Culture

ANN ARBOR--Fully vaccinating children reduces the risk of hospitalization associated with influenza by 54%, according to a study by researchers at the University of Michigan, the Clalit Research Institute, and Ben-Gurion University in Israel.

The study, published in the December 2019 issue of the journal Clinical Infectious Disease, is one of the few studies worldwide that has tested the effectiveness of childhood vaccination against influenza and risk of hospitalization due to influenza complications.

In Israel, as in the United States, government guidelines recommend that children 8 or younger who have never been vaccinated, or who have only gotten one dose of flu vaccine previously, should receive two doses of vaccine.

Children vaccinated according to government guidelines are much better protected from influenza than those who only receive one vaccine, said Hannah Segaloff, a research fellow at the U-M School of Public Health and lead author of the study.

"Over half of our study population had underlying conditions that may put them at high risk for severe influenza-related complications, so preventing influenza in this group is critically important," she said. "Our results also showed that the vaccine was effective in three different seasons with different circulating viruses, reinforcing the importance of getting an influenza vaccine every year no matter what virus is circulating."

The retrospective study used data from Clalit Health Services, the largest health fund in Israel, to review the vaccination data of 3,746 hospitalizations of children 6 months to 8 years old at six hospitals in Israel. They were tested for influenza over three winter seasons 2015-16, 2016-17 and 2017-18.

Not only do the findings reveal that the flu vaccine reduced hospitalizations associated with the flu by 54%, but they show that giving two vaccine doses to children up to age 8 who have never been vaccinated or only received one dose previously is more effective than administering one dose, in accordance with the Israel Ministry of Health's recommendations.

"Young children are at high risk of hospitalization due to influenza complications," said study co-author Mark Katz, a senior researcher at the Clalit Research Institute, the research arm of Clalit Health Services, and an adjunct associate clinical professor at the BGU School of Public Health and Medical School for International Health.

"Children with underlying illnesses such as asthma and heart disease have an even greater risk of getting the complications. It is important to prevent influenza infections in these populations."

The findings support health organizations' recommendations, including the Israel Ministry of Health to vaccinate children against influenza every year, preferably before the onset of winter or early childhood. Children under 5 are defined as having a high risk of influenza complications.

"This study mirrors a previous study we conducted at Clalit Institute where we found that flu vaccine reduces 40% risk of hospitalizations in pregnant women," said Ran Balicer, director of the Clalit Research Institute and professor at the BGU School of Public Health.

"It reaffirms that vaccination is the most effective way to prevent both the flu and hospitalization. We hope parents will be aware of these facts and make an informed decision about the importance of vaccinating their children."

In a range of experiments, scientists have reactivated resting immune cells that were latently infected with HIV or its monkey relative, SIV, in cells in the bloodstream and a variety of tissues in animals. As a result, the cells started making copies of the viruses, which could potentially be neutralized by anti-HIV drugs and the immune system. This advance, published today in two papers in the journal Nature, marks progress toward a widely accessible cure for HIV.

The new research was conducted by investigators from the Collaboratory of AIDS Researchers for Eradication (CARE) based at the University of North Carolina at Chapel Hill and from the Emory Consortium for Innovative AIDS Research (E-CIAR) in Nonhuman Primates, both funded by the National Institutes of Health. Scientists from ViiV Healthcare and Qura Therapeutics collaborated on the research. CARE is part of the Martin Delaney Collaboratories for HIV Cure Research, the flagship NIH-supported HIV cure research program. The joint efforts of scientists from a variety of specialties made the new findings possible.

"A simple, safe and scalable cure for HIV is an aspirational goal that, if achieved, would accelerate progress toward ending the HIV pandemic," said Anthony S. Fauci, M.D., director of the National Institute of Allergy and Infectious Diseases, part of NIH. "These new findings help sustain our cautious optimism that an HIV cure is possible."

While consistent antiretroviral therapy (ART) maintains the health of people living with HIV and prevents transmission of the virus, it is not a cure. Developing an HIV cure has been extremely difficult due to the persistence of viral reservoirs, where the virus hides from the immune system. These reservoirs consist of HIV-infected cells containing HIV genetic material that can generate new virus particles if a person's treatment is interrupted. The cells have entered a resting state that they maintain until they are activated to produce the virus. The immune system cannot recognize and kill HIV-infected cells in a resting state, and ART has no effect on them.

Consequently, scientists have been attempting to activate the HIV reservoir so therapeutic agents or an enhanced immune system can recognize and kill the infected cells, eliminating HIV. This strategy is often called "kick and kill." Previous attempts to reactivate or "kick" the HIV reservoir worked well in the laboratory but were either ineffective or too toxic when tested in animals and people.

One of today's reports describes the testing of a compound called AZD5582, which belongs to a class of molecules that have proven safe as experimental cancer therapeutics.

CARE scientists obtained 20 mice with human immune systems, infected the animals with HIV, and then gave them ART that suppressed the virus. Next, the scientists injected AZD5582 into 10 of the mice and a placebo into the other 10.

Within 48 hours, high levels of HIV RNA were detected in the blood of six of the AZD5582-treated mice. HIV RNA levels in resting immune cells of the bone marrow, thymic organoid, lymph node, spleen, liver and lung were up to 24-fold higher in the AZD5582-treated mice than in the controls. This indicated that AZD5582 had activated resting cells in the HIV reservoir throughout the treated mice. The compound did not cause toxicity in the mice or activate their immune systems.

The E-CIAR and CARE investigators also obtained 21 rhesus macaques, infected them with SIV and gave them suppressive ART. More than a year after the monkeys began ART, the scientists gave 12 of them weekly intravenous infusions of AZD5582 for either three or 10 weeks.

The level of SIV increased in the blood of five of the nine monkeys (55%) that received 10 doses of AZD5582 and in none of the three monkeys that received fewer doses. Thus, SIV levels increased in five of 12 monkeys (42%) overall, even as they remained on ART. SIV RNA levels in resting immune cells from the monkeys' lymph nodes were significantly higher in animals treated with 10 doses of AZD5582 than in the nine monkeys that did not receive the compound. The investigators found AZD5582 treatment to be safe for most of the monkeys. The scientists did not detect a consistent reduction in the size of SIV reservoir in the AZD5582-treated monkeys, however, suggesting that it may be necessary to pair the compound with another agent to kill activated reservoir cells.

The researchers have begun additional animal studies to determine the best dose and timing of treatment and to be sure AZD5582 activates the reservoirs of many different HIV and SIV strains. It also will be important to test other compounds in the same class as AZD5582 to determine which might work best in humans, according to the scientists. If the results of these follow-up studies are successful, a preliminary clinical trial of treatment with AZD5582 or a related compound in people living with HIV may follow.

This study was led by J. Victor Garcia, Ph.D., Ann Chahroudi, M.D., Ph.D., and Richard Dunham, Ph.D. Dr. Garcia is director of the International Center for the Advancement of Translational Science, an Oliver Smithies Investigator and a professor of medicine, microbiology and immunology at University of North Carolina at Chapel Hill. Dr. Chahroudi is an associate professor of pediatrics in the division of pediatric infectious diseases Emory University School of Medicine and director of the Emory + Children's Center for Childhood Infections and Vaccines. Dr. Dunham is a director at ViiV Healthcare and an adjunct assistant professor at University of North Carolina at Chapel Hill.

The other new report published today describes how a combination of two agents strongly activated the SIV reservoir in ART-treated rhesus macaques and the HIV reservoir in ART-treated mice with human immune systems. One agent, an antibody called MT807R1, depletes the body of immune cells called CD8+ T cells. The other agent is an engineered protein complex called N-803, a more powerful version of a naturally occurring molecule that activates certain immune cells to fight pathogens.

E-CIAR scientists obtained 35 rhesus macaques, infected them with SIV and gave them ART, which suppressed the virus in 33 of the animals. At least a year after ART began, the scientists gave seven monkeys N-803 alone, 14 monkeys MT807R1 alone, and 14 monkeys both MT807R1 and N-803.

N-803 alone had no impact on the SIV reservoir. MT807R1 alone led to a moderate but significant increase in the level of SIV in the animals' blood (their viral load). But the combination of MT807R1 plus N-803 led to a robust and persistent increase in the SIV viral load of all 14 animals--even the six in which fewer than three copies of SIV were detected before the experimental treatment began.

CARE scientists at UNC replicated these outcomes in 23 mice that had been given human immune systems, infected with HIV and given suppressive ART.

In addition, investigators demonstrated in cell culture that N-803 could reactivate human immune cells latently infected with HIV, but that adding CD8+ T cells to the culture suppressed the latency-reversing activity of N-803.

Taken together, the findings illustrate that CD8+ T cells play a role in maintaining the SIV reservoir in monkeys. The scientists hope to clarify exactly how CD8+ T cells do this so they can develop a latency-reversing strategy that does not require eliminating all CD8+ T cells and is thus gentler on the body.

A team of researchers at CHU Sainte-Justine and Université de Montréal has shed light on the mechanisms that underlie a rare genetic condition by creating the first cellular model of the disease. The study's findings were published today in the Journal of Allergy and Clinical Immunology.

Chronic granulomatous disease (CGD) is a rare hereditary condition that affects one in every 217,000 people worldwide and typically strikes patients at an early age.

"It is a primary innate immune defect that typically leads to severe, recurrent infections caused by bacteria and fungi, as well as potentially disabling lung inflammation or inflammatory colitis similar to Crohn's disease," said senior author Dr. Fabien Touzot, a clinical assistant professor in pediatric medicine at UdeM and researcher in pediatric immunology and hematology at CHU Sainte-Justine.

"Currently, patients are forced to take antibiotics and anti-inflammatory drugs for the rest of their lives."

Gene editing shows the way forward

To better understand the mechanisms that trigger inflammation in patients with CGD, Touzot and his research team created the very first cellular model of the disease in their labs at CHU Sainte-Justine. They then used a technique known as gene editing to recreate and introduce into their model a genetic mutation that causes the disease. This allowed them to model the inflammatory response observed in patients and to study its mechanisms.

"CGD is a hereditary illness caused by mutations in the NADPH oxidase enzyme. These mutations prevent white blood cells from working properly and, as a result, the patient's body can no longer defend itself against certain kinds of bacteria and fungi," said researcher Aissa Benyoucef, the study's first author.

"More than 90% of affected patients have inflammation that appears to be unrelated to infectious agents," he added. "Treating this inflammation is difficult, since it can put patients at increased risk of infection, which can sometimes be fatal. A better understanding of the mechanisms underlying the disease could help us develop new and more effective treatment strategies."

The research team showed that restoring NADPH oxydase function in defective cells would put the immune process back on track, thereby proving that this genetic mutation plays a direct role in causing inflammation.

"CHU Sainte-Justine is one of Quebec's leading centres of expertise in rare genetic diseases," said Touzot. "We're proud to serve patients by expanding the knowledge base in this area and by contributing to the development of precision medicine."

The new cellular model will be useful for the development of targeted treatments that are less toxic and more effective in treating inflammation, significantly improving patient quality of life, according to the researchers.

Caused by a herpesvirus, fibropapillomatosis (FP) is the most significant infectious disease affecting sea turtle populations worldwide. It is widespread in warmer climates like Florida, where almost 70 percent of sea turtles in a population have FP in some places; it has been documented in the Caribbean, South America, Hawaii, Japan, Australia, and beyond. The disease leads to the formation of tumors on the turtles' eyes, flippers and internal organs, which often debilitate them by inhibiting feeding and movement, obscuring vision, and/or leading to organ failure.

FP is of major concern in sea turtle rehabilitation facilities and requires extensive quarantine measures to accommodate infected turtles. Even after surgical removal, there is still potential for tumor regrowth since the underlying associated herpesvirus infection remains dormant. These clinical factors, along with the infectious and potentially life-threatening nature of FP, complicate prognoses and extend rehabilitation times of sea turtles diagnosed with this disease.

Annie Page-Karjian, D.V.M., Ph.D., a researcher from Florida Atlantic University's Harbor Branch Oceanographic Institute and collaborators, conducted a large-scale, retrospective case series review evaluating tumor score, removal and regrowth in rehabilitating green sea turtles with FP in four rehabilitation facilities in the southeastern United States from 2009 to 2017.

The objective was to assess FP tumor score and regrowth and provide information on tumor regrowth and survival in turtles with different tumor scores. Applying a standardized method for quantifying and qualifying the extent of the disease is necessary to objectively understand the various clinical manifestations of the disease.

Results of the study, published in the journal Diseases of Aquatic Organisms, showed that the majority (75 percent) of the turtles with FP did not survive following admission into a rehabilitation facility, irrespective of whether or not tumor regrowth occurred following surgery. FP is of greatest concern in juvenile sea turtles in nearshore habitats. All of the green turtles with FP in this study were classified as juveniles.

Of the 756 cases, 312 (41 percent) underwent tumor removal surgery, 155 (50 percent) of those had tumor regrowth within an average of 46 days, and 85 (27 percent) had multiple (more than one) regrowth events. Of the 756 turtles with FP, 283 (37 percent) were euthanized and 280 (37 percent) died without euthanasia. Of the 756 turtles with FP, 193 survived, including 186 (25 percent) that were released and seven (1 percent) that were placed in permanent captive care.

"Evaluating cases of rehabilitating wildlife can be an extremely valuable approach for improving our understanding of pathogen activity in both captive and free-ranging wildlife, and for developing recommendations for treatment and management of important wildlife diseases," said Page-Karjian, senior author, an assistant research professor and clinical veterinarian at FAU's Harbor Branch. "Results from our study could help guide clinical decision-making and determine prognoses for rehabilitating sea turtles with fibropapillomatosis."

Tumor removal surgery increased the odds of tumor regrowth, but also enhanced survivorship, whereas tumor regrowth was not a significant predictor of case outcome. Three FP tumor-scoring systems were used to assign tumor scores to 449 cases, and differing results emphasize that tumor-scoring systems should be applied to the situations and/or location(s) for which they were intended. FP tumor score was not a significant predictor for the event or extent of FP tumor regrowth after surgical excision.

"Internal tumors or severe fibropapillomatosis irreversibly diminishes an animal's well-being and ability to survive," said Page-Karjian. "Application of the appropriate scoring system coupled with rigorous triage and admission criteria for stranded turtles with this disease can effectively help reduce facilities' burden in terms of rehabilitating fewer turtles with poor prognoses."

In situations of limited resources, and taking into account any co-morbid conditions, focusing rehabilitation efforts on turtles with lower tumor scores (i.e. one to two) will help further streamline admission and triage of turtles with FP in rehabilitation facilities, and lead to higher rehabilitation success rates.

Study collaborators represent Loggerhead Marinelife Center in Juno Beach; The Turtle Hospital, in Marathon; Clearwater Marine Aquarium in Clearwater; the Sea Turtle Healing Center at Brevard Zoo in Melbourne; and Georgia Sea Turtle Center/Jekyll Island Authority, in Jekyll Island, Georgia.

This project was funded in part by a grant awarded from the Sea Turtle Grants Program, which is funded from proceeds from the sale of the Florida Sea Turtle License Plate.

BEER-SHEVA...January 22, 2020 - Researchers at Ben-Gurion University of the Negev (BGU) and The Hebrew University of Jerusalem (HU) have developed a powerful tool that will streamline and accelerate the development of disease therapies, transforming a multi-year process into just a few days.

Until now, existing technologies only enabled scientists to observe one mutation at a time, each one taking weeks or months. Constructing protein mutants and measuring their effect on binding affinity -- the strength with which proteins interact with their target proteins in cells -- slows the study of how and why diseases progress. With thousands of potential mutations for every protein-protein interaction (PPI), the process was costly, labor-intensive and time-consuming.

The new approach, published in Nature Communications, simultaneously evaluates the effect of thousands of mutations in protein-protein complexes. It is an important step for both applied and theoretical scientists. Most of the promising new drugs in production are proteins that destroy certain disease-associated protein-protein interactions, which control virtually all processes in the cell. It will help researchers design protein drugs that are both potent and specific, causing minimal side effects.

"Our new approach will increase the understanding of the mechanisms and evolutionary origins of specific PPIs, and facilitate the rational design of specific inhibitors that can discriminate between structurally similar protein targets," says Prof. Niv Papo of BGU's Avram and Stella Goldstein-Goren Department of Biotechnology Engineering and the National Institute for Biotechnology in the Negev (NIBN).

"Indeed, as many disease-related proteins belong to large families of related proteins, increasing target selectivity is a highly desirable but challenging goal in drug development. This tool offers great promise for designing novel target-specific therapeutics," he says.

As cancer researchers, BGU's Prof. Papo and HU Prof. Julia Shifman were facing a bottleneck in their work, which led them to develop the tool. They needed to understand the relationships created by cellular proteins, particularly the mutations that occur when those relationships go awry. To streamline the process of mapping and cataloguing the reactions, they combined a sophisticated protein library screening technology, deep sequencing and data normalization to identify and categorize protein mutations according to their function.

"Just like people, proteins maintain 'social networks'," says Prof. Shifman, a member of HU's Department of Biological Chemistry. "Some 'couples' partner for the long-term, while others prefer numerous and promiscuous interactions. When the proteins act the way they are supposed to, the body is healthy. But when the binding affinity becomes affected - that is, when stable relationships break up too quickly, or fleeting ones fail to disengage - that's when disease happens."

Profs. Papo and Shifman intend to apply their unique approach to map the binding specificity landscapes of broad-spectrum inhibitors of the human matrix metalloproteinases (MMPs) and serine proteases and test the therapeutic efficacy of these inhibitors in cellular and pre-clinical models of bone diseases and cancer. Ultimately, the inhibitors will be commercialized.

Harnessing bound states in the continuum (BICs) in photonic integrated circuits (PICs) allows for low-loss light guidance and routing with a low-refractive-index waveguide on a high-refractive-index substrate. PICs operating under the BIC principle do not require patterning micro- or nanostructures in the functional photonic material. Without the stringent requirement of high-quality etching, many single-crystal materials that exhibit excellent optical functionalities in bulk form can now be introduced to the integrated photonic platform.

Acousto-optics involves the study of phonon-photon interactions based on changes in the refractive index of a medium due to the presence of acoustic waves in that medium. Surface acoustic waves (SAWs) that propagate on surfaces of a thin-film piezoelectric material can be confined within a thickness less than the acoustic wavelength, producing phonons with a very high density in the region near the surface. The small acoustic modal area, which is comparable to the optical modal area, results in a large overlap between the two modes in photonic waveguides. Therefore, SAWs can be used to achieve strong acousto-optic interactions in nanophotonic devices.

Lithium niobate (LiNbO3) is an ideal platform for research on phonon-photon interactions because it has large piezoelectric coefficients and is optically transparent over a wide wavelength range. It can be used to generate SAWs efficiently and support photonic cavities with high quality factors. As PICs operating under the BIC mechanism allow for flexible selection of piezoelectric materials, LiNbO3 can be adopted to fabricate high-quality photonic microcavities on a chip without the need for etching.

In a new paper published in Light: Science & Applications, researchers from The Chinese University of Hong Kong demonstrated a high-quality photonic microcavity based on the BIC mechanism, which was integrated with an SAW interdigital transducer monolithically on a thin-film LiNbO3-on-insulator platform. The cavity was constructed simply by patterning low-refractive-index waveguides on the high-refractive-index LiNbO3 substrate without facing the challenge of high-quality etching of LiNbO3.

The devices were fabricated on a 400-nm LiNbO3-on-insulator wafer with a standard top-down nanofabrication approach. The optical resonances of the fabricated racetrack microcavity were measured, with the highest intrinsic optical quality factor reaching ~500,000. Acousto-optic modulation of the cavity resonant BIC modes was demonstrated for the first time, with the modulation frequency exceeding 4 GHz. The combination of the high frequency of the SAW and the sub-GHz linewidth of the cavity resonance enables acousto-optic coupling in the resolved-sideband regime, yielding coherent coupling between microwave and optical photons, as evidenced by the observed electro-acousto-optically induced transparency and absorption.

The unique feature and main advantage of the present scheme are that by harnessing the low-loss light guidance under the BIC mechanism, the single-crystal LiNbO3 layer is free from etching, thus producing SAWs of uniform acoustic wavelengths and low acoustic propagation loss, which facilitates highly efficient phonon?photon coupling. The obtained strong phonon?photon coupling can be harnessed to develop a wide range of Brillouin-scattering-based photonic applications, including delay lines, light storage, microwave signal processing, Brillouin lasers and amplifiers, and nonreciprocal light transmission. Additionally, the travelling acoustic waves here were electrically excited, being much stronger than those excited by optical methods. By using a piezoelectric material, it is not necessary to fabricate delicate suspended structures similar to those in conventional on-chip stimulated-Brillouin-scattering-based devices. Therefore, our demonstrated devices have great promise in achieving high performance in Brillouin-effect-based applications with a more robust architecture.

SAN ANTONIO -- Jan. 22, 2020 -- A Southwest Research Institute team developed a new geochemical model that reveals that carbon dioxide (CO2) from within Enceladus, an ocean-harboring moon of Saturn, may be controlled by chemical reactions at its seafloor. Studying the plume of gases and frozen sea spray released through cracks in the moon's icy surface suggests an interior more complex than previously thought.

"By understanding the composition of the plume, we can learn about what the ocean is like, how it got to be this way and whether it provides environments where life as we know it could survive," said SwRI's Dr. Christopher Glein, lead author of a paper in Geophysical Research Letters outlining the research. "We came up with a new technique for analyzing the plume composition to estimate the concentration of dissolved CO2 in the ocean. This enabled modeling to probe deeper interior processes."

Analysis of mass spectrometry data from NASA's Cassini spacecraft indicates that the abundance of CO2 is best explained by geochemical reactions between the moon's rocky core and liquid water from its subsurface ocean. Integrating this information with previous discoveries of silica and molecular hydrogen (H2) points to a more complex, geochemically diverse core.

"Based on our findings, Enceladus appears to demonstrate a massive carbon sequestration experiment," Glein said. "On Earth, climate scientists are exploring whether a similar process can be utilized to mitigate industrial emissions of CO2. Using two different data sets, we derived CO2 concentration ranges that are intriguingly similar to what would be expected from the dissolution and formation of certain mixtures of silicon- and carbon-bearing minerals at the seafloor."

Another phenomenon that contributes to this complexity is the likely presence of hydrothermal vents inside Enceladus. At Earth's ocean floor, hydrothermal vents emit hot, energy-rich, mineral-laden fluids that allow unique ecosystems teeming with unusual creatures to thrive.

"The dynamic interface of a complex core and seawater could potentially create energy sources that might support life," said SwRI's Dr. Hunter Waite, principal investigator of Cassini's Ion Neutral Mass Spectrometer (INMS). "While we have not found evidence of the presence of microbial life in the ocean of Enceladus, the growing evidence for chemical disequilibrium offers a tantalizing hint that habitable conditions could exist beneath the moon's icy crust."

The scientific community continues reaping the benefits of Cassini's close flyby of Enceladus on Oct. 28, 2015, prior to the end of the mission. INMS detected H2 as the spacecraft flew through the plume, and a different instrument had earlier detected tiny particles of silica, two chemicals that are considered to be markers for hydrothermal processes.

"Distinct sources of observed CO2, silica and H2 imply mineralogically and thermally diverse environments in a heterogeneous rocky core," Glein said. "We suggest that the core is composed of a carbonated upper layer and a serpentinized interior." Carbonates commonly occur as sedimentary rocks such as limestone on Earth, while serpentine minerals are formed from igneous seafloor rocks that are rich in magnesium and iron.

It is proposed that hydrothermal oxidation of reduced iron deep in the core creates H2, while hydrothermal activity intersecting quartz-bearing carbonated rocks produces silica-rich fluids. Such rocks also have potential to influence the CO2 chemistry of the ocean via low-temperature reactions involving silicates and carbonates at the seafloor.

"The implications for possible life enabled by a heterogeneous core structure are intriguing," said Glein. "This model could explain how planetary differentiation and alteration processes create chemical (energy) gradients needed by subsurface life."

Researchers have discovered a method to control biomolecular machines over a wide temperature range using deep-sea osmolyte trimethylamine N-oxide (TMAO). This finding could open a new dimension in the application of artificial machines fabricated from biomolecular motors and other proteins.

Biomolecular motors are the smallest natural machines that keep living organisms dynamic. They can generate force and perform work on their own by consuming chemical energy. In recent years, reconstructed biomolecular motors have appeared as promising substitutes of synthetic motors and expected to be key components in biomimetic artificial micro- or nano-devices. However, reconstructed biomolecular motors lose their ability to function due to thermal instability in artificial environments.

Tasrina Munmun, Arif Md. Rashedul Kabir, Kazuki Sada and Akira Kakugo of Hokkaido University and Yukiteru Katsumoto of Fukuoka University were inspired by seeing how proteins remain stable in living organisms such as sharks, teleosts, skates, and crabs that survive in harsh environments like deep sea hydrothermal vents or under thermal perturbations. Although proteins are generally denatured by heat, the proteins in deep-sea animals remain stable and active with heat thanks to TMAO.

"Based on this fascinating defense mechanism in deep-sea animals, we attempted to control the activity of kinesin, a biomolecular motor associated with microtubule proteins, over a wide temperature range," said Arif Md. Rashedul Kabir. To investigate the activity of kinesins, the team conducted in vitro motility assays in which kinesin motors propelled the microtubules on a two-dimensional substrate.

According to the study published in Chemical Communications, they discovered that TMAO suppresses thermal denaturation of kinesins in a concentration dependent manner. Within a temperature range of 22-46 °C, kinesins propelled microtubules for a prolonged time (almost 2.5 times longer) when TMAO was present. This shows the team successfully controlled the dynamics between kinesins and microtubules over a broad temperature range. "This study is the first example showing successful utilization of a deep-sea osmolyte in maintaining biomolecular motors for a prolonged time over a wide temperature range in engineered environments," Arif Md. Rashedul Kabir commented.

Arif Md. Rashedul Kabir continued, "The idea of utilizing natural defense mechanisms against heat-induced inactivation of proteins and enzymes will now be encouraged further."

"Our work will open a new dimension in sustainable applications of reconstructed biomolecules which will benefit various fields including biomimetic engineering, biochemical and biomedical engineering as well as materials science," Akira Kakugo added.

Many companies work hard to present an environmentally responsible public image. But how well do these claims stack up? In a new study led by the University of Göttingen, researchers investigated the claims regarding sustainability, including conservation and fair-pay, as presented by the French Michelin Group. The researchers then compared these claims with the effects described by local people in the village of Muara Sekalo in Indonesia. The villagers' reports indicated that land-ownership, ecosystems and biodiversity all suffered; and the researchers found that the pay at the rubber plantation fell well short of the minimum wage for the province. The results were published in the Journal of Land Use Science.

The scientists' long-standing relationship with Indonesian researchers (as part of the collaborative German-Indonesian research project EFForTS - Ecological and Socioeconomic Functions of Tropical Lowland Rainforest Transformation Systems) enabled them to stay with local villagers to conduct their fieldwork. In 2017, they carried out interviews in the village of Muara Sekalo close to the Thirty Hills National Park in Indonesia. The researchers used different techniques such as explorative interviews, narrative interviews and focus group discussions. They then carried out intensive qualitative content analysis, studying press releases and media coverage about Michelin's plantation project.

The "Sustainable Natural Rubber Policy" of the French Michelin Group was developed in collaboration with the World Wide Fund for Nature (WWF). Michelin has established "model" rubber plantations in Indonesia which they consider a pilot to show that sustainable rubber cultivation is possible. The tyre industry consumes about 75% of the world's natural rubber so this is big business globally. The company's claims include that the model plantations were sustainable both environmentally and socially, UN Environment adds that they were climate-smart, wildlife-friendly and created fair-wage jobs. Michelin also uses the term "zero deforestation" which could give the impression that no forests are being cleared.

The experiences of the villagers and farmers told a different story. Their reports included conflicts over land-use and environmental destruction due to deforestation. This resulted in elephants, who had lost their habitat, invading the villagers' plots in search for food and destroying their crops. Some farmers were forced to abandon their farming because they could not afford to replant and were left no choice but to assign their land to the company. And it turns out that "zero deforestation" only refers to certain areas - such as protected or primary forests or areas of high conservation value - and does not include forests which have regrown following the harvest of timber in the past for instance.

"We recognise that some villagers benefited from the presence of the company because new jobs were created. None-the-less, this project cannot be considered 'sustainable' at all." says Fenna Otten from the University of Göttingen's Department of Human Geography and first author of the study. She goes on to say, "Just because a product is labelled or even certified to be green or sustainable, this does not mean that the conditions on the ground reflect conditions that we would consider eco-friendly: there is a clear mismatch between what many people expect sustainability to mean and what is really happening".

"We welcome the introduction of sustainable production processes," says Otten. "However, it's vitally important that companies' commitment isn't just corporate greenwash."

Did the chicks of dinosaurs from the group oviraptorid hatch from their eggs at the same time? This question can be answered by the length and arrangement of the embryo's bones, which provide information about the stage of development. But how do you look inside fossilized dinosaur eggs? Paleontologists from the University of Bonn used the neutron source of the Technical University of Munich at the Heinz Maier-Leibnitz Zentrum (MLZ) in Garching. This showed that oviraptorids developed at different speeds in their eggs and that they resemble modern birds in this respect. The results have been published in the journal Integrative Organismal Biology.

Until now, researchers have assumed that the two-legged dinosaurs known as oviraptorids, which lived in Central Asia during the Upper Cretaceous (from 88 to 66 million years), should be placed between modern crocodiles and birds with regard to their reproductive biology. Crocodiles bury their eggs and the offspring hatch at the same time. With birds, however, hatching in the nest often happens at different times.

Together with scientists from Taiwan, Switzerland and the Heinz Maier-Leibnitz Zentrum in Garching, paleontologists from the University of Bonn have now investigated how differently the development of embryos in three 67 million years old oviraptorid egg fossils from the Ganzhou Basin of Jiangxi Province in China had progressed. "Oviraptorid eggs are found relatively frequently in Central Asia, but most of them are removed from the context of their discovery," says Thomas Engler from the Institute for Geosciences at the University of Bonn. Often it is then no longer discernible whether the eggs are from a single clutch.

Important find in China

"This is different with the fossils we've examined: We found a pair of eggs and another egg together embedded in a block of rock," reports Dr. Tzu-Ruei Yang, who discovered the unusual find during an excavation near the city of Ganzhou in China. This led the researchers to conclude that the 7-inch (18cm) eggs were laid almost at the same time by a female oviraptorid. Yang completed his doctorate at the Institute for Geosciences at the University of Bonn and now works as a researcher at the National Museum of Natural Sciences in Taiwan.

The researchers tried to estimate whether the baby dinosaurs would have hatched at the same time or at different times based on the developmental stage of the embryos in the three eggs. The length of the bones in the egg plays an important role here. "The embryo with comparatively longer bones is more developed," explains Yang. Another indication is the extent to which the bones are connected to each other. A more strongly connected skeleton suggests a higher developmental stage of the dinosaur embryo.

A look inside the dinosaur egg

But how is it possible to determine the position of bones inside a fossilized dinosaur egg? The paleontologists at the University of Bonn initially tried to do this with the institute's own X-ray microcomputer tomograph. "Unfortunately, it was not possible to distinguish the bones from the surrounding rock," says Engler. For this reason, the researchers took the dinosaur eggs to the research neutron source of the Technical University of Munich at the Heinz Maier-Leibnitz Zentrum (MLZ) in Garching. "The high penetration depth of the neutrons at the NECTAR and ANTARES facilities made it possible to visualize the internal structures," says Dr. Malgorzata Makowska, who was in charge of measurements and analyses at the MLZ and is now carrying out research at the Swiss neutron source PSI.

The length and position of the embryo bones led the researchers to conclude that the single egg must have been laid earlier than the pair of eggs in the same clutch. However, the embryos of the pair were also at different developmental stages. Thin sections confirm these results. The researchers used these to measure the thickness of the eggshells. The developing embryo absorbs part of the shell because it needs calcium for its growing skeleton. "The more material is removed from the egg shell, the more advanced the embryo's development," explains Yang.

On the basis of these indications, the scientists conclude that the reproductive biology of oviraptorids were similar to that of modern birds, whose chicks hatch at different times. The results argue against the strategy of crocodiles or turtles, which all emerge from their eggs at the same time. This has brought the researchers one step closer to the life of the long extinct oviraptorids, who roamed Central Asia on two legs. "Furthermore, the study shows that exploring fossils with neutrons yields novel scientific results," says Engler.

New findings from University of Exeter researchers reveal how bacterial immune systems can be harmful for their hosts and explain why they are not found in many bacteria.

CRISPR-Cas is an immune system that protects bacteria against infection by viruses (called phages).

The system works by stealing a small piece of viral DNA and using this to target and destroy matching sections of virus genome during a future infection.

Targeting by CRISPR-Cas breaks down the virus genome, meaning that new copies of the virus cannot be made.

Previously, the Westra and van Houte groups of the Environment and Sustainability Institute on the University's Penryn Campus in Cornwall showed that CRISPR-Cas can provide excellent protection against "lytic" phages, that is phages that multiply inside the host cell and cause the bacterial cell to burst releasing more viral particles (10.1016/j.cub.2015.01.065, 10.1038/nature17436).

However, it is common for viruses to follow a "lysogenic" lifestyle, meaning they can integrate into the host genome and become dormant until a trigger (often associated with host stress, or signals from other phages) causes them to re-enter the lytic pathway.

Lead authors of the current study, Clare Rollie and Anne Chevallereau, both working in the Westra group, explain that: "Our new results show that the immune system was not able to eliminate lysogenic phages and often led to damaging autoimmunity for the host during phage infection."

This type of autoimmunity was caused by the CRISPR-Cas system targeting viral DNA that had been incorporated into the host's own genome, leading to host cell death and virus release.

They found that bacterial cells that had lost the CRISPR-Cas system from their genome avoided the damage caused by autoimmune targeting, survived and proliferated.

"Here, the absence of this key immune system was an advantage," explain the authors.

They also highlight that "anti-CRISPR proteins, which are small inhibitors produced by the phage to counteract the host CRISPR-Cas immune response and had previously been thought to only benefit the phage that makes them, also provide protection for the host. In this scenario, disabling the host immune system blocks autoimmunity and prevents bacterial death."

Bacterial autoimmunity is brought about by imperfectly matching "spacers" - sequences that guide the CRISPR-Cas system to viral DNA.

The authors showed that these imperfect matches to phages occur frequently in nature and so this autoimmune effect was likely to be a common consequence of possessing a CRISPR-Cas system.

Importantly, this may help to explain why CRISPR-Cas is only present in about 40% of bacterial genomes and is frequently gained and lost from closely related strains.

The research was carried out in collaboration with theoreticians from the University of Montpellier (France) and bioinformaticians from University of Otago (New Zealand).

University of Exeter researchers were funded by the European Research Council, NERC Independent Research Fellowship and a Marie Sk?odowska-Curie fellowship under the European Union's Horizon 2020 research and innovation programme.

Cavities, or dental caries, are the most widespread non-communicable disease globally, according to the World Health Organization. Having a cavity drilled and filled at the dentist's office can be painful, but untreated caries could lead to worse pain, tooth loss, infection, and even illness or death. Now, researchers in ACS Applied Materials & Interfaces report a bioactive peptide that coats tooth surfaces, helping prevent new cavities and heal existing ones in lab experiments.

Conventional treatment for dental cavities involves removing decayed tissue and filling the hole with materials, such as amalgam or composite resin. However, this procedure can damage healthy tissue and cause severe discomfort for patients. Hai Ming Wong, Quan Li Li and colleagues wanted to develop a two-pronged strategy to prevent and treat tooth decay: 1) prevent colonization of the tooth surface by the plaque-forming bacteria that cause cavities, and 2) reduce demineralization, or the dissolving of tooth enamel, while increasing remineralization, or repair.

The researchers based their anti-cavity coating on a natural antimicrobial peptide called H5. Produced by human salivary glands, H5 can adsorb onto tooth enamel and destroy a broad range of bacteria and fungi. To promote remineralization, the team added a phosphoserine group to one end of H5, which they thought could help attract more calcium ions to repair the enamel than natural H5. They tested the modified peptide on slices of human molars. Compared with natural H5, the new peptide adsorbed more strongly to the tooth surface, killed more bacteria and inhibited their adhesion, and protected teeth from demineralization. Surprisingly, however, both peptides promoted remineralization to a similar degree. After brushing, people could someday apply the modified peptide to their teeth as a varnish or gel to protect against tooth decay, the researchers say.

With 48 drugs approved by the U.S. Food and Drug Administration (FDA), 2019 was another highly productive year for the pharmaceutical industry. The new medicines include treatments for various cancers, sickle cell disease, migraines and postpartum depression. However, the steady flow of drugs could be masking troubling signs about the health of the industry, according to Chemical & Engineering News (C&EN), the weekly newsmagazine of the American Chemical Society. 

2019 showed several notable trends for new drugs, according to Senior Correspondent Lisa M. Jarvis. First, about 42% of the medicines had new mechanisms of action -- so-called "first-in-class drugs" -- to treat a disease. As in past years, most of FDA's approvals were for small-molecule drugs, but 2019 also saw an influx of new molecular entities, including antibody-drug conjugates, an antisense oligonucleotide and a small interfering RNA. Another trend was the introduction of new therapies for underserved diseases, such as sickle cell anemia, treatment-resistant tuberculosis and postpartum depression.

Despite these successes, some analysts say certain aspects of the list point to trouble ahead for the pharmaceutical industry. For example, the proportion of new drugs produced by big pharma is declining. One explanation is that the industry has shifted its focus from primary-care treatments, which require large, expensive clinical trials, to rare diseases and specialty care indications, like cancer. These classes of drugs can be approved on the basis of much smaller studies, making it easier for small companies to bring a drug to market. Another concerning trend is that the number of companies directly contributing to drug development is shrinking, as large companies acquire the most productive small and medium biotech firms. Analysts worry that this industry consolidation will threaten the ability to introduce new medicines.

The smell of cut grass, freshly baked bread, childhood memories, lost loved ones, Christmas. What happens when it's all gone?

A new study from the University of East Anglia reveals the huge range of emotional and practical impacts caused by a loss of smell.

It finds that almost every aspect of life is disrupted - from everyday concerns about personal hygiene to a loss of sexual intimacy and the break-down of personal relationships.

The researchers hope that their findings will help motivate clinicians to take smell problems more seriously, with better help and support offered to patients.

Prof Carl Philpott, from UEA's Norwich Medical School, said: "Smell disorders affect around five per cent of the population and cause people to lose their sense of smell, or change the way they perceive odours. Some people perceive smells that aren't there at all.

"There are many causes - from infections and injury to neurological diseases such as Alzheimer's and as a side effect of some medications.

"Most patients suffer a loss of flavour perception which can affect appetite and can be made even worse if distortions in their sense of smell also co-exist.

"Previous research has shown that people who have lost their sense of smell also report high rates of depression, anxiety, isolation and relationship difficulties.

"We wanted to find out more about how a loss of smell affects people."

The researchers worked with the Smell and Taste clinic at the James Paget University Hospital, Gorleston-On-Sea. The clinic opened in 2010 and was the UK's first clinic dedicated to taste and smell.

The study involved 71 participants aged between 31-80 who had written to the clinic about their experiences. It was carried out in collaboration with Fifth Sense, the charity for people affected by smell and taste disorders.

The research shows that sufferers experience wide-ranging impairments to their quality of life. These included a negative emotional impact, feelings of isolation, impaired relationships and daily functioning, impacts on physical health and the difficulty and financial burden of seeking help.

Prof Philpot said: "One really big problem was around hazard perception - not being able to smell food that had gone off, or not being able to smell gas or smoke. This had resulted in serious near misses for some.

"But smell is not just a life-saving sense - it is also life-enhancing.

"A large number of the participants no longer enjoyed eating, and some had lost appetite and weight. Others were eating more food with low nutritional value that was high in fat, salt and sugar - and had consequently gained weight.

"Participants had lost interest in preparing food and some said they were too embarrassed to serve dishes to family and friends which had an impact on their social lives.

"The inability to link smells to happy memories was also a problem. Bonfire night, Christmas smells, perfumes and people - all gone. Smells link us to people, places and emotional experiences. And people who have lost their sense of smell miss out on all those memories that smell can evoke.

"We found that personal hygiene was a big cause for anxiety and embarrassment, because the participants couldn't smell themselves.

"Parents of young children couldn't tell when their nappies needed changing, and this led to feelings of failure. One mother found it difficult bonding with her new baby because she couldn't smell him.

"Many participants described a negative impact on relationships - ranging from not enjoying eating together to an impact on sexual relationships," he added.

All of these problems led to diverse range of negative emotions including anger, anxiety, frustration, depression, isolation, loss of confidence, regret and sadness. And the problems were compounded by a lack of understanding about the disorder among clinicians.

Prof Philpott said: "The participants described a lot of negative and unhelpful interactions with healthcare professionals before coming to the James Paget Smell and Taste clinic. Those that did manage to get help and support were very pleased - even if nothing could be done about their condition, they were very grateful for advice and understanding."

Duncan Boak, Founder and Chair of Fifth Sense, said: "Anosmia can have a huge impact on people's quality of life in many ways, as this research demonstrates. An important part of Fifth Sense's work is giving our beneficiaries a voice and the opportunity to change the way society understands smell and taste disorders, whether through volunteering or participating in research studies like this one. The results of this study will be a big help in our ongoing work to improve the lives of those affected by anosmia."

Researchers of Peter the Great St.Petersburg Polytechnic University (SPbPU) in collaboration with colleagues from the Physikalisch Technische Bundesanstalt (PTB) and a number of German scientific organizations, calculated previously unexplored effects in atoms. The results were published in the PHYSICAL REVIEW A, highlighted as an Editor's Choice article.

For many years, researchers all over the world have been looking for new particles beyond the currently accepted Standard Model of fundamental interactions in physics. Such research is most famously carried out at the Large Hadron Collider. A group of scientists from Russia and Germany is engaged in another approach to this problem based on methods of atomic spectroscopy. Such studies are less resource-intensive, but very promising due to the fact that the accuracy of experiments is higher in atomic physics than in high-energy physics.

SPbPU scientists calculated frequencies of electronic transitions in different isotopes of one element, in this case, argon.

Researchers examined several states of argon ions with four, five, and six electrons. These are optimal electronic configurations.On one hand, they can be reliably calculated, and on the other hand, they are accessible for experiments. Scientists analyzed their results using the King plot, a widely used method for systematic studies of the isotope shifts of two atomic transitions in a chain of isotopes.

Modern theory claims that the King plot should be linear to a very high accuracy. Until recently, possible nonlinear effects were considered much to small to be of any practical interest. Butthe international scientific group calculated thenew effectsand found that the nonlinearities in the King plot are by four orders stronger than was previously expected (at the 10 kHz level). Previously, due to the limitations of the instruments, such effects couldn't be detected, but a new generation of spectroscopic experiments increases the achievable accuracy by several orders of magnitude, thus making these effects observable. This is an important contribution to science, confirming that generally accepted ideas should to be adjusted.

"If the King plot turns out to be slightly curved, this may be a manifestation of new particles beyond the Standard Model of physics. It is necessary to continue studying these effects in other atoms with a larger number of electrons in order to reduce the influence of calculation errors,"said Vladimir Yerokhin, chief researcher at the Center for Advanced Studies of SPbPU.

In the near future, the theoretical predictions obtained by scientists of St. Petersburg Polytechnic University will be verified experimentally at the Physikalisch Technische Bundesanstalt using the facilities which trap ions in the magnetic and electric fields and investigate them using the quantum logic methods.

"If the experiment is successful, we can obtain restrictions on parameters of the proposed new particle beyond the Standard Model. In addition, such experiments will help to determine whether the fundamental constants change over time, which is of great importance for our understanding of the development of the Universe, "commented Vladimir Yerokhin.