Culture

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.

The Journal of Clinical Investigation (JCI) recently published "Viewpoint" articles by Johns Hopkins University School of Medicine professors who warn that global climate change is likely to unlock dangerous new microbes, as well as threaten humans' ability to regulate body temperature.

Johns Hopkins Bloomberg Distinguished Professors Rexford Ahima, M.D., Ph.D., and Arturo Casadevall, M.D., Ph.D., M.S., along with William Dietz, M.D., Ph.D., director of the George Washington University's Sumner M. Redstone Global Center for Prevention and Wellness, and Susan Pacheco, M.D., associate professor in the Department of Pediatrics at the University of Texas Health Science Center at Houston, authored journal articles relevant to their fields that detail how rising temperatures around the world pose dangerous threats to humanity.

Ahima, director of Johns Hopkins' Division of Endocrinology, Diabetes and Metabolism, wrote in the journal that "global warming threatens human thermoregulation and survival."

Ahima explains that people generate body heat and have the capacity to regulate their temperature within a few degrees. But "as heat waves become more common, more severe, and longer, we expect to see more heat-related illnesses and deaths," he writes.

Ahima cites a recent study that examined global heat-related mortality, pointing out that tropical and subtropical countries and regions will experience the sharpest surge in illness and death stemming from higher temperatures, while the United States and Europe can also expect increases.

Casadevall's article explores "the specter of new infectious diseases" as a result of the changing climate.

"Given that microbes can adapt to higher temperatures," writes the professor of molecular microbiology and immunology, and infectious diseases, at Johns Hopkins' schools of medicine and public health, "there is concern that global warming will select for microbes with higher heat tolerance that can defeat our endothermy defenses and bring new infectious diseases."

Endothermy allows humans and other warm-blooded mammals to maintain high temperatures that can protect against infectious diseases by inhibiting many types of microbes.

Casadevall cites a particular climate threat from the fungal kingdom.

"We have proposed that global warming will lead many fungal species to adapt to higher temperatures," he writes, "and some with pathogenic potential for humans will break through the defensive barrier provided by endothermy."

As an example, Casadevall points to the rise of Candida auris, a species of fungus identified in 2009 and called a "catastrophic threat" by the U.S. Centers for Disease Control and Prevention in 2017.

"The nearly simultaneous emergence of Candida auris on three continents, an event proposed to result from global warming, has raised the specter that increased warmth by itself will trigger adaptations on certain microbes to make them pathogenic for humans."

Casadevall says that, while fungi present the most immediate threat, other microbes also adapt to evolving conditions such as temperature. He writes that "the conceptual threat originally identified with fungi, and exemplified by C. auris as the canary in the coal mine, applies across the microbial world."

Dietz's article addresses climate change and malnutrition, calling obesity, undernutrition and climate change a "syndemic," or multiple epidemics that interact and share common underlying social or economic determinants and policy drivers. In her article, Pacheco discusses climate change's adverse consequences regarding pregnancy and maternal, fetal and child health.

In all four JCI "Viewpoint" articles, long-term strategies are urged to reduce greenhouse gas emissions and slow the trend of rising temperatures.

It is estimated that around 114,000 people disappeared throughout Spain during the Spanish Civil War and subsequent dictatorship. Unfortunately, eight decades on, only a small percentage of these people have been found or identified, with around 9,000 victims from 700 mass graves (of which it is thought there are approximately 2,000) being recovered in the last fifteen years. As time goes by and the samples themselves continue to deteriorate, conventional methods are no longer precise enough to identify the remains of all these unknown people. However, genetic analyses constitute an effective tool for this purpose.

The BIOMICs research team at the UPV/EHU has spent the last ten years working to identify these disappeared persons by genetically analysing bone and teeth samples taken from remains recovered from various mass graves dating from the Spanish Civil War and subsequent dictatorship and comparing the results with DNA taken from family members. 'Once DNA has been obtained from the remains, we analyse a series of specific genetic markers, depending on the type of kinship relationship we wish to study,' explains Doctor Miriam Baeta, a member of the BIOMICs research team working at the University of the Basque Country's Department of Zoology and Cellular Animal Biology.

The aim of the genetic analyses is to determine the profile of the remains or to gather enough information to enable the team to compare them with the profiles of presumed family members or the information contained in the database of the DNA bank of relatives of disappeared persons. Data is also sometimes stored in the database itself in the hope that it will match future family profiles yet to be included. Each case is different because 'for example, if you want to analyse paternal lineage, you study the Y chromosome; but it you want to analyse maternal lineage, then you have to focus on mitochondrial DNA,' explains Dr Baeta.

We are increasingly able to study smaller and smaller markers

The task of identifying human remains is a complex one 'because we are talking about post mortem DNA, which is often extremely degraded, making it hard to obtain a complete genetic profile,' continues Dr Baeta. 'Identification or coincidence is easier to prove when more markers are studied. Moreover, in many cases, the most suitable relatives are not available, meaning that the ones still alive are not close enough or the markers obtained cannot be compared with those from the DNA samples of living family members,' she adds. Dr Baeta highlights the importance of the DNA bank of relatives of victims, 'so that more comparisons can be done during future exhumations'.

She claims to be optimistic, since 'thanks to technological advances, we are increasingly able to study smaller and smaller markers, which have a greater chance of success in the analysis, because being smaller, they are better able to survive degradation.' Over the ten years that the team has been working in this field, many advances have been made that have enabled them to optimise the identification system. 'Among other things, we have optimised the DNA extraction systems, as well as various different steps throughout the process with the aim of obtaining more informative profiles. We are constantly striving to improve every part of the process,' she explains. The latest advance proposed by the team 'enables us to study smaller fragments of mitochondrial DNA. Thanks to this technique, we can do an initial screening to dismiss, in a cost-effective manner, possible relationships through the maternal lineage; in other words, it makes it easier to determine maternal kinship: only if there is a coincidence in this first phase is it worth applying the methodologies used to date to analyse mitochondrial DNA.'

Researchers in the team have published a paper in which they present all the knowledge acquired over the past ten years. In specific terms, they explain the techniques and procedures used to identify 525 human remains. To enable this identification, they obtained saliva samples from 879 presumed relatives, enabling them to identify 137 disappeared persons. No informative profile was obtained for 17% of the samples analysed, as a result of limited DNA or degraded samples; however, profiles were obtained for another 297 human remains that, despite everything, had previously remained unidentified. 'In general, we obtain profiles for the majority of skeletal remains, but we do not have suitable relatives with which to compare them,' clarifies Dr Baeta.

She then comments that 'when we manage to identify someone it is a very happy moment, because in addition to the joy of the outcome itself, we know there is a lot of complicated work behind the result. At the end of the day, it is a collective effort by our team and the Aranzadi Science Society, the Gogora Institute and the associations of victims and relatives of people who disappeared during the Spanish Civil War and subsequent dictatorship.'

INDIANAPOLIS -- Regenstrief Institute and Indiana University School of Medicine researchers have identified blood-based biomarkers associated with both delirium duration and severity in critically ill patients. This finding opens the door to easy, early identification of individuals at risk for longer delirium duration and higher delirium severity and could potentially lead to new treatments of this brain failure for which drugs have been shown to be largely ineffective.

An estimated 7 million hospitalized Americans suffer from the acute confusion and disorientation, characteristics of delirium, including a majority of patients in medical or surgical intensive care units (ICUs). Individuals who experience delirium in the ICU are more likely to have more hospital-associated complications, longer stays and higher risk of readmission. They are more likely to experience cognitive impairment and also have a greater likelihood of dying for up to a year after their hospital stay than ICU patients who did not experience delirium.

"If you can tell which patients will have higher delirium severity and longer duration and therefore greater probability of death, there are important treatment implications," said Regenstrief Institute research scientist and IU School of Medicine faculty member Babar Khan, M.D., who led the research and is the president of the American Delirium Society. "Analyzing biomarkers to stratify risk for delirium is a promising approach with the potential to be applied regularly in ICU patients in the near future."

In a new observational study, Dr. Khan and colleagues report that biomarkers for astrocyte and glial activation as well as for inflammation were associated with increased delirium duration and severity and greater in-hospital mortality.

Biomarkers of the 321 study participants, all of whom experienced delirium in an ICU, were identified from samples obtained via simple blood draws. Delirium severity was determined using a tool developed by a team including Regenstrief, IU School of Medicine and Purdue College of Pharmacy scientists. The CAM-ICU-7, short for Confusion Assessment Method for the Intensive Care Unit 7 -- is easy to administer, even to patients on mechanical ventilators. More than half of ICU patients in the U.S. receive mechanical ventilation.

Each day with delirium in the ICU is associated with a 10 percent increased likelihood of death, according to Dr. Khan, so diminishing its duration and ultimately preventing it is critical. Regenstrief, IU School of Medicine and research scientists from other institutions have conclusively shown in several large trials that antipsychotics, such as the widely used haloperidol, are not effective for the management of delirium duration or severity.

Regenstrief and IU School of Medicine researchers are actively exploring other approaches to delirium. Dr. Khan is co-principal investigator of an ongoing study that is the first to test whether listening to music, a non-pharmacological strategy that has been shown to decrease over-sedation, anxiety and stress in critically ill patients -- all factors that predispose to ICU delirium - and lowers the likelihood of developing delirium. In a completed study, Regenstrief researchers determined that waking ICU patients and having them breathe on their own decreased acute brain failure.

The new study, "Biomarkers of Delirium Duration and Delirium Severity in the ICU" has been published online ahead of print in the journal Critical Care Medicine.