Culture

Researchers at the National Institute of Standards and Technology (NIST) and their colleagues have proposed a novel method for finding dark matter, the cosmos' mystery material that has eluded detection for decades. Dark matter makes up about 27% of the universe; ordinary matter, such as the stuff that builds stars and planets, accounts for just 5% of the cosmos. (A mysterious entity called dark energy accounts for the other 68%.)

According to cosmologists, all the visible material in the universe is merely floating in a vast sea of dark matter -- particles that are invisible but nonetheless have mass and exert a gravitational force. Dark matter's gravity would provide the missing glue that keeps galaxies from falling apart and account for how matter clumped together to form the universe's rich galactic tapestry.

The proposed experiment, in which a billion millimeter-sized pendulums would act as dark matter sensors, would be the first to hunt for dark matter solely through its gravitational interaction with visible matter. The experiment would be one of the few to search for dark matter particles with a mass as great as that of a grain of salt, a scale rarely explored and never studied by sensors capable of recording tiny gravitational forces.

Previous experiments have sought dark matter by looking for nongravitational signs of interactions between the invisible particles and certain kinds of ordinary matter. That's been the case for searches for a hypothetical type of dark matter called the WIMP (weakly interacting massive particles), which was a leading candidate for the unseen material for more than two decades. Physicists looked for evidence that when WIMPs occasionally collide with chemical substances in a detector, they emit light or kick out electric charge.

Researchers hunting for WIMPs in this way have either come up empty-handed or garnered inconclusive results; the particles are too light (theorized to range in mass between that of an electron and a proton) to detect through their gravitational tug.

With the search for WIMPs seemingly on its last legs, researchers at NIST and their colleagues are now considering a more direct method to look for dark matter particles that have a heftier mass and therefore wield a gravitational force large enough to be detected.

"Our proposal relies purely on the gravitational coupling, the only coupling we know for sure that exists between dark matter and ordinary luminous matter," said study co-author Daniel Carney, a theoretical physicist jointly affiliated with NIST, the Joint Quantum Institute (JQI) and the Joint Center for Quantum Information and Computer Science (QuICS) at the University of Maryland in College Park, and the Fermi National Accelerator Laboratory.

The researchers, who also include Jacob Taylor of NIST, JQI and QuICS; Sohitri Ghosh of JQI and QuICS; and Gordan Krnjaic of the Fermi National Accelerator Laboratory, calculate that their method can search for dark matter particles with a minimum mass about half that of a grain of salt, or about a billion billion times the mass of a proton. The scientists report their findings today in Physical Review D.

Because the only unknown in the experiment is the mass of the dark matter particle, not how it couples to ordinary matter, "if someone builds the experiment we suggest, they either find dark matter or rule out all dark matter candidates over a wide range of possible masses," said Carney. The experiment would be sensitive to particles ranging from about 1/5,000 of a milligram to a few milligrams.

That mass scale is particularly interesting because it covers the so-called Planck mass, a quantity of mass determined solely by three fundamental constants of nature and equivalent to about 1/5,000 of a gram.

Carney, Taylor and their colleagues propose two schemes for their gravitational dark matter experiment. Both involve tiny, millimeter-size mechanical devices acting as exquisitely sensitive gravitational detectors. The sensors would be cooled to temperatures just above absolute zero to minimize heat-related electrical noise and shielded from cosmic rays and other sources of radioactivity. In one scenario, a myriad of highly sensitive pendulums would each deflect slightly in response to the tug of a passing dark matter particle.

Similar devices (with much larger dimensions) have already been employed in the recent Nobel-prize-winning detection of gravitational waves, ripples in the fabric of space-time predicted by Einstein's theory of gravity. Carefully suspended mirrors, which act like pendulums, move less than the length of an atom in response to a passing gravitational wave.

In another strategy, the researchers propose using spheres levitated by a magnetic field or beads levitated by laser light. In this scheme, the levitation is switched off as the experiment begins, so that the spheres or beads are in free fall. The gravity of a passing dark matter particle would ever so slightly disturb the path of the free-falling objects.

"We are using the motion of objects as our signal," said Taylor. "This is different from essentially every particle physics detector out there."

The researchers calculate that an array of about a billion tiny mechanical sensors distributed over a cubic meter is required to differentiate a true dark matter particle from an ordinary particle or spurious random electrical signals or "noise" triggering a false alarm in the sensors. Ordinary subatomic particles such as neutrons (interacting through a nongravitational force) would stop dead in a single detector. In contrast, scientists expect a dark matter particle, whizzing past the array like a miniature asteroid, would gravitationally jiggle every detector in its path, one after the other.

Noise would cause individual detectors to move randomly and independently rather than sequentially, as a dark matter particle would. As a bonus, the coordinated motion of the billion detectors would reveal the direction the dark matter particle was headed as it zoomed through the array.

To fabricate so many tiny sensors, the team suggests that researchers may want to borrow techniques that the smartphone and automotive industries already use to produce large numbers of mechanical detectors.

Thanks to the sensitivity of the individual detectors, researchers employing the technology needn't confine themselves to the dark side. A smaller-scale version of the same experiment could detect the weak forces from distant seismic waves as well as that from the passage of ordinary subatomic particles, such as neutrinos and single, low-energy photons (particles of light).

The smaller-scale experiment could even hunt for dark matter particles -- if they impart a large enough kick to the detectors through a nongravitational force, as some models predict, Carney said.

"We are setting the ambitious target of building a gravitational dark matter detector, but the R&D needed to achieve that would open the door for many other detection and metrology measurements," said Carney.

New research by a University of Georgia scientist reveals that girls who are maltreated show higher levels of inflammation at an early age than boys who are maltreated or children who have not experienced abuse. This finding may forecast chronic mental and physical health problems in midlife.

Led by psychologist Katherine Ehrlich, the study is the first to examine the link between abuse and low-grade inflammation during childhood.

Inflammation plays a role in many chronic diseases of aging--diabetes, cardiovascular disease, stroke, obesity--as well as mental health outcomes, and the findings suggest that maltreatment's association with inflammation does not lie dormant before emerging in adulthood. Instead, the study shows that traumatic experiences have a much more immediate impact.

"We and others have speculated that there's something about the immune system that's getting calibrated, particularly during childhood, that might be setting people up on long-term trajectories toward accelerated health problems," said Ehrlich, assistant professor in the Franklin College of Arts and Sciences. "What I'm struck by is just how early in development we can see these effects. What our study highlights is that, even as early as childhood, we can see that a substantial portion of the children have levels of inflammation that the American Heart Association considers 'moderate risk' for heart disease. This is concerning from a public health perspective and suggests that these children may be at risk for significant health problems at an earlier age than their nonmaltreated peers."

Participants in the study included 155 children aged 8-12 from low-income backgrounds who attended a weeklong day camp. The sample was racially diverse and included maltreated and nonmaltreated children.

Researchers captured detailed information on children's exposure to abuse by utilizing Department of Human Services records about maltreatment experiences in families. The children-documented experiences included neglect (55%), emotional maltreatment (67%), physical abuse (35%) and sexual abuse (8%). Many children experienced more than one type of abuse, and 35% of children experienced abuse across multiple developmental periods.

The team measured five biomarkers of low-grade inflammation using non-fasting blood samples from the children.

Results revealed that childhood maltreatment--for girls--was associated with higher levels of low-grade inflammation in late childhood. Girls who had been abused over multiple periods or had multiple kinds of exposures had the highest levels of inflammation. Girls' greatest risk for elevated inflammation emerged when they were abused early in life, before the age of 5.

For boys in the study, exposure to maltreatment was not reflected in higher levels of inflammation, but Ehrlich cautioned against drawing conclusions without additional research targeted to boys.

"One question is, are these variations due to developmental timing differences?" she said. "We know that girls mature faster than boys in terms of their biological and physical development. If we tested these same boys two years later, would we find the same patterns of inflammation that we found for the girls?"

English has become the de facto language of science: International conferences are held in English, the world's top scientific journals are in English and academics in non-English speaking countries get promoted based on their publications in English language journals. Even scientific jargon is in English -- most non-English speakers use English terms and don't bother inventing equivalent words in their native languages.

Yet, for much of the world -- in particular, the global south, where English is not a common second language -- English limits entry into the the world of science and limits public access to scientific results, even when they pertain to a person's own country.

Valeria Ramírez-Castañeda, a graduate student in the Department of Integrative Biology at the University of California, Berkeley, encountered this firsthand when she began writing her master's thesis at the University of Los Andes in Bogota, Colombia, her native country. While she was one of the lucky ones -- growing up in Bogota, her mother had the foresight to insist she take Saturday English classes -- she found it impossible to write in English. To her, Spanish felt natural, not English.

"When I was writing the thesis, a lot of people told me, 'Just write it in English.' And I couldn't. It was too difficult to write it in English," she said. "I was like, 'No, I have already enough pressure to finish this on time, and it is already difficult to write science -- so, I am going to write it in Spanish.'"

But she also wanted to submit it to a scientific journal, which requires that she translate her thesis -- about how snakes adapt to eating poisonous frogs -- into English.

"Since then, I haven't published that paper. I am still working on that," she admitted. "I felt that English was kind of a handicap for me just to advance, to progress in research."

Her introduction to the "language hegemony in scientific publishing," as she calls it, led her to ask other Colombian doctoral students about the impact this has had on their careers. The results of her survey, published last month in the journal PLOS ONE, document the negative consequences of English dominance in science.

She found that more than 90% of articles published by Colombian researchers are in English, and that this has created financial burdens. More than 40% of those she surveyed reported that one of their papers had been rejected because of English grammar, forcing them to pay for a native English speaker to review the manuscript or ask a favor of an English-speaking friend. Translation and editing services charge between one-quarter and one-half of a typical doctoral student's monthly salary in Colombia, she found.

Fully one-third of the 49 respondents, recruited through Twitter with the hashtag #CienciaCriolla, used between Colombian researchers, reported that they had elected to not attend a scientific conference or meeting because of the requirement that oral presentations be in English.

"When I published this on bioRxiv and tweeted, a lot of people started writing to me with very emotional things like, 'I left science because of English,' 'I cannot graduate with a master's thesis because of English,' 'I thought about studying abroad, but then I had the interview and I froze because of English,' (and) 'I couldn't do it.' Super difficult things," said Ramírez-Castañeda. "People are leaving science because of English. It is not something that is isolated."

She found, too, that colleagues with high English proficiency were more likely to have backgrounds higher on the socioeconomic ladder. In Colombia, as in the U.S., socioeconomic status is correlated with race.

"Now that we (in the U.S.) are speaking about the Black community, in many places, including Colombia, race means socioeconomic differences, poverty," she said. "We don't see a lot of Black scientists from Colombia, not only because being from a political minority and being a scientist is difficult, but also because of English. At the end, it is another layer to the difficulty, and we are not talking about it. That is the thing that worries me the most, that it is something that is super-quiet and silent, as if if didn't exist."

Even for U.S. citizens, English can be a barrier

Poor English skills are even an issue for those raised in the U.S., said José Pablo Vázquez-Medina, an assistant professor of integrative biology who came to UC Berkeley three years ago.

"I have friends who are Latinos, but born and raised in the U.S. They send in a paper, and they are asked to run it by a native speaker," he said. "With students who have come from disadvantaged backgrounds, you can see that in how they write. I see it as another hurdle."

He ascribes this to poor schools that fail to teach English to students from non-English speaking families.

"That comes back to segregation. Where you live is where you go to school, and if you live in a rich neighborhood, you go to a school with resources; if you live in a poor neighborhood, you go to a school with less resources," he said. "Without fixing that problem, I don't see us making a lot of impact."

Growing up in San Luis Potosi in Mexico, Vázquez-Medina had access to some English education. His parents were teachers. But he still has flashbacks about the writing suggestions of mentors and friends, most of them offered graciously, he said.

"I remember my very first paper. I wrote it in Spanish, and I translated it (into English). It was horrible," said Vázquez-Medina, who obtained his undergraduate degree from the Autonomous University of Baja California Sur in La Paz. Luckily, a coauthor on the paper made helpful comments. "It is definitely a barrier when you want to move up and go to grad school. Even if you go to grad school in Mexico, you have to publish papers in English."

Vázquez-Medina benefitted from working with a mentor who had studied in Canada and the U.S. and provided English tips. This mentor also sparked his interest in the physiology of marine mammals, which led him to a Ph.D. program at UC Merced, where he studied the diving and fasting physiology of elephant seals and was supported by the UC MEXUS program.

"I always thought, 'Why don't more people apply to this program? This is a great opportunity,'" he said. "But I felt that English was probably one of the main reasons why people didn't feel comfortable applying for scholarships to study abroad."

Betsabé Castro Escobar, a doctoral candidate in integrative biology, saw how the hurdle of English fluency affected the lives of her friends, family and even her future husband. She grew up in Puerto Rico, which, as an unincorporated U.S. territory, mandates 12 years of English in K-12 education. All other instruction is in Spanish, and it's the language of preference for more than 85% of Puerto Ricans, both at home and in their daily activities.

While some people have the privilege and access to a good education and exposure to English, she said, as a society, many Puerto Ricans still struggle with poor class curriculums in many public schools, as well as lack of exposure to opportunities to speak English, lack of interest in learning it and even resistance to learning and becoming fluent in English. Spanish, though a colonial language like English, is preferred in Puerto Rico and is, in fact, a majority language worldwide: one of the top 5 languages spoken.

"I see people leave their academic fields because they don't feel like they belong, many struggling with very clear language exclusion barriers. One thing about belonging is not just being part of a community, but also, how do we communicate? And one of those factors is language. There are clear language hurdles, and some people just don't make it through because they have been excluded from the start," said Castro Escobar, who is studying the ethnobotany of the calabash tree in the Caribbean. "Sadly, this is a funnel, and not everyone is going to make it through, due to language and communication obstacles. Unfortunately, this is how the system has been set up in order to participate in the globalized world; against others that don't speak the 'majority' language, basically."

Language hegemony

"It is very much an issue," agreed UC Berkeley professor of linguistics Lev Michael, who studies and seeks to revitalize indigenous languages in Perú.

"If you are Dutch, the fact that the language of science is English really is not a big hurdle, since, in my experience, many Dutch people speak better English than many English speakers," he said, jokingly. "But in Perú, for example, many people where I work -- even in some universities -- don't have great access to English education. It even plays out to the level where some people at that level have a hard time reading important works in English."

Michael admits to encountering a language hurdle when translating his English works -- recently, a dictionary of the Iquito language -- into Spanish and Portuguese.

In his field, multilingualism is common, and academic meetings about South American indigenous languages are typically trilingual, he said. Speakers can deliver talks in Spanish, Portuguese or English, and most people in the audience understand. A small journal he edits, Cadernos de Etnolingüística, also is trilingual.

But that is not typical in other areas of science. Few journals even publish abstracts in other languages, let alone full papers in translation.

English hasn't always been the language of science and scholarship, of course. Latin was the gatekeeper until 200 years ago, Michael pointed out, while German, French and Russian -- and, recently, Chinese -- have given English a run for the money.

Aside from the issue of fairness, forcing people to communicate in a language other than their native tongue affects how clearly and effectively they interact with others. For Augusto Berrocal, who is from Mexico City and recently earned his Ph.D. from UC Berkeley in molecular and cell biology, English is a barrier to networking with colleagues at conferences, because his mind slows down when speaking English and, frankly, it can be exhausting.

"It is my opinion that language is the main burden," said Berrocal, who investigates the genetics of development in fruit flies. "I feel that my mind runs faster in my native tongue, which is Spanish. In a debate, for example, my conversations are more fluent in my native language. I think that has an impact at meetings or when discussing and getting ideas."

Castro Escobar says she gets more out of meetings where she can converse with colleagues in Spanish, and her field of ethnobotany has been gaining a critical mass of Spanish speakers. Spanish-speaking students and postdocs at UC Berkeley also are a growing community, a network where students and faculty members can discuss their work more naturally, or just let down their hair.

"Throughout the years, there has been a growing number of us Latinx people on campus," Castro Escobar said. "In my home department now, there are both grad students and professors I can talk to in Spanish. I find it refreshing to escape and speak my own language. I am more expressive, my ideas and connections are much faster, and my energy comes through more. I have more expressions I can use in Spanish. Sorry, I am biased, but Spanish is a beautiful language."

One of those professors is her adviser, Paul Fine, who actively recruits Latin American students to join his lab and converses with them in both Spanish and Portuguese. He studies tree diversity in the Amazon rainforest and has had students from Brazil, Ecuador, Colombia, Perú, Mexico and Costa Rica, not to mention Puerto Rico.

Castro Escobar said that when she finishes her dissertation, she hopes -- if her committee approves -- to present her thesis in Spanglish: that is, both in English and Spanish.

"It will certainly be an interesting exercise for our department," she said. "My slides would be in English -- the idea is not to lose everyone in this language code-switching, but to actually show other people that their voice matters, too."

Solutions

As Michael noted, scholarship in the past was conducted in Latin, a language that no one spoke natively. That put everyone in the same boat, assuming you were among the elite who could learn Latin. English is different, he said, having achieved ascendency because the rise of science after World War II coincided with the hegemony of two English-speaking world powers, Britain and the U.S..

"When you are engaged in some type of project, like science, where you have participants from all sorts of different groups speaking all sorts of different languages, there is a tension between adopting a lingua franca which facilitates intergroup communication and the fact that that very same move creates inequities, because that language is the native language of some people and not of others," he said.

Ramírez-Castañeda noted that most of those whom she surveyed preferred English as the common language of science for its ease of communicating internationally. But she argues that scientists, universities and journals should acknowledge and address the costs to non-English speakers, in terms of time, finances, productivity and anxiety.

Science could, for example, encourage more multilingualism, she said, including publishing abstracts or entire articles in multiple languages. She chose to publish her survey in PLOS ONE because the journal allowed her to co-publish the complete article in Spanish.

"We need to encourage diversity, and that needs to take into account language and taking more effort to do multilingual science," she said. "All the actors have to be involved: journals, universities, governments, institutions. We need to stress more affordable or free translating and editing services at journals. Scientists can volunteer to edit papers, not just for English, but both ways. Simultaneous translation at conferences and meetings. Editing and translating services at universities and journals. Promoting annual editions in other languages."

She and many others look with hope to Google Translate or other platforms, which in the future could make Star Trek's sci-fi "universal translator" a reality, obviating the language problem. At the moment, however, Google Translate is still "awful" for translating the technical terms and prose that permeate science, Michael said.

"We, as scientists, have to do the work," Ramírez-Castañeda said. "(That means) translating papers with the tools that we have, so that students (in these countries) and local communities can read them. We don't need to put more effort on these communities, they already have to deal with a lot of things to be a scientist. We just have to make them feel it is easy to be a scientist, not more difficult."

Lockdowns initiated to curb the spread of the coronavirus in China and Europe at the beginning of the pandemic improved air quality, averting tens of thousands of deaths in regions where air pollution has a significant impact on mortality, a new study shows.

According to research published in The Lancet Planetary Health, scientists at the University of Notre Dame found that particulate matter concentrations in China dropped by an unprecedented 29.7 percent, and by 17.1 percent in parts of Europe, during lockdowns that took place between Feb. 1 and March 31 in China and Feb. 21 to May 17 in Europe. Particulate matter (PM2.5) -- tiny airborne particles smaller than 1/10,000 of an inch in diameter -- comes from various combustion-related sources including industrial emissions, transportation, wildfires and chemical reactions of pollutants in the atmosphere.

"We look on these lockdowns as the first global experiment of forced low-emission scenarios," said Paola Crippa, assistant professor in the Department of Civil and Environmental Engineering and Earth Sciences at Notre Dame and corresponding author of the study. "This unique, real-world experiment shows us that strong improvements in severely polluted areas are achievable even in the short term, if strong measures are implemented."

Air pollution is considered the leading environmental cause of death. In 2016, the World Health Organization attributed air pollution to 4.2 million premature deaths worldwide, with Western Pacific and Southeast Asian regions being the most affected. Long-term exposure can be hazardous to human health, with premature death associated to lung cancer, ischemic heart disease, stroke and chronic obstructive pulmonary diseases.

Crippa and her team integrated advanced computer simulations with measured particulate matter concentrations from more than 2,500 sites in Europe and China in total between Jan. 1, 2016, and June 30, 2020 -- during which both regions initiated lockdowns as COVID-19 began spreading rapidly.

The team estimated rates of premature death against four different economic recovery scenarios: an immediate resumption to normal activity and subsequent emissions, a gradual resumption with a three-month proportional increase of emissions, the potential of a second outbreak of COVID-19 between October and December in each region, and a permanent lockdown for the remainder of 2020 in the case of ineffective control strategies.

"The most surprising part of this work is related to the impact on human health of the air quality improvements," Crippa said. "It was somewhat unexpected to see that the number of averted fatalities in the long term due to air quality improvements is similar to the COVID-19 related fatalities, at least in China where a small number of COVID-19 casualties were reported. These results underline the severity of air quality issues in some areas of the world and the need for immediate action."

From February to March, the study found an estimated 24,200 premature deaths associated with particulate matter were averted throughout China compared to 3,309 reported COVID-19 fatalities, and "improvements in air quality were widespread across China because of extended lockdown measures." The study found the situation in Europe to be quite different. While COVID-19 related deaths were far higher in Europe compared to what was reported in China, an estimated 2,190 deaths were still avoided during the lockdown period when compared to averages between 2016 and 2019. The averted fatalities figures become much larger (up to 287,000 in China and 29,500 in Europe) when considering long-term effects, which will depend on the future pathway of economic recovery.

The study serves as an example of the need for ad hoc control policies to be developed to achieve effective air quality improvements, said Crippa, and highlights the issue of risk perception between the current immediate crisis of the coronavirus pandemic versus the ongoing crisis of hazardous pollutants in the atmosphere.

"In China, we saw that lockdowns implied very significant reductions in PM2.5 concentrations, which means that policies targeting industrial and traffic emissions might be very effective in the future," Crippa said. "In Europe those reductions were somewhat smaller but there was still a significant effect, suggesting that other factors might be considered to shape an effective mitigation strategy."

Those strategies could include subsidies to electric vehicles, prioritizing public transport in heavily trafficked cities and adoption of more stringent emission limitations for industries. Heating emissions and agriculture are also contributors to total particulate matter concentrations. In the study, researchers stressed that aggressive mitigation strategies to reduce air pollution could achieve significant improvements to health, stating, "If interventions of a similar scale to those adopted to address the COVID-19 pandemic were widely and systematically adopted, substantial progress towards solving the most pressing environmental and health crisis of our time could be achieved."

Scientists have engineered tissue grafts that, in pigs, regenerated both bone and cartilage in the temporomandibular joint (TMJ), a part of the jaw that can cause debilitating pain and disability when damaged. The results represent a stride toward a safer and more effective intervention for patients with TMJ disorders, which affect approximately 10 million people in the U.S. alone. The TMJ routinely experiences high loads due to its complexity and involvement in various jaw movements, and can develop damage from congenital defects, traumatic injuries, and arthritis. TMJ disorders can be a huge burden on quality of life - causing symptoms such as jaw pain and difficulty chewing - and in the worst cases can only be repaired with surgeries. However, surgical interventions are imprecise and involve multiple operations; other treatments, including medical implants and steroid injections, can cause side effects such as allergies or cannot provide permanent relief. David Chen and colleagues took a different approach where they engineered tissue grafts that, unlike previous bone-focused designs, can repair both cartilage and bone within the ramus-condyle unit of the TMJ. The researchers grew their cartilage-bone grafts using several bioreactor designs over 5 weeks and then implanted the grafts into the TMJs of pigs. The grafts remained intact 6 months after transplantation, and boosted the regeneration of TMJ tissue more effectively than other graft designs that could only repair bone. "Overall, this study resulted in a promising approach to large-scale joint reconstruction using viable tissues and opens several avenues of investigation," Chen et al. write.

The immune response to infections is a delicate balance. We need just enough action to clear away the offending bacteria or viruses, but not so much that our own bodies suffer collateral damage.

Macrophages are immune cells at the front line, detecting pathogens and kicking off an inflammatory response when needed. Understanding how macrophages determine when to go all-out and when to keep calm is key to finding new ways to strike the right balance -- particularly in cases where inflammation goes too far, such as in sepsis, colitis and other autoimmune disorders.

In a study published October 14, 2020 in the Proceedings of the National Academy of Sciences, researchers at University of California San Diego School of Medicine discovered that a molecule called Girdin, or GIV, acts as a brake on macrophages.

When the team deleted the GIV gene from mouse macrophages, the immune cells rapidly overacted to even small amounts of live bacteria or a bacterial toxin. Mice with colitis and sepsis fared worse when lacking the GIV gene in their macrophages.

The researchers also created peptides that mimic GIV, allowing them to shut down mouse macrophages on command. When treated with the GIV-mimic peptide, the mice's inflammatory response was tempered.

"When a patient dies of sepsis, he or she does not die due to the invading bacteria themselves, but from an overreaction of their immune system to the bacteria," said senior author Pradipta Ghosh, MD, professor at UC San Diego School of Medicine and Moores Cancer Center. "It's similar to what we're seeing now with dangerous 'cytokine storms' that can result from infection with the novel coronavirus SARS-CoV-2. Macrophages, and the cytokines they produce, are the body's own immune-stimulating agents and when produced in excessive amounts, they do more harm than good."

Digging deeper into the mechanism at play, Ghosh and team discovered that the GIV protein normally cozies up to a molecule called Toll-like receptor 4 (TLR4). TLR4 is stuck right through the cell membrane, with bits poking inside and outside the cell. Outside of the cell, TLR4 is like an antenna, searching for signs of invading pathogens. Inside the cell, GIV is nestled between the receptor's two "feet." When in place, GIV keeps the feet apart, and nothing happens. When GIV is removed, the TLR4 feet touch and kick off a cascade of immune-stimulating signals.

Ghosh's GIV-mimicking peptides can take the place of the protein when it's missing, keeping the feet apart and calming macrophages down.

"We were surprised at just how fluid the immune system is when it encounters a pathogen," said Ghosh, who is also director of the Institute for Network Medicine and executive director of the HUMANOID Center of Research Excellence at UC San Diego School of Medicine. "Macrophages don't need to waste time and energy producing more or less GIV protein, they can rapidly dial their response up or down simply by moving it around, and it appears that such regulation happens at the level of gene transcription."

Ghosh and team plan to investigate the factors that determine how the GIV brake remains in place when macrophages are resting or is removed to mount a response to a credible threat. To enable these studies, the Institute for Network Medicine at UC San Diego School of Medicine recently received a new $5 million grant from the National Institute of Allergy and Infectious Diseases, part of the National Institutes of Health. Ghosh shares this award with her colleagues Debashis Sahoo, PhD, assistant professor at UC San Diego School of Medicine and Jacobs School of Engineering, and Soumita Das, PhD, associate professor of pathology at UC San Diego School of Medicine.

A new species of small pterosaur - similar in size to a turkey - has been discovered, which is unlike any other pterosaur seen before due to its long slender toothless beak.

The fossilised piece of beak was a surprising find and was initially assumed to be part of the fin spine of a fish, but a team of palaeontologists from the universities of Portsmouth and Bath spotted the unusual texture of the bone - seen only in pterosaurs - and realised it was a piece of beak.

Professor David Martill of the University of Portsmouth, who co-authored the study, said: "We've never seen anything like this little pterosaur before. The bizarre shape of the beak was so unique, at first the fossils weren't recognised as a pterosaur."

Careful searching of the late Cretaceous Kem Kem strata of Morocco, where this particular bone was found, revealed additional fossils of the animal, which led to the team concluding it was a new species with a long, skinny beak, like that of a Kiwi.

Lead author of the project, University of Portsmouth PhD student Roy Smith, said: "Just imagine how delighted I was, while on field work in Morocco, to discover the lower jaw to match the upper jaw found by Dr Longrich of this utterly unique fossil animal."

The new species, Leptostomia begaaensis, used its beak to probe dirt and mud for hidden prey, hunting like present-day sandpipers or kiwis to find worms, crustaceans, and perhaps even small hard-shelled clams.

Pterosaurs are the less well-known cousins of dinosaurs. Over 100 species of these winged-reptiles are known, some as large as a fighter jet and others as small as a sparrow.

Professor Martill said: "The diets and hunting strategies of pterosaurs were diverse - they likely ate meat, fish and insects. The giant 500-pound pterosaurs probably ate whatever they wanted.

"Some species hunted food on the wing, others stalked their prey on the ground. Now, the fragments of this remarkable little pterosaur show a lifestyle previously unknown for pterosaurs."

The scientists used a computerised tomography (CT) scan to reveal an incredible network of internal canals for nerves that helped detect the prey underground.

Dr Nick Longrich, from the Milner Centre for Evolution at the University of Bath, said: "Leptostomia may actually have been a fairly common pterosaur, but it's so strange - people have probably been finding bits of this beast for years, but we didn't know what they were until now."

Long, slender beaks evolved in many modern birds. Those most similar to Leptostomia are probing birds - like sandpipers, kiwis, curlews, ibises and hoopoes. Some of these birds forage in earth for earthworms while others forage along beaches and tidal flats, feeding on bristle worms, fiddler crabs, and small clams.

Leptostomia could probably have done either, but its presence in the Cretaceous age Kem Kem strata of Africa - representing a rich ecosystem of rivers and estuaries - suggests it was drawn there to feed on aquatic prey.

"You might think of the pterosaur as imitating the strategy used successfully by modern birds, but it was the pterosaur that got there first," said Dr Longrich. "Birds just reinvented what pterosaurs had already done tens of millions of years earlier."

Dr Longrich suggests the new species shows how, more than a century after pterosaurs were first discovered, there's still so much to learn about them. He said: "We're underestimating pterosaur diversity because the fossil record gives us a biased picture.

"Pterosaur fossils typically preserve in watery settings - seas, lakes, and lagoons - because water carries sediments to bury bones. Pterosaurs flying over water to hunt for fish tend to fall in and die, so they're common as fossils. Pterosaurs hunting along the margins of the water will preserve more rarely, and many from inland habitats may never preserve as fossils at all.

"There's a similar pattern in birds. If all we had of birds was their fossils, we'd probably think that birds were mostly aquatic things like penguins, puffins, ducks and albatrosses. Even though they're a minority of the species, their fossil record is a lot better than for land birds like hummingbirds, hawks, and ostriches."

Over time, more and more species of pterosaurs with diverse lifestyles have been discovered. That trend, the new pterosaur suggests, is likely to continue.

COVID-19 continues to wreak havoc globally, with over one million deaths to date. Yet what if an existing vaccine could make COVID-19 less deadly? A study just published put the theory to test, with promising results.

A research team led by Dr. Larenas-Linnemann working at Medica Sur, Mexico City, reported on their clinical observations in 255 subjects vaccinated with the measles-mumps-rubella (MMR) vaccine since the start of the Coronavirus disease-2019 (COVID-19) pandemic. Many vaccinated patients were family members or caregivers of patients who already had contracted COVID-19, and thus at extremely high risk. Thirty-six of the patients have now contracted COVID-19, but all with a remarkably mild course, with less severe symptoms than would be expected given their health status and age. The paper, published in the September issue of Allergy, the European Journal of Allergy and Immunology, is now available for free download.

MMR vaccination in the context of COVID-19, taking advantage of a measles outbreak

At the start of the COVID-19 pandemic, observing the highly contagious and virulent nature of the virus and the lack of available preventive measures, the investigators searched for methods to enhance innate immunity -- in effect, give the immune system a boost to prepare it for a variety of assaults. Since COVID-19 was new to humans, there was no existing treatment or vaccine to specifically fight it. But Dr. Larenas-Linnemann, being Dutch and having done her basic training in the Netherlands, had followed with admiration the work of a fellow countryman on a little-known concept called "trained immunity." In technical terms, trained immunity refers to the enhanced immune response to a certain pathogen, after being exposed (by vaccination or natural illness) to another non-related pathogen; the immune reaction after a subsequent exposure to a non-related pathogen is faster in onset and accompanied by an increased production of certain cytokines. This means that, surprisingly, some vaccinations could not only prevent the target disease (such as measles), but also help people fight other diseases.

Trained immunity is a form of non-specific immunity. It was controversial at first, but after decades of pioneering fieldwork from a Danish team studying the tuberculosis vaccine and the live polio vaccine in both Northern Europe and Africa, followed by years of authoritative laboratory work from Dr. Larenas-Linnemann's countryman Mihai Netea and others, it is now accepted that certain live-attenuated vaccines can make the body better prepared to fight off a range of pathogens.

Dr. Larenas-Linnemann's team wondered: Could a live-attenuated vaccine be protective against this entirely new disease, COVID-19, for their patients? Taking advantage of the fact that the pandemic in Mexico coincided with a rise in measles cases, which had motivated the Ministry of Health to recommend measles re-vaccination, the team decided to put the concept of trained immunity to the test. As such, from March 2020 onward, the researchers recommended MMR vaccination to their patients, especially among family members of COVID-19 cases.

Observational trial of MMR for COVID-19 prevention

In a prospective observational trial in Hospital Médica Sur, ranked since 2011 as the best hospital of Mexico City, the team gave their patients boosters of a standard childhood vaccine, measles-mumps-rubella (MMR), which is considered safe worldwide (a booster is even required in many places to start college or military service). The patients were followed closely to watch for COVID-19 infection. The patients were considered high risk for COVID infection because many were caring for ill family members and were vulnerable due to their age or other risk factors.

COVID-19 infection was considered confirmed with a positive result of a SARS-CoV-2 antigen test, the detection of specific antibodies, or the combined presence of a direct contact with a confirmed case plus anosmia/ageusia and at least two classic COVID-19 symptoms. Direct contact with a confirmed case, accompanied by classic symptoms, but without smell or taste changes were considered highly probable cases. The clinical severity of COVID-19 was graded on a simplified scale from zero for asymptomatic cases, through 1 for mild, 2 for moderate, 3 for lower respiratory symptoms without the need for oxygen, up to 6 for fatality. Also, home measurements of pulse oximetry and peak-expiratory-flow rate (PEFR) were used to determine severity.

Outcomes: none of the 36 cases needed supplementary oxygen

Among the 255 vaccinated subjects, there were 24 confirmed and 12 (highly) probable COVID-19 cases, thirteen with risk factors that can often make COVID-19 more serious (hypertension, diabetes, obesity, smoking, or uncontrolled asthma). In their publication, the authors detail the risk factors for each patient. All received general supportive measures; some received off-label high-dose ivermectin the first two days. In general, the cases were less severe than would be expected. All had minor respiratory symptoms at most. Only one patient, with uncontrolled asthma, had one day of mild low blood oxygen. No patients had respiratory insufficiency to the degree of needing oxygen.

"We were relieved that MMR, which is commonly thought of as a childhood vaccination, seemed to help our older adult patients weather the storm too," said Dr. Larenas-Linnemann.

Reaction

"We would not be surprised if MMR could provide some protection against severe COVID-19," said researcher Peter Aaby, of Bandim Health Project in Guinea-Bissau and Research Centre for Vitamins and Vaccines (CVIVA), Statens Serum Institut, a governmental public health and research institution under the Danish Ministry of Health in Copenhagen, Denmark and a pioneer in the field. "Together with my partner Dr. Christine Stabell Benn, we've been reporting on mortality reductions from live-attenuated vaccines such as polio, BCG and measles vaccine/MMR for multiple decades now, and arguing for optimized vaccine schedules. With the COVID-19 crisis adding urgency, it's good to see the potential of non-specific immune effects being taken seriously."

Global research applying trained immunity to COVID-19 prevention

Researchers around the world are studying the ability of existing live-attenuated vaccines to prevent severe complications of COVID-19.

Several clinical trials are now ongoing with tuberculosis (BCG) vaccination of SARS-CoV-2 exposed health-care workers to reduce the severity of an eventual infection. However, one of the effects described in experiments with BCG-trained-immunity was a rise in interleukin 6 cytokine (IL-6), which made the Médica Sur team reluctant to use this method due to immune over-activation linked to high IL-6 levels described in severe COVID-19 cases. In addition, BCG vaccine and live polio vaccine are not used in the United States of America or Canada, making work with the BCG and polio vaccines harder to apply widely across North America. Existing supplies of BCG are also critically needed to save infant lives around the globe. Dr. Larenas-Linnemann's team instead chose the MMR vaccine for its safety profile, as well as for previous research describing trained immunity from MMR in newborns of hepatitis-infected mothers and retrospective studies showing 26-49% decreases in all-cause mortality rates after measles vaccination programs.

What's next

These first observational data gathered by Dr. Larenas-Linnemann and her group in Mexico City, demonstrating a milder course of COVID-19 in recently MMR-vaccinated individuals, are promising. The investigators are continuing their strategy to recommend MMR vaccination to household contacts of COVID-19 patients and plan to keep collecting data on further clinical cases. They are also searching for cooperation with basic immunologists to study the immunologic background of their observations. Said Dr. Larenas-Linnemann, "We are grateful to be able to have been able to offer this to our patients and hope these first real-life data will spark interest in the approach."

Conclusive evidence of the value of MMR vaccine to reduce COVID-19 complications requires a prospective, randomized trial. This is exactly what microbiologist Dr. Paul Fidel of Louisiana State University has recently launched. He has hypothesized that live attenuated vaccines induce myeloid-derived suppressor cells (MDSCs), another form of trained innate immunity, to suppress the fatal sepsis often seen in severe COVID-19 cases, as outlined in an opinion/hypothesis piece in mBio. With funding from the Parsemus Foundation and Fast Grants, the MMR randomized controlled trial is enrolling first responders and healthcare workers in the hard-hit New Orleans region. Dr. Fidel's team is still seeking funding to test whether MMR can provide protection to nursing home residents, who are particularly vulnerable to this disease.

Southampton researchers have identified a blood profile that could help identify COVID-19 patients at greatest risk of deterioration and direct them towards trials of specific treatments that could modify their immune systems' responses.

A new study jointly led by Professor Tom Wilkinson and Dr Tristan Clark of the University of Southampton, has shown a blood test for five cytokines could help predict those at risk of life-threating overstimulation of immune defences by COVID-19, and potentially tailor their treatment to tackle this.

'Preventing a cytokine storm'

Cytokines are cell signalling molecules with many associated with inflammation released into the bloodstream after an infection, helping to drive protective immune responses.

In patients with severe COVID-19, the immune system can overreact leading to massively increased cytokine levels in the blood - a 'cytokine storm'. Instead of helping the body fight the virus, this overreaction is extremely damaging to the cells and tissues of the body itself and can be fatal.

Identifying those more prone to this response, and tackling the hyperinflammation could be a key route to reducing the severity of COVID-19 and deaths.

'Identifying patients most at risk'

The study, published in Respiratory Research, analysed blood samples from 100 COVID-19 positive patients admitted to University Hospital Southampton NHS Foundation Trust (UHS) between 20 March and 29 April 2020, during the first phase of the pandemic.

They found that high levels of cytokines IL-6, IL-8, TNF, IL-1β and IL-33 in the patients' blood on admission were associated with greater chance of needing intensive care, artificial ventilation and of dying. IL-1β and IL-33 showed the biggest effect.

This study formed part of the CoV-19POC study - a trial led by Dr Clark looking at the clinical impact of molecular point-of-care testing in patients at UHS with suspected COVID-19, including tests that dramatically cut the time taken to diagnose COVID-19.

Combining this cytokine test with a clinical assessment of the patients' condition could help doctors identify and treat those most at risk of deteriorating.

Dr Anna Freeman and Dr Hannah Burke, Respiratory Clinical Research Fellows and joint first authors commented: "This project was a great opportunity for collaboration within the Faculty of Medicine, using resource from both the respiratory and infectious diseases teams.

"As early career researchers this study provided us with a valuable learning opportunity about how to deliver academic impact within the evolving COVID-19 pandemic."

'Investigating new treatments'

Two treatments for those hospitalised with COVID-19 have been found so far, with the steroid dexamethasone shown to reduce deaths by up to a third, in patients needing oxygen. The mechanism for Dexamethasone's protective effects isn't known, but as a non-specific anti-inflammatory it points to the potential benefit of controlling the inflammatory immune response.

The Southampton team hope that by accurately identifying which cytokines are driving hyperinflammation in each COVID-19 patient, doctors could target them (such as with an IL-33 blocker current in UK trials), yielding the biggest benefits for individual patients- an approach known as 'precision medicine'.

Professor Tom Wilkinson said: "These findings, from the ongoing COVID research programme in Southampton, have identified important inflammatory signals which will help steer the development of treatment strategies for this new disease.

"It is increasingly apparent that COVID is highly heterogeneous. Only by applying these techniques to stratify the condition will we be able to target the key mechanisms of disease with the best treatment for that individual."

Dr Tristan Clark said: "Our findings suggest that testing for both COVID-19 and cytokines at the point-of-care is feasible and in the future may identify infected patients and the most appropriate treatment for them, in near real-time."

Dogs' personality changes over time, but these changes occur unevenly during the dogs' life, and each trait follows a distinct age trajectory, according to a study published in Scientific Reports by researchers from the ELTE Eötvös Loránd University, Budapest and the University of Veterinary Medicine, Vienna. The authors also identified some aged dogs with potential age-related impairments, which had very low problem orientation and extremely high levels of activity.

Human personality is characterized by a peculiar dualism: it is both stable and malleable, depending on the point of reference. If we compare ourselves to our peers, it is stable as our personality rankings relative to others remain consistent over time. However, personality changes became obvious if we compare ourselves across time, as people become more conscientious, more emotionally stable, and more agreeable as they get older.

But what about personality stability and change in dogs? "Even though dog personality is a highly popular topic in the literature, there are still gaps about the long-term stability, as well as about the dynamics of personality development. That is, if personality rankings remain consistent over several years, at what age personality changes most prominently occur, and how much dogs actually change throughout their life." - explains Borbála Turcsán, first author of the study (ELTE, Department of Ethology).

To address these gaps, the authors investigated the personality of 217 Border collies across a wide age range (from 6 months to 15 years) using a comprehensive test battery known as the Vienna Dog Personality Test (VIDOPET). The researchers also invited the owners and the dogs back to the lab four years later, and tested 37 subjects again.

Associate Professor Friederike Range (Clever Dog Lab) describes why dogs were re-tested. "Longitudinal studies covering multiple years and using the same method at both time points are very rare in the dog literature. Following up the same dogs across ~4 years allowed us to address not only the question of personality stability, but also if there are individual differences in personality development, that is, if dogs with certain personality profiles change more than others."

The researchers showed that dog personality also has a 'stable' component, the dogs' ranks on all five personality traits remained fairly consistent across the investigated time period. So, for example, the most active individuals in the sample remained the most active 4 years later. However, individuals with a more 'mature' initial personality profile (that were less active, less curious and more oriented to problems) changed less in these traits than their peers - similar to what has been found in humans.

To investigate the general age-related changes in personality the researchers compared the personality of dogs belonging to seven age groups. "We found that dogs' personality changes with age, and these changes occur unevenly during the dogs' life course, just like in humans. Crucially, however, the dynamics of change seem to be specific for each personality trait." - said Zsofia Viranyi (Clever Dog Lab). "For example, the Problem orientation trait, which describes the dogs' attentiveness and ability to solve problems, changes largely during early life, increasing strongly until ~6 years of age, after which further changes became negligible. In contrast, the Novelty seeking trait did not change markedly during the younger life stages, but ~3 years of age their curiosity about novel objects and situations started to decrease which continued until geriatric age."

The Activity-independence of the dogs also decreased continuously over the dogs' life course, but in this trait the most pronounced decrease occurred from puppyhood to adolescence (1-2 years of age). Not all traits showed such a marked change with age. For example, dogs showed only a small tendency to be better at tolerating frustrating situations as they aged, and the dogs' level of Sociability seemed to remain constant throughout the dogs' life course.

Interestingly, the authors also identified some aged dogs with potential age-related impairments, which had very low problem orientation and extremely high levels of activity. "By describing in detail the normative patterns of personality development throughout different life stages, our study can help in the identification of age-related impairments". - explained Enik? Kubinyi, principal investigator at the Senior Family Dog Project (ELTE), supported by an ERC grant. "Dogs are already recognized as a natural model for human cognitive ageing, and our results suggest that similar rules govern the age-related changes in both human and dog personality."

While the ongoing Corona pandemic continues to threaten millions of lives around the world, the first half of 2020 saw an unprecedented decline in CO2 emissions - larger than during the financial crisis of 2008, the oil crisis of the 1979, or even World War II. An international team of researchers has found that in the first six months of this year, 8.8 percent less carbon dioxide was emitted than in the same period in 2019 - a total decrease of 1551 million tonnes. The groundbreaking study not only offers a much more precise look at COVID-19's impact on global energy consumption than previous analyses. It also suggests what fundamental steps could be taken to stabilize the global climate in the aftermath of the pandemic.

"What makes our study unique is the analysis of meticulously collected near-real-time data" explains lead author Zhu Liu from the Department of Earth System Science at Tsinghua University in Beijing. "By looking at the daily figures compiled by the Carbon Monitor research initiative we were able to get a much faster and more accurate overview, including timelines that show how emissions decreases have corresponded to lockdown measures in each country. In April, at the height of the first wave of Corona infections, when most major countries shut down their public life and parts of their economy, emissions even declined by 16.9 %. Overall, the various outbreaks resulted in emission drops that we normally see only on a short-term basis on holidays such as Christmas or the Chinese Spring Festival."

The study, published in the latest issue of Nature Communications, shows which parts of the global economy were most impacted. "The greatest reduction of emissions was observed in the ground transportation sector," explains Daniel Kammen, professor and Chair of the Energy and Resources Group and also professor in the Goldman School of Public Policy, University of California, Berkeley. "Largely because of working from home restrictions, transport CO2 emissions decreased by 40 % worldwide. In contrast, the power and industry sectors contributed less to the decline, with -22 % and -17 %, respectively, as did the aviation and shipping sectors. Surprisingly, even the residential sector saw a small emissions drop of 3 %: largely because of an abnormally warm winter in the northern hemisphere, heating energy consumption decreased with most people staying at home all day during lockdown periods."

To paint this comprehensive and multidimensional picture, the researchers based their estimates on a wide array of data: precise, hourly datasets of electricity power production in 31 countries, daily vehicle traffic in more than 400 cities worldwide, daily global passenger flights, monthly production data for industry in 62 countries as well as fuel consumption data for building emissions in more than 200 countries.

The researchers also found strong rebound effects. With the exception of a continuing decrease of emissions stemming from the transportation sector, by July 2020, as soon as lockdown measures were lifted, most economies resumed their usual levels of emitting CO2. But even if they remained at their historically low levels, this would have a rather minuscule effect on the long-term CO2 concentration in the atmosphere.

Thus, the authors stress that the only valid strategy to stabilize the climate is a complete overhaul of the industry and commerce sector. "While the CO2 drop is unprecedented, decreases of human activities cannot be the answer," says Co-Author Hans Joachim Schellnhuber, founding director of the Potsdam Institute for Climate Impact Research. "Instead we need structural and transformational changes in our energy production and consumption systems. Individual behavior is certainly important, but what we really need to focus on is reducing the carbon intensity of our global economy."

Based on the new study published in Scientific Reports by researchers of the Department of Ethology at Eötvös Loránd University, Budapest, adult, intensively socialised wolves form individualized social bonds with their human handlers.

One of the key features of the dog's success is that they show attachment towards their owners. However, the origin of the ability to form these interspecific bonds is still unclear. To uncover this specific bond we need to investigate the attachment-related behaviours, but to understand its origins it is not enough to take a closer look on the dog's behaviour. Though, it is widely accepted that the common ancestor of the dog and the grey wolf probably was a highly social species, what had an important role during the domestication and the emergence of the dog as a new species, we still know nothing about the evolutionary origin of the dog-human attachment. By studying the dog's closest living relative, the grey wolf, we can have an insight - though indirectly - how the common ancestor's social system might have affected the early domestication process of the dog.

"Attachment is a so-called behaviour-complex, what has several manifestations. For instance, dogs seek protection from their owners in threat or they are calmer in new situations when their owner is present, but they show signs of stress in their absence. We were wondering whether intensively socialised adult wolves show at least some features of the attachment behaviour towards their handlers" - explained Rita Lenkei, the first author of the publication.

The researchers tested hand-raised wolves and family dogs in a separation test, where the subjects were left alone by their handler or by a stranger for three minutes at an unfamiliar place.

"We were surprised how little difference was between the wolves' and dogs' behaviour during the test. When their handler - or owner in case of the dogs - was present they were calmer, they spent their time exploring their vicinity and sniffing around. But when they were left by their handler, they became stressed, whined and pulled the leash towards her hiding place. However, when the stranger disappeared these behaviours barely appeared" - explained Tamás Faragó, leading author of the study.

Naturally, the researchers also found species specific differences, as besides the domestication, the artificial selection and also rearing conditions markedly shaped the dog's behaviour. For instance, dogs were more interested towards humans, regardless of her familiarity. This result is in line with earlier findings that dogs are generally more attracted towards humans from early puppyhood what might be caused by genetic differences between dogs and wolves. Besides, wolves pulled the leash more persistently what the researchers explained with the assumption that owners usually teach their dogs not to pull it from their early age.

Though the dog-human relationship resembles to the offspring-parent bond from several aspects, based on earlier studies wolf puppies do not show attachment towards their human caregivers. As in this experiment the subjects were adult individuals and their handler was not their original caretaker, these results raise the possibility that the evolutional origin of the human-dog attachment is the social bond between the members of the pack. Wolves live in families, usually consisting a mating pair and their offspring of different ages. Presumably the common ancestor also lived in a similar complex social environment what might provide a good basis for developing abilities to easily integrate into human social groups.

"It is important to emphasize the hand-rearing and the intensive socialisation of our wolf subjects. Without this process they would never show these behaviours towards humans. Contrary to them, as a result of genetic changes, dogs are able to form attachment easily from their puppyhood and they can develop it thorough their whole life. Thus, we must keep in mind that though during our test they showed similar behaviour, we are talking about separate species and the dog is not just a tame wolf, while the wolf will never became a pet." - added Lenkei.

Bottom Line:

The histone deacetylase (HDAC) inhibitor vorinostat (Zolinza) in combination with the mTOR inhibitor sirolimus (Rapamune) or everolimus (Afinitor) showed clinical efficacy in patients with relapsed/refractory Hodgkin lymphoma, according to results from a phase I clinical trial.

Journal in Which the Study was Published:

Clinical Cancer Research, a journal of the American Association for Cancer Research

Author:

Filip Janku, MD, PhD, an associate professor at The University of Texas MD Anderson Cancer Center

Background:

"While the majority of patients with Hodgkin lymphoma have favorable outcomes with standard treatment, approximately 20-30 percent of patients with advanced disease develop refractory disease after primary treatment," said Janku. "These patients typically have poor outcomes with five-year survival rates as low as 30 percent."

Histone deacetylases (HDACs) are cellular proteins that regulate gene expression. Aberrant HDAC expression is associated with cancer, and HDAC inhibitors have been approved for the treatment of certain blood cancers. Resistance to HDAC inhibition in Hodgkin lymphoma has been suggested to develop through activation of mTOR signaling, which regulates cellular proliferation and cell death, explained Janku. Thus, combining HDAC inhibition with an mTOR inhibitor could help prevent resistance and improve responses to treatment, he noted.

Prior preclinical research demonstrated that combined inhibition of HDACs and mTOR signaling had antitumor effects against Hodgkin lymphoma. Furthermore, a patient with relapsed/refractory Hodgkin lymphoma who received treatment with vorinostat and sirolimus as part of a phase I clinical trial had a partial response to the treatment.

How the Study was Conducted:

In this study, Janku and colleagues examined the clinical efficacy of vorinostat in combination with either sirolimus or everolimus in a larger cohort of patients with heavily pretreated relapsed/refractory Hodgkin lymphoma who had received a median of five prior therapies. The cohort included 40 adult patients; of these patients, 22 received the vorinostat and sirolimus combination, and 18 received the vorinostat and everolimus combination.

Results:

The objective response rate for patients in the vorinostat and sirolimus arm was 55 percent, with six complete responses and six partial responses. After a median follow-up of 43.3 months, the median progression-free survival was 5.3 months. Median overall survival had not been reached at the time of analysis.

The objective response rate for patients in the vorinostat and everolimus arm was 33 percent, with two complete responses and four partial responses. After a median follow-up of 21 months, the median progression-free survival was 4.8 months. Median overall survival had not been reached at the time of analysis.

All 40 patients were evaluated for adverse events. The most common grade 3 or 4 treatment-related adverse events in both treatment groups were thrombocytopenia, neutropenia, and anemia. There were no treatment-related deaths.

Author's Comments:

"In our study, we observed a relatively high objective response rate in a patient population that would otherwise have poor outcomes," said Janku. "Based on our results, I believe further investigation is warranted for these combination treatments."

Janku added that his future research will examine the efficacy of these combinations with immune checkpoint inhibition. "There is evidence that both mTOR and HDAC inhibitors affect the tumor microenvironment, so there may be a benefit to combining these inhibitors with immunotherapy," he noted.

Study Limitations:

A limitation of the study is that it was conducted prior to the approval of immune checkpoint inhibitors for relapsed/refractory Hodgkin lymphoma and therefore does not account for prior treatment with immune checkpoint inhibitors. An additional limitation is that the trial was conducted at a single institution.

What if you could instruct a swarm of robots to paint a picture? The concept may sound far-fetched, but a recent study in open-access journal Frontiers in Robotics and AI has shown that it is possible. The robots in question move about a canvas leaving color trails in their wake, and in a first for robot-created art, an artist can select areas of the canvas to be painted a certain color and the robot team will oblige in real time. The technique illustrates the potential of robotics in creating art, and could be an interesting tool for artists.

Creating art can be labor-intensive and an epic struggle. Just ask Michelangelo about the Sistine Chapel ceiling. For a world increasingly dominated by technology and automation, creating physical art has remained a largely manual pursuit, with paint brushes and chisels still in common use. There's nothing wrong with this, but what if robotics could lend a helping hand or even expand our creative repertoire?

"The intersection between robotics and art has become an active area of study where artists and researchers combine creativity and systematic thinking to push the boundaries of different art forms," said Dr María Santos of the Georgia Institute of Technology. "However, the artistic possibilities of multi-robot systems are yet to be explored in depth."

This latest study looks at the potential for robot swarms to create a painting. The researchers designed a system whereby an artist can designate different regions of a canvas to be painted a specific color. The robots interact with each other to achieve this, with individual robots traversing the canvas and leaving a trail of colored paint behind them, which they create by mixing paints of different colors available on-board.

"The multi-robot team can be thought of as an "active" brush for the human artist to paint with, where the individual robots (the bristles) move over the canvas according to the color specifications provided by the human," explained Santos.

In their experiments, the researchers used a projector to simulate a colored paint trail behind each robot, although they plan to develop a robot that can handle paint in the future. They found that even when some robots didn't have access to all the colors required to create the assigned color, they were still able to work together and approximate the color reasonably well.

This system could allow artists to control the robot swarm as it creates the artwork in real time. The artist doesn't need to provide instructions for each individual robot, or even worry whether they have access to all the colors needed, allowing them to focus on creating the painting.

In the current study, the resulting images are abstract, and resemble a child's crayon drawing. They show unique areas of color that flow into each other, revealing the artist's input, and are pleasing to the eye. Future versions of the system may allow for more refined images.

Most importantly, the images confirm that it is possible for an artist to successfully instruct a robot swarm to paint a picture. The technique may also have potential in other fields where easily controlling the actions of a swarm of robots could be valuable. Robot orchestra, anyone?

It might look like a little game at the molecular scale.

Filament-like proteins in heart muscle cells have to be exactly the same length so that they can coordinate perfectly to make the heart beat.

Another protein decides when the filament is the right size and puts a wee little cap on it. But, if that protein makes a mistake and puts the cap on too early, another protein, leiomodin, comes along and knocks the cap out of the way.

This little dance at the molecular scale might sound insignificant, but it plays a critical role in the development of healthy heart and other muscles. Reporting in the journal, Plos Biology, a WSU research team has proven for the first time how the mechanism works.

The finding could someday lead to improved diagnostics and medical treatments for serious and sometimes devastating hereditary heart conditions that come about from genetic mutations in the proteins. One of these conditions, cardiomyopathy, affects as many as one in 500 people around the world and can often be fatal or have lifetime health consequences. A similar condition called nemaline myopathy affects skeletal muscles throughout the body with often devastating consequences.

"Mutations in these proteins are found in patients with myopathy," said Alla Kostyukova, associate professor in the Gene and Linda Voiland School of Chemical Engineering and Bioengineering and leader of the project. "Our work is to prove that these mutations cause these problems and to propose strategies for treatment."

Heart muscle is made of tiny thick and thin filaments of proteins. With the help of electrical signals, the rope-like filaments bind and unbind in an intricate and precise architecture, allowing heart muscle to contract and beat.

The thin filaments are made of actin, the most abundant protein in the human body. Tropomysin, another protein, wraps itself around the actin filaments. Tropomyosin together with two other proteins, tropomodulin and leiomodin, at the end of the actin filaments act as a sort of cap and determine the filament length.

"It's beautifully designed," said Kostyukova, whose research is focused on understanding protein structures.

And, tightly regulated.

To keep heart muscle healthy, the actin filaments, which are about a micron long, all have to be the exact same length. In families with cardiomyopathy, genetic mutations result in formation of filaments that are either too short or too long. Those affected can have significant heart problems that cause disability, illness and death.

In a project that spanned seven years, the researchers proved that leiomodin attaches to the end of the actin filament and kicks out the other protein, tropomodulin, to assure the actin filament's proper length.

"This is the first time that this has been shown with the atomic-level precision," said Dmitri Tolkatchev, research assistant professor in the Voiland School and lead author on the paper. "Previously, several laboratories attempted to solve this problem with very little success. With our data we finally have a direct proof."

The researchers used state-of-the-art approaches to make the key proteins and study them at the molecular and cellular level.  The work entailed designing the molecules, constructing them at the gene level in a plasmid, and then producing them into bacterial or cardiac cells. The researchers used nuclear magnetic resonance, which works on the same physical principle as Magnetic Resonance Imaging (MRIs), to understand the proteins' binding at the atomic level.  They also used molecular dynamic simulation to model them.

"The probability of being able to show this mechanism was not high, but the impact of the discovery is," said Tolkatchev, an expert in nuclear magnetic resonance. "This was a very important problem to study and could have a significant impact in the field of muscle mechanics."

The researchers hope to continue the work, identifying additional components and molecular mechanisms that regulate thin filament architecture, whether diseased or healthy.