Culture

DUARTE, Calif. -- In order for cancer to form in the human body, normal cells must acquire multiple mutations before they develop toward the disease. It was previously believed that these mutations acted in concert in the progression of cancer. But a new Nature study led by City of Hope's Markus Müschen, M.D., Ph.D., chair of the Department of Systems Biology and The Norman and Sadie Lee Foundation Professor in Pediatrics, uncovered a new aspect of this theory.

In a paper published today, Müschen and an international team of researchers outline their findings that individual mutations only promote progression toward leukemia if they converge on one single pathway. In addition, some mutations actually generate "noise" that drown out central elements of cancer development.

"Surprisingly, mutations that are not aligned with the central cancer pathway but instead promote growth and survival in divergent directions are counterproductive and even prevent overt transformation into cancer," said Müschen, who is the corresponding author of the new study. "The concept of multistep cancer progression suggested that acquisition of additional mutations would invariably promote cancer, but we found that many of these mutations, in fact, lead to a dead end and stop cancer progression rather than promoting it."

The team reached this conclusion after analyzing 1,148 patient-derived B cell leukemia samples to see how mutations either cooperated or antagonized each other. Current targeted therapies in cancer are based mainly on suppressing the principal driver of cancer, but the study's findings offer a previously unrecognized strategy to enhance treatment responses.

As a strategy for preventing drug resistance and relapse, Müschen and his colleagues explored an alternative approach based on reactivating suppressed pathways in order to interfere with the principal oncogenic driver and potentially amplify treatment responses.

"We have developed drug combinations that would mimic these effects," Müschen said. "Like a mutation that activates a divergent pathway, we found drugs to reactivate pathways that diverge from the central oncogenic driver to disrupt oncogenic signal transduction in these cells."

Müschen and his team are now testing various drug combinations.

"In these combinations, one drug directly inhibits the central oncogenic driver, while the second drug reactivates divergent pathways that were silenced during the transformation process," Müschen said. "If successful for leukemia, we may be able to test this approach for the treatment of other cancers."

Studies through the decades have linked higher wages to education, with the greatest returns in developing countries. However, the correlation between higher wages and education doesn't always account for an individual's innate cognitive abilities, or the mental processes of gathering and processing information to solve problems, adapt to situations and learn from experiences.

How much of those wage gains come from schooling, and how much from cognitive abilities developed long before the student sets foot in a classroom?

Data on measures of cognitive performance have been limited historically, particularly in developing countries. Using data sets that only became available in recent years, Binghamton University Assistant Professor of Economics Plamen Nikolov, and graduate students, Nusrat Jimi and Jerray Chang, analyzed the wage impact of cognitive skills in "The Importance of Cognitive Domains and the Returns to Schooling in South Africa: Evidence of Two Labor Surveys" in the August 2020 edition of Labour Economics.

Economics research dating back to the 1970s links higher wages to more education; however, it wasn't until the 1990s that economists made headway in designing research that could tease out the true causes of such phenomena rather than just the correlation, Nikolov explained.

If non-experimental studies that explore the effects of education on wages don't account for cognitive performance in addition to schooling, the wage effect of school alone will seem higher than it really is, he pointed out. While cognitive skills may be further developed in the classroom, previous economics and psychology research shows that most of these skills are developed before people start elementary school.

In addition to the innate cognitive factor, the quality of education can also impact wages. During the Apartheid period, schools in South Africa were race-based, with those of worse quality attended by Black South Africans; this system was dismantled in 1994, although disparities remain. Black South Africans often had substantially less education than their white counterparts as a result.

"It is possible that people who have better cognitive performance are likely either to do better in school or to get more schooling. In our estimation, our conceptual argument is that both cognition and schooling separately and distinctly exert a positive effect on wages," said Nikolov, the lead author, adding that the empirical analysis already accounts for other factors that could potentially affect wages, such as socio-economic factors.

Cognitive skills and wages

The study used two surveys conducted between 2002 and 2014 in two distinct areas of South Africa: urban and rural. The surveys collected extensive household information, including dimensions of cognition: memory, orientation, numeracy and attention in one, and literacy and numeracy in the other.

Findings show that each additional year of school equates to an earnings increase of 18 to 20 percent. Returns are higher in the urban sector due to the preponderance of service-oriented and technical jobs, compared to rural South Africa, which has mostly low-paying agricultural work, Nikolov said.

Urban and rural environments also show differences in which types of cognitive skills are rewarded, once again connected with the types of jobs available. In rural environments, memory and orientation -- an awareness of one's time, place and person -- are most important when it comes to higher wages. In more urban environments, earnings are connected with higher order cognitive skills, such as arithmetic, literacy and planning.

A standard deviation increase in cognitive skills -- memory in rural areas and numeracy in cities -- is roughly equivalent to one more year of school. However, an extra year of school in a developing country such as South Africa has double the rate of return as an equivalent year in a high-income country such as the United States, according to the research.

While cognitive skills may predate schooling, that doesn't mean that classrooms aren't a worthwhile investment for developing countries -- quite the opposite, in fact.

"This wage effect implies that both cognitive skills and schooling matters, but schooling matters a lot more," Nikolov said.

The European Southern Observatory's Very Large Telescope (ESO's VLT) has taken the first ever image of a young, Sun-like star accompanied by two giant exoplanets. Images of systems with multiple exoplanets are extremely rare, and -- until now -- astronomers had never directly observed more than one planet orbiting a star similar to the Sun. The observations can help astronomers understand how planets formed and evolved around our own Sun.

Just a few weeks ago, ESO revealed a planetary system being born in a
new, stunning VLT image. Now, the same telescope, using the same instrument, has taken the first direct image of a planetary system around a star like our Sun, located about 300 light-years away and known as TYC 8998-760-1.

"This discovery is a snapshot of an environment that is very similar to our Solar System, but at a much earlier stage of its evolution," says Alexander Bohn, a PhD student at Leiden University in the Netherlands, who led the new research published today in the Astrophysical Journal Letters.

"Even though astronomers have indirectly detected thousands of planets in our galaxy, only a tiny fraction of these exoplanets have been directly imaged," says co-author Matthew Kenworthy, Associate Professor at Leiden University, adding that "direct observations are important in the search for environments that can support life." The direct imaging of two or more exoplanets around the same star is even more rare; only two such systems have been directly observed so far, both around stars markedly different from our Sun. The new ESO's VLT image is the first direct image of more than one exoplanet around a Sun-like star. ESO's VLT was also the first telescope to directly image an exoplanet, back in 2004, when it captured a speck of light around a brown dwarf, a type of 'failed' star.

"Our team has now been able to take the first image of two gas giant companions that are orbiting a young, solar analogue," says Maddalena Reggiani, a postdoctoral researcher from KU Leuven, Belgium, who also participated in the study. The two planets can be seen in the new image as two bright points of light distant from their parent star, which is located in the upper left of the frame (click on the image to view the full frame). By taking different images at different times, the team were able to distinguish these planets from the background stars.

The two gas giants orbit their host star at distances of 160 and about 320 times the Earth-Sun distance. This places these planets much further away from their star than Jupiter or Saturn, also two gas giants, are from the Sun; they lie at only 5 and 10 times the Earth-Sun distance, respectively. The team also found the two exoplanets are much heavier than the ones in our Solar System, the inner planet having 14 times Jupiter's mass and the outer one six times.

Bohn's team imaged this system during their search for young, giant planets around stars like our Sun but far younger. The star TYC 8998-760-1 is just 17 million years old and located in the Southern constellation of Musca (The Fly). Bohn describes it as a "very young version of our own Sun."

These images were possible thanks to the high performance of the SPHERE instrument on ESO's VLT in the Chilean Atacama desert. SPHERE blocks the bright light from the star using a device called coronagraph, allowing the much fainter planets to be seen. While older planets, such as those in our Solar System, are too cool to be found with this technique, young planets are hotter, and so glow brighter in infrared light. By taking several images over the past year, as well as using older data going back to 2017, the research team have confirmed that the two planets are part of the star's system.

Further observations of this system, including with the future ESO Extremely Large Telescope (ELT), will enable astronomers to test whether these planets formed at their current location distant from the star or migrated from elsewhere. ESO's ELT will also help probe the interaction between two young planets in the same system. Bohn concludes: "The possibility that future instruments, such as those available on the ELT, will be able to detect even lower-mass planets around this star marks an important milestone in understanding multi-planet systems, with potential implications for the history of our own Solar System."

Cancer patients diagnosed more than 24 months ago are more likely to have a severe COVID-19 infection, research has found. Cancer patients of Asian ethnicity or who were receiving palliative treatment for cancer were also at a higher risk of death from COVID-19.

The research published today in Frontiers in Oncology by researchers at King's College London and Guy's and St Thomas' Foundation Trust, and supported by the NIHR Guy's and St Thomas' BRC, examined the relationship between cancer and COVID-19.

There are limited studies investigating cancer patients and COVID-19, with small sample sizes that have yet to distinguish between the effects of age, cancer, and other comorbidities on COVID-19 in the cancer population. It can be difficult to diagnose COVID-19 in cancer patients as symptoms can look similar to cancer symptoms and adverse effects of cancer treatments. This can result in a delayed or missed COVID-19 diagnosis, which could lead to severe infection or higher death rates.

The study analysed the outcomes of 156 cancer patients with confirmed COVID-19 diagnosis between 29 February and 12 May 2020. 82% of patients had presented with mild or moderate COVID-19 infection and 18% with severe disease at Guy's Cancer Centre, at Guy's and St Thomas' in London. Advanced statistical methods were employed to identify which demographic and/or clinical characteristics were associated with COVID-19 severity or death.

Patient follow ups conducted 37 days later found 22% of patients from the cohort had died from COVID-19 infection. Patients with Asian ethnicity, palliative treatment, or a diagnosis of cancer more than 24 months before onset of COVID-19 symptoms were at higher risk of dying. Patients who presented with dyspnoea (shortness of breath) or high CRP levels (common blood marker of inflammation) were also at higher risk of dying from COVID-19.

Severe COVID-19 infection was associated with presenting with fever, dyspnoea, gastro-intestinal symptoms or a diagnosis of cancer more than 24 months previously.

Most patients in the cohort were male, from a lower socio-economic background; half were White, 22% Black and 4% Asian. Hypertension was the most reported comorbidity followed by diabetes, renal impairment and cardiovascular disease.

The most common tumour types were urological/gynaecological (29%), haematological (18%), and breast (15%). When classified according to COVID-19 severity, the largest proportion of cancers were haematological (36%), while 40% of patients had stage IV cancer and 46% of patients were diagnosed with malignancy in the last 12 months. Benign lung conditions were more commonly reported for those who presented with severe COVID-19.

Dr Mieke Van Hemelrijck, from King's College London, said: "Large studies with detailed information on COVID-19 safety measures and oncological care are urgently warranted to explore the intersection of COVID-19 and cancer in terms of clinical outcomes, so as to inform oncological care during this outbreak and potential future pandemics. Our findings provide a first insight into possible effects of cancer and its treatments on COVID-19 outcomes."

Dr Saoirse Dolly, Consultant Medical Oncologist, Guy's and St Thomas' and King's College Hospital, said: "We report the first large UK single Centre analysis. Over 11 weeks, 1507 cancer patients were PCR tested for COVID-19. 156 (10%) were positive for COVID-19 infection and 18% developed severe infection and 34 patients had sadly died (22%). Age, gender, ethnicity or cancer treatment were not associated with severity of COVID-19 infection. With median of 37 days follow-up, Asian ethnicity, being on palliative treatment or having cancer for more than 2 years was positively associated with COVID-19 related death.

"This real-world observation provides valuable insights into our cancer patients during the COVID pandemic. The data needs to be validated in larger series with longer follow-up of patients to provide more definitive guidance on the management of oncology patients through the COVID-19 outbreak."

COLUMBUS, Ohio - Your perceptions of someone you just met are influenced in part by what they look like and how they sound.

But can you ignore how someone looks or how they sound if you're told it is not relevant?

Probably not, at least in most cases, a new Ohio State University study found.

For example, some study participants were shown a photo of a face and heard a brief snippet of speech at the same time and were told that the photo and voice belonged to different people.

In some cases, participants were told to rate how strong an accent they thought the person shown in the photo would have.

Participants thought the person in the photo would have a more accented voice if the words they heard also had a stronger accent - despite being told the image and sound represented two different people.

"Even though we told them to ignore the voice, they couldn't do it completely," said study author Kathryn Campbell-Kibler, an associate professor of linguistics at Ohio State.

"Some of the information from the voice seeped into their evaluation of the face."

The same was true when participants were asked to evaluate how "good-looking" the person with a particular voice was - they were influenced by the photo they viewed, even when told it was a different person from the speaker they heard.

Although study participants usually could not ignore the irrelevant information, there was one intriguing exception in which participants feared showing a racial stereotype when it came to gauging accented voices.

The study was published online this week in the Journal of Sociolinguistics.

The study included 1,034 people who visited an exhibit hosted by Ohio State's Department of Linguistics at the Center of Science and Industry, a science museum in Columbus.

Participants were shown photos of 15 men on a television screen. As each photo was shown, they heard a single-word recording repeated three times over the course of five seconds, also by one of 15 men. Depending on what group they were in, participants had to rate how accented or good-looking the face or the voice was.

Some of the speakers these study participants heard had been rated by people in a previous study as sounding relatively unaccented. Other voices were from people who had learned English at older ages and had been rated as having more of an accent.

When participants evaluated the combined face and voice and were not told to ignore anything, they evaluated "good-looking" mostly based on the face, and "accented" on the voice - as expected.

But some people were told to evaluate the face while ignoring the voice, or evaluate the voice while ignoring the face, because they represented two different people.

In those cases, some people evaluated the face on the "good-looking" dimension and some evaluated the face on the "accented" dimension. The same was true for evaluating the voice. In both cases, they had to ignore the other input, voice or face.

"We found that people could exercise some control over what information to favor, the voice or the face, depending on what we told them to do," Campbell-Kibler said.

"But in most cases, they were unable to entirely eliminate the irrelevant information."

There was one exception: People were able to completely ignore the face when rating how accented the voice sounded.

Campbell-Kibler said the reason seems to be that the participants, most of whom were white, were being careful not to show any racial stereotyping.

"Some of the participants explicitly told us they were attempting to avoid responses that could be seen as stereotypical," she said.

They knew that how a person looks has no real connection to how they sound, even though racial stereotypes often prompt people to associate strong accents with people who don't look white.

"They sensed a danger is showing racial bias when it came to evaluating accents. That's why they were careful to exclude what the face looked like when evaluating if the voice sounded accented," Campbell-Kibler said.

"They didn't have that issue when evaluating 'good-looking,' because that is seen as subjective enough that you can't really be wrong," Campbell-Kibler said.

Because this study used photographs rather than video, the audio people heard had a stronger influence on them than it might in real life, she said. Videos would probably have a stronger effect on people's evaluations than these still images.

But the main message is the same: We are influenced by all the information we have available, whether it is applicable or not.

"It is hard to ignore socially relevant information your senses perceive, even if we tell you it is not relevant to the task you have right now," Campbell-Kibler said.

TORONTO, CANADA - We have known for decades that mental health plays an important role in one's quality of life, but a study released this week suggests it is also an important factor in one's quantity of life.

A new University of Toronto study that followed 12,424 adult Canadians from the mid-1990s until 2011 found that those who were in suboptimal mental health at the beginning of the study died, on average, 4.7 months earlier than their peers who were in excellent mental health.

The study took into account the 'usual suspects for premature mortality' including the respondents' functional limitations; health behaviors, such as smoking, heavy drinking and physical activity level; physical diseases, such as cancer, heart disease, diabetes, and chronic pain; and social support at baseline.

"Ever after fully adjusting for these risk factors, we still found that those with suboptimal mental health at the beginning of the study had a 14% higher risk of all-cause mortality over the 18 years of the study," says Esme Fuller-Thomson, lead author of the study. Fuller-Thomson is Director of the University of Toronto's Institute for Life Course and Aging and Professor at the Factor-Inwentash Faculty of Social Work (FIFSW) and the Department of Family and Community Medicine.

A dichotomous flourishing indicator was created to identify people who were happy and satisfied with life and had good psychological functioning at baseline (in 1994 and 1995), in contrast to those with suboptimal mental health.

"The flourishing scale we developed set a very high bar," reports Yu Lung, a doctoral student at the FIFSW.

In 1994 and 1995, 81% of the sample were flourishing and 19% were in suboptimal mental health.

"The findings of this Canadian study are in keeping with my previous research in the US, where I found that baseline suboptimal mental health was associated with higher 10-year mortality," says co-author Corey L.M. Keyes, Professor of Sociology at Emory University in Atlanta.

Unfortunately, the study's secondary data analysis did not have sufficient information to understand why excellent mental health is associated with longer life.

"We have several hypotheses that we would like to investigate in future research," says co-author Keri J. West, a doctoral candidate at the FIFSW. "Previous research has found that positive affect is associated with lower levels of cortisol, reduced inflammation, and better cardiovascular activity. Furthermore, individuals with high levels of mental well-being are more likely to consume nutritious foods, adhere to treatment regimens, maintain strong social ties, and have better sleep quality, which may contribute to longevity."

In addition to mental health, the researchers looked at other factors at baseline that were associated with premature mortality.

"As expected, modifiable risk factors, including smoking, heavy drinking, and infrequent physical activity, were associated with a higher probability of all-cause mortality," reports co-author Philip Baiden, Assistant Professor of Social Work at the University of Texas at Arlington. "Cancer, heart disease, diabetes, chronic obstructive pulmonary disease, and high blood pressure were associated with a higher probability of death over the follow-up period."

The researchers examined data from a nationally representative sample of 12,424 respondents aged 18 years and older in the Canadian National Population Health Survey. Participants were first interviewed in 1994 and 1995 (wave 1) and then were followed until 2010 and 2011 (wave 9). Mortality data was ascertained by the Canadian Vital Statistics-Death Database in wave 9. By the end of the study period, 2,317 of the participants had died. This research was published online ahead of press this week in the Journal of Psychosomatic Research.

"The association between suboptimal mental health and premature death is a robust relationship that is independent of health conditions, pain, functional limitations, and negative health behaviors at baseline," says Fuller-Thomson. "Our findings underline the importance of considering the mind and body as a true continuum."

Pinto beans are good for us. They are nutritious, packed with protein and fiber. They also contain a host of micronutrients like B vitamins and folate.

But being good isn't enough for pinto beans. They also need to look good.

Typically, pinto beans have a striking mottled pattern of dark and light brown. However, the beans can darken after harvesting.

Consumers perceive pinto beans with darker colors to be older, harder to cook, and less nutritious than lighter beans.

"We eat with our eyes," says Juan Osorno. Osorno is a researcher at North Dakota State University.

And it's not only consumers who are skeptical about dark pinto beans. "Farmers see darker pinto bean seeds as being of poorer quality," says Osorno. "And when farmers try to sell darker beans, they often have to accept discounted prices."

That's a big deal because pinto beans are the most common type of dry bean grown and consumed in the United States.

In the recent study, Osorno and colleagues describe the process of developing a promising new variety of slow-darkening pinto bean. "The study found no major differences in the agronomic performance of regular versus the slow-darkening pintos," says Osorno.

He believes these slow-darkening pinto beans can be a good alternative for the existing pinto bean value chain. "Both farmers and consumers will benefit from it in many ways," he says.

For example, the slow-darkening beans cooked faster than regular beans. Needing less time to cook can be a great benefit in areas where cooking fuel is scarce.

The key advancement has been improving agronomic performance - such as yield and bean size - of the slow-darkening beans. That's huge progress, because past plants with the slow darkening gene have had many issues associated with agronomic performance.

For example, one older variety of slow-darkening pinto beans has low yields. Another won't flower under farming conditions in the United States. Yet another grows in such a way that it makes mechanical harvesting of the beans difficult.

At the root of these difficulties lies pinto bean genetics. Physical characteristics, such as yield, bean size, or rate of darkening, are all affected by one or more genes.

Turns out, a single gene - aptly named slow darkening or SD - controls how quickly pinto beans darken after harvesting. Researchers can breed this gene into new pinto bean varieties fairly easily without creating a genetically modified organism (GMO).

But whenever they incorporated this gene in the past, other genes responsible for lower yields or smaller beans would come along with the slow darkening gene.

Osorno and colleagues tested several varieties of slow-darkening and regular pinto beans over the past decade. The tests were carried out in research plots in Washington and North Dakota.

The researchers compared traits such as seed weight, yield, and cooking time between slow-darkening and regular pinto beans.

The initial tests - from 2010 to 2012 - did not yield encouraging results. The slow-darkening beans performed poorly compared to regular pinto beans.

But the latest round of field trials using slow-darkening pinto beans was more promising. According to the 2018 tests, the newer slow-darkening pinto bean varieties are catching up to regular varieties in yield and bean size.

In fact, a second generation of slow-darkening pinto beans is already showing higher yields compared to the previous generation.

Osorno is encouraged but says there's still work to be done. "Remember that breeding yields gains in a stepwise manner rather than through big jumps," he says.

As the SARS-CoV-2 virus, or COVID-19 has unfurled its tentacles across the globe, the severe respiratory and pulmonary disorders associated with the infection have become well known. However, recent case studies also have strongly suggested the presence of cerebrovascular-neurological dysfunction in COVID-19 patients, including large artery ischemic strokes that originate in one of the brain's larger blood-supplying arteries such as the carotid.

Luca Cucullo, Ph.D., and other researchers from the Texas Tech University Health Sciences Center (TTUHSC) have for years studied the effects smoking and vaping have on the cerebrovascular and neurological systems. Their research, and that of others, has shown smokers of tobacco and vaping products are more vulnerable to viral and bacterial infection than are non-smokers.

Based on those findings and the recent COVID-19 patient case studies, Cucullo and TTUHSC graduate research assistant Sabrina Rahman Archie reviewed the role smoking and vaping may play in the cerebrovascular and neurological dysfunction of those who contract the virus. Their study, "Cerebrovascular and Neurological Dysfunction under the Threat of COVID-19: Is There a Comorbid Role for Smoking and Vaping?" was published May 30 in the International Journal of Molecular Sciences.

In his previous research, Cucullo demonstrated how tobacco smoke can impair a person's respiratory function. From there, it can affect the vascular system and eventually the brain. Because COVID-19 also attacks the respiratory and vascular systems, he and Archie wanted to see if there were any reported cases indicating the virus may also affect the brain and lead to the onset of long-term neurological disorders like ischemic strokes. They also looked for evidence showing smoking and vaping can otherwise worsen the outcomes for COVID-19 patients, which Cucullo said seems to be the case.

Archie said some case studies demonstrate there are indeed stroke occurrences in COVID-19 patients and the rates appear to be increasing every day. In fact, one study comprised of 214 patients found that 36.45% of COVID patients had neurological symptoms, further indicating the virus is able to affect the cerebral vascular system. But how does this happen?

There are within the human body approximately 13 blood coagulation factors that can be increased due to hypoxia, a condition that occurs when the body is deprived of sufficient amounts of oxygen at the tissue level, as occurs with smoking. Archie said COVID-19 appears to also raise some blood procoagulant, especially the von Wellebrand Factor, a blood clotting protein that primarily binds carries coagulation factor VIII and promotes platelet adhesion at the site of wounds.

"When the coagulant factor will be increased in our body, there will be a higher chance of clot formation," Archie explained. "Ultimately, it will be responsible for several vascular dysfunctions, for example, hemorrhagic or ischemic stroke."

Because COVID-19 and smoking or vaping each increases blood coagulation factors that may eventually affect the cerebral vascular system, Cucullo believes the stroke risk may be higher still for COVID-19 patients who smoke.

"COVID-19 seems to have this ability to increase the risk for blood coagulation, as does smoke," Cucullo added. "This may ultimately translate in higher risk for stroke."

Recent clinical study data also shows some of the damage caused by COVID-19, especially to the respiratory system, is permanent. Cucullo said the same data indicates that patients who recover from COVID-19 still have an elevated risk for stroke and that age and physical activity don't seem to be factors. Some of those with the highest risk factors for long-term problems related to COVID-19 are young adults in their 20s and 30s who were active and considered to be in their physical prime.

"After COVID-19, some of those can barely take few steps without having breathing issues, so the recovery, it's kind of formal recovering, but some of these long-term effects remain," he added.

In addition to impairing the immune and vascular systems and triggering cerebrovascular and neurological dysfunction, smoking and vaping often worsen the outcomes for patients who contract influenza or other respiratory or pulmonary diseases. Because COVID-19 appears to affect many of the same systems within the body, Cucullo said it would seem logical to think the health risks are increased for COVID-19 patients who smoke, but the virus is too new to know for certain.

"We don't even know whether COVID-19 can get into the brain because nobody has actually checked for it yet," Cucullo said. "I think it's very early for this kind of study; the prime clinical concern is either a vaccine or trying to alleviate the symptoms, in particular the respiratory symptoms, so they didn't even get that far. We are planning to do something from that point of view; this is something we will definitely research."

Dr. Herbert asks what if our genome was far smarter than everyone previously believed? What if in the many DNA repeat elements lay the foundation for building a novel type of biocomputer? This approach would enable calculations performed with self-renewing wetware rather than stone-cold hardware, opening the door to logic circuits based on DNA that flips from one state to another, analogous to the way silicon switches "on" and "off".

How might this kind of DNA computer work? Simple repeats are called that because the DNA sequence repeats itself over and over again a number of times. The repeats actually are great for building DNA structures with useful properties. Instead of the everyday B-DNA described by Watson and Crick, repeats of certain DNA sequences can morph into some rather exotic higher-energy 3D structures. They can form left-handed duplexes, three-stranded triplexes, and four-stranded quadruplexes. The different DNA structures change how information is read out from DNA to make RNA.

Those repeat sequences that are able to switch from one DNA structure to another are called flipons. Collectively, Dr. Herbert refer to these flipons and their associated functionality as fliponware. Fliponware sets the stage for a cell to make the right wetware tools and run the right genetic program to get the job at hand done. It allows assembly of gene pieces into different RNA-based programs for a cell to overcome challenges from its environment.

Dr. Herbert provides examples of how flipons can be used to create genetic programs, describing ways they can be wired into the logic gates that computers need to function. The flipon logic gates can perform 'AND' or 'NOT' operations. Many can be combined to perform the Boolean operations essential to a universal computer as first described by Turing. Their use in the genome for logical operations resembles how Turing machines work, but instead of a Turing tape, the cell uses RNA to record the results. The series of processing steps decides whether the RNA message is stable or not and the genetic program to execute.

Many of the novel RNA assemblies are trashed without ever being used--they may not be needed or their assembly is defective (equivalent to a FALSE result from a Turing machine). Those messages that persist become the codonware of the cell (logically the same as a TRUE result from a Turing machine). The codonware that results then defines the cell's biology by the wetware they direct the production of..

This form of computation differs from previously described DNA computers built without flipons. These other devices depend on whether or not pairs of DNA sequences match each other. If they do, the matches enable the next calculation step. Flipon computers differ in many ways from those using DNA matching. First, some flipons switch very fast (in milliseconds) because all they need to do is change from one 3D structure to another without the need to search for a matching DNA to pair with. Turning a flipon ON or OFF is possible in many different ways. For example, just stretching the DNA can cause flipons to morph, or they can flip due to a change in temperature or variations in salt concentration.

The combination of fliponware, wetware and codonware is analogous to program code, machine language and hardware in a silicon computer. Each of these bioware sets has memory to enable learning. They use error correction to prevent bad outcomes. While flipons are made with simple sequences, codonware is made from complex sequence mixes. The information provides the cell very detailed information on the wetware to make. In simple terms, fliponware instructs which tools to use for a particular job, codonware tells how to make the tools, and wetware does the job.

Dr. Herbert adds, "I expect that soon there will be many exciting and beneficial applications for fliponware. Simple sequences are not your grandparent's junk--instead they are like the rules of thumb that simplify life, acquired over many years of evolution."

Fliponware has several immediate applications:

1. Therapeutic applications (target drugs to flipon states that enable cancers or inflammatory diseases)
2. Biosensors (to detect environmental changes)
3. Persistent DNA memory (exploiting the extreme stability of quadruplexes after they form)
4. Cellular switches (change of output in response to a change of input)
5. Novel DNA nano-architectures (the 3D structure formed depends on flipon state)

COLUMBUS, Ohio -- Just a few negative online restaurant reviews can determine early on how many reviews a restaurant receives long-term, a new study has found.

The study, published online earlier this month in the journal Papers in Applied Geography, also found that a neighborhood's median household income affected whether restaurants were rated at all.

"These online platforms advertise themselves as being unbiased, but we found that that is not the case," said Yasuyuki Motoyama, lead author of the paper and an assistant professor of city and regional planning at The Ohio State University.

"The way these platforms work, popular restaurants get even more popular, and restaurants with some initial low ratings can stagnate."

The study evaluated reviews in Franklin County, Ohio, from the websites Yelp and Tripadvisor of about 3,000 restaurants per website. Franklin County, home to Columbus and Ohio State, is also home to the headquarters of more than 20 restaurant chains. Previous research has found that the food industry considers consumer preferences in the area to be a litmus test for the broader U.S. market.

The researchers collected reviews for restaurants published in May 2019, then analyzed those reviews by rating and geographic location. They considered demographics for each neighborhood, and noted the socioeconomics of each neighborhood, too, based on household income.

The study found that restaurants with a smaller number of reviews on sites like Yelp and TripAdvisor had higher likelihood of a low rating.

"The more reviews a restaurant received, the higher the average rating of the restaurant," said Kareem Usher, co-author of the paper and an assistant professor of city and regional planning at Ohio State. "But this has implications: If one of the first reviews a restaurant receives comes from a dissatisfied customer, and people check that later and think 'I don't want to go there' based on that one review, then there will be fewer reviews of that restaurant."

The opposite is true for restaurants that receive positive reviews or a large number of reviews: More people are likely to review those restaurants, improving the likelihood that a restaurant's average rating will be higher.

The study found that 17.6 percent of restaurants with only one to four reviews received a low rating on Yelp. But that decreased to 9.3 percent for those with between five and 10 reviews. On Tripadvisor, those with one to four reviews had a 5.6 percent probability of having a poor review, going down to 0.6 percent for those with five to 10 reviews.

Researchers also found that restaurants in several of the poorest neighborhoods in Franklin County tend not to be rated on the sites. However, the researchers did not find a direct link between a neighborhood's socioeconomics or racial makeup and the average rating of the restaurants there.

Motoyama cautioned that the study had some limits: It was conducted in one county, and future work could expand to include other areas around the country. The high level multivariate analysis could only use the Yelp data, as the majority of key information in Tripadvisor was missing. The researchers also did not analyze the content of the reviews, which could offer additional clues about bias.

But, he said, the study does indicate that online review sites can have significant effects on a restaurant's success or failure - and suggests that, perhaps, the sites can set up policies that might be more fair.

"Maybe these online platforms can withhold reviews until a restaurant gets a certain number of reviews - say, 10 or more," he said. "That way if there are two or three customers who are very dissatisfied with a particular experience, they are not directing the restaurant's success or failure."

Correction Note:

Due to a math miscalculation in the study, a previous version of this release contained an error in the rate at which COVID-19 antibodies decline after infection. The correct rate is 36 days, not 73 as previously reported, which is actually a more dramatic rate of decay. The change is reflected under the findings section of the release.

FINDINGS

A study by UCLA researchers shows that in people with mild cases of COVID-19, antibodies against SARS-CoV-2 -- the virus that causes the disease -- drop sharply over the first three months after infection, decreasing by roughly half every 36 days on average. If sustained at that rate, the antibodies would disappear within about a year.

BACKGROUND

Previous reports have suggested that antibodies against the novel coronavirus are short-lived, but the rate at which they decrease has not been carefully defined. This is the first study to carefully estimate the rate at which the antibodies disappear.

METHOD

The researchers studied 20 women and 14 men who recovered from mild cases of COVID-19. Antibody tests were conducted at an average of 36 days and 82 days after the initial symptoms of infection.

IMPACT

The findings raise concerns about antibody-based "immunity passports," the potential for herd immunity and the reliability of antibody tests for estimating past infections. In addition, the findings may have implications for the durability of antibody-based vaccines.

A plant pathologist at Cornell University, Sarah J. Pethybridge supplies New York vegetable growers with the information they need to control soilborne diseases and adopt effective management strategies. She crafts her research around conversations with table beet growers about productivity issues in the field. These growers continuously expressed frustration with maintaining healthy foliage.

Cercospora leaf spot (CLS), which appears as small gray to black-colored lesions on leaves, is the dominant disease affecting table beet foliage in New York. CLS epidemics occur annually and can lead to defoliation and significant crop loss as healthy leaves are important to facilitate harvest by top-pulling.

Growers control CLS using fungicides. Through current management practices, growers begin spraying fungicides once they see one lesion per leaf then continue applying fungicides on a calendar basis.

Pethybridge and her team conducted a study to examine the efficacy of this treatment using three different fungicides and assessed the potential of using a risk-based model to improve fungicide timings. They found that two of the fungicides significantly improved CLS control if treatment was applied before the pathogen was present while the third fungicide worked best based on the current treatment model. Moreover, application of the first two fungicides were reduced from three to two using a weather-based risk model.

"This shows there is an opportunity to reduce spray frequency by scheduling on weather-based risk rather than calendar applications," Pethybridge explained. "But different fungicides vary in the optimal risk threshold. The action thresholds and risk thresholds need to be assessed for each fungicide to be used for optimal disease management, but there are opportunities for improving disease control and reducing fungicide use with these tactics."

Use of a weather-based decision support system to schedule fungicides for the control of CLS in table beet reduces unnecessary expense to the grower and unnecessary exposure of a fungal population to single-site modes of action posing a high risk of resistance development. For more information, read "Optimizing Cercospora Leaf Spot Control in Table Beet Using Action Thresholds and Disease Forecasting" in Plant Disease.

Mental health declined substantially after the first month of COVID-19 lockdown, a survey of UK households published today in The Lancet Psychiatry journal suggests.

Among the 17,452 people who responded to the survey, the average level of mental distress increased in April 2020, compared to average scores before the pandemic (1.1 point increase in average mental distress score, from 11.5/36 points to 12.6/36 points). This increase in mental distress was 0.5 points higher than would be expected based on upward trends that have been observed over the past five years.

During late April 2020, more than one quarter of study participants reported a level of mental distress that is potentially clinically significant (27.3%), compared with one in five people before the pandemic (18.9%). However, the researchers stress their study is based on survey responses rather than clinical assessment and this does not mean that one in four people has a clinical mental illness.

The study reveals that some mental health inequalities that were present before the pandemic have widened. The increase in mental distress was greater among women than men (women: average adjusted increase of 0.92/36, men: 0.06/36), and in younger age groups than older people (16-24 year olds average adjusted increase: 2.69 points, 70 and over average increase: 0.17 points).

The findings also reveal new mental health inequalities after one month of lockdown, with people living with young children showing greater increases in mental distress than people from child-free homes.

The researchers say the increase in mental health distress in April 2020 may represent a spike in emotional response that might have stabilised or reduced as people adjusted to the restrictions imposed on daily life. However, as the economic fallout from the pandemic progresses, when furloughs turn into redundancies and mortgage holidays time out, the researchers say mental health inequalities will likely widen and deepen and must be monitored closely so that steps can be taken to mitigate against a rise in mental illness in these groups.

Dr Matthias Pierce, a co-author from the University of Manchester, said: "This is the first peer-reviewed study to track changes in UK population mental health from before the COVID-19 pandemic and into the subsequent lockdown period. Previous studies have focused on specific groups, such as key workers, rather than a random sample of the whole population. And many have used non-validated measures of mental health, or lacked comparable pre-COVID-19 baseline data against which to measure change." [1]

The latest findings are based on a long-term study of more than 40,000 UK households that has been tracking the mental health of the nation at annual intervals for more than ten years, called the UK Household Longitudinal Study (UKHLS).

The researchers used the 12-item General Health Questionnaire, which is a validated tool for measuring levels of mental distress. Participants are asked to reflect on the previous two weeks and report how often they have experienced symptoms such as difficulties sleeping or concentrating, problems with decision making or feeling overwhelmed. Each question is rated between 0 and 3, giving a total potential score of 36, where higher scores represent higher levels of mental distress. The researchers defined a clinically-relevant threshold of mental distress as experiencing four or more different symptoms at a higher level than usual. This was used to calculate the proportion of respondents experiencing clinically-relevant levels of mental distress.

Between 23 and 30 April 2020, one month after the UK lockdown was introduced, people who had responded to the most recent UKHLS surveys were invited to complete an online version of the questionnaire.

Some 17,452 people responded to the online survey out of a total study population of 42,330. All those included in the study were aged 16 and over in April 2020. Baseline data of mental health levels before the pandemic were available for comparison for 15,376 participants who were aged over 16 when they responded to either of the two previous UKHLS questionnaires.

The results highlight mental health inequalities that were present before the pandemic. Women had higher levels of mental distress than men on average (women: 13.6/36, men: 11.5/36). When comparing data from individuals from before and after lockdown and adjusting for prior trends, women also showed a greater increase in mental distress (women: average increase of 0.92/36, men: 0.06/36). Around one in three women had a score above the clinically-relevant threshold compared with one in five men (women: 33.3%, men: 20.4%). However, the researchers say mental distress in men may be more likely to manifest in ways not captured by the General Health Questionnaire, such as alcohol misuse, and further research is needed to examine this.

When scores from individual participants were compared before COVID-19 and in April 2020, the greatest increase in mental distress was seen in young people aged 18 to 24 (average increase of 2.69 points) and those aged 25 to 34 (average increase of 1.57 points), after adjustment for prior trends and other factors.

Other mental health inequalities that were present before the pandemic persisted, but did not widen. People living without a partner (13.8/36) and those with a pre-existing health condition that would make them more vulnerable to COVID-19 infection (13.7/36) had higher levels of mental distress than the average population (12.6/36). However, comparison of individuals' responses before and after lockdown did not reveal a larger than average increase in mental distress for these groups.

Mental distress was more common among people living in low income households (average score 13.9/36 in households of lowest income, compared with 12.0/36 for highest income homes). In addition, people who were unemployed before the lockdown had higher mental distress scores than those in employment (unemployed: 15.0/36, employed: 12.5/36).

However, the increase in mental distress relative to prior trends was greater among those who had jobs before the pandemic (average increase 0.63/36 points for employed vs -0.48/36 points for unemployed, after adjusting for other factors). This group includes those who may have been furloughed, lost their job or worried about losing their job, as well as those shifting to working from home. The researchers say this trend should be monitored closely as the effects of the pandemic on employment take hold and expected redundancies come to fruition.

Another inequality that emerged is that people living with young children aged 5 and under also showed a substantial increase in levels of mental distress scores (average increase of 1.45/36 points), compared with child-free households (average increase of 0.33/36 points).

There were too few responses to examine changes in mental health within ethnic groups from before and after the pandemic. However, average mental distress scores were higher for Asian people than white British (Asian: 13.7/36, white British: 12.5/36), but the the study was not powered to detect a change for other ethnic groups.

Key workers had a similar average score of mental distress to the general population (keyworker: 12.7/36, general population: 12.6/36), but were more likely to have a score above the clinically relevant threshold (keyworker: 29.9%, general population: 27.3%).

Sally McManus, joint senior author, of City, University of London, UK, said: "The pandemic has brought people's differing life circumstances into stark contrast. We found that, overall, pre-existing inequalities in mental health for women and young people have widened. At the same time new inequalities have emerged, such as for those living with pre-school children. These findings should help inform social and educational policies aimed at mitigating the impact of the pandemic on the nation's mental health, so that we can try to avoid a rise in mental illness in the years to come." [1]

Before the pandemic, the UKHLS questionnaire was carried out in person or over the phone using an interview format. The April wave of the study was carried out entirely online. The researchers caution that this may affect the answers that are given and could introduce bias. However, the degree of change in mental distress they observed means it is likely that these are attributable to the virus and the events associated with the pandemic.

Professor Kathryn Abel, joint senior author, of the University of Manchester, UK, said: "While COVID-19 infection is a greater physical health risk to older people, our study suggests that young people's mental health is being disproportionately affected by efforts to stop transmission of the virus. We would recommend policies focused on women, young people and those with preschool aged children as a priority to prevent future mental illness." [1]

A research team led by Osaka University investigated the formation ages of 59 lunar craters with a diameter of approximately 20 km using the Terrain Camera (TC) onboard the lunar orbiter spacecraft Kaguya.

Kaguya (formerly SELENE, for SELenological and ENgineering Explorer), is a Japanese Space Agency (JAXA) lunar orbiter mission.

This group demonstrated that an asteroid of 100 km in diameter was disrupted 800 million years ago (800 Ma) and that at least (4–5)×1016 kg of meteoroids, approximately 30–60 times more than the Chicxulub impact, must have plunged into the Earth-Moon system. Their research results were published in Nature Communications.

Since a thin layer of iridium (Ir) enrichment (a rare earth element) 65.5 Ma had been detected worldwide, it is thought that an asteroid of 10–15 km in diameter hit the Earth and caused or greatly contributed to the Cretaceous mass extinction.

The probability of an asteroid of this size striking Earth is thought to be once in 100 million years. It is known that impact craters on Earth created before 600 Ma have been erased over the years by erosion, volcanism, and other geologic processes. Thus, to find out about ancient meteoroid impacts on Earth, they investigated the Moon, which has almost no erosion.

They investigated the formation age distribution of 59 large craters with diameters larger than approximately 20 km by examining the density of 0.1–1 km-diameter craters in the ejecta of these 59 craters. One of these examples is the Copernicus crater (93 km in diameter) and its surrounding craters (Figure 2). The density of 860 craters with diameter of 0.1–1 km (shown in green) was examined to derive the age of the Copernicus crater. As a result, 8 of 59 craters were found to be formed simultaneously (17 by a spike model), a world first. (Figure 3)

Considering crater scaling laws and collision probabilities with the Earth and Moon, at least (4–5)×1016 kg of meteoroids, approximately 30–60 times more than the Chicxulub impact, must have struck the Earth immediately before the Cryogenian (720–635 Ma), which was an era of great environmental and biological changes.

In addition, given the disruption age and orbit elements of existing asteroid families, it is highly likely that the disruption of the parent body of C-type asteroid Eulalia caused an asteroid shower. A C-type asteroid is a class expected to contain carbon in analogy to the carbonaceous chondrites (meteorites).

Because Eulalia's surface reflectance is similar to that of near-Earth C-type asteroid Ryugu, Eulalia has drawn attention as a parent body of a C-type Rubble pile, a celestial body consisting of numerous pieces of rock near the Earth. (Sugita et al. 2019)

Ryugu was probed by the asteroid explorer Hayabusa2, an asteroid sample-return mission operated by JAXA.

From these considerations, they concluded that sporadic meteorite bombardment due to the disruption of asteroids 800 Ma caused the following:

-Some of the resulting fragments fell on terrestrial planets and the Sun,

-Others stayed in an asteroid belt as the Eulalia family, and

-Remnants had orbital evolution as a member of near-Earth asteroids.

This research suggests the following possibilities:

1. An asteroid shower may have brought a large amount of phosphorus (P) to the Earth, affecting the terrestrial surface environment,

2. A recent C-type asteroid shower may have contaminated the lunar surface with volatile elements,

3. The Eulalia family, the parent body of a near-Earth C-type asteroid, may have brought an asteroid shower to the Earth and the Moon.

Lead author Professor Terada says, "Our research results have provided a novel perspective on earth science and planetary science. They will yield a wide range of positive effects in various research fields."

Women who do not need pain relief during childbirth may be carriers of a key genetic variant that acts a natural epidural, say scientists at the University of Cambridge. In a study published today in the journal Cell Reports, the researchers explain how the variant limits the ability of nerve cells to send pain signals to the brain.

Childbirth is widely recognised as a painful experience. However, every woman's experience of labour and birth is unique, and the level of discomfort and pain experienced during labour varies substantially between women.

A collaboration between clinicians and scientists based at Addenbrooke's Hospital, part of Cambridge University Hospitals NHS Foundation Trust (CUH), and the University of Cambridge sought to investigate why some mothers report less pain during labour.

A group of women was recruited and characterised by the team led by Dr Michael Lee from the University's Division of Anaesthesia. All the women had carried their first-born to full term and did not request any pain relief during an uncomplicated vaginal delivery. Dr Lee and colleagues carried out a number of tests on the women, including applying heat and pressure to their arms and getting them to plunge their hands into icy water.

Compared to a control group of women that experienced similar births, but were given pain relief, the test group showed higher pain thresholds for heat, cold and mechanical pressure, consistent with them not requesting pain relief during childbirth. The researchers found no differences in the emotional and cognitive abilities of either group, suggesting an intrinsic difference in their ability to detect pain.

"It is unusual for women to not request gas and air, or epidural for pain relief during labour, particularly when delivering for the first time," said Dr Lee, joint first author. "When we tested these women, it was clear their pain threshold was generally much higher than it was for other women."

Next, senior co-author, Professor Geoff Woods, and his colleagues at the Cambridge Institute for Medical Research sequenced the genetic code of both groups of women and found that those in the test group had a higher-than-expected prevalence of a rare variant of the gene KCNG4. It's estimated that one approximately 1 in 100 women carry this variant.

KCNG4 provides the code for the production of a protein that forms part of a 'gate', controlling the electric signal that flows along our nerve cells. As the joint first author Dr Van Lu showed, sensitivity of this gatekeeper to electric signals that had the ability to open the gate and turn nerves on was reduced by the rare variant.

This was confirmed in a study involving mice led by Dr Ewan St. John Smith from the Department of Pharmacology, who showed that the threshold at which the 'defective' gates open, and hence the nerve cell switches 'on', is higher - which may explain why women with this rare gene variant experience less pain during childbirth.

Dr St. John Smith, senior co-author, explained: "The genetic variant that we found in women who feel less pain during childbirth leads to a 'defect' in the formation of the switch on the nerve cells. In fact, this defect acts like a natural epidural. It means it takes a much greater signal - in other words, stronger contractions during labour - to switch it on. This makes it less likely that pain signals can reach the brain."

"Not only have we identified a genetic variant in a new player underlying different pain sensitivities," added senior co-author Professor Frank Reimann, "but we hope this can open avenues to the development of new drugs to manage pain."

"This approach of studying individuals who show unexpected extremes of pain experience also may find wider application in other contexts, helping us understand how we experience pain and develop new drugs to treat it," said Professor David Menon, senior co-author.