions to be studied inside the nucleus of living cells, and for more molecules, such as those which are not fluorescent and can't be seen under the microscope, to be better understood. Professor Ramon Vilar, from the Department of Chemistry at Imperial, explained: "Many researchers have been interested in the potential of G-quadruplex binding molecules as potential drugs for diseases such as cancers. Our method will help to progress our understanding of these potential new drugs."

Peter Summers, another lead author from the Department of Chemistry at Imperial, said: "This project has been a fantastic opportunity to work at the intersection of chemistry, biology and physics. It would not have been possible without the expertise and close working relationship of all three research groups."

The three groups intend to continue working together to improve the properties of their probe and to explore new biological problems and shine further light on the roles G-quadruplexes play inside our living cells. The research was funded by Imperial's Excellence Fund for Frontier Research.

As marijuana outlets open after the drug is legalized, the density of those recreational retailers is associated with more use and a greater intensity of use among young adults, according to a new RAND Corporation study.

The study is among the first to examine associations between the density of marijuana outlets and marijuana use over time, and is the first to include unlicensed dispensaries in such an analysis.

Studying young adults in Los Angeles County the year before and the year after marijuana was available for recreational purchase in retail shops in California, the study found that the density of licensed marijuana outlets was associated with young adults' marijuana use, heavy use and intentions to use. The density of unlicensed outlets was associated with young adults' heavy marijuana use and symptoms of cannabis use disorder.

The findings are published by The American Journal on Addictions.

"Efforts to regulate unlicensed retailers and reduce the density of marijuana retailers may be important factors to be considered when developing strategies to mitigate potential public health harms from expanded legal access to marijuana," said Eric Pedersen, lead author of the study and an adjunct researcher at RAND, a nonprofit research organization.

Young adults are an at increased risk group for heavy and problematic marijuana use. More than half of young adults initiate marijuana use by the age of 21, and heavy use in young adulthood can lead to subsequent physical and cognitive health problems.

Researchers have begun to examine how the density of marijuana outlets near schools and residential addresses are associated with use, but thus far most of that work has examined medical marijuana dispensaries in a time prior to the opening of recreational retail outlets.

The RAND study is based on two surveys of 1,097 young adults aged 21 and older from Los Angeles County who were asked about their marijuana use a year apart -- before and after the substance became available for purchase for recreational use in California in January 2018. Those surveyed are part of an ongoing RAND project examining multiple factors about the use of alcohol, marijuana and other drugs.

The study used geocoding techniques and multiple data sources about marijuana businesses to determine the density of both licensed and unlicensed marijuana retailers within four miles of participants' homes.

The study found that a higher number of licensed marijuana outlets within 4 miles of one's home was significantly associated with a greater likelihood of past?month marijuana use after controlling for any use the prior year.

For each additional licensed marijuana outlet, there was an expected 0.7% increase in the odds of using marijuana in the past month. For example, there was an approximate 10% increase in the odds of using marijuana for someone with 14 licensed outlets within a 4?mile radius compared with someone with no outlets.

The findings varied by specific marijuana outcome and by marijuana retailer licensure status. For licensed outlets, higher density was significantly associated with an increased likelihood of past?month use, increased likelihood of past month daily or near?daily use, and stronger intentions to use marijuana in the next 6 months.

For unlicensed outlets, which made up 62% of all outlets at the time of the second survey, higher density of outlets was significantly associated with an increased likelihood of past?month daily or near?daily use, and for those with past?year use, greater quantity consumed, and more symptoms of cannabis use disorder.

"Unlicensed retailers are illegal and do not abide by licensing requirements that prohibit the sale of products from unlicensed producers or limiting the amount of marijuana that can be purchased by an adult each day," said Pedersen, who also is an associate professor of psychiatry and behavioral sciences at the Keck School of Medicine at USC. "Adults who use marijuana more frequently may be drawn to purchasing from unlicensed shops because of discounted prices and lack of regulation on purchase quantities."

Research led by the University of Wyoming shows that physical weathering is far more important than previously recognized in the breakdown of rock in mountain landscapes. Because it is difficult to measure, physical weathering has commonly been assumed to be negligible in previous studies.

Cliff Riebe, a professor in UW's Department of Geology and Geophysics, headed a research group that discovered that climate and erosion rates strongly regulate the relative importance of subsurface physical and chemical weathering of saprolite, the zone of weathered rock that retains the relative positions of mineral grains of the parent bedrock and lies between the layer of soil and harder rock underneath. Saprolite is much like the weathered granite found on the flat areas surrounding the hard granite of Vedauwoo.

"Our work shows that physical strain can no longer be ignored in studies of subsurface weathering. It's not just a chemical process. It is physical as well," Riebe says. "What we found is that anisovolumetric weathering is much more common than previously thought, and that variations in this process can be explained by climate and erosion."

Riebe is lead author of a paper, titled "Anisovolumetric Weathering in Granitic Saprolite Controlled by Climate and Erosion Rates," which was published in the Jan. 12 issue of Geology. The journal publishes timely, innovative and provocative articles relevant to its international audience, representing research from all fields of the geosciences.

The study looked at three sites -- with differing climates and elevations of granitic bedrock -- of the Sierra Nevada, a mountain range in California.

In the lingo of geochemists, weathering has long been assumed to be "isovolumetric," meaning without a change in volume caused by physical strain.

"Our work shows that, to the contrary, weathering is commonly 'anisovolumetric,' meaning that strain caused by physical weathering is important," Riebe says.

Riebe credits some of the tools and instruments that were purchased from the Wyoming Center for Environmental Hydrology and Geophysics (WyCEHG) EPSCoR (Established Program to Stimulate Competitive Research) project that ended a few years ago as the reason his team could measure both physical and chemical weathering at several sites in California.

"The reason why weathering was difficult to measure in the past is you have to be able to access the deep subsurface and sample it without disturbing it," Riebe explains. "You need a Geoprobe push coring system, which is basically a big track-mounted drill rig, to do this.

"It's expensive work, especially if you do not happen to own a Geoprobe and have to hire someone to do the work," he continues. "Fortunately, we have access to this equipment and the expertise to operate it through Wyoming's Near Surface Geophysics facility, which is ably managed by Brad Carr, one of the study's co-authors."

The research was funded by grants from the National Science Foundation (NSF), NASA and the Natural Sciences and Engineering Research Council of Canada.

Riebe says there is a direct correlation between the research in this paper and the $5.33 million NSF grant he received last September. The grant focuses on connections among rock, water and life at Earth's surface.

"This research is partly supported by that grant and also helped inspire it," Riebe says.

A compound developed at Oregon Health & Science University appears to protect nerve fibers and the fatty sheath, called myelin, that covers nerve cells in the brain and spinal cord.

The discovery, published in the Journal of Neuroimmunology, could be important in treating or preventing the progression of multiple sclerosis and other central nervous system disorders. The new research in a mouse model advances earlier work to develop the compound - known as sobetirome - that has already showed promise in stimulating the repair of myelin.

"Sobetirome and related drugs are effective at stimulating myelin repair after damage has occurred. Our new findings now suggest that these drugs could also prove to be beneficial for preventing damage from occurring," said senior author Dennis Bourdette, M.D., former chair and professor emeritus of neurology in the OHSU School of Medicine. "It means that these drugs have a dual effect that we didn't know about before."

Nerve fibers carry electrical impulses between nerve cells, and myelin is an insulation-like protective sheath covering nerve fibers.

Myelin and nerve fibers become damaged in multiple sclerosis, slowing or blocking electrical signals required for us to see, move our muscles, feel sensations and think. Researchers previously developed sobetirome as a compound that mimics the effect of the thyroid hormone in stimulating the maturation of precursor cells known as oligodendrocytes, which generate myelin. OHSU scientists developed a strategy to greatly increase the delivery of sobetirome into the brain of mice - remyelinating nerve fiber sheaths after damage had occurred.

The OHSU technology related to these findings is licensed to a startup biotechnology company committed to developing new medications for demyelinating diseases such as MS. Co-founders of the company include Bourdette along with two other co-authors on the new study: Tom Scanlan, Ph.D., professor of physiology and pharmacology in the OHSU School of Medicine, and Ben Emery, Ph.D., associate professor of neurology in the OHSU School of Medicine.

In the new research, scientists tested the compound by inducing an autoimmune disease in a mouse model of MS, causing inflammation damage to myelin and nerve fibers.

Lead author Priya Chaudhary, Ph.D., assistant professor of neurology in the OHSU School of Medicine who is focused on developing therapies for neurodegenerative diseases, said that the technique is a common step in drug discovery.

"It is important to show the effectiveness of potential drugs in a model that is most commonly used for developing new therapies," Chaudhary said.

The researchers discovered that they were able to prevent damage to myelin and nerve fibers from occurring, by stimulating a protective response in the cells that make and maintain myelin. They also reduced the activity of migroglia, a type of inflammatory cell in the brain and spinal cord that's involved in causing damage in multiple sclerosis and other diseases.

"The effects are impressive and are at least in part consistent with a neuroprotective effect with particular inhibition of myelin and axon degeneration, and oligodendrocyte loss," the authors write.

The discovery, if proven in clinical trials involving people, could be especially useful for people who are diagnosed with multiple sclerosis early in the disease's progression.

"The drug could protect the nervous system from damage and reduce the severity of the disease," Bourdette said.

With the impact of climate change increasing by the day, scientists are studying the ways in which human behavior contributes to the damage. A recent study at Walla Walla University, by a collaboration of researchers from Walla Walla University and La Sierra University, examined the effects of acidic water on octopuses, potentially bringing new insight into both how our activities impact the world around us, and the way that world is adapting in response.

The study, "Impact of Short- and Long-Term Exposure to Elevated Seawater PCO2 on Metabolic Rate and Hypoxia Tolerance in Octopus rubescens," focused on the metabolic rate of octopuses exposed to water acidified by carbon dioxide, and the changes it made to the animals. CO2 is a key indicator of the growing acidity of our oceans because much of the gas released into the air by humans is dissolving into the seawater.

Initial work in the field focused on the negative effects of ocean acidity: the impaired growth of affected species such as hermit crabs, for example, or reduced survival rates of certain types of fish over time. Adaptability, however, has not received as much attention, particularly when it comes to octopuses and other cephalopods. What studies have been conducted showed conflicting results, particularly when it comes to short-term vs. long-term exposure to increased ocean acidity (OA).

For instance, studies on cuttlefish show no significant change in their metabolism after exposure to increased OA, while squid subjected to the same conditions showed a reduction in aerobic metabolism, indicating reduced oxygen circulation in the subjects.

For purposes of this experiment, researchers used octopus rubescens a small and easily maintained species of octopus common to the west coast of North America. The subjects were exposed to increased CO2-created acidity for a period of 5 weeks. Researchers measured their routine metabolic rate (RMR) with no prior acclimation to the acidic water, and then again at 1 week and at 5 weeks. The subjects' critical oxygen pressure was measured at 5 weeks as well.

Metabolic rates are very telling in such circumstances because most significant physiological changes - such as smaller organs or reduced growth - are reflected in the shift in metabolism. (Changes in physiology are essentially changes in energy use, which can be observed by monitoring metabolism.)

The results demonstrated a surprising amount of adaptability in the subjects, as well as possible causes for data variation in other experiments. The subjects experienced high levels of metabolic change within the first 24 hours of exposure to increased acidity: a departure from earlier studies on different cephalopods, which showed a decrease in metabolic change.

However, when the same subjects were evaluated after one week, their RMR had returned to normal. The normal readings remained after 5 weeks as well, though their ability to function in low oxygen levels suffered in response to the increased acidity.

The results suggest that octopuses may be better able to withstand changes in ocean-acidity levels, which may have long-term bearings on our understanding of climate change. It also marks the first study to compare long-term and short-term effects of increased acid exposure. Further research is needed to clarify the mechanism driving the change in RMR, but the experimental parameters - and the use of octopus rubescens as test subjects - provide an excellent model system for studying the effects of OA on cephalopods.

The human organism requires a variety of small molecules, such as sugars or fats, in order to function properly. The composition of these so-called metabolites and their interaction - the metabolism - varies from person to person and is dependent not only on external influences, such as nutrition, but also to a significant extent on natural variations in our genetic make-up. In an international study, scientists from the Berlin Institute of Health (BIH) and Charité - Universitätsmedizin Berlin joined forces with colleagues from the United Kingdom, Australia and the United States and discovered hundreds of previously unknown variations in genes that have a sometimes drastic impact on the concentration of these small molecules in the blood. The researchers have now published their findings in the journal Nature Genetics.

The concentration and composition of metabolites - small molecules in the blood or tissue fluid - provide information about biological processes in the human body. They therefore serve as important biomarkers in clinical medicine, for example in the diagnosis of diseases or in checking the effectiveness of a therapy. Interestingly, the composition of metabolites differs from person to person, independent of external influences such as illness or diet. This is because the blueprints for the proteins that influence metabolite concentration, such as enzymes and transporter proteins, also differ between individuals. Often, the tiniest genetic variants can cause a metabolic enzyme to be more or less active or a transporter protein to be more or less efficient, thus raising or lowering the concentration of metabolites.

Data analyzed from 85,000 people

The team led by Claudia Langenberg, BIH Professor of Computational Medicine, has now investigated the effect of genetic variants on 174 different metabolites. "We found a surprising number of correlations between certain genetic variants and changes in the concentration of small molecules in the blood," reports the epidemiologist. "In most cases, the genetic variants cause changes in the blueprint of key metabolism regulators, like enzymes or transporters."

To explore these correlations, Langenberg's team needed huge amounts of data. "For our studies, we used large databases that gave us the blood test results and genetic information of a total of around 85,000 people," explains Maik Pietzner, lead author of the study and a scientist in Langenberg's laboratory. "In doing so, we were able to successfully demonstrate that it is possible to jointly evaluate data from a variety of small individual studies, even across technological boundaries."

Genetic variants can contribute to common diseases

The scientists' work is highly relevant to medicine, because it can explain how naturally occurring genetic variants that influence the metabolism contribute to the onset of common diseases, such as diabetes mellitus, as well as rare diseases. For example, high levels of the amino acid serine in the blood seem to provide protection against a rare eye disease called macular telangiectasia - knowledge that opens up new therapeutic avenues. In another study, the authors were also able to show that an individual's genetic risk for altered serine metabolism can aid in the early diagnosis of this serious eye disease. They have also identified a new mechanism that explains how the disrupted transmission of signals via the GLP-2 receptor increases the risk of developing type 2 diabetes.

"What was special about our study were the extreme effects that we observed and their potential relevance for medical research," explains Langenberg. "For example, we were able to detect genetic variants that have an influence on metabolism a good three times as strong as the already known effects of more common genetic variations, for example on body mass index."

Data is only relevant if used

To enable scientists around the world to link up their particular fields of expertise with their data, the team has set up an interactive website at http://www.omicscience.org. After all, Langenberg emphasizes, data is only relevant if it can also be used: "We very much hope that these compelling examples will encourage other scientists and doctors to apply our results to their specific research or disease cases."

There are things in life that can be predicted reasonably well. The tides rise and fall. The moon waxes and wanes. A billiard ball bounces around a table according to orderly geometry.

And then there are things that defy easy prediction: The hurricane that changes direction without warning. The splashing of water in a fountain. The graceful disorder of branches growing from a tree.

These phenomena and others like them can be described as chaotic systems, and are notable for exhibiting behavior that is predictable at first, but grows increasingly random with time.

Because of the large role that chaotic systems play in the world around us, scientists and mathematicians have long sought to better understand them. Now, Caltech's Lihong Wang, the Bren Professor in the Andrew and Peggy Cherng department of Medical Engineering, has developed a new tool that might help in this quest.

In the latest issue of Science Advances, Wang describes how he has used an ultrafast camera of his own design that recorded video at one billion frames per second to observe the movement of laser light in a chamber specially designed to induce chaotic reflections.

"Some cavities are non-chaotic, so the path the light takes is predictable," Wang says. But in the current work, he and his colleagues have used that ultrafast camera as a tool to study a chaotic cavity, "in which the light takes a different path every time we repeat the experiment."

The camera makes use of a technology called compressed ultrafast photography (CUP), which Wang has demonstrated in other research to be capable of speeds as fast as 70 trillion frames per second. The speed at which a CUP camera takes video makes it capable of seeing light--the fastest thing in the universe--as it travels.

But CUP cameras have another feature that make them uniquely suited for studying chaotic systems. Unlike a traditional camera that shoots one frame of video at a time, a CUP camera essentially shoots all of its frames at once. This allows the camera to capture the entirety of a laser beam's chaotic path through the chamber all in one go.

That matters because in a chaotic system, the behavior is different every time. If the camera only captured part of the action, the behavior that was not recorded could never be studied, because it would never occur in exactly the same way again. It would be like trying to photograph a bird, but with a camera that can only capture one body part at a time; furthermore, every time the bird landed near you, it would be a different species. Although you could try to assemble all your photos into one composite bird image, that cobbled-together bird would have the beak of a crow, the neck of a stork, the wings of a duck, the tail of a hawk, and the legs of a chicken. Not exactly useful.

Wang says that the ability of his CUP camera to capture the chaotic movement of light may breathe new life into the study of optical chaos, which has applications in physics, communications, and cryptography.

"It was a really hot field some time ago, but it's died down, maybe because we didn't have the tools we needed," he says. "The experimentalists lost interest because they couldn't do the experiments, and the theoreticians lost interest because they couldn't validate their theories experimentally. This was a fun demonstration to show people in that field that they finally have an experimental tool."