Culture

Breast cancer diagnosis: Around 88 percent of patients survive the dangerous disease in the first five years. Work is important for getting back to normality. Researchers from the University of Bonn and the German Cancer Society investigated how satisfied former patients are with their occupational development over a period of five to six years since diagnosis. About half experienced at least one job change during the study period. Around ten percent of those affected even report involuntary changes. The researchers conclude that there is a need for long-term support measures for patients. The study is now published in the Journal of Cancer Survivorship.

Breast cancer is the most commonly occurring cancer in women. Almost 70,000 cases are diagnosed every year in Germany alone. Studies show that the five-year survival rate is 88 percent. "Returning to work is important; it provides a sense of normality and meaning after a crisis caused by cancer," explains sociologist Kati Hiltrop from the Center for Health Communication and Health Services Research at University Hospital Bonn (UKB). But a breast cancer diagnosis and successful treatment are often followed by long-term difficulties such as fatigue syndrome, which means a feeling of persistent tiredness, exhaustion and listlessness. Other after-effects of chemotherapy and the fear that the cancer will return can also limit productivity.

How do breast cancer patients succeed in returning to work? "There are numerous studies on this. Our long-term study now focuses on the post-return phase from the patient's perspective," says Hiltrop. Together with the head of the research center, Prof. Dr. Nicole Ernstmann, who is also a member of the Transdisciplinary Research Area "Life and Health" at the University of Bonn, and the German Cancer Society, the sociologist investigated how a total of 184 former breast cancer patients fared after returning to work over a period of five to six years after diagnosis.

From the perspective of breast cancer patients

The study focused on how satisfied the patients were with their occupational development since diagnosis. About half experienced at least one job change during the study period. "The main finding is that we found no relationship between the number of job changes and satisfaction, but that greater involuntariness of change was associated with lower satisfaction," Hiltrop says. "The results suggest that the quality of change matters more than the quantity." About 16 percent of job changes did not happen by choice. These changes included, for example, increased workload or retirement. The results suggest that the former breast cancer patients have difficulties in meeting the job requirements in the long term after their return, resulting in changes at work.

The research team's findings show what can contribute to satisfaction at work. "Providing a welcoming work environment and showing patients understanding and support can facilitate a satisfactory return to work," Hiltrop explains. This can help avoid involuntary job changes that are perceived as particularly drastic. The researchers conclude from the results that a satisfactory return to work and, in particular, remaining at work requires long-term support, for example because chemotherapies and aftercare have to be continued, there is a fear of a recurrence of the tumor, or fatigue symptoms have to be managed.

The current study is a follow-up study of the project "Strengthening patient competence: Breast cancer patients' information and training needs" (PIAT), which surveyed approximately 1000 breast cancer patients. The researchers interviewed the PIAT participants again 5-6 years after diagnosis. At four measurement points, surveys and interviews were used to explore the subjective assessment of health status, how often job changes occurred, and how fulfilling the job was. Socioeconomic data, such as age, number of children, and education, were also surveyed. Satisfaction with occupational development was associated with higher age, better perceived health status, and lower levels of involuntariness of job changes.

"Open communication with managers and colleagues about expectations and what can be accomplished is very important," explains Hiltrop. In addition, handling the situation more flexibly, can increase the likelihood that patients will be satisfied when they return to work.

Even though more and more vaccines against the coronavirus are being administered all over the world, many countries are still battling with outbreaks and face difficulties providing help to those in need.

One of those countries is Brazil. Here, they are facing a massive second wave outbreak, many daily deaths and instances of the health care systems collapsing. In the city of Manaus things have looked exceptionally bleak from December and through to the early spring.

The city was hit so hard by the first wave in 2020 that it was actually thought to be one of the few places in the world to have reached herd immunity. An estimated 75 percent of the population in the city had been infected. But then the second wave hit in November and December.

Now, a new study published in Science with collaborators from Brazil, the UK and University of Copenhagen has shed a light on why Manaus is facing these difficulties again.

'Our main explanation is that there is an aggressive variant of the coronavirus called P.1 which seems be the cause of their problems. Our epidemiological model indicates that P.1 is likely to be more transmissible than previous strains of coronavirus and likely to be able to evade immunity gained from infection with other strains', says corresponding author to the new study, Samir Bhatt, a researcher at the Department of Public Health at University of Copenhagen.

Emerged in November

The researchers used many forms of data from Manaus to characterize P.1 and its properties including 184 samples of genetic sequencing data. They find that genetically speaking P.1 is different from the previous strains of coronavirus. It has acquired 17 mutations including an important trio of mutations in the spike protein (K417T, E484K and N501Y).

'Our analysis shows that P.1 emerged in Manaus around November 2020. It went from not being detectable in our genetic samples to accounting for 87 percent of the positive samples in just seven weeks. It has since spread to several other states in Brazil as well as many other countries around the world', says Samir Bhatt.

Modelling using machine learning

The researchers then used an epidemiological model to estimate how transmissible P.1 seemed to be. As well as estimating signs of P.1 evading immunity gained from previous infection.

'Roughly speaking, our model incorporates many data sources such as mortality counts and genetic sequences and compares two different virus strains to see which one best explains the scenario that unfolded in Manaus. One was the 'normal coronavirus' and the other was dynamically adjusted using machine learning to best fit the actual events in Brazil', says Samir Bhatt.

This modeling allowed the researchers to conclude that P.1 is likely to be between 1.7 and 2.4 times more transmissible than non-P1-lineages of the coronavirus.

They also conclude that P.1 is likely to be able to evade between 10 and 46 percent of the immunity gained from infection with non-P.1 coronavirus.

'As researchers, we have to caution extrapolating these results to be applicable anywhere else in the world. However, our results do underline the fact that more surveillance of the infections and of the different strains of the virus is needed in many countries in order to get the pandemic fully under control', ends Samir Bhatt.

COLUMBUS, Ohio - Tiny molecules called nanobodies, which can be designed to mimic antibody structures and functions, may be the key to blocking a tick-borne bacterial infection that remains out of reach of almost all antibiotics, new research suggests.

The infection is called human monocytic ehrlichiosis, and is one of the most prevalent and potentially life-threatening tick-borne diseases in the United States. The disease initially causes flu-like symptoms common to many illnesses, and in rare cases can be fatal if left untreated.

Most antibiotics can't build up in high enough concentrations to kill the infection-causing bacteria, Ehrlichia chaffeensis, because the microbes live in and multiply inside human immune cells. Commonly known bacterial pathogens like Streptococcus and E. coli do their infectious damage outside of hosts' cells.

Ohio State University researchers created nanobodies intended to target a protein that makes E. chaffeensis bacteria particularly infectious. A series of experiments in cell cultures and mice showed that one specific nanobody they created in the lab could inhibit infection by blocking three ways the protein enables the bacteria to hijack immune cells.

"If multiple mechanisms are blocked, that's better than just stopping one function, and it gives us more confidence that these nanobodies will really work," said study lead author Yasuko Rikihisa, professor of veterinary biosciences at Ohio State.

The study provided support for the feasibility of nanobody-based ehrlichiosis treatment, but much more research is needed before a treatment would be available for humans. There is a certain urgency to coming up with an alternative to the antibiotic doxycycline, the only treatment available. The broad-spectrum antibiotic is unsafe for pregnant women and children, and it can cause severe side effects.

"With only a single antibiotic available as a treatment for this infection, if antibiotic resistance were to develop in these bacteria, there is no treatment left. It's very scary," Rikihisa said.

The research is published this week in Proceedings of the National Academy of Sciences.

The bacteria that cause ehrlichiosis are part of a family called obligatory intracellular bacteria. E. chaffeensis not only requires internal access to a cell to live, but also blocks host cells' ability to program their own death with a function called apoptosis - which would kill the bacteria.

"Infected cells normally would commit suicide by apoptosis to kill the bacteria inside. But these bacteria block apoptosis and keep the cell alive so they can multiply hundreds of times very rapidly and then kill the host cell," Rikihisa said.

A longtime specialist in the Rickettsiales family of bacteria to which E. chaffeensis belongs, Rikihisa developed the precise culture conditions that enabled growing these bacteria in the lab in the 1980s, which led to her dozens of discoveries explaining how they work. Among those findings was identification of proteins that help E. chaffeensis block immune cells' programmed cell death.

The researchers synthesized one of those proteins, called Etf-1, to make a vaccine-style agent that they used to immunize a llama with the help of Jeffrey Lakritz, professor of veterinary preventive medicine at Ohio State. Camels, llamas and alpacas are known to produce single-chain antibodies that include a large antigen binding site on the tip.

The team snipped apart segments of that binding site to create a library of nanobodies with potential to function as antibodies that recognize and attach to the Etf-1 protein and stop E. chaffeensis infection.

"They function similarly to our own antibodies, but they're tiny, tiny nano-antibodies," Rikihisa said. "Because they are small, they get into nooks and crannies and recognize antigens much more effectively.

"Big antibodies cannot fit inside a cell. And we don't need to rely on nanobodies to block extracellular bacteria because they are outside and accessible to ordinary antibodies binding to them."

After screening the candidates for their effectiveness, the researchers landed on a single nanobody that attached to Etf-1 in cell cultures and inhibited three of its functions. By making the nanobodies in the fluid inside E. coli cells, Rikihisa said her lab could produce them at an industrial scale if needed - packing millions of them into a small drop.

She collaborated with co-author Dehua Pei, professor of chemistry and biochemistry at Ohio State, to combine the tiny molecules with a cell-penetrating peptide that enabled the nanobodies to be safely delivered to mouse cells.

Mice with compromised immune systems were inoculated with a highly virulent strain of E. chaffeensis and given intracellular nanobody treatments one and two days after infection. Compared to mice that received control treatments, mice that received the most effective nanobody showed significantly lower levels of bacteria two weeks after infection.

With this study providing the proof of principle that nanobodies can inhibit E. chaffeensis infection by targeting a single protein, Rikihisa said there are multiple additional targets that could provide even more protection with nanobodies delivered alone or in combination. She also said the concept is broadly applicable to other intracellular diseases.

"Cancers and neurodegenerative diseases work in our cells, so if we want to block an abnormal process or abnormal molecule, this approach may work," she said.

RESEARCH TRIANGLE PARK, N.C. -- New Army-funded synthetic biology research manipulated micro-compartments in cells, potentially enabling bio-manufacturing advances for medicine, protective equipment and engineering applications.

Bad bacteria can survive in extremely hostile environments -- including inside the highly acidic human stomach--thanks to their ability to sequester toxins into tiny compartments.

In a new study, published in ACS Central Science, Northwestern University researchers controlled protein assembly and built these micro-compartments into different shapes and sizes, including long tubes and polyhedrons. Because this work illuminates how biological units, such as viruses and organelles, develop, it also could inform new ways to design medicine, synthetic cells and nano-reactors that are essential for nanotechnology.

"These results are an exciting step forward in our ability to design complex protein-based compartments," said Dr. Stephanie McElhinny, program manager at the U.S. Army Combat Capabilities Development Command, known as DEVCOM, Army Research Laboratory. "Being able to control the size and shape of these compartments could enable sophisticated bio-manufacturing schemes that are customized to support efficient production of complex molecules and multi-functional materials that could provide the future Army with enhanced uniforms, protective equipment and environmental sensors."

Further down the road, these insights potentially could lead to new antibiotics that target micro-compartments of pathogens while sparing good bacteria.

Researchers control protein assembly and build cell micro-compartments into different shapes and sizes that could lead to bio-inspired building blocks for various engineering applications.

"By carefully designing proteins to have specific mutations, we were able to control assembly of the proteins that form bacterial micro-compartments," said Dr. Monica Olvera de la Cruz, professor of materials science and engineering and chemistry at Northwestern who led the theoretical computation. "We used this also to predict other possible formations that have not yet been observed in nature."

Many cells use compartmentalization to ensure that various biochemical processes can occur simultaneously without interfering with one another. Made of proteins, these micro-compartments are a key to survival for a wide variety of bacterial species.

"Based on previous observations, we have known that the geometry of micro-compartments can be altered," said Dr. Danielle Tullman-Ercek, associate professor of chemical and biological engineering at Northwestern who led the experimental work. "But our work provides the first clues into how to alter them to achieve specific shapes and sizes."

To study these crucial compartments, the Northwestern team turned to Salmonella enterica, which rely on micro-compartments to break down the waste products of good bacteria in the gut. When the researchers genetically manipulated a protein isolated from Salmonella, they noticed the micro-compartments formed long tubes.

"We saw these weird, extended structures," Tullman-Ercek said. "It looked like they used the varying building blocks to form different shapes with different properties."

By coupling the mechanical properties of the compartment with the chemicals inside the compartment, Olvera de la Cruz and her team used theoretical computation to predict how different mutations led to different shapes and sizes. When six-sided proteins assembled together, they formed long tubes. When five-sided proteins assembled together, they formed soccer ball-shaped icosahedrons. The team also predicted that proteins could assemble into a triangular samosa shape, resembling the fried, South Asian snack.

Understanding this process could lead to bio-inspired building blocks for various engineering applications that require components of varying shapes and sizes.

"It's like building with Legos," Tullman-Ercek said. "It's not desirable to use the same shape block over and over again; we need different shapes. Learning from bacteria can help us build new and better structures at this microscopic scale."

Every day, the sun ejects large amounts of a hot particle soup known as plasma toward Earth where it can disrupt telecommunications satellites and damage electrical grids. Now, scientists at the U.S. Department of Energy's (DOE) Princeton Plasma Physics Laboratory (PPPL) and Princeton University's Department of Astrophysical Sciences have made a discovery that could lead to better predictions of this space weather and help safeguard sensitive infrastructure.

The discovery comes from a new computer model that predicts the behavior of the plasma in the region above the surface of the sun known as the solar corona. The model was originally inspired by a similar model that describes the behavior of the plasma that fuels fusion reactions in doughnut-shaped fusion facilities known as tokamaks.

Fusion, the power that drives the sun and stars, combines light elements in the form of plasma -- the hot, charged state of matter composed of free electrons and atomic nuclei -- that generates massive amounts of energy. Scientists are seeking to replicate fusion on Earth for a virtually inexhaustible supply of power to generate electricity.

The Princeton scientists made their findings while studying roped-together magnetic fields that loop into and out of the sun. Under certain conditions, the loops can cause hot particles to erupt from the sun's surface in enormous burps known as coronal mass ejections. Those particles can eventually hit the magnetic field surrounding Earth and cause auroras, as well as interfere with electrical and communications systems.

"We need to understand the causes of these eruptions to predict space weather," said Andrew Alt, a graduate student in the Princeton Program in Plasma Physics at PPPL and lead author of the paper reporting the results in the Astrophysical Journal.

The model relies on a new mathematical method that incorporates a novel insight that Alt and collaborators discovered into what causes the instability. The scientists found that a type of jiggling known as the "torus instability" could cause roped magnetic fields to untether from the sun's surface, triggering a flood of plasma.

The torus instability loosens some of the forces keeping the ropes tied down. Once those forces weaken, another force causes the ropes to expand and lift further off the solar surface. "Our model's ability to accurately predict the behavior of magnetic ropes indicates that our method could ultimately be used to improve space weather prediction," Alt said.

The scientists have also developed a way to more accurately translate laboratory results to conditions on the sun. Past models have relied on assumptions that made calculations easier but did not always simulate plasma precisely. The new technique relies only on raw data. "The assumptions built into previous models remove important physical effects that we want to consider," Alt said. "Without these assumptions, we can make more accurate predictions."

To conduct their research, the scientists created magnetic flux ropes inside PPPL's Magnetic Reconnection Experiment (MRX), a barrel-shaped machine designed to study the coming together and explosive breaking apart of the magnetic field lines in plasma. But flux ropes created in the lab behave differently than ropes on the sun, since, for example, the flux ropes in the lab have to be contained by a metal vessel.

The researchers made alterations to their mathematical tools to account for these differences, ensuring that results from MRX could be translated to the sun. "There are conditions on the sun that we cannot mimic in the laboratory," said PPPL physicist Hantao Ji, a Princeton University professor who advises Alt and contributed to the research. "So, we adjust our equations to account for the absence or presence of certain physical properties. We have to make sure our research compares apples to apples so our results will be accurate."

Discovery of the jiggling plasma behavior could also lead to more efficient generation of fusion-powered electricity. Magnetic reconnection and related plasma behavior occur in tokamaks as well as on the sun, so any insight into these processes could help scientists control them in the future.

Support for this research came from the DOE, the National Aeronautics and Space Administration, and the German Research Foundation. Research partners include Princeton University, Sandia National Laboratories, the University of Potsdam, the Harvard-Smithsonian Center for Astrophysics, and the Bulgarian Academy of Sciences.

PPPL, on Princeton University's Forrestal Campus in Plainsboro, N.J., is devoted to creating new knowledge about the physics of plasmas -- ultra-hot, charged gases -- and to developing practical solutions for the creation of fusion energy. The Laboratory is managed by the University for the U.S. Department of Energy's Office of Science, which is the single largest supporter of basic research in the physical sciences in the United States and is working to address some of the most pressing challenges of our time. For more information, visit https://energy.gov/science

Although plants may look fairly inactive to casual observers, research into plant biology has shown that plants can send each other signals concerning threats in their local environments. These signals take the form of airborne chemicals, called volatile organic compounds (VOCs), released from one plant and detected by another, and plant biologists have found that a diverse class of chemicals called terpenoids play a major role as airborne danger signals.

Past studies have shown that soybean and lima bean plants both release terpenoid signals that activate defense-related genes in neighboring plants of the same species, and this chemically induced gene activation can help the plants protect themselves from threats like herbivorous pests.

In recent years, scientists have realized that the capacity of these chemical signals to boost plant defense mechanisms could make them useful pest control tools for agriculture and horticulture. One such scientist is Prof. Gen-ichiro Arimura of the Tokyo University of Science, Japan. Prof. Arimura notes that "the development of agricultural technology to date has been largely reliant on the use of pesticides and chemical fertilizers, which has resulted in environmental pollution and the destruction of ecosystems." As a greener alternative to pesticides, terpenoid signaling molecules may help farmers continue their production of vital foodstuffs while lessening the associated environmental costs.

In pursuit of this goal, Prof. Arimura and his colleagues chose to investigate the terpenoid compound menthol, which is derived from mint leaves and can activate plant immune systems. The aim of this project, which the researchers describe in an article recently published in the journal Plant Molecular Biology, was to develop compounds that are structurally similar to menthol but improve upon menthol's ability to activate plant immune systems. The researchers therefore experimented with chemically modifying menthol by attaching amino acids, which are a structurally diverse set of compounds that living cells use to construct proteins. In total, the researchers synthesized six different menthol derivatives with attached amino acids.

The researchers then tested the resulting menthol derivatives to see whether the modified compounds could outperform unmodified menthol at activating plant defense mechanisms. To do this, they treated soybean leaves with either menthol or one of the six menthol derivatives to see which of the derivatives, if any, could outclass menthol itself at boosting the expression levels of two defense-related soybean genes after 24 hours of exposure. The found that only one of the modified compounds bested menthol, and this compound is called valine menthyl ester, or "ment-Val" for short.

The researchers found that spraying soybean leaves once with a ment-Val solution boosted expression of the defense-related genes for three days, and a second spraying on the fourth day worked to boost the expression of those genes again. These findings suggest that ment-Val could provide sustainable pest control for farmers growing soybeans. Further experiments showed that ment-Val also increased the expression of defense-related genes in other crops, including peas, tobacco, lettuce, and corn. Ment-Val also proved to be quite stable under various conditions, which suggests that farmers would probably not lose the compound to degradation during storage.

Overall, these results suggest that ment-Val could be extremely useful as an alternative to the chemical pesticides that so many farmers rely on. Prof. Arimura notes that spraying ment-Val may be an effective way "to reduce pest damage to soybeans and other crops." He has applied for a patent on ment-Val's use as a crop protection agent, and he predicts that the commercialization of ment-Val "will generate billions of yen in economic benefits through its usage by companies operating in the fields of horticulture and agriculture." He also notes that ment-Val's anti-inflammatory properties could make it useful for human medicine.

The future is certainly going to be exciting for research into menthol derivatives like ment-Val!

It's well established that infectious disease is the greatest threat to the endangered chimpanzees made famous by the field studies of Jane Goodall at Gombe National Park in Tanzania. Now, new research led by scientists at Emory University shows that nearly half of the fecal samples from wild chimpanzees contain bacteria that is resistant to a major class of antibiotics commonly used by people in the vicinity of the park.

The journal Pathogens published the findings.

"Our results suggest that antibiotic-resistant bacteria is actually spreading from people to non-human primates by making its way into the local watershed," says Thomas Gillespie, senior author of the study and associate professor in Emory's Department of Environmental Sciences and Rollins School of Public Health. "People are bathing and washing in the streams, contaminating the water with drug-resistant bacteria where wild chimpanzees and baboons drink."

The researchers tested for genes conferring resistance to sulfonamides -- drugs often used by people in the region to treat diarrheal diseases -- in fecal samples from humans, domestic animals, chimpanzees and baboons in and around Gombe National Park. They also tested stream water used by these groups.

Sulfonamide resistance appeared in 74 percent of the human samples overall, 48 percent of chimpanzee samples, 34 percent of baboon samples, and 17 percent of the domestic animal samples. Sulfonamide also showed up in 19 percent of the samples taken from streams shared by people, domestic animals and wildlife.

The researchers also tested all the groups in the study for genes conferring resistance to tetracycline -- another class of antibiotics that is used much less frequently by people in the vicinity, likely due to its greater expense and the fact that it is less available in the area. As expected, very few of the fecal samples from any of the groups, and none of the water samples from the streams, showed evidence of tetracycline resistance.

First author of the study is Michelle Parsons, who did the work as an Emory doctoral student in Environmental Sciences. Parsons has since graduated and works at the Centers for Disease Control and Prevention (CDC). Co-authors include researchers from the Jane Goodall Institute, the CDC, the University of Minnesota and Franklin and Marshall College.

Gillespie is a disease ecologist who helped pioneer the "One Health" approach to protect humans, ecosystems and biodiversity. His projects in Africa, including the collaboration with the Jane Goodall Institute in Tanzania, are focused on helping farmers subsisting amid fragmented forests co-exist with primates and other wildlife in ways that minimize the risk of pathogen exchange between species, known as "spillover." The virus that causes AIDS, for example, spilled over from chimpanzees to people.

"It's important to consider both sides of the story -- human health and well-being, as well as conservation of chimpanzees and other species," Gillespie says.

Human encroachment has taken a toll on the great apes, due to fragmented habitat and the exchange of pathogens. Today, the number of chimpanzees in Gombe National Park are down to about 95.

Diarrheal diseases are common in the area and people often turn to cheap sulfonamide antibiotics that are available without a prescription at small stores that act as informal pharmacies, selling drugs, soap and other necessities. Wild chimpanzees also suffer from wasting diseases that can be related to bacterial and other enteric pathogens that affect their ability to maintain calorie intake and absorb nutrients.

"The majority of people in our sampling harbored bacteria resistant to the sulfonamide medication they are taking," Gillespie says. "In those cases, they're spending their money on a drug that is not helping them get better. Overuse of such drugs creates the potential for more lethal, antibiotic-resistant 'super bugs' to emerge."

The research findings will now support the development of interventions. More guidance is needed locally regarding the proper use of antibiotics, Gillespie says. He adds that it is also important to improve hygiene for wash-related activities in area streams, as well as to improve disposal of human waste materials.

"By misusing antibiotics, people can actually harm not only themselves, but also the species they share an environment with," Gillespie says. "After drug-resistant bacteria jump into chimpanzees, it can further evolve with the chimpanzees and then spill back into humans. We need to be thinking about infectious diseases within evolutionary and ecological frameworks, something that's not often done in medicine."

LAWRENCE -- College students across the country struggle with a vicious cycle: Test anxiety triggers poor sleep, which in turn reduces performance on the tests that caused the anxiety in the first place.

New research from the University of Kansas just published in the International Journal of Behavioral Medicine is shedding light on this biopsychosocial process that can lead to poor grades, withdrawal from classes and even students who drop out. Indeed, about 40% of freshman don't return to their universities for a second year in the United States.

"We were interested in finding out what predicted students' performance in statistics classes -- stats classes are usually the most dreaded undergrad class," said lead author Nancy Hamilton, professor of psychology at KU. "It can be a particular problem that can be a sticking point for a lot of students. I'm interested in sleep, and sleep and anxiety are related. So, we wanted to find out what the relationship was between sleep, anxiety and test performance to find the correlation and how it unfolds over time."

Hamilton and graduate student co-authors Ronald Freche and Ian Carroll and undergraduates Yichi Zhang and Gabriella Zeller surveyed the sleep quality, anxiety levels and test scores for 167 students enrolled in a statistics class at KU. Participants completed an electronic battery of measures and filled out Sleep Mood Study Diaries during the mornings in the days before a statistics exam. Instructors confirmed exam scores. The study showed "sleep and anxiety feed one another" and can hurt academic performance predictably.

"We looked at test anxiety to determine whether that did predict who passed, and it was a predictor," Hamilton said. "It was a predictor even after controlling for students' past performance and increased the likelihood of students failing in class. When you look at students who are especially anxious, it was almost a five-point difference in their score over students who had average levels of anxiety. This is not small potatoes. It's the difference between a C-minus abd a D. It's the difference between a B-plus and an A-minus. It's real."

Beyond falling grades, a student's overall health could suffer when test anxiety and poor sleep reinforce each other.

"Studies have shown students tend to cope with anxiety through health behaviors," Hamilton said. "Students may use more caffeine to combat sleep problems associated with anxiety, and caffeine can actually enhance sleep problems, specifically if you're using caffeine in the afternoon or in the evening. Students sometimes self-medicate for anxiety by using alcohol or other sedating drugs. Those are things that we know are related."

Hamilton said universities could do more to communicate to students the prevalence of test anxiety and provide them with resources.

"What would be really helpful for a university to do is to talk about testing anxiety and to talk about the fact that it's very common and that there are things that can be done for students who have test anxiety," she said. "A university can also talk to instructors about doing things that they can do to help minimize the effect of testing anxiety."

According to Hamilton, instructors are hindered by the phenomenon as well: Anxiety and associated sleep problems actually distort instructors' ability to measure student knowledge in a given subject.

"As an instructor, my goal when I'm writing a test is to assess how much a student understands," she said. "So having a psychological or an emotional problem gets in the way of that. It actually impedes my ability to effectively assess learning. It's noise. It's unrelated to what they understand and what they know. So, I think it behooves all of us to see if we can figure out ways to help students minimize the effects of anxiety on their performance."

The KU researcher said testing itself isn't the problem and suggested an increase in regular tests might reduce anxiety through regular exposure. However, she said a few small changes to how tests are administered also could calm student anxiety.

"In classes that use performance-based measures like math or statistics, classes that tend to really induce a lot of anxiety for some students, encouraging those students to take five minutes right before an exam to physically write about what they're anxious about can help -- that's cheap, that's easy," Hamilton said. "Also, eliminating a time limit on a test can help. There's just really nothing to be gained by telling students, 'You have an hour to complete a test and what you don't get done you just don't get done.' That's really not assessing what a student can do -- it's only assessing what a student can do quickly."

Hamilton said going forward she'd like research into the link between test anxiety and poor sleep broadened to include a more diverse group of students and also to include its influence on remote learning.

"The students in this study were mostly middle-class, Caucasian students," she said. "So, I hesitate to say these results would generalize necessarily to universities that have a more heterogeneous student body. I also would hesitate to say how this would generalize into our current Zoom environment. I don't know how that shakes out because the demands of doing exams online are likely to be very different."

Seasonally occurring fields of aufeis (icing) constitute an important resource for the water supply of the local population in the Upper Indus Basin. However, little research has been done on them so far. Geographers at the South Asia Institute of Heidelberg University have now examined the spreading of aufeis and, for the first time, created a full inventory of these aufeis fields. The more than 3,700 accumulations of laminated ice are important for these high mountain areas between South and Central Asia, particularly with respect to hydrology and climatology.

In the semi-arid Himalaya regions of India and Pakistan, meltwater from snow and glaciers plays an essential role for irrigation in local agriculture and hydropower generation. In this context, aufeis has been given little attention. It appears as thin sheet-like layers of ice that form through successive freezing of water and can be several meters thick. This phenomenon occurs on a seasonal basis below springsheds, along rivulets or streams under conditions of frequent freeze-thaw cycles. "In individual cases, this process is deliberately fostered through the construction of stone walls. These artificial reservoirs are used in some valleys of Upper Indus tributaries as water harvesting measures to bridge the seasonal water shortage in spring. However, the amount of ice, size and number of natural aufeis fields have been unknown so far," underlines Prof. Dr Marcus Nüsser from the South Asia Institute of Heidelberg University.

The Heidelberg geographers have now compiled an inventory of these fields for the whole Upper Indus Basin and, in this context, also analysed the role of topographical parameters such as altitude and slope. The basis were several field campaigns spent in the region along with the evaluation of almost 8,300 Landsat satellite images taken between 2010 and 2020. With this imagery, the scientists were able to record the characteristic seasonal formation of aufeis and map the annually recurring bodies of ice. They detected over 3,700 aufeis fields, covering a total area of approximately 300 square kilometers. The majority of the aufeis fields lie in the Trans-Himalaya of Ladakh and on the Tibetan Plateau. In contrast, they hardly occur at all in the western part of the Upper Indus region, Marcus Nüsser explains.

The study is part of a project funded by the German Research Foundation about the significance of aufeis and ice reservoirs for the population and agriculture in the Indian region of Ladakh. The participating scientists are studying the effectiveness of the different types of ice reservoirs and whether they function efficiently on a seasonal basis. "Climate change alters both the melt rate and the annual timing of runoff, which causes increasing uncertainties for irrigated agriculture," emphasises Prof. Nüsser. "Our findings may contribute to identifying suitable locations for ice reservoirs that can improve seasonal water availability for local farming. In addition, we are going to investigate the extent to which bodies of aufeis can serve as appropriate indicators of climate change."

The current research findings were published in the journal Science of the Total Environment.

April 28, 2021 - Injectable dermal fillers provide a minimally invasive approach to reduce facial lines and wrinkles while restoring volume and fullness in the face. More than 2.7 million dermal filler procedures were performed in 2019, according to the most recent statistics from the American Society of Plastic Surgeons (ASPS).

Even as the popularity of dermal fillers continues to skyrocket, plastic surgeons are still working out how to maximize their benefits for patients seeking nonsurgical facial rejuvenation. Most studies have used subjective rating systems, with little objective evidence on the outcomes achieved.

One recent study suggested that in addition to their "volumizing" effects, dermal fillers may also have variable "lifting" effects. Sebastian Cotofana, MD, PhD, of the Mayo Clinic, Rochester, Minn., and colleagues designed a study to measure the true lifting effect of soft tissue fillers in different areas of the face. Their study appears in the May issue of Plastic and Reconstructive Surgery®, the official medical journal of the ASPS.

In the experimental study, the researchers performed standardized dermal filler injections in specially prepared facial cadaver specimens. Injections were made in areas commonly targeted in minimally invasive facial rejuvenation procedures: the forehead and temple; the midface region, including both the medial (central) and the lateral (sides) areas; and the perioral area (mouth and chin) and jawline.

To measure the effects of the injections, Dr. Cotofana and colleagues performed before-and-after scans of the facial surface using an advanced three-dimensional scanning technology (Vectra 3D imaging system). The same type of 3D digital imaging system is now commonly used to assess and even simulate the results of plastic and reconstructive surgery procedures.

Scans taken after dermal filler injections showed significant increases in local soft tissue volume in central areas of the face. That was consistent with the well-established clinical effects of "injectable" treatment in the medial forehead, midface, and mouth and chin areas.

Central facial injections also showed local lifting effects, including up to one millimeter of vertical "lift" in the forehead area. However, there was no accompanying regional lifting effect - for example, forehead injection produced no lifting effect in the central areas of the middle or lower face.

Injections in lateral facial areas like the temple, midface, and jawline also produced local volumizing and lifting effects. In addition, the lateral facial injections created "additional regional lifting effects" in neighboring areas of the face. For example, injection in the temple had a small but significant lifting effect on the lateral midface and jawline.

Combined injection techniques provided even larger benefits. Added to deep filler injection, a superficial temple injection technique produced an additional 17.5 percent increase in the lifting effect of the temple, plus a 100 percent increase in the jawline lifting effect.

"These results indicate that lateral face injections co-influence adjacent lateral facial regions and can thus induce regional lifting effects," Dr. Cotofana and coauthors write. The results are consistent with previous knowledge of the in-depth anatomy of the face: filler injections may lead to a change in tension of the connective tissue (fascia) under the skin, resulting in "re-positioning" of the upper skin layers.

In this way, filler injections can provide a small but significant lifting effect in a minimally invasive, repeatable procedure. Of course, the gravity-defying lifting effects don't approach the impact of facelift surgery. In addition to confirming previous findings on the lifting effects of facial injectables, the study also "broadens their applicability to the total lateral face...to achieve local and regional lifting effects."

Constantina Theofanopoulou wanted to study oxytocin. Her graduate work had focused on how the hormone influences human speech development, and now she was preparing to use those findings to investigate how songbirds learn to sing. The problem was that birds do not have oxytocin. Or so she was told.

"Everywhere that I looked in the genome," she says, "I was unable to find a gene called oxytocin in birds."

Theofanopoulou eventually came across mesotocin, the analogue for oxytocin in birds, reptiles, and amphibians. But as she plumped the literature in Erich Jarvis's lab at Rockefeller, the waters grew muddier. If she and Jarvis wanted to find studies on oxytocin in fish, they had to remember to search for the unique term isotocin. Unless, of course, they were looking for studies of oxytocin in certain species of shark, in which case they were obliged to scour abstracts for valitocin--the oxytocin of spiny dogfish. Similar issues arose when they tried studying the hormone vasotocin in birds, which is called vasopressin in humans. And the oxytocin receptor, typically abbreviated OXTR in mammalian studies, could be named VT3, MTR, MesoR, or ITR in studies of other species.

"I started getting lost," Jarvis admits. "I said, before we dig deeper, we need to make sure we've made the right assumptions about which human and bird genes are evolutionarily related."

Now, in a new study in Nature, Theofanopoulou and Jarvis demonstrate that the human hormone known as oxytocin is in fact the one and the same gene across all major vertebrate lineages. The similarities are in fact so striking that the scientists advocate for cleaning up the jargon once and for all by applying new standard nomenclature for the hormones known as oxytocin and vasopressin in humans, as well as their respective receptors.

This updated naming convention would, at the very least, make life easier for scientists studying oxytocin. But it could also serve as a model for how to translate a vast range of biological findings across species--ultimately leading to a better understanding of how the same genes function in different organisms.

A Whole-Genome Approach

Before whole genome sequencing gave scientists a big picture view of just how similar many genetic sequences are, biochemists would often assign unique names to near-identical genes in recognition of slight, often inconsequential, differences. This gave rise to the odd naming conventions across species that so baffled Theofanopoulou and Jarvis. "Oxytocin in mammals has one different amino acid than mesotocin in turtles," Theofanopoulou says. "Before we had a whole-genome perspective, we might have thought that it was an entirely different gene."

But sequence similarity isn't the only sign that two genes from different species are related. Another is each gene's surrounding gene territory on its respective chromosome, which scientists refer to as synteny. In other words, the identity of a gene is not made up only by the sequence 'inside' the gene, but also by the genes that surround it, those genes found 'outside' that gene. And while mammalian oxytocin differs slightly, in sequence, from its turtle analogue, this new study demonstrates that there is synteny in oxytocin, vasotocin, and each hormone's receptor, across the genomes of 35 species that span all major vertebrate lineages and four invertebrate lineages.

"With synteny, we can show that oxytocin in mammals is the same gene as mesotocin in turtles, because it is located in the same syntenic position in all these genomes, namely surrounded by the same genes across species. Gene sequence within a gene tends to change fast, but the gene order, how genes are located the one after the other, tends to be much more conserved in evolutionary time." Theofanopoulou says.

This broader perspective would not have been possible without recent updates that made whole genomes more complete and accurate, a project spearheaded by the international Vertebrate Genomes Project, which Jarvis chairs. These use long-sequence reads and long-range data to generate nearly complete chromosomal level genome assemblies. Cleaner genomes with fewer errors allow scientists to search for syntenic subtleties in new ways. "Many of the genomes that we have been looking at don't have mixed up chromosomes or errors," Jarvis says. "Nobody had this before."

What's in a name?

Many more genes may require just this sort of re-evaluation, to facilitate translational research and bring scientific vocabulary into the post-genomic era. For instance, similar nomenclature issues exist within two genes pertinent to Jarvis's work on vocal learning, SRGAP and FOXP2, and Theofanopoulou suspects that naming conventions for dopamine and estrogen receptors may need revisions as well. "This paper serves as a model for how to revamp genome nomenclature in biology, based on gene evolution," Jarvis says.

But whether such new names will stick remains an open question. Jarvis and Theofanopoulou are already experiencing pushback from researchers who are reluctant to see the long legacy of mesotocin research renamed and bundled up with oxytocin, or vasopressin with vasotocin. "We've spoken with several people who knew that these genes were analogues but insisted that they cannot be called by the same name," Jarvis says. "Some argued that 'this is the way it has been for decades.'"

Others worry that, however syntenic these genes may be across species, it would be inaccurate and perhaps even misleading to use the same name for the gene that promotes lactation in mammals and clearly plays a different role in birds and turtles. Jarvis disagrees. "A name shouldn't be based solely on function, but also on genetic and evolutionary similarities," he says.

"We can now show that these are the same genes because they are located in the same conserved blocks of gene order in the genome across species," Theofanopoulou adds. "Had the genes for these hormones been discovered in today's genomics era, they would have been named with the same and not different names."

Researchers from Erasmus School of Economics, IESE Business School, and New York University published a new paper in the Journal of Marketing that examines what business schools do wrong when conducting academic research and what changes they can make so that research contributes to improving society.

The study, forthcoming in the Journal of Marketing, is titled "Faculty Research Incentives and Business School Health: A New Perspective from and for Marketing" and is authored by Stefan Stremersch, Russell Winer, and Nuno Camacho.

In February 2020, an article in the Financial Times stated that business schools' research model is "ill," with faculty increasingly focusing on "abstract, abstruse and overly academic topics with little resonance beyond the higher education sector."

The researchers demonstrate that business schools use the wrong research metrics and incentives with research faculty. As Stremersch explains, "We show that business schools focus excessively on the quantity of research and insufficiently on other critical aspects such as the quality, rigor, relevance, and creativity of such research." To gauge whether research incentives in business schools are indeed badly designed, they surveyed 234 marketing professors in business schools across 20 countries and completed 22 interviews with 14 (associate) deans and eight external institution stakeholders.

Results show that business schools' research incentives are badly designed for three main reasons. First, business schools use the wrong research metrics to monitor their faculty's research, often harming the quality (rigor and relevance) of the research produced by their research faculty. Second, research with lower-than-desired practical importance may hurt teaching quality, which negatively impacts business school health. Third, while research faculty feel undercompensated for the research they do, (associate) deans feel that the current compensation levels for faculty are not sustainable.

The researchers assert that business schools need to recalibrate their faculty research incentives. To do so, business schools can start with three concrete actions. First, business schools need to develop better research metrics. "Schools need to reduce the weight they place in low-effort metrics (such as the mere number of publications or citations) and increase the weight they place in effortful metrics such as awards, research creativity, literacy, and relevance to non-academic audiences," says Winer.

Second, business schools need to develop a high commitment working environment where research faculty internalize and actively contribute to the health of the business school. Such high commitment environments should improve alignment between schools and their research faculty in terms of compensation.

Third, business schools need to improve the practical importance of their faculty's research. Several (associate) deans at top business schools whom the researchers interviewed report that the business schools they lead have made more progress on rigor than on practical importance and that they are concerned about a further decline in such practical importance in recent years.

In sum, business schools need to revise their faculty research incentives to ensure their faculty produce research that lives up to society's expectations and improves managers and firms' decision making.

The flightless kakapo of New Zealand is in trouble. The world's heaviest parrot--representing one of the most ancestral branches of the parrot family tree--is nearly extinct, with barely 200 adults plodding the underbrush of four small islands. Whether the last of the kakapos had the genetic resilience to survive was a question that only high-quality genomic analysis could answer.

But a high-quality genome assembly did not exist for the kakapo--nor for most of the 70,000 vertebrate species alive today.

Questions about how best to prevent the extinction of species ranging from the flightless kakapos to the adorable small vaquita dolphins were left unanswered. Had inbreeding left these populations genetically non-viable? Were humans the only reason that these animals stood on the brink of extinction, or was something inherently broken in their DNA?

The solution was the Vertebrate Genomes Project, an ambitious initiative launched to generate high-quality reference genomes for every extant vertebrate species. Now in their flagship study published in Nature, they present methods and principles for sequencing and assembling high-quality reference genome.

The team has applied this approach and principles to produce 16 high-quality reference genomes, one of which was the endangered kakapo, to help reveal if it is hardy enough to rebuild its population. The researchers found that extremely small populations of the endangered kakapo and vaquita have been able to survive their low numbers in the past since the last ice age over 10,000 years ago, by purging deleterious mutations that cause disease from inbreeding. As long as humans do not kill of more of the last remaining animals, findings from the high-quality reference genomes give hope that these species could survive from less than 100 individuals each.

"We call it the 'kitchen sink approach'--combining tools from several biotech companies to make this one high-quality genome assembly pipeline," says Rockefeller's Erich D. Jarvis, Chair of the Vertebrate Genomes Project. "Endangered species were the first to benefit from the new technology because, even though conservation is not my area of research, I felt it was a moral duty."

Working with low-quality genomes

High-quality reference genomes only exist for the celebrities of laboratory science--mice, fruit flies, zebrafish, and, of course, humans. For less popular species, there is often no reference genome or, perhaps worse, messy genomes stitched together from sequences obtained via quick and dirty methods. Compared to the new VGP genomes, up to 60 percent of the genes in such genomes have missing sequence, are entirely missing, or incorrectly assembled, the researchers found. It can take years to untangle the thousands of assembly errors per species.

Many false gene duplications were found, most caused by algorithms that due not properly separate out maternal and paternal chromosome sequences and instead interpret them as a two separate sister genes. "We have thousands of genes in the literature that are false duplications. The genes are not actually there!" Jarvis says. "It is unconscionable to be working with some of these genomes."

The Vertebrate Genomes Project was born from the frustrations of hundreds of scientists working in its parent organization, the Genome 10K consortium, whose mission it was to generate genome assemblies of 10,000 vertebrate species. The initial genome assemblies that the G10K and other groups generated were based on short 35 to 200 base pair reads, but these assemblies were highly incomplete. The VGP goal is to build a library of error-free reference genomes for all vertebrate species, which researchers and conservationists will be able to use readily, without dedicating months or years to fixing individual genes. "We said, let's do some hard work on the front end, so that we can get high quality data on the back end," Jarvis says.

The "kitchen sink" approach

Many companies approached the Vertebrate Genomes Project, promising a single sequencing technology that would solve every problem with messy reference genomes. The Vertebrate Genomes Project assembly team tested each method on a single hummingbird, chosen both for its relatively small genome and because of Jarvis' research interests in vocal learning among bird species ("two birds with one stone," he quips). But every technology fell short. "None had all of the necessary components to make a high-quality assembly," Jarvis says. "So we combined many tools into one pipeline."

Their approach works. Organizations including the Earth Biogenome Project, the Darwin Tree of Life Project, and the New Zealand Genome Sequencing Project are already using the most advance version of the novel pipeline. Reference genomes that once took years to generate are now rolling out in weeks and months--all without the false duplications and other errors endemic to previous assemblies. Scientists are already using the new data to study genes that render bats immune to COVID-19, and question long-standing conventions in basic science, such as whether there are meaningful differences between oxytocin and its receptors found in humans, birds, reptiles, and fish.

All told, 20 studies and 25 high-quality vertebrate genomes accompany the rollout of the novel pipeline. "The first high-quality genomes that we sequenced taught us so much about the technology and the biology that we decided to publish in these initial papers," Jarvis says. But plenty of work still lies ahead. "The next step is to sequence all 1,000 vertebrate genera, and then all 10,000 vertebrate families, and eventually every single vertebrate species"

The highly infectious SARS-CoV-2 variant that recently emerged in South Africa, known as B.1.351, has scientists wondering how existing COVID-19 vaccines and therapies can be improved to ensure strong protection. Now, researchers reporting in ACS' Journal of Medicinal Chemistry have used computer modeling to reveal that one of the three mutations that make variant B.1.351 different from the original SARS-CoV-2 reduces the virus' binding to human cells -- but potentially allows it to escape some antibodies.

Since the original SARS-CoV-2 was first detected in late 2019, several new variants have emerged, including ones from the U.K., South Africa and Brazil. Because the new variants appear to be more highly transmissible, and thus spread rapidly, many people are worried that they could undermine current vaccines, antibody therapies or natural immunity. Variant B.1.351 bears two mutations (N501Y and E484K) that can enhance binding between the receptor binding domain (RBD) of the coronavirus spike protein and the human ACE2 receptor. However, the third mutation (K417N; a lysine to asparagine mutation at position 417) is puzzling because it eradicates a favorable interaction between the RBD and ACE2. Therefore, Binquan Luan and Tien Huynh from IBM Research wanted to investigate potential benefits of the K417N mutation that could have caused the coronavirus to evolve along this path.

The researchers used molecular dynamics simulations to analyze the consequences of the K417N mutation in variant B.1.351. First, they modeled binding between the original SARS-CoV-2 RBD and ACE2, and between the RBD and CB6, which is a SARS-CoV-2-neutralizing antibody isolated from a recovered COVID-19 patient. They found that the original amino acid, a lysine, at position 417 in the RBD interacted more strongly with CB6 than with ACE2, consistent with the antibody's therapeutic efficacy in animal models. Then, the team modeled binding with the K417N variant, which changes that lysine to an asparagine. Although this mutation reduced the strength of binding between the RBD and ACE2, it decreased the RBD's binding to CB6 and several other human antibodies to a much greater extent. Thus, variant B.1.351 appears to have sacrificed tight binding to ACE2 at this site for the ability to evade the immune system. This information could prove useful to scientists as they work to enhance the protection of current vaccines and therapies, the researchers say.

People of color, those with a higher income and younger individuals are more likely to participate in clinical trials during their cancer treatment according to a new study from the University of Missouri School of Medicine.

Clinical trials are research studies that involve people who volunteer to take part in tests of new drugs, current approved drugs for a new purpose or medical devices.

The study analyzed data collected from the Centers for Disease Control and Prevention (CDC) Behavioral Risk Factor Surveillance System Survey, which is an annual national telephone survey designed to collect health-related data from U.S. adults. Survey years selected included the question, "Did you participate in a clinical trial as part of your cancer treatment?" The analysis of 20,053 respondents revealed an average overall clinical trial participation rate of 6.51%. Among 17,600 white respondents, participation was 6.24%; among 445 Hispanic respondents, participation was 11%; and among 943 Black respondents, participation was 8.27%.

"This study informs our understanding of who is participating in cancer clinical trials," said Lincoln Sheets, MD, PhD, assistant research professor at the MU School of Medicine. "We found people of color were more likely to participate in cancer clinical trials than white cancer patients when controlling for other demographic factors. It could be that in previous studies, the effects of income, sex or age were muddling the true picture."

Sheets said the analysis also indicated people who earn more than the national median household income of $50,000 annually and the young were more likely to participate in clinical trials during cancer treatment.

"Taken in total, the results of this study help confirm that there are sociodemographic disparities in cancer clinical trials, indicating there are deficiencies in the system as it stands now," Sheets said. "We must lessen financial barriers to participation, improve logistical accessibility of cancer clinical trials and loosen restrictions on the enrollment of patients with comorbidities."

Sheets said improving access to transportation, childcare and health insurance would remove some of the structural and logistical barriers that prevent people from participating in cancer clinical trials.