Culture

Minneapolis, Minn. - February 24, 2020 - A new website developed by researchers at Hennepin Healthcare Research Institute (HHRI) and the University of Minnesota (UMN) is making it easier for organ transplant candidates to choose which transplant center is right for them.

The website, transplantcentersearch.org, was developed for candidates seeking kidney, liver, heart and lung transplants. Data for liver centers is currently live. Data for other organs will soon be available.

"In order for patients to join a waiting list for an organ transplant they must complete an evaluation at a transplant center. Different transplant centers have different criteria for candidates. For example, some centers are more likely to accept an older candidate. They also have different waiting times and outcomes," said first author Cory Schaffhausen, PhD. "Patients can use the website to see how many transplant recipients at any US center have characteristics like themselves."

This personalized decision guide uses information about the patient's donor type and medical profile to match factors important to the individual. It uses data from the Scientific Registry of Transplant Recipients, a national transplant registry operated by HHRI under contract from the US Department of Health and Human Services.

Schaffhausen recently published an article about the new tool entitled "Tool to Aid Patients in Selecting a Liver Transplant Center," in the March issue of Liver Transplantation journal. This article is featured on the front cover of the journal. The Principal Investigator and senior author on the project is Ajay Israni, MD, MS and other researchers and co-author include Warren McKinney, PhD at HHRI. The HHRI team is also working with multiple collaborators at UMN.

Many patients with rare, fast-growing neuroendocrine tumors respond well to a common immunotherapy drug combination, according to the first peer-reviewed publication out of DART, short for Dual Anti-CTLA-4 and Anti-PD-1 Blockade in Rare Tumors, a unique rare cancer clinical trial.

DART offers the immunotherapy combination of ipilimumab and nivolumab to patients with 53 classes of rare cancers through an innovative "basket" design, which allows a single drug or drug combination to be tested in a variety of tumor types. The trial has rapidly expanded the opportunities for immunotherapy drug development in rare cancers, which make up almost a quarter of all cancers diagnosed worldwide.

DART is managed by SWOG Cancer Research Network, a clinical trials group that is part of the National Cancer Institute's (NCI) National Clinical Trials Network (NCTN), the oldest and largest publicly-funded cancer research network in the U.S.

The study results appear in Clinical Cancer Research. When presented in March 2019 at the annual meeting of the American Association of Cancer Research, initial findings were met with excitement. That's because patients with high-grade, or fast-growing, neuroendocrine carcinoma have few treatment options.

"We're very encouraged by these results," said Sandip Pravin Patel, MD, the DART clinical study chair, an associate professor of medicine at the University of California at San Diego School of Medicine, and a medical oncologist with Moores Cancer Center at UC San Diego Health. "Based on the response, we opened another study enrolling only patients with high-grade neuroendocrine carcinoma to see if we can replicate our results. We're eager to share those findings later this year."

Patel's fellow DART chairs are Razelle Kurzrock, MD, of UCSD Moores Cancer Center and Young Kwang Chae, MD, PhD, of Northwestern University.

For this neuroendocrine cohort, 32 eligible patients received the ipilimumab and nivolumab combination. Of the 32, 18 had high-grade cancer, with tumors most commonly appearing in the lungs or gastrointestinal tract. Regardless of where their tumors appeared, eight out of 18 high-grade patients - or 44 percent - saw them shrink partially or completely. By contrast, patients with intermediate or low-grade tumors saw no response.

Since its 2017 launch, physicians at 823 cancer centers, academic medical centers, and community clinics and hospitals have opened DART. As of February 13, 715 patients have enrolled out of a goal of 818 - beating all expectations. Historically, rare cancer trials struggle to find patients, leading many investigators to abandon rare cancer research.

UNIVERSITY PARK, Pa. -- Stress has a justifiably bad reputation for making people feel crummy. But new research suggests that despite its negative side effects, it may also lead to a surprising social benefit.

In a study, a team of scientists including Penn State researchers found that experiencing stress made people both more likely to give and receive emotional support from another person. This was true on the day they experienced the stressor as well as the following day.

David Almeida, professor of human development and family studies, said the results -- recently published in the journal Stress & Health -- suggest that while stress can certainly lead to negative health outcomes, there are potential benefits, as well.

"Our findings suggest that just because we have a bad day, that doesn't mean it has to be completely unhealthy," Almeida said. "If stress can actually connect us with other people, which I think is absolutely vital to the human experience, I think that's a benefit. Stress could potentially help people deal with negative situations by driving them to be with other people."

Almeida said that while the negative effects of stress -- such as heart disease, compromised immune function and depressive symptoms -- are well-documented, he and the other researchers were curious if there were potential benefits to stress, such as emotional support.

"Looking at the current research, I realized that a lot of studies looked at how emotional support is beneficial to other health outcomes, but not many looked at the determinants of social support," said Hye Won Chai, a Penn State graduate student in health and human development. "We thought that stress could be a facilitator in these interpersonal exchanges."

For the study, the researchers interviewed 1,622 participants every night for eight nights. They asked the participants about their stressors and whether they gave or received emotional support on that day. Stressors included arguments, stressful events at work or school, and stressful events at home.

The researchers found that on average, participants were more than twice as likely to either give or receive emotional support on days they experienced a stressor. Additionally, they were 26 percent more likely to give or receive support the following day. The researchers said that while this effect, on average, was found across the participants, it differed slightly between men and women.

"Women tended to engage in more giving and receiving emotional support than men," Chai said. "This supports previous findings that women tend to seek more emotional support from other people when they're stressed. In our study, men were also more likely to engage in emotional support on days they were stressed, but to a lesser extent than women."

The researchers said they were surprised that stress was linked to people not just receiving emotional support, but giving it, as well. Almeida said he initially thought that giving emotional support was the stressor itself, but he reconsidered when they discovered the effect lasted through the next day.

"We saw that someone experiencing a stressor today actually predicted them giving emotional support the next day," Almeida said. "This made me think that it's actually possible that stress helps to drive you to other people and allows it to be ok to talk about problems -- your problems, my problems."

Almeida added that the results could help practitioners enhance and design better interventions for targeting stress.

"The findings suggest that an intervention geared toward social interaction rather than individual may be very beneficial," Almeida said. "If we're naturally being drawn toward other people when we're stressed to get help, then interventions may benefit by incorporating the people around us."

Barcelona, 24 February 2020. Lung function declines naturally over the course of the human lifespan. However, this decline is steeper in individuals who experience moderate or high weight gain. This was the conclusion of a new study led by the Barcelona Institute for Global Health (ISGlobal), a centre supported by "la Caixa", which analysed the effect of weight changes on respiratory health over a 20-year period.

The study, published in the journal Thorax, was based on data collected from 3,700 participants living in different countries in Europe and in Australia and recruited between the ages of 20 and 44 years. Participants repeatedly underwent measurements of weight and lung function--by means of spirometry--between 1991 and 2014. "Although previous research has shown that weight gain is linked to lung function decline, ours is the first study to analyse such a varied population sample over a longer period of time," commented Judith Garcia Aymerich, leader of the study and head of the Non-communicable Diseases and Environment programme at ISGlobal. Most earlier studies have had relatively short follow-up periods--ten years at the most--and focused on adults up to 50 years of age.

The study found that people with a body mass index within the recommended rates, overweight people and obese people all experienced accelerated lung function decline when they gained weight. Conversely, weight loss helped to attenuate lung function decline in obese people. Moreover, people who kept their weight low throughout adulthood exhibited a much less pronounced decline in respiratory health.

Two mechanisms could explain the association between weight gain and pulmonary health. First, weight gain can affect lung function through mechanical effects. "Abdominal and thoracic fat mass is likely to limit the room for lung expansion during inspiration," commented ISGlobal researcher Gabriela Prado Peralta, lead author of the study. Second, weight gain can impair lung function through inflammatory processes, since adipose tissue--the area where fat accumulates--is a source of inflammatory substances that can damage lung tissue and reduce airway diameter.

Maintaining good lung function during adulthood is crucial to prevent chronic respiratory diseases, which nowadays represent a serious public health problem around the world. "Given the epidemic levels of overweight and obesity that we are currently seeing, it is fundamental to understand the effects of weight changes on lung function, which is a powerful predictor of morbidity and mortality in the general population," commented Garcia Aymerich. "The good news is that the negative pulmonary health effects of excess weight and obesity can be reversed through weight loss. Therefore, public health policies that promote healthy lifestyles can be the key to achieving good pulmonary health."

The study formed part of the Ageing Lungs in European Cohorts (ALEC) Study, coordinated by Imperial College London. It was financed by the European Union's Horizon 2020 research and innovation programme.

Bottom Line: An analysis of annual surveys from graduating students at all U.S. allopathic medical schools suggests self-reported medical student mistreatment remains common and varies by sex, race/ethnicity and sexual orientation. This observational study included 27,504 unique student surveys, representing 72.1% of graduating medical school students in 2016 and 2017. The types of mistreatment students were questioned about included public humiliation, being threatened, physical harm and unwanted sexual advances, as well as discrimination based on gender, race/ethnicity and sexual orientation. Researchers report self-reported medical student mistreatment was common, with 35.4% reporting at least one type of mistreatment, the most common of which was public humiliation. A larger proportion of female students compared with male students reported at least one episode of mistreatment; Asian, underrepresented minority and multiracial students reported higher rates of mistreatment and discrimination based on race/ethnicity than white students; and a larger proportion of lesbian, gay or bisexual students reported an episode of mistreatment compared with heterosexual students. Limitations of the study include self-reported information and differences in how students may classify experiences. Authors acknowledge the results may underreport medical student mistreatment because some students who experienced mistreatment may have left medical school before graduation.

Authors: Katherine A. Hill, B.A., B.S., Yale School of Medicine, New Haven, Connecticut, and coauthors.

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

(doi:10.1001/jamainternmed.2020.0030)

Bottom Line: Cannabis use apparently continues to increase among older adults in the U.S. based on findings reported in this research letter. Researchers analyzed national survey data from 2015-2018 for nearly 15,000 adults 65 and older to estimate how common past-year cannabis use was. Previous studies have indicated sharp increases from 2006-2016. Cannabis has been legalized in many states for medical and recreational use. Authors of the current study estimate the proportion of adults who reported past-year marijuana use increased from 2.4% to 4.2% from 2015 to 2018. There appeared to be significant increases in use during that time among women, people who were white or nonwhite racial/ethnic minorities, adults with a college education, people with higher incomes, those who are married, and adults who reported receiving mental health treatment or using alcohol, and people with diabetes. A limitation of the study is the possibility of limited recall by the respondents. There is a need to better understand both the benefits and risks of marijuana use among older adults.

Authors: Benjamin H. Han, M.D., M.P.H., and Joseph J. Palamar, Ph.D., M.P.H., of the New York University School of Medicine, New York.

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

(doi:10.1001/jamainternmed.2019.7517)

The Neolithic revolution, and the corresponding transition to agricultural and pastoralist lifestyles, represents one of the greatest cultural shifts in human history, and it has long been hypothesized that this might have also provided the opportunity for the emergence of human-adapted diseases. A new study published in Nature Ecology & Evolution led by Felix M. Key, Alexander Herbig, and Johannes Krause of the Max Planck Institute for the Science of Human History studied human remains excavated across Western Eurasia and reconstructed eight ancient Salmonella enterica genomes - all part of a related group within the much larger diversity of modern S. enterica. These results illuminate what was likely a serious health concern in the past and reveal how this bacterial pathogen evolved over a period of 6,500 years.

Searching for ancient pathogens

Most pathogens do not cause any lasting impact on the skeleton, which can make identifying affected archeological remains difficult for scientists. In order to identify past diseases and reconstruct their histories, researchers have turned to genetic techniques. Using a newly developed bacterial screening pipeline called HOPS, Key and colleagues were able to overcome many of the challenges of finding ancient pathogens in metagenomics data.

"With our newly developed methodologies we were able to screen thousands of archaeological samples for traces of Salmonella DNA," says Herbig. The researchers screened 2,739 ancient human remains in total, eventually reconstructing eight Salmonella genomes up to 6,500 years old - the oldest reconstructed bacterial genomes to date. This highlights an inherent difficulty in the field of ancient pathogen research, as hundreds of human samples are often required to recover just a single microbial genome. The genomes in the current study were recovered by taking samples from the teeth of the deceased. The presence of S. enterica in the teeth of these ancient individuals suggests they were suffering from systemic disease at their time of death.

The individuals whose remains were studied came from sites located from Russia to Switzerland, representing different cultural groups, from late hunter-gatherers to nomadic herders to early farmers. "This broad spectrum in time, geography and culture allowed us, for the first time, to apply molecular genetics to link the evolution of a pathogen to the development of a new human lifestyle," explained Herbig.

"Neolithization process" provided opportunities for pathogen evolution

With the introduction of domesticated animals, increased contact with both human and animal excrement, and a dramatic change in mobility, it has long been hypothesized that "Neolithization" - the transition to a sedentary, agricultural lifestyle - enabled more constant and recurrent exposure to pathogens and thus the emergence of new diseases. However, prior to the current study, there was no direct molecular evidence.

"Ancient metagenomics provides an unprecedented window into the past of human diseases," says lead author Felix M. Key, formerly of the Max Planck Institute for the Science of Human History and now at the Massachusetts Institute of Technology. "We now have molecular data to understand the emergence and spread of pathogens thousands of years ago, and it is exciting how we can utilize high-throughput technology to address long standing questions about microbial evolution."

Humans, Pigs, and the Origin of Paratyphi C

The researchers were able to determine that all six Salmonella genomes recovered from herders and farmers are progenitors to a strain that specifically infects humans but is rare today, Paratyphi C. Those ancient Salmonella, however, were probably not yet adapted to humans, and instead infected humans and animals alike, which suggests the cultural practices uniquely associated with the Neolithization process facilitated the emergence of those progenitors and subsequently human-specific disease. It was previously suggested that this strain of Salmonella spread from domesticated pigs to humans around 4000 years ago, but the discovery of progenitor strains in humans more than 5000 years ago suggests they might have spread from humans to pigs. However, the authors argue for a more moderate hypothesis, where both human and pig specific Salmonella evolved independently from unspecific progenitors within the permissive environment of close human-animal contact.

"The fascinating possibilities of ancient DNA allow us to examine infectious microbes in the past, which sometimes puts the spotlight on diseases that today most people don't consider to be a major health concern," says Johannes Krause, director at the Max Planck Institute for the Science of Human History.

The current study allows the scientists to gain a perspective on the changes in the disease over time and in different human cultural contexts. "We're beginning to understand the genetics of host adaptation in Salmonella," says Key, "and we can translate that knowledge into mechanistic understanding about the emergence of human and animal adapted diseases."

The scientists hope that the current study will illuminate the possibilities of these methods and that future research will further examine the ways that human cultural evolution has impacted and driven the evolution of human-adapted diseases.

ORLANDO, Feb. 24, 2020 - Speculation about where laws come from ranges from crediting judges and legal scholars to God.

However new research co-authored by a University of Central Florida researcher and appearing in the journal Nature Human Behaviour today offers evidence that criminal laws come from an intuitive and shared, universal sense of justice that humans possess.

"We sometimes think of the law as this completely rational enterprise that is the result of wise experts sitting around a table and working from logical principles," says Carlton Patrick, an assistant professor in the University of Central Florida's Department of Legal Studies and study co-author. "And instead, what this study suggests is that these intuitions that people tend to share about justice may be the things that are becoming institutionalized."

Patrick and Daniel Sznycer, an assistant professor of psychology at the University of Montreal and the study's lead author, made the finding by comparing modern and ancient people's sense of whether a punishment fits a crime.

And while previous studies have examined people's intuitions about justice, this is the first one that compared them across thousands of years.

Using participants from the United States and India, the researchers had people rate offenses from one of three legal codes: the Laws of Eshnunna, Sumerian laws from nearly 3,800 years ago; the Tang Code, Chinese laws from nearly 1,400 years ago; and the Criminal Code of Pennsylvania, which reflects modern U.S. laws.

Participants were shown the offenses, but not the punishments that the law established.

The crimes ranged from ancient offenses, such as not keeping an ox in check, which caused a person to be gored, to modern ones, such as assault.

Some participants were asked to determine the appropriate fines for each offense, while others were asked to determine prison sentences.

The researchers found that the more seriously modern people judged a crime to be, the higher the actual legal punishment for the crime.

This was despite participants living in different countries and legal codes that were separated by thousands of years.

"The match between participants' intuitions and ancient laws was notable," Sznycer says.

"Criminal laws, like the writing that supports those laws, are cultural inventions: present in some societies, absent in others," he says. "However, this new research adds empirical weight to the possibility that the capacity to make laws--the brain mechanisms that appraise offenses and generate justice intuitions--are universal, and a part of human nature."

Patrick says the study is an important step in helping to demystify the origin of laws.

"I think what this study does is lead us into the black box a little bit," he says. "It removes one layer of the shroud of mystery that surrounds the lawmaking process, and it also gets us closer to understanding why we sometimes feel that something's wrong, even when we can't explain why."

HOUSTON - (Feb. 24, 2020) - In one pot, at room temperature, chemists at Rice University are able to make valuable pharmaceutical precursors they say could change the industry.

The Rice group of chemist László Kürti introduced an inexpensive organic synthesis technique that catalyzes the transfer of nitrogen atoms to olefins, unsaturated organic compounds also known as alkenes.

Exposed nitrogen atoms are critical to drug discovery. The Rice process combines nitrogen and hydrogen atoms in triangular aziridine products that are readily available to react with other agents.

Most important, Kürti said, is that his lab's organocatalytic aziridination process transfers nitrogen to olefins that haven't already been modified, or functionalized.

"These unactivated olefins are commodity chemicals, but very difficult to functionalize," he said. "We are able to do that now with this chemistry under operationally simple and mild conditions."

Turning them into nitrogen-containing small molecules makes them far more useful, he said. "You can then convert them to more complex molecules," he said. "These N-H aziridines are essential building blocks."

The lab detailed its new aziridination technique in Nature Catalysis.

Kürti and his crew have been stepping toward this point for years, first eliminating expensive catalysts from the process of transferring nitrogen to arylmetals, and later taking enol ethers and transferring nitrogen to them to make amino ketones, a feedstock for the chemical industry.

"The direct amination of enol ethers was a nice breakthrough because we didn't need any catalyst," he said. "The solvent was promoting the actual nitrogen-transfer process. Then we asked if we could replace the currently used precious metal catalysts with a small organic molecule at just a fraction of the cost to make aziridines."

The new study provides a definitive yes. "This has been a dream of ours for a long time," Kürti said.

Kürti and postdoctoral associate and co-author Zhe Zhou estimated the commercially available organic small molecule catalyst needed for the process is about 4,000 times less expensive than the rhodium-based catalysts in common use. They also make the process more sustainable.

"Everybody thinks catalysis is the answer for our problems, and in many cases it's true," Kürti said. "In a difficult reaction, a small amount of catalyst will accelerate the process and save time and money.

"But many people forget the cost of the catalyst, and whether it's sustainable," he said. "Unfortunately, it's become pretty clear that we're using high-value catalysts that contain precious metals. The world supply is limited, and the prices of these metals are at best erratic."

The Rice process comes with one disadvantage, however. "It's slower than the rhodium-catalyzed process," Kürti said. "What we disclose here takes about six hours at room temperature, where the rhodium-catalyzed process, depending on the substrate, ranges between 10 minutes and a half hour.

"You definitely give up a little bit there," he said. "But six hours is tolerable if you're making big batches. That's what I hope people will recognize in the long run."

Kürti hopes to refine the process to control how the nitrogen attaches to the olefin and then, in turn, control the essential chirality, or handedness, of the product. The chirality of a drug is critical to how well it works, if at all.

Until then, the current process could be of great interest to industry, he said.

"Easier access to previously difficult-to-obtain precursors can actually influence the compound structures that chemists will make in the in the lab," Kürti said. "Simple procedures that are straightforward to use tend to dominate in pharmaceutical drug development."

Cancer cells are notorious for their genetic disarray. A tumor cell can contain an abundance of DNA mutations and most have the wrong number of chromosomes. A missing or extra copy of a single chromosome creates an imbalance called aneuploidy, which can skew the activity of hundreds or thousands of genes. As cancer progresses, so does aneuploidy. Some advanced tumors can harbor cells that have accumulated more than 100 chromosomes, instead of 46 in normal cells.

High levels of aneuploidy are associated with aggressive cancers and a poor prognosis for patients. But according to Cold Spring Harbor Laboratory investigator Jason Sheltzer and colleagues, not all aneuploidies spur cancer's progression. In the journal Developmental Cell, they report that some aneuploidies inhibit a cancer's ability to metastasize.

Sheltzer says that although aneuploidy is very common in cancer cells, it hasn't been clear whether these abnormalities help drive the disease. His team collaborated with Zuzana Storchová at the University of Kaiserslautern, developing new tools to investigate how cancer cells' behavior changes when they acquire an extra chromosome. They engineered sets of human cells that each had an extra copy of a different chromosome, but were otherwise identical.

When postdoctoral researcher Anand Vasudevan tested these cells in the laboratory, the results were surprising. "Since highly aggressive cancers tend to be aneuploid, we expected that all or most aneuploidies would contribute to metastatic behavior," Sheltzer says. "But it is actually a more complicated relationship. We found that different chromosomes can have all sorts of different impacts." Some extra chromosomes had no impact on metastasis, whereas others actually suppressed it.

Analysis of patient data revealed something similar. While survival is poorest among patients whose cancers have a high level of aneuploidy overall, the team identified certain chromosomes for which extra copies were associated with increased survival. These beneficial aneuploidies were less common than those linked to poor survival. This is probably because changes that help a tumor flourish are the ones most likely to persist as the disease progresses. Their presence indicates that the clinical impacts of aneuploidy are likely to be just as complicated as the lab experiments suggest, Sheltzer says.

Sheltzer's team is exploring the single aneuploidy that enhanced metastasis in their experiments to understand how an extra copy of that chromosome strengthens cancer cells' invasive behavior. They will also use their new aneuploid cell lines to screen for potential drugs and genetic changes that eliminate cancer cells by targeting these abnormalities.

Cameras, light barriers, and movement sensors have one thing in common: They work with light sensors that are already found in many applications. In future, these sensors might also play an important role in telecommunications, as they enable data transmission via light. At the InnovationLab in Heidelberg, scientists of Karlsruhe Institute of Technology (KIT) succeeded in making decisive progress: Printable light sensors that can see colors. The results are now reported in Advanced Materials (DOI: 10.1002/adma.201908258).

New technologies will increase the demand for optical sensors for a variety of applications, including visible light communication (VLC). VLC uses interior lighting of buildings for optical communication. In terms of security, speed, and accessibility, this technology has a number of advantages over conventional transmission processes, such as WLAN or Bluetooth. "Our research is based on the idea of combining the advantages of a special type of materials, namely, organic semiconductors, and their production by printing processes," says Dr. Gerardo Hernandez-Sosa of KIT's Light Technology Institute, one of the authors of the publication.

Semiconductors are the basis of computers, smartphones, solar cells, and many other technologies. Some of the semiconducting materials react to light by changing their conductivity. Light intensity can be measured as electrical current. Using a printer, some materials can be applied to a carrier material like printing ink. These materials react to varying wavelengths, which means that they can distinguish colors. The team of Hernandez-Sosa has now succeeded in finding a composition of materials suited for use as wavelength-sensitive light detector as well as for printing onto flexible carriers. Printing can be performed on very small to very large areas. The layout can be designed easily with the help of a computer. "High numbers of these photodetectors of any design can be produced on flexible, light materials. Hence, they are particularly suited for mobile devices," first author Noah Strobel points out.

Printing of semiconductor components is a relatively young process, but has a considerable potential for future applications. Industry is already making large investments in the production of printed OLED displays for TVs and smartphones. Printed flexible solar cells or pressure sensors are commercially available already. Production of printed light detectors has also reached the industrial scale. It is therefore highly probable that these elements will be used in many applications in future, even more so, as the demand for sensors is increasing in the internet of things, in smart cities, and in Industry 4.0.

The addition of dietary L-serine, a naturally occurring amino acid necessary for formation of proteins and nerve cells, delayed signs of amyotrophic lateral sclerosis (ALS) in an animal study.

The research also represents a significant advance in animal modeling of ALS, a debilitating neurodegenerative disease, said David A. Davis, Ph.D., lead author and research assistant professor of neurology and associate director of the Brain Endowment Bank at the University of Miami Miller School of Medicine.

The new research protocol using vervets appears more analogous to how ALS develops in humans, Dr. Davis said, compared to historic models using rodents. When he and colleagues gave the vervets a toxin produced by blue-green algae known as β-N-methylamino-L-alanine or BMAA, they developed pathology that closely resembles how ALS affects the spinal cords in humans.

When a group of these animals were fed L-serine together with BMAA for 140 days, the strategy was protective - the vervets showed significantly reduced signs of protein inclusions in spinal cord neurons and a decrease in pro-inflammatory microglia. The results were published on Thursday, February 20 at 5 a.m. EST in the prestigious Journal of Neuropathology & Experimental Neurology.

"The big message is that dietary exposure to this cyanobacterial toxin triggers ALS-type pathology, and if you include L-serine in the diet, it could slow the progression of these pathological changes," Dr. Davis said.

"I was surprised at how close the model mirrored ALS in humans," he added. Beyond looking at changes in the brain, "When we looked at the spinal cord, that was really surprising." The investigators observed changes specific to ALS seen in patients, including presence of intracellular occlusion such as TDP-43 and other protein aggregates.

Walter G. Bradley D.M., F.R.C.P., founder of the ALS Clinical and Research Center at the University of Miami Miller School of Medicine, said: "ALS is a progressive neurological disease, also known as Lou Gehrig's disease, causing progressive limb paralysis and respiratory failure. There is a great unmet need for effective therapies in this disease. After clinical trials of more than 30 potential drugs to treat ALS, we still have only two that slow the disease progression."

ALS can rapidly progress in some people, leading to death in 6 months to 2 years after diagnosis. For this reason, it is difficult to enroll people in clinical trials, a reality that supports development of a corresponding animal model, Dr. Davis said.

In addition, prevention remains essential. "This is a pre-clinical model, which is really the most important type of model, because once people have full-blown disease, it's hard to reverse or slow its progression," he added.

The research builds on earlier findings from Dr. Davis and colleagues in a 2016 study that demonstrated cyanotoxin BMAA can cause changes in the brain that resemble Alzheimer's disease in humans, including neurofibrillary tangles and amyloid deposits.

Even with the promise of L-serine, the researchers note there is a bigger picture to their new ALS animal model. "Other drugs can also be tested, making this very valuable for clinical affirmation," Davis said.

The research also has implications for Florida, as BMAA comes from harmful blue-green algae blooms, which have become more common in the summer months in Florida.

According to Larry Brand, Ph.D., professor of marine biology at the Rosenstiel School at the University of Miami, "We have found that the BMAA from these blooms has biomagnified to high concentrations in South Florida aquatic food chains, thus our seafood."

"We are very curious about how BMAA affects individuals in South Florida," Davis said. "That's our next step."

Future research could attempt to answer multiple questions, including: How common is BMAA in local seafood? What are the risks of exposure through exposure to aerosolized cyanotoxins? Is there a specific group of people who are more vulnerable from this exposure to developing diseases like Alzheimer's and ALS?

The current research would not have been possible, Dr. Davis said, without interdisciplinary collaboration both inside and outside the University of Miami. Another essential factor is the "very unique research environment" in the UM Department of Neurology. For example, the Brain Endowment Bank allows Miller School researchers access to other investigators and to essential research material.

Healthy lung cells support the survival of breast cancer cells, allowing them to hibernate in the lung before forming secondary tumours, according to new research from the Crick. The findings could help the development of new treatments that interfere with this behaviour, reducing the number of secondary cancers.

The study, published in Nature Cell Biology, used a mouse model to show that, after cancer cells from a breast tumour arrive in the lungs, a signal sent out from the lung cells causes cancer cells to change shape and grow protrusions that latch onto the lung tissue. The lung cells then protect them within the lung tissue.

By using a treatment that interferes with the growth of these protrusions on the breast cancer cells, the researchers found that mice who received the treatment grew fewer secondary tumours than the control mice.

The researchers then analysed the genes that are turned on in the hibernating cells. This enabled them to find a key gene, sFRP2, that regulates the formation of cell protrusions and the survival of breast cancer cells in the lung.

"Cancer can survive, hibernating in different parts of the body, for many years. By showing how the microenvironment around the cancer cell can support its survival, in our case how the lung cells help the breast cancer cells, opens the door to potential new treatments which target this relationship," says Erik Sahai, co-lead author and group leader of the Crick's Tumour Cell Biology Laboratory.

The cancer cells were tested over the course of up to four weeks, during which they remained inactive. In comparison, other cell types continued to remain active, showing that the hibernation of these cells is due to a special relationship they have with the lung environment around them.

"The mechanism behind how cancer cells survive in tissues they have travelled to is not yet well understood. But with many cancers spreading around the body and consequently many patients suffering from relapses, a deeper understanding of the process is vital and something we'll continue to explore," says Marco Montagner, co-lead author and former postdoc in the Crick's Tumour Cell Biology Laboratory, who is now based at the University of Padua.

Around 55,000 people in the UK are diagnosed with breast cancer each year. This cancer can spread through the blood or lymphatic system to another part of the body, commonly the lungs, liver, brain or bones. Where breast cancer spreads to the lungs, there can be a long time between the cells arriving in the lungs and the formation of a secondary tumour. This gap is one factor that explains why people may relapse a long time after the initial disease.

The researchers are continuing to explore the relationship between cancer and non-cancerous cells in a secondary location in the body. At the Crick, researchers are now studying what happens when cells from colorectal cancer and melanomas form secondary tumours in the liver. While at the University of Padua, studies are ongoing into the genes which are over-expressed in hibernating breast cancer cells.

Taking a cat to the vets can be a stressful experience, both for cat and owner. However, a study published in this month's issue of the Journal of Feline Medicine and Surgery (JFMS)1 has shown that playing cat-specific music during the visit can help.

The use of music has become increasingly popular in human medicine, with studies showing a range of benefits, from improving motor and cognitive function in stroke patients to reducing anxiety associated with medical examinations, diagnostic procedures and surgery. The benefits of music are also being investigated in cats and other animals. Research published previously in JFMS has indicated that cats that are under general anaesthesia remain physiologically responsive to music;2 furthermore, they appear to be in a more relaxed state when played classical music, compared with pop and heavy metal.3

In this latest study, researchers at Louisiana State University (LSU), USA, have taken the analysis of the impact of different types of music a step further by exploring the calming effects of music composed specifically for cats. Musical pieces that are considered pleasing to the human ear often have a beat similar to the human resting pulse rate and contain frequencies from the human vocal range. This principle has been extended to cat-specific music, which is composed of lines based on affiliative cat vocalisations, such as purring and suckling sounds, as well as frequencies similar to the feline vocal range, which is two octaves higher than for humans.

In order to assess the effects of cat-specific music, 20 pet cats enrolled in the LSU study were played 20 minutes of cat-specific music ('Scooter Bere's Aria' by David Teie - http://www.youtube.com/watch?v=vGyElqvALbY), classical music ('Élégie' by Fauré) or no music (silence) in a random order at each of three physical examinations at the veterinary clinic, 2 weeks apart. Cat stress scores, based on the behaviour and body posture of the cats, and handling scale scores, based on the cats' reactions to the handler, were assigned for each of the cats from video recordings of the examinations; neutrophil:lymphocyte ratios from blood samples were also measured to look for a physiological stress response.

The study found that the cats appeared to be less stressed during the examination - as indicated by lower cat stress scores and handling scale scores - when played the cat-specific music, compared with both classical music and no music. This effect was not reflected in the neutrophil:lymphocyte ratio, but the researchers suggest that 20 minutes may not have been long enough to allow music to affect this measure.

By decreasing stress levels, the researchers conclude that cat-specific music may not only have benefits in terms of the welfare of the cat, but owners can feel reassured that their cat will have a more comfortable visit, and the veterinary team will be able to assess their feline patients more accurately.

In search of new ways to sequence human genomes and read critical alterations in DNA, researchers at Johns Hopkins Medicine say they have successfully used the gene cutting tool CRISPR to make cuts in DNA around lengthy tumor genes, which can be used to collect sequence information.

A report on the proof-of-principle experiments using genomes from human breast cancer cells and tissue appears in the Feb. 10 issue of Nature Biotechnology.

The researchers say that pairing CRISPR with tools that sequence the DNA components of human cancer tissue is a technique that could, one day, enable fast, relatively cheap sequencing of patients' tumors, streamlining the selection and use of treatments that target highly specific and personal genetic alterations.

"For tumor sequencing in cancer patients, you don't necessarily need to sequence the whole cancer genome," says Winston Timp, Ph.D., assistant professor of biomedical engineering and molecular biology and genetics at the Johns Hopkins University School of Medicine. "Deep sequencing of particular areas of genetic interest can be very informative."

In conventional genome sequencing, scientists have to make many copies of the DNA at issue, randomly break the DNA into segments, and feed the broken segments through a computerized machine that reads the string of chemical compounds called nucleic acids, made up of the four "bases" that form DNA, and are lettered A, C, G and T. Then, scientists look for overlapping regions of the broken segments and fit them together like tiles on a roof to form long regions of DNA that make up a gene.

In their experiments, Timp and M.D./Ph.D. student Timothy Gilpatrick were able to skip the DNA-copying part of conventional sequencing by using CRISPR to make targeted cuts in DNA isolated from a sliver of tissue taken from a patient's breast cancer tumor.

Then, the scientists glued so-called "sequencing adaptors" to the CRISPR-snipped ends of the DNA sections. The adaptors serve as a kind of handle that guide DNA to tiny holes or "nanopores" which read the sequence.

By passing DNA through the narrow hole, a sequencer can build a read-out of DNA letters based on the unique electrical current that occurs when each chemical code "letter" slides through the hole.

Among 10 breast cancer genes the team focused on, the Johns Hopkins scientists were able to use nanopore sequencing on breast cancer cell lines and tissue samples to detect a type of DNA alteration called methylation, where chemicals called methyl groups are added to DNA around genes that affect how genes are read.

The researchers found a location of decreased DNA methylation in a gene called keratin 19 (KRT19), which is important in cell structure and scaffolding. Previous studies have shown that a decrease in DNA methylation in KRT19 is associated with tumor spread.

In the breast cancer cell lines they studied, the Johns Hopkins team was able to generate an average of 400 "reads" per basepair, a reading "depth" hundreds of times better than some conventional sequencing tools.

Among their samples of human breast cancer tumor tissue taken at biopsies, the team was able to produce an average of 100 reads per region. "This is certainly less than what we can do with cell lines, but we have to be more gentle with DNA from human tissue samples because it's been frozen and thawed several times," says Timp.

In addition to their studies of DNA methylation and small mutations, Timp and Gilpatrick sequenced the gene commonly associated with breast cancer: BRCA1, which spans a region on the genome more than 80,000 bases long. "This gene is really long, and we were able to collect sequencing reads which went all the way through this large and complex region," says Gilpatrick.

"Because we can use this technique to sequence really long genes, we may be able to catch big missing blocks of DNA we wouldn't be able to find with more conventional sequencing tools," says Timp.

In addition to its potential to guide treatment for patients, Timp says the combination of CRISPR technology and nanopore sequencing provides such depth that it may help scientists find new disease-linked gene alterations specific to one allele (inherited from one parent) and not another.

Timp and Gilpatrick plan to continue refining the CRISPR/nanopore sequencing technique and testing its capabilities in other tumor types.