Earth

Washington, DC - From online forums to community groups, research and experience shows people are more willing to insult and use menacing language online than in person, especially when there's the protection of anonymity behind a computer. New research appearing in Social Psychological and Personality Science indicates that people react less strongly to malicious speech on digital platforms and see the victims as less "harmed" than if the words were said directly to a person.

"Many of us are taken aback when people like Milo Yiannopoulos target and harass people on Twitter, then go on TV and say that digital words don't hurt anyone," says Curtis Puryear (University of South Florida), lead author of the study.

"Yet our data finds that Yiannopoulos's perspective resonates with many of us to some degree," says Puryear.

"We expect people to be less hurt by malicious words in certain digital contexts, and we respond with less outrage. This may make it easy to discount the experiences of victims of online harassment."

Puryear and Joseph Vandello tested people's reactions to negative comments and situations through four studies, examining reactions to malicious comments made in face-to-face and various online environments.

In one study of 270 students, people saw an image of someone participating in "nerd culture," with a comment of "go back to your mommy's basement nerd," in one of three environments: face-to-face; online with social information, such as names and photos, or online with little social information.

In another study, of 283 people, participants read a remark insulting a woman for making a comment about infrastructure, and were presented with the negative comment being made on an online forum with little social information or as taking place at a public event.

Through each study, people expressed more concern and reaction to negative comments stated in person than to those stated in a digital environment.

Comparing the digital environments, they found mixed results. The presence of more social information, from names to photos, brought about more reactions to inflammatory comments. But even when people are identifiable, they found initial evidence that inflammatory speech is less shocking in digital contexts.

The cues that help to identify people as individuals, can be dulled in the online environment, suggests Puryear. This lack of "personalization" can dampen the social cues that tell people someone is a victim, making observers less likely to experience anger or act on behalf of the victim.

Another part of the dulled reactions to comments comes from what one could describe as "numbing," either through the sheer volume of reports of harassment online, or from over-exposure of online harassment.

As more moral and social cues are communicated online, could people's attitudes change and start to reflect standards similar to in-person situations? The results depend on how we shape our online communities, say Puryear and Vandello.

Building digital platforms that depersonalize users and foster norms accepting of malicious speech may increasingly dull our responses to victimization.

"But if our norms and expectations begin to reflect that digital words really do matter then the disparity between how we react to victimization in digital and physical space may fade," says Puryear.

EXPLORER, the world's first medical imaging scanner that can capture a 3-D picture of the whole human body at once, has produced its first scans.

The brainchild of UC Davis scientists Simon Cherry and Ramsey Badawi, EXPLORER is a combined positron emission tomography (PET) and x-ray computed tomography (CT) scanner that can image the entire body at the same time. Because the machine captures radiation far more efficiently than other scanners, EXPLORER can produce an image in as little as one second and, over time, produce movies that can track specially tagged drugs as they move around the entire body.

The developers expect the technology will have countless applications, from improving diagnostics to tracking disease progression to researching new drug therapies.

The first images from scans of humans using the new device will be shown at the upcoming Radiological Society of North America meeting, which starts on Nov. 24th in Chicago. The scanner has been developed in partnership with Shanghai-based United Imaging Healthcare (UIH), which built the system based on its latest technology platform and will eventually manufacture the devices for the broader healthcare market.

"While I had imagined what the images would look like for years, nothing prepared me for the incredible detail we could see on that first scan," said Cherry, distinguished professor in the UC Davis Department of Biomedical Engineering. "While there is still a lot of careful analysis to do, I think we already know that EXPLORER is delivering roughly what we had promised.

Badawi, chief of Nuclear Medicine at UC Davis Health and vice-chair for research in the Department of Radiology, said he was dumbfounded when he saw the first images, which were acquired in collaboration with UIH and the Department of Nuclear Medicine at the Zhongshan Hospital in Shanghai.

"The level of detail was astonishing, especially once we got the reconstruction method a bit more optimized," he said. "We could see features that you just don't see on regular PET scans. And the dynamic sequence showing the radiotracer moving around the body in three dimensions over time was, frankly, mind-blowing. There is no other device that can obtain data like this in humans, so this is truly novel."

Badawi and Cherry first conceptualized a total-body scanner 13 years ago. Their idea was kick-started in 2011 with a $1.5 million grant from the National Cancer Institute, which allowed them to establish a wide-ranging consortium of researchers and other collaborators. And it got a giant boost in 2015 with a $15.5 million grant from the NIH. The funding allowed them to team up with a commercial partner and get the first EXPLORER scanner built.

Cherry said he expects EXPLORER will have a profound impact on clinical research and patient care because it produces higher-quality diagnostic PET scans than have ever been possible. EXPLORER also scans up to 40 times faster than current PET scans and can produce a diagnostic scan of the whole body in as little as 20-30 seconds.

Alternatively, EXPLORER can scan with a radiation dose up to 40 times less than a current PET scan, opening new avenues of research and making it feasible to conduct many repeated studies in an individual, or dramatically reduce the dose in pediatric studies, where controlling cumulative radiation dose is particularly important.

"The tradeoff between image quality, acquisition time and injected radiation dose will vary for different applications, but in all cases, we can scan better, faster or with less radiation dose, or some combination of these," Cherry said.

For the first time, an imaging scanner will be able to evaluate what is happening in all the organs and tissues of the body simultaneously. For example, it could quantitatively measure blood flow or how the body takes up glucose everywhere in the body. Researchers envision using the scanner to study cancer that has spread beyond a single tumor site, inflammation, infection, immunological or metabolic disorders and many other diseases.

UC Davis is working closely with UIH to get the first system delivered and installed at the EXPLORER Imaging Center in leased space in Sacramento, and the researchers hope to begin research projects and imaging patients using EXPLORER as early as June 2019. The UC Davis team also is working closely with Hongcheng Shi, director of Nuclear Medicine at Zhongshan Hospital in Shanghai to continue and expand the scope of early human studies on the scanner.

"I don't think it will be long before we see at a number of EXPLORER systems around the world," Cherry said. "But that depends on demonstrating the benefits of the system, both clinically and for research. Now, our focus turns to planning the studies that will demonstrate how EXPLORER will benefit our patients and contribute to our knowledge of the whole human body in health and disease."

It's known that cancer involves unchecked cell growth and that a biological pathway that regulates organ size, known at the Hippo pathway, is also involved in cancer. It's further known that a major player in this pathway, YAP, drives many types of tumors. Now, researchers at Boston Children's Hospital have solved an ongoing problem: how to turn this knowledge into a practical drug target. In a study published November 16 in Nature Communications, they show that YAP acts largely through another downstream player called NUAK2 that can readily be inactivated with a small molecule.

"The Hippo pathway, and especially YAP, has been hard to target with drugs," says senior study author Fernando Camargo, PhD, of Boston Children's Stem Cell Research program. "This is the first demonstration of a 'druggable' molecule that could be targeted in any type of tumor driven by YAP."

Although the study involved liver cancer, the findings could be relevant to many YAP-driven oral cancers, head and neck squamous carcinomas, pancreatic cancers, ovarian cancers and squamous cell skin cancers, Camargo adds. The team hopes to test that in future studies.

Finding a druggable cancer target

YAP is a transcription factor, a type of target that's been considered "undruggable," since transcription factors lack structural features that enable a drug to bind to them. But YAP in turn regulates the activity of many other genes, and Wei-Chien Yuan, PhD, in the Camargo lab set out to identify these genes, in hopes of finding something else to target.

Using human liver cancer cell lines and a mouse model of liver cancer, Yuan combined several assays to zero in on what downstream genes YAP influences. She found 14, then narrowed her search to kinases, enzymes that are especially amenable to being targeted with drugs. Just one emerged: NUAK2.

Further experiments showed that NUAK2 (also known as sucrose nonfermenting [SNF1]-like kinase, or SNARK) is critical for YAP-driven growth in human cancer cell lines and for liver cancer proliferation in mouse models.

Finally, they showed that a small-molecule compound that inactivates NUAK2 strongly curbed YAP-driven cancer cell proliferation and liver overgrowth.

Targeting NUAK2 has an added benefit, says Camargo, who is also affiliated with the Dana-Farber/Boston Children's Cancer and Blood Disorders Center. "It feeds back to further activate YAP itself, so inhibiting NUAK2 further decreases activity of YAP, which is exactly what you want."

Future plans

Yuan and her colleagues now hope to extend their findings.

"We know that inhibiting NUAK2 works in liver cancer. We now need to see if same mechanism is in play in other cancers," says Camargo.

They also plan to modify their small molecule, originally synthesized in the lab of Nathanael Gray, PhD, at the Dana-Farber Cancer Institute.

"We want to see if we can make the compound more selective," says Yuan, first author on the paper. "It has other nonspecific targets, so we need to modify it to make it usable."

A growth mindset

The story of YAP began over a decade ago with the discovery of the size-control pathway Hippo - so named because manipulating it in fruit flies led to growth of enormous tumors, oversized eyes and wings eight times the normal size. Larger animals with defects in Hippo were also found to have overgrown body parts, and Camargo showed that activating YAP can quadruple the size of a mouse liver. Hippo and YAP later became of interest to cancer researchers.

Bridgett vonHoldt is best known for her work with dogs and wolves, so she was surprised when a bird biologist pulled her aside and said, "I really think you can help me solve this problem." So she turned to a mystery he'd been wrestling with for more than 20 years.

"I love a good challenge and especially working on new questions!" said vonHoldt, an assistant professor of ecology and evolutionary biology at Princeton. "I was presented with a new problem in an entirely new system, which was an incredible opportunity to explore how different ecologies could promote different evolutionary patterns."

The birder and biologist was Tom Smith, who has spent his career studying finches -- specifically, black-bellied seedcrackers (Pyrenestes ostrinus) -- in Cameroon and in his lab at the University of California-Los Angeles.

He and his colleagues have spent years investigating why some of these finches have small beaks while others have large beaks. Much of their original work identified differences in the hardness of the seeds they eat, a story quite similar to that of Darwin's finches. Smith, who is a professor at UCLA as well as the founding director of the Center for Tropical Research, established a breeding colony of these finches to understand the inheritance of beak size.

The result was startlingly and elegantly simple: Mendelian genetics, best known to generations of high school students through Punnett squares. The larger beak was the dominant trait, so two small-billed parents could only have small-billed offspring, but if either parent had a large bill, their offspring would have a mix of large and small bills, perfectly matching the 3:1 pattern predicted by Gregor Mendel centuries ago.

"You never get this!" said vonHoldt with a laugh. "Traits rarely show such a clean pattern of inheritance, especially traits that are very central to fitness in a wild population."

That Mendelian pattern was the key, said vonHoldt. With new technology to analyze the entire genome, combined with the Smith's years of ecological data and insights, they had all the pieces to find and understand the genes behind this mystery.

Smith had found the Mendelian pattern in these Cameroonian birds through observation, but he hadn't been able to identify the gene responsible for it. But when vonHoldt compared the genes of the large-beaked birds to those of their smaller-beaked counterparts, she found one stretch of DNA -- 300,000 base pairs, apparently inherited as a chunk -- that always varied between finches of large and small beak size. And right in the middle of that piece of chromosome was the gene IGF-1, familiar to vonHoldt from canine genetics.

"In dogs, this is a giant gene, literally and figuratively," she said. "It's a growth-factor gene. In dogs, if you change how it's expressed, with just a few genetic changes you can change a normal-sized dog into a dwarfed, teacup-sized dog."

The gene can affect a specific trait or a whole animal, depending where it's located on the genome and when it is expressed. "If this gene is expressed more, you expect a larger trait: a larger body, a larger foot, a larger ear, whatever it is controlling. It then is easy to imagine that with a small change to this gene, traits could very easily change in size or shape. We suspect this is the story here, with these beaks," vonHoldt said.

Smith and his colleagues had already determined that beak size affected diet -- whether a finch lived on large or small seeds -- but it didn't seem to have any impact on mate selection. "Females don't prefer males with a large beak, or vice-versa," said vonHoldt.

In these birds, the bill was the only trait changing size; large-beaked and small-beaked black-bellied seedcrackers are otherwise identical. But Smith also discovered a third morph of these finches, which he called the "mega" variety, with an even bigger bill and a larger overall body size.

After examining the genes, vonHoldt discovered that the "mega" is genetically distinct from the small- and large-beaked morphs. Not only does it carry two copies of the large allele -- like the large-beaked finches -- but it also has other chromosomal changes, apparently the product of an additional evolutionary step.

VonHoldt said she appreciated the opportunity to branch out from her usual subjects. "Dogs and wolves have helped me ask the questions I find exciting, from domestication to conservation," she said, such as her work with the wolves in Yellowstone National Park. "There is so much to explore beyond canines. This was a great opportunity to make new collaborations, think about a different problem and use new methods to tackle an old question."

WASHINGTON, D.C., November 18, 2018 -- Wombats, the chubby and beloved, short-legged marsupials native to Australia, are central to a biological mystery in the animal kingdom: How do they produce cube-shaped poop? Patricia Yang, a postdoctoral fellow in mechanical engineering at the Georgia Institute of Technology, set out to investigate.

Yang studies the hydrodynamics of fluids, including blood, processed food and urine, in the bodies of animals. She was curious how the differences in wombats' digestive processes and soft tissue structures might explain their oddly shaped scat.

During the American Physical Society's Division of Fluid Dynamics 71st Annual Meeting, which will take place Nov. 18-20 at the Georgia World Congress Center in Atlanta, Georgia, Yang and her co-authors, Scott Carver, David Hu and undergraduate student Miles Chan, will explain their findings from dissecting the alimentary systems, or digestive tracts, of wombats.

"The first thing that drove me to this is that I have never seen anything this weird in biology. That was a mystery," said Yang. "I didn't even believe it was true at the beginning. I Googled it and saw a lot about cube-shaped wombat poop, but I was skeptical."

Yang and her co-authors studied the digestive tracts of wombats that had been euthanized following motor vehicle collisions in Tasmania, Australia. Carver, the biologist and Australian counterpart to the group of American mechanical engineers, supplied the wombat intestinal specimens.

Near the end of the intestine, they found that feces changed from liquidlike states to solid states made up of small, separated cubes. The group concluded that the varying elastic properties of wombats' intestinal walls allowed for the cube formation.

In the built world, cubic structures -- sugar cubes, sculptures, and architectural features -- are common, and produced by injection molding or extrusion. Cubes, however, are rare in the natural world. Currently, wombats are the only known species capable of producing cubes organically.

"We currently have only two methods to manufacture cubes: We mold it, or we cut it. Now we have this third method," Yang said. "It would be a cool method to apply to the manufacturing process -- how to make a cube with soft tissue instead of just molding it."

So, why do wombats poop cubes? Wombats pile their feces to mark their home ranges and communicate with one another through scent. They pile their feces in prominent places (e.g., next to burrows, or on logs, rocks and small raises) because they have poor eye sight. The higher and more prominently placed the pile of feces, the more visually distinctive it is to attract other wombats to smell and engage in communication. Therefore, it is important that their droppings do not roll away, and cube-shaped poop solves this problem.

Yang hopes that the group's research on wombats will contribute to current understandings of soft tissue transportation, or how the gut moves. She also emphasized that the group's research involved mechanical engineering and biology, and their findings are valuable to both fields. "We can learn from wombats and hopefully apply this novel method to our manufacturing process," Yang said. "We can understand how to move this stuff in a very efficient way."

Carver added, "There is much general interest from the public, both in Australia and internationally, about how and why wombats create cube-shaped feces. Many ideas, some more entertaining than others, have been put forward to explain this, but until this study nobody had ever investigated the cause. This has been a fantastic collaboration which shows the value of interdisciplinary research for making new scientific discoveries."

SEATTLE (November 16, 2018) - If the thought of sucking your baby's pacifier to clean it and then popping it in your baby's mouth grosses you out, think again. New research being presented at the American College of Allergy, Asthma and Immunology (ACAAI) Annual Scientific Meeting suggests a link between parental sucking on a pacifier and a lower allergic response among young children.

"We interviewed 128 mothers of infants multiple times over a period of 18 months and asked how they cleaned their child's pacifier," says allergist Eliane Abou-Jaoude, MD, ACAAI member and lead author on the study conducted by Henry Ford Health System in Detroit. "We found the children of mothers who sucked on the pacifier had lower IgE levels." IgE is a type of antibody related to allergic responses in the body. Although there are exceptions, higher IgE levels indicate a higher risk of having allergies and allergic asthma."

Of the 128 mothers completing multiple interviews, 58 percent reported current pacifier use by their child. Of those who had a child using a pacifier, 41 percent reported cleaning by sterilization, 72 percent reported hand washing the pacifier, and 12 percent reported parental pacifier sucking.

"We found that parental pacifier sucking was linked to suppressed IgE levels beginning around 10 months, and continued through 18 months," says allergist Edward Zoratti, MD, ACAAI member and co-author of the study. "Further research is needed, but we believe the effect may be due to the transfer of health-promoting microbes from the parent's mouth. It is unclear whether the lower IgE production seen among these children continues into later years."

"We know that exposure to certain microorganisms early in life stimulates development of the immune system and may protect against allergic diseases later," says Dr. Abou-Jaoude. "Parental pacifier sucking may be an example of a way parents may transfer healthy microorganisms to their young children. Our study indicates an association between parents who suck on their child's pacifier and children with lower IgE levels but does not necessarily mean that pacifier sucking causes lower IgE."

The number of critically endangered animals has been increasing in recent years. According to data from the International Union for the Conservation of Nature (IUCN), 1375 avian species are categorized as being endangered animals, and around 12% of the endangered species are avian. The conservation of endangered species is an important task for our next generation in order to maintain genetic diversity. The Okinawa rail, which is a species endemic to northern Okinawa Island, is an example of an endangered (EN) avian species. The Okinawa rail is categorized EN on the IUCN red list, because its individual numbers are estimated to be approximately 1500.

As part of the cellular conservation of endangered avian species, our group initiated a primary cell culture project aimed at preserving endangered avian species in Japan, such as the Okinawa rail. However, primary cells cannot be cultured indefinitely because of cellular senescence and stresses caused by cell culture. To overcome these cell culture limitations, primary cells have to be immortalized. Although immortalized cultured cells are useful for various functional assays or transcriptome analysis, highly efficient and reproducible immortalization methods have not been developed in avian-derived cells. We firstly introduced the simian Virus 40T antigen (SV40T) and human papillomavirus (HPV)-E6E7 to chick and Okinawa rail (endangered species) derived fibroblast. However, neither the SV40T nor E6E7 genes could induce avian cell immortality. Accordingly, we attempted to use a recently developed immortalization method, which involves the co-expression of mutant CDK4, Cyclin D and TERT (K4DT method) in these avian cells. Cellular division until the senescence was significantly extended by K4DT although the K4DT method could not induce the efficient immortalization in mass cell population. As a result, we succeeded to obtain the immortalized avian cells with K4DT expression. We conclude that the K4DT method is useful to extend the cell division and immortalization of avian-derived cells.

UCLA biologists have discovered how head injuries adversely affect individual cells and genes that can lead to serious brain disorders. The life scientists provide the first cell "atlas" of the hippocampus -- the part of the brain that helps regulate learning and memory -- when it is affected by traumatic brain injury. The team also proposes gene candidates for treating brain diseases associated with traumatic brain injury, such as Alzheimer's disease and post-traumatic stress disorder.

The researchers studied more than 6,000 cells in 15 hippocampal cell types -- the first study of individual cell types subject to brain trauma. Each cell has the same DNA, but which genes are activated varies among different cell types. Among the 15 cell types are two that were previously unknown, each with a unique set of active genes.

"Every cell type is different," said Fernando Gomez-Pinilla, a UCLA professor of neurosurgery and of integrative biology and physiology, and co-senior author of the study, which was published in the journal Nature Communications.

The biologists found that hundreds of genes are adversely affected by mild traumatic brain injury, such as a concussion. These altered genes can later lead to Alzheimer's, Parkinson's and other diseases.

The researchers reproduced a concussion-like brain injury in mice, and studied other mice that did not receive a brain injury. The researchers analyzed thousands of cells in the hippocampus of both groups of mice. Among their findings:

The mice without an injury had very low levels in 14 of the 15 cell types of a gene called Ttr that regulates metabolism, controls thyroid hormones and performs other functions. Brain trauma increased the level of Ttr in essentially all of the cell types, the researchers found. They concluded Ttr is important to brain health and may function to bring more thyroid hormone to the brain to maintain metabolism. A thyroid hormone called T4 was injected in mice. T4 improved traumatic brain injury-induced learning deficits and reversed changes in 93 genes that affect learning and memory. This reversal in damage caused by traumatic brain injury is a major new finding. After brain injury, metabolism is substantially reduced. The biologists think T4 may "reboot" metabolism.

Researchers found evidence that at least 12 of 15 cell types are negatively affected by brain trauma, some more strongly than others.

The researchers were able to see how genes that have been linked to Alzheimer's disease acted within different cell types, providing new details about where these genes act when they are affected by brain trauma. "We are learning which cell types we may want to target in future research," said Xia Yang, a senior author of the study and a UCLA associate professor of integrative biology and physiology. "Maybe Alzheimer's disease-related genes do not have to be active in all different cell types."

For the first time, the biologists found several genes that are affected by traumatic brain injury, which has recently been linked to neurotic behavior in humans. Traumatic brain injury has been associated with depression, anxiety and schizophrenia. This research could lead to new treatments for these conditions.

Injury to the brain can lead to what is known as post-traumatic epilepsy. The researchers found a gene that could serve as a potential target for treating this kind of epilepsy.

Traumatic brain injury causes changes in how cells communicate with one another (see attached image).

"Knowing which genes in which cells are changing in a particular person can lead to the right treatment for that person," said Yang, who is a member of UCLA's Institute for Quantitative and Computational Biology.

Gomez-Pinilla, who also is a member of UCLA's Brain Injury Research Center, describes the new research as an advance in precision medicine, which holds the promise of individualized treatments for diseases.

Male salmon are maturing earlier and becoming smaller, and it shows in their genes. This was the discovery of a study that examined scale samples from salmon in the River Teno in Northern Finland over a 40-year period, and looked at the population genetic profile of a gene that determines salmon's age of maturity and size. The results show that the 'big salmon gene version' has become rarer in the population over time, and has been replaced by the 'small salmon gene version'.

The study, conducted by scientists from the University of Helsinki in co-operation with Natural Resources Institute Finland and the University of Turku, was published in the journal Nature Ecology and Evolution and was featured on the magazine's November issue's cover.

Previous work by the consortium has shown that the age at which salmon mature is getting younger, and consequently also the size of salmon that are spawning is getting smaller. They also identified a single gene Vgll3 that has a large influence in determining the age at which salmon reach sexual maturity. They identified two forms or alleles of the gene that appear to signal to the salmon to either mature later at a larger size or mature earlier at a smaller size. The later salmon mature, the bigger they grow.

"We knew from our earlier research that the age at maturity had been decreasing over this period. Now we wanted to see if there were signs of this also at the genetic level, that is, whether it was an evolutionary change," professor Craig Primmer from the Faculty of Biological and Environmental Sciences at the University of Helsinki explains.

"Basically, if we see that 'salmon are shrinking', we can't be sure if it is evolution. For that, we need to know there are also changes in their genes. Now we also have that information, and we can say that we can demonstrate 'evolution in action'."

The change in genes indicates that the size decrease is not just a 'plastic' or a temporary change brought on by other factors that do not necessarily require changes in gene sequences, such as changes in hormone levels. Instead the change has an evolutionary basis. Being big is not as much of an advantage to salmon as it used to be, and the salmon are adapting to this new reality.

"This is another example de-bunking the myth that evolution takes millions of years," said Yann Czorlich, the first author of the study from the Natural Resources Institute Finland and the University of Turku. "On the one hand, this can be considered a good thing seeing it means there is hope for salmon to adapt to their changed conditions. But on the other, it's bad news for anglers want to catch big salmon and join the '20 kilogram club' as there may be fewer big salmon in the future unless we can identify and halt the factors causing their decline."

As a part of his PhD studies, Czorlich is preparing to address the reasons for why salmon might benefit from being smaller in a future paper, but one theory is that salmon today are more likely to die during their time at sea either because of fishing or other reasons, and would thus benefit from returning to the rivers to spawn sooner rather than later.

The scale samples used for the study came from a long-term scale archive maintained by the Natural Resources Institute Finland. The archive keeps samples from more than 150,000 salmon individuals collected by volunteer fishermen since the 1970's from River Teno, one of the most prolific salmon rivers in Europe. The scales were then used to determine the age structure of the salmon population. They were also the source of DNA for genetic analysis.

Dublin, Ireland: A combination of two drugs, which prompt the body's immune system to identify and kill cancer cells, is a safe treatment for patients with advanced non-small cell lung cancer and has shown some signs of efficacy.

Results from a phase I/II clinical trial in 25 patients, presented at the 30th EORTC-NCI-AACR [1] Symposium on Molecular Targets and Cancer Therapeutics in Dublin, Ireland, today (Thursday), identified the maximum tolerated doses at which NIR178 (PBF-509) and spartalizumab (PDR001) could be given to patients whose disease had either failed to respond or stopped responding to previous treatments. The disease shrank or disappeared in two patients and it remained stable, without progressing, in 14 patients.

Tumours are surrounded by blood vessels, normal cells and molecules that make up the tumour's microenvironment. In order to grow and spread, tumours recruit various molecules to suppress the body's immune system, which would otherwise recognise and kill cancer cells. Adenosine is one molecule that suppresses the immune system in the tumour microenvironment, but previous research has shown that its activity can be blocked by NIR178. Spartalizumab is a monoclonal antibody that blocks PD-1, a molecule that acts as a checkpoint to regulate the immune response.

Researchers, led by Professor Alberto Chiappori (MD) from the Moffitt Cancer Center, Tampa, USA, wanted to investigate whether the combination of these two immunotherapies might be more effective against non-small cell lung cancer than either drug on its own.

Between August 2016 and January 2018, the study enrolled 25 patients with advanced non-small cell lung cancer who had been treated already with at least one therapy and either failed to respond or relapsed. "Most of these patients were heavily pre-treated with chemotherapy, radiation and immunotherapy," said Prof Chiappori. However, they were still fairly fit, being either fully active, with everyday life unaffected by their disease, or restricted in physically strenuous activity, but able to carry out work of a light or sedentary nature (ECOG performance status 0-1). The average age was 64, 60% were men, and 44% had received prior anti-PD-1 or PD-L1 therapy.

Spartalizumab was administered intravenously at a fixed dose of 400 mg once every four weeks. NIR178 was given orally in pill form, twice daily at escalating doses of 160 mg, 240 mg and 320 mg.

By August 2018, 23 (92%) of the patients had discontinued the treatment due to disease progression (13), death for reasons unrelated to the treatment (4), adverse side effects of the treatment (4), and withdrawal of consent to continue in the trial (2). Two patients remained on the treatment.

In 14 other patients who had not received prior anti-PD-1/L1 therapies, one (7%) experienced a complete response to the treatment, with the cancer disappearing, a second (7%) had a partial response, with the cancer shrinking, and six (43%) had stable disease. In 11 patients who had been pre-treated with anti-PD-1/L1 therapies and experienced a disease progression, eight (73%) had stable disease.

The most frequent treatment-related side effects were nausea, liver problems, fatigue and an increase in the pancreatic enzyme, lipase. Two patients suffered from severe but not life-threatening (grade 3) inflammation of lung tissues. There were no life-threatening (grade 4) treatment-related side effects.

The maximum tolerated dose was determined as 240 mg of NIR178 twice daily, and 400 mg of spartalizumab every four weeks.

"This was an early phase I/II trial of the combined treatment," said Prof Chiappori. "We believe that observing responses in these heavily pre-treated patients is always a positive sign that represents the potential anti-tumour activity of the regimen and gives a preliminary measure of the importance of continuing to investigate it in further, more definitive studies. The regimen is already being tested in phase II trials of several other solid tumours and non-small cell lung cancer. We are also working on further understanding the mechanism of action of the combination of the two drugs in the body."

Co-chair of the EORTC-NCI-AACR Symposium, Professor Antoni Ribas from the University of California Los Angeles, who was not involved in the research, commented: "Non-small cell lung cancer is one of the hardest cancers to treat successfully, particularly when it has spread to other parts of the body. Increasingly, we are seeing that drugs that encourage the immune system to attack the cancer may work better together than alone. The results from this early clinical trial suggest that further testing of the combination of NIR178 and spartalizumab is warranted in this type of lung cancer."

Ever since the isolation of graphene was first achieved in 2004, there has been an explosion in graphene-related research and development, with hundreds of business opportunists producing graphene to capitalise on this rapidly expanding industry. However, a new study by researchers from the National University of Singapore (NUS) has uncovered a major problem - a lack of production standards has led to many cases of poor quality graphene from suppliers. Such practices can impede the progress of research that depend fundamentally on the use of high-quality graphene.

"It is alarming to uncover that producers are labelling black powders as graphene and selling them for top dollar, while in reality, they contain mostly cheap graphite. There is a strong need to set up stringent standards for graphene characterisation and production to create a healthy and reliable graphene market worldwide," said Professor Antonio Castro Neto, Director of the NUS Centre for Advanced 2D Materials, who led the study.

The results of the study were published in the journal Advanced Materials on 13 September 2018.

How to tell a graphene flake from a graphene fake

Graphene has been tipped as the miracle material of the future due to its remarkable properties. Despite being the thinnest material on Earth, it is 200 times stronger than steel. At just one atom thick, it is also an incredible electrical conductor, but remains light, flexible, and is transparent. Therefore, graphene is finding potential applications in everything from transistors to biomedical devices, and has even been proposed as a material for building an elevator to space.

Graphene is typically produced by exfoliating graphite, which can be found in common pencil leads, into a powder, submerging this powder into a liquid, and then separating the tiniest graphene flakes by using sound energy to vibrate the mixture. The aim of this synthesis is to produce the thinnest graphene possible. Pure graphene would be just one atomic layer thick, however the International Organization for Standardisation (ISO) states that stacks of graphene flakes up to ten layers thick can still behave like graphene.

With this in mind, Prof Castro Neto and his team set out to develop a systematic and reliable method for establishing the quality of graphene samples from around the world. They were able to achieve this by using a wide range of analytical techniques and tested samples from many suppliers.

Upon analysing samples from over 60 different providers from the Americas, Asia and Europe, the NUS team discovered that the majority contained less than 10 per cent of what can be considered graphene flakes. The bulk of the samples was graphite powder that was not exfoliated properly.

"Whether producers of the counterfeit graphene are aware of the poor quality is unclear. Regardless, the lack of standards for graphene production gives rise to bad quality of the material sold in the open market. This has been stalling the development of the future applications," elaborated Prof Castro Neto.

Graphite powder and graphene have wildly different properties, so any research conducted under the pretext that the sample was pure graphene would give inaccurate results. In addition, just one of the samples tested in the study contained more than 40 per cent of high-quality graphene. Moreover, some samples were even contaminated with other chemicals used in the production process. These findings mean that researchers could be wasting valuable time and money performing experiments on a product that is falsely advertised.

"This is the first ever study to analyse statistically the world production of graphene flakes. Considering the important challenges related to health, climate, and sustainability that graphene may be able to solve, it is crucial that research is not hindered in this way," explained Prof Castro Neto.

Overcoming the barrier to graphene innovation

With this discovery, and the development of a reliable testing procedure, graphene samples may now be held to a higher standard.

"We hope that our results will speed up the process of standardisation of graphene within ISO as there is a huge market need for that. This will urge graphene producers worldwide to improve their methods to produce a better, properly characterised product that could help to develop real-world applications," said Prof Castro Neto.

In addition, testing graphene using a universal and standardised way could ensure easy quantitative comparisons between data produced from different laboratories and users around the world.

DARIEN, IL - A new study conducted among more than 177,000 students suggests that insufficient sleep duration is associated with an unhealthy lifestyle profile among children and adolescents.

Results show that insufficient sleep duration was associated with unhealthy dietary habits such as skipping breakfast (adjusted odds ratio 1.30), fast-food consumption (OR 1.35) and consuming sweets regularly (OR 1.32). Insufficient sleep duration also was associated with increased screen time (OR 1.26) and being overweight/obese (OR 1.21).

"Approximately 40 percent of schoolchildren in the study slept less than recommended," said senior author Labros Sidossis, PhD, distinguished professor and chair of the Department of Kinesiology and Health at Rutgers University in New Brunswick, New Jersey. "Insufficient sleeping levels were associated with poor dietary habits, increased screen time and obesity in both genders."

The study results are published in the Oct. 15 issue of the Journal of Clinical Sleep Medicine.

The American Academy of Sleep Medicine recommends that children 6 to 12 years of age should sleep nine to 12 hours on a regular basis to promote optimal health. Teenagers 13 to 18 years of age should sleep eight to 10 hours.

Population data were derived from a school-based health survey completed in Greece by 177,091 children (51 percent male) between the ages of 8 and 17 years. Dietary habits, usual weekday and weekend sleeping hours, physical activity status, and sedentary activities were assessed through electronic questionnaires completed at school. Children who reported that they usually sleep fewer than nine hours per day, and adolescents sleeping fewer than eight hours per day, were classified as having insufficient sleep. Anthropometric and physical fitness measurements were obtained by physical education teachers.

A greater proportion of males than females (42.3 percent versus 37.3 percent) and of children compared with adolescents (42.1 percent versus 32.8 percent) reported insufficient sleep duration. Adolescents with an insufficient sleep duration also had lower aerobic fitness and physical activity.

"The most surprising finding was that aerobic fitness was associated with sleep habits," said Sidossis. "In other words, better sleep habits were associated with better levels of aerobic fitness. We can speculate that adequate sleep results in higher energy levels during the day. Therefore, children who sleep well are maybe more physically active during the day and hence have higher aerobic capacity."

The authors noted that the results support the development of interventions to help students improve sleep duration.

"Insufficient sleep duration among children constitutes an understated health problem in Westernized societies," Sidossis said. "Taking into consideration these epidemiologic findings, parents, teachers and health professionals should promote strategies emphasizing healthy sleeping patterns for school-aged children in terms of quality and duration."

Tokyo, Japan - Researchers from Tokyo Metropolitan University have shown that the environment-driven evolution of a unique ovipositor in the female fruit fly Drosophila suzukii may have caused coevolution of the male genitalia; new features were found to cause mechanical incompatibility during reproduction with similar species, impeding crossbreeding and isolating the species. The dual role of the female genitalia was found to trigger coevolution and speciation, a generic pathway which may apply to many other organisms.

The Drosophila suzukii fruit fly is a fruit-damaging pest. The thin, saw-like serrated ovipositor, the egg-laying organ of the female, allows it to penetrate the hard skin of ripening fruit, unlike most other species of fruit fly which prefer softer, rotting fruit. They are thus a serious problem in invaded areas, now including Europe and America where they have recently been introduced. But a team of researchers from Tokyo Metropolitan University led by Assoc. Prof. Aya Takahashi saw a unique opportunity to study how such ecologically-driven evolutionary traits might affect the coevolution of male and female genitalia. Such a study would help us understand how the specific functions of reproductive organs might influence how different species of organisms develop.

The team found that the unique ovipositor of D. suzukii had benefits for offspring, but required significant changes in the male genitalia to accommodate the obstacle during copulation. By making the cuticle transparent, the team were able to directly confirm that changes to the ovipositor had caused drastic changes in the position in which the flies copulated. This included structural changes in the male genitalia to firmly latch onto the end of the ovipositor without relying on parameres, spikes which help the male fly to latch on during sex. They confirmed that surgical changes to prevent the proper contact of the parameres to female genitalia in sibling species led to a significant decline in reproductive success, whereas D. suzukii were less affected. However, this did not somehow make them more prone to reproduce. In fact, the new morphology adopted by the male genitalia of D. suzukii made them incompatible with the shorter ovipositors of other fruit flies. This made it more difficult for crossbreeding to occur, effectively isolating D. suzukii and setting them on a different evolutionary track.

It is clear that evolution of the ovipositor was driven by a need to give offspring a better chance of survival in an open niche. However, the team's discoveries show that the dual function it plays, as a means of copulation as well as laying eggs, has caused a feedback to genital coupling mechanics, driving significant changes in the shape and function of the other sexes' genitalia and changing the evolutionary pathway the species follows in the process. Thus, their work provides a rare glimpse into how ecological changes drive the coevolution of male and female genitalia, which may be a more generic mechanism for evolution and speciation in the natural world.

The history of the peopling of the Americas has just been interpreted afresh. The largest and most comprehensive study ever conducted on the basis of fossil DNA extracted from ancient human remains found on the continent has confirmed the existence of a single ancestral population for all Amerindian ethnic groups, past and present.

Over 17,000 years ago this original contingent crossed the Bering Strait from Siberia to Alaska and began peopling the New World. Fossil DNA shows an affinity between this migratory current and the populations of Siberia and northern China. Contrary to the traditional theory it had no link to Africa or Australasia.

The new study also reveals that once they had settled in North America the descendants of this ancestral migratory flow diversified into two lineages some 16,000 years ago.

The members of one lineage crossed the Isthmus of Panama and peopled South America in three distinct consecutive waves.

The first wave occurred between 15,000 and 11,000 years ago. The second took place at most 9,000 years ago. There are fossil DNA records from both migrations throughout South America. The third wave is much more recent but its influence is limited as it occurred 4,200 years ago. Its members settled in the Central Andes.

An article on the study has just been published in the journal Cell a group of 72 researchers from eight countries, affiliated with the University of São Paulo (USP) in Brazil, Harvard University in the United States, and Max Planck Institute for the Science of Human History in Germany, among others.

According to the researchers' findings, the lineage that made the north-south journey between 16,000 and 15,000 years ago belonged to the Clovis culture, named for a group of archeological sites excavated in the western US and dating from 13,500-11,000 years ago.

The Clovis culture was so named when flint spearheads were found in the 1930s at a dig in Clovis, New Mexico. Clovis sites have been identified throughout the US and in Mexico and Central America. In North America, the Clovis people hunted Pleistocene megafaunas such as giant sloth and mammoth. With the decline of the megafauna and its extinction 11,000 years ago, the Clovis culture eventually disappeared. Long before that, however, bands of hunter-gatherers had traveled south to explore new hunting grounds. They ended up settling in Central America, as evidenced by 9,400-year-old human fossil DNA found in Belize and analyzed in the new study.

At a later date, perhaps while pursuing herds of mastodons, Clovis hunter-gatherers crossed the Isthmus of Panama and spread into South America, as evidenced by genetic records from burial sites in Brazil and Chile revealed now. This genetic evidence corroborates well-known archeological finds such as the Monte Verde site in southern Chile, where humans butchered mastodons 14,800 years ago.

Among the many known Clovis sites, the only burial site associated with Clovis tools is in Montana, where the remains of a baby boy (Anzick-1) were found and dated to 12,600 years ago. DNA extracted from these bones has links to DNA from skeletons of people who lived between 10,000 and 9,000 years ago in caves near Lagoa Santa, Minas Gerais State, Brazil. In other words, the Lagoa Santa people were partial descendants of Clovis migrants from North America.

"From the genetic standpoint, the Lagoa Santa people are descendants of the first Amerindians," said archeologist André Menezes Strauss, who coordinated the Brazilian part of the study. Strauss is affiliated with the University of São Paulo's Museum of Archeology and Ethnology (MAE-USP).

"Surprisingly, the members of this first lineage of South Americans left no identifiable descendants among today's Amerindians," he said. "Some 9,000 years ago their DNA disappears completely from the fossil samples and is replaced by DNA from the first migratory wave, prior to the Clovis culture. All living Amerindians are descendants of this first wave. We don't yet know why the genetic stock of the Lagoa Santa people disappeared."

One possible reason for the disappearance of DNA from the second migration is that it was diluted in the DNA of the Amerindians who are descendants of the first wave and cannot be identified by existing methods of genetic analysis.

According to Tábita Hünemeier, a geneticist at the University of São Paulo's Bioscience Institute (IB-USP) who took part in the research, "one of the main results of the study was the identification of Luzia's people as genetically related to the Clovis culture, which dismantles the idea of two biological components and the possibility that there were two migrations to the Americas, one with African traits and the other with Asian traits".

"Luzia's people must have resulted from a migratory wave originating in Beringia," she said, referring to the now-submerged Bering land bridge that joined Siberia to Alaska during the glaciations, when sea levels were lower.

"The molecular data suggests population substitution in South America since 9,000 years ago. Luzia's people disappeared and were replaced by the Amerindians alive today, although both had a common origin in Beringia," Hünemeier said.

Brazilian contribution

The Brazilian researchers' contribution to the study was fundamental. Among the 49 individuals from which fossil DNA was taken, seven skeletons dated to between 10,100 and 9,100 years ago came from Lapa do Santo, a rock shelter in Lagoa Santa.

The seven skeletons, alongside dozens of others, were found and exhumed in successive archeological campaigns at the site, led initially by Walter Alves Neves, a physical anthropologist at IB-USP, and since 2011 by Strauss. The archeological campaigns led by Neves between 2002 and 2008 were funded by São Paulo Research Foundation - FAPESP.

Altogether the new study investigated fossil DNA from 49 individuals found at 15 archeological sites in Argentina (two sites, 11 individuals dated to between 8,900 and 6,600 years ago), Belize (one site, three individuals dated to between 9,400 and 7,300 years ago), Brazil (four sites, 15 individuals dated to between 10,100 and 1,000 years ago), Chile (three sites, five individuals dated to between 11,100 and 540 years ago) and Peru (seven sites, 15 individuals dated to between 10,100 and 730 years ago).

The Brazilian skeletons come from the archeological sites Lapa do Santo (seven individuals dated to about 9,600 years ago), Jabuticabeira II in Santa Catarina State (a sambaqui or shell midden with five individuals dated to about 2,000 years ago), as well as from two river middens in the Ribeira Valley, São Paulo State: Laranjal (two individuals dated to about 6,700 years ago), and Moraes (one individual dated to about 5,800 years ago).

Paulo Antônio Dantas de Blasis, an archeologist affiliated with MAE-USP, led the dig at Jabuticabeira II, which was also supported by FAPESP through a Thematic Project.

The digs at the river midden sites in São Paulo State were led by Levy Figuti, also an archeologist at MAE-USP, and were also supported by FAPESP.

"The Moraes skeleton (5,800 years old) and the Laranjal skeleton (6,700 years old) are among the most ancient from the South and Southeast of Brazil," Figuti said. "These locations are strategically unique because they're between the highlands of the Atlantic plateau and the coastal plain, contributing significantly to our understanding of how the Southeast of Brazil was peopled."

These skeletons were found between 2000 and 2005. From the start, they presented a complex mixture of coastal and inland cultural traits, and the results of their analysis generally varied except in the case of one skeleton diagnosed as Paleoindian (analysis of its DNA is not yet complete).

"The study that's just been published represents a major step forward in archeological research, exponentially increasing what we knew until only a few years ago about the archaeogenetics of the peopling of the Americas," Figuti said.

Hünemeier has also recently made a significant contribution to the reconstruction of human history in South America using paleogenomics.

Amerindian genetics

Not all the human remains found at some of the most ancient archeological sites in Central and South America belonged to genetic descendants of the Clovis culture. The inhabitants of several sites did not have Clovis-associated DNA.

"This shows that besides its genetic contribution the second migration wave to South America, which was Clovis-associated, may also have brought with it technological principles that would be expressed in the famous fishtail points that are found in many parts of South America," Strauss said.

How many human migrations from Asia came to the Americas at the end of the Ice Age more than 16,000 years ago was hitherto unknown. The traditional theory, formulated in the 1980s by Neves and other researchers, was that the first wave had African traits or traits similar to those of the Australian Aboriginals.

The well-known forensic facial reconstruction of Luzia was performed in accordance with this theory. Luzia is the name given to the fossil skull of a woman who lived in the Lagoa Santa region 12,500 years ago and is sometimes referred to as the "first Brazilian".

The bust of Luzia with African features was built on the basis of the skull's morphology by British anatomical artist Richard Neave in the 1990s.

"However, skull shape isn't a reliable marker of ancestrality or geographic origin. Genetics is the best basis for this type of inference," Strauss explained.

"The genetic results of the new study show categorically that there was no significant connection between the Lagoa Santa people and groups from Africa or Australia. So the hypothesis that Luzia's people derived from a migratory wave prior to the ancestors of today's Amerindians has been disproved. On the contrary, the DNA shows that Luzia's people were entirely Amerindian."

A new bust has replaced Luzia in the Brazilian scientific pantheon. Caroline Wilkinson, a forensic anthropologist at Liverpool John Moores University in the UK and a disciple of Neave, has produced a facial reconstruction of one of the individuals exhumed at Lapa do Santo. The reconstruction was based on a retrodeformed digital model of the skull.

"Accustomed as we are to the traditional facial reconstruction of Luzia with strongly African features, this new facial reconstruction reflects the physiognomy of the first inhabitants of Brazil far more accurately, displaying the generalized and indistinct features from which the great Amerindian diversity was established over thousands of years," Strauss said.

The study published in Cell, he added, also presents the first genetic data on Brazilian coastal sambaquis.

"These monumental shell mounds were built some 2,000 years ago by populous societies that lived on the coast of Brazil. Analysis of fossil DNA from shell mound burials in Santa Catarina and São Paulo shows these groups were genetically akin to the Amerindians alive today in the South of Brazil, especially the Kaingang groups," he said.

According to Strauss, DNA extraction from fossils is technically very challenging, especially if the material was found at a site with a tropical climate. For almost two decades extreme fragmentation and significant contamination prevented different research groups from successfully extracting genetic material from the bones found at Lagoa Santa.

This has now been done thanks to methodological advances developed by the Max Planck Institute. As Strauss enthusiastically explained, much more remains to be discovered.

"Construction of Brazil's first archaeogenetic laboratory is scheduled to begin in 2019, thanks to a partnership between the University of São Paulo's Museum of Archeology and Ethnology (MAE) and its Bioscience Institute (IB) with funding from FAPESP. When it's ready, it will give a new thrust to research on the peopling of South America and Brazil," Strauss said.

"To some extent, this study not only changes what we know about how the region was peopled but also changes considerably how we study human skeletal remains," Figuti said.

Human remains were first found in Lagoa Santa in 1844, when Danish naturalist Peter Wilhelm Lund (1801-1880) discovered some 30 skeletons deep in a flooded cave. Almost all these fossils are now at the Natural History Museum of Denmark in Copenhagen. A single skull has stayed in Brazil. It was donated by Lund to the Brazilian History and Geography Institute in Rio de Janeiro.

Colonization by leaps and bounds

On the same day as the Cell article was published (November 8, 2018), a paper in the journal Science also reported new findings on fossil DNA from the first migrants to the Americas. André Strauss is one of the authors.

Among the 15 ancient skeletons from which genetic material was taken, five belong to the Lund Collection in Copenhagen. They date from between 10,400 and 9,800 years ago. They are the oldest in the sample, alongside an individual from Nevada estimated to be 10,700 years old.

The sample comprised fossilized human remains from Alaska, Canada, Brazil, Chile, and Argentina. The results of its molecular analysis suggested the peopling of the Americas by the first human groups out of Alaska did not come about merely through gradual occupation of territory concomitantly with population growth.

According to the researchers responsible for the study, the molecular data suggests that the first humans to invade Alaska or neighboring Yukon, split into two groups. This happened between 17,500 and 14,600 years ago. One group colonized North and Central America, the other South America.

The peopling of the Americas ensued by leaps and bounds, as small bands of hunter-gatherers traveled far and wide to settle in new areas until they reached Tierra del Fuego in a movement lasting one or at most two millennia.

Among the 15 individuals whose DNA was analyzed, three of the Lagoa Santa five were found to have some genetic material from Australasia, as suggested by the theory proposed by Neves for the occupation of South America. The researchers are unable to explain the origin of this Australasian DNA or how it ended up in only a few of the Lagoa Santa people.

"The fact that the genomic signature of Australasia has been present for 10,400 years in Brazil but is absent in all the genomes tested to date, which are as old or older, and found farther north, is a challenge considering its presence in Lagoa Santa," they said.

Other fossils collected during the twentieth century include the Luzia skull, found in the 1970s. Almost 100 skulls excavated by Neves and Strauss in the past 15 years are now held at USP. A similar number of fossils are held at the Pontifical Catholic University of Minas Gerais (PUC-MG).

But the vast majority of these osteological and archeological treasures, belonging to perhaps more than 100 individuals, were deposited at the National Museum in Rio de Janeiro and were presumably destroyed in the fire that raged through this historic building on September 2, 2018.

The Luzia skull was on display at the National Museum alongside Neave's facial reconstruction. Scientists feared it had been lost to the fire but fortunately it was one of the first objects to be recovered from the ruins. It had broken up but survived. The fire destroyed the original facial reconstruction (of which there are several copies).

There is widespread concern that global warming will have a strong negative effect on crop yields. Recent research published in Proceedings of the National Academy of Sciences on historical maize yields across the U.S. Corn Belt suggests that a continuation of the historical yield trend will depend on a stable climate and continued farmer adjustments.

This research, conducted by Ethan Butler, postdoctoral associate in the Department of Forest Resources in the College of Food, Agricultural and Natural Resource Sciences at the University of Minnesota and his colleagues from Harvard University and University of California, Irvine, analyzes how both climate and management have influenced the increase in yields. Overall, the research shows farmers have adapted to historical climate change. The combination of changes in climate, primarily cooling of the hottest temperatures, and farmer adjustments, including earlier planting and planting longer maturing varieties, increased maize yield trends 28 percent since 1981.

"We wanted to add the farmer into the picture of how climate change will affect crops," said Butler. "Sometimes, it feels like climate change is a juggernaut that is going to trample our way of life. In this research we've shown that farmers have already made adjustments to better align their planting practices with historical climate changes, and we hope this can be a guide to changes in the future."

Butler and the research team used a statistical model to study how rainfed maize yields reported by the U.S. Department of Agriculture (USDA) are affected by temperature using three crop development phases: vegetative, early grain filling and late grain filling. They found that planting is occurring earlier and that the late grain filling phase lasts longer. At the same time, the hottest temperatures have cooled. The earlier planting and longer grain filling are primarily associated with management decisions, while the cooling of hot temperatures appears to be an unintended benefit of widespread planting of high-yielding modern cultivars.

"One of farmers' biggest decisions is what they plant and when they plant it," said Butler. "We are seeing that farmers are planting earlier--not only because they have hardier seeds and better planting equipment--but also because it's getting warmer sooner."

The research also suggests the adjustments farmers have made have increased yields more than they would have in the absence of the historical changes in climate. However, in the Corn Belt, this means accentuating a surprisingly beneficial climate trend rather than reducing damages from a harmful change. This implies farmers have proven adept at adjusting to environmental changes, but that these benefits may evaporate in a warming climate.

It is unclear whether these historical patterns of adaptation will be maintained in a hotter environment, but farmer decisions must be considered in future analyses of how crop yields will be affected by a changed climate. The team hopes that by studying farmer adaptations, which have received relatively little attention, they will help to improve concrete actions that can be taken to reduce damages from a hotter world in the future.