Culture

A furry social robot can reduce pain and increase happiness -- Ben-Gurion University researchers

image: Levy-Tzedek and her team discovered that a single, 60-minute interaction with PARO actually improved mood as well as reduced mild or severe pain. When participants touched PARO, they experienced greater pain reduction than when it was simply present in their room.

Image: 
Ben-Gurion University of the Negev

BEER-SHEVA, Israel...June 23, 2020 - Could furry social robots help bolster moods and reduce pain when human to human contact isn't an option, for example, during a pandemic?

According to a new study by Ben-Gurion University of the Negev (BGU) researchers published in Scientific Reports, a one-time, hour-long session with a plush, seal-like social robot reduced pain and oxytocin levels, and increased happiness. The Japanese social robot, PARO, emits seal-like sounds and moves its head and flippers in response to being spoken to and touched.

Human-to-human contact has been found to bolster mood and reduce pain in previous studies. Dr. Shelly Levy-Tzedek of the BGU Department of Physical Therapy and her team investigated whether a furry social robot could induce similar effects when normal human-to-human contact is not available.

Levy-Tzedek and her team discovered that a single, 60-minute interaction with PARO actually improved mood as well as reduced mild or severe pain. When participants touched PARO, they experienced greater pain reduction than when it was simply present in their room.

Surprisingly, the BGU researchers discovered lower oxytocin levels in those who interacted with PARO than in the control group participants, who did not meet PARO. Typically, oxytocin, sometimes called "the love homone," is elevated among romantic partners or mothers playing with their children, so a lower level of oxytocin wasn't expected. However, more recent studies have shown that outside of close relationships, oxytocin production is a stress indicator and therefore, a reduction could indicate relaxation.

"These findings offer new strategies for pain management and for improving well-being, which are particularly needed at this time, when social distancing is a crucial factor in public health," says Dr. Levy-Tzedek.

Credit: 
American Associates, Ben-Gurion University of the Negev

Vets walking pets: Strolls with shelter dogs may reduce PTSD symptoms in military veterans

image: A veteran takes a stroll with rescue Dachshunds 12-year-old Daisy (right) and three-year-old Heidi.

Image: 
Alex Dolce, Florida Atlantic University

The United States is home to more than 21 million military veterans, many of whom have difficulty reintegrating into civilian life. A staggering 20 percent of them suffer from post-traumatic stress disorder (PTSD), one of the most common trauma-induced mental illnesses. Moreover, it is estimated that 20 veterans die of suicide each day, resulting in about 6,000 deaths by suicide each year. With President Trump's announcement last week for a roadmap to increase public awareness and training to curb these deaths in our military veterans, a unique study exploring the human-animal bond could play an important role in helping this initiative.

Human-animal interaction is known to reduce stress. Yet, few studies have examined the health effects of interacting with dogs, specifically in the veteran population. With about 6 to 8 million dogs ending up in shelters in the U.S. each year - half of which won't get adopted - researchers enlisted the help of two no-kill shelters for a study evaluating the effects of walking with a shelter dog on psychological and physiological stress indicators in military veterans.

The randomized study was led by Cheryl Krause-Parello, Ph.D., lead author, a professor and director of Canines Providing Assistance to Wounded Warriors® ( C-P.A.W.W.®), within Florida Atlantic University's Christine E. Lynn College of Nursing, and a faculty fellow of FAU's Institute for Human Health and Disease Intervention (I-HEALTH), who conducted the study while at the University of Colorado, in collaboration with researchers from the University of Maryland's School of Nursing and SUNY Fredonia. The study was funded in part by the ISAZ/Waltham Petcare Science Institute Collaborative Research Award and C-P.A.W.W.®.

Results, published in the journal Anthrozoös, provide evidence that walking with a shelter dog may affect psychological and physiological stress indicators in veterans - with particular potential benefits for veterans with an increase in PTSD symptom severity.

Researchers compared the effects of walking with a shelter dog versus walking with a human on psychological stress indicators, PTSD symptoms, and perceived stress in reintegrating military veterans.

Krause-Parello and collaborators evaluated three physiological stress biomarkers: heart rate variability, salivary cortisol, and the enzyme alpha-amylase over four weeks of walking with a dog and walking with a human. The body's reaction to stress affects these biomarkers. The researchers included the heart rate variability biomarker because of its strong correlations with human physical stress and psychosocial stress.

The clearest indicator for decreases in stress came from the heart rate variability data, which was most apparent for veterans with greater PTSD symptom severity. Heart rate variability was measured before, during and for 30 minutes after walking.

"Based on heart rate variability, our study provides evidence that walking with a shelter dog may benefit veterans with higher symptoms of post-traumatic stress. Severity of symptoms and perceived stress tended to decrease more after walks with a dog than walks with a human," said Krause-Parello.

Responses to walking with a dog and a human from week one to week four were different depending on PTSD symptom severity. Walking with another person did not change stress levels, as measured with cortisol, in those with high PTSD symptom severity. Walking with a dog or another person led to decreases in cortisol among those with low PTSD symptom severity. For individuals with high PTSD symptom severity, walking with a dog did not change stress levels, as indicated by alpha amylase, but walking with a person led to increased stress. For individuals with lower PTSD symptoms, alpha amylase did not change significantly for either type of walk.

"Our findings emphasize the need for more research to determine if this form of human-animal interaction is beneficial to veterans with PTSD and to help us identify the optimal level of interaction that will be most impactful for them," said Krause-Parello.

This unique pairing has the potential to be mutually beneficial for veterans and humankind's "best friend" alike. The researchers emphasize the obvious benefits of human-animal interaction for shelter dogs. They need to be walked and socialized on a consistent basis to develop a positive relationship with humans, maintain a good quality of life, reduce their stress, expand the boundaries of a mundane kennel cage, and improve the likelihood that they will be successfully adopted. The dogs involved in the study resided in the two shelters and were awaiting adoption.

"Considering the large number and availability of shelter dogs in the United States, it really makes sense to consider the potential for these dogs to be involved in a unique intervention that combines the benefits of human-animal interaction with the benefits of altruistic action like volunteerism," said Erika Friedmann, Ph.D., co-author, a professor and associate dean for research at the University of Maryland School of Nursing.

Men and women ages 22 to 69 years old participated in the study. A total of 72 different dogs participated in 124 walks and ranged in size from toy (7.2 pounds) to giant (90 pounds). Each dog walked one to six times. Veterans were asked to draw a name to determine what dog they would be walking with to ensure randomization and to minimize the risk of becoming attached to a shelter dog that might be adopted during the course of the study.

"This innovative research confirms the importance of the human-animal bond. It brings to life an unexpected connection between shelter dogs and veterans, serving to meet a need for both and providing direction for holistic programming that addresses both the health of veterans and that of shelter dogs. It is a win-win," said Patricia Liehr, Ph.D., associate dean of research and scholarship at FAU's Christine E. Lynn College of Nursing.

Study co-authors are former C-P.A.W.W.® research assistants Kelly Blanchard and Megan Payton; and Nancy R. Gee, Ph.D., a professor of psychiatry, Department of Psychiatry, and director of the Center for Human-Animal Interaction, Virginia Commonwealth University School of Medicine, who conducted the research while at SUNY Fredonia.

"At Mars Petcare we believe we have a responsibility to take scientific exploration further when evidence to date shows us that pets can be part of addressing conditions like PTSD," said Kay O'Donnell, vice president, Waltham Petcare Science Institute. "It's important we undertake rigorous studies to understand how companion animals may provide a benefit and we're proud to be part of this study, which takes us another step forward in understanding the human-animal bond."

Credit: 
Florida Atlantic University

New opportunities for ocean and climate modelling

image: Schematic Diagram of the FOCI Model System with the difference components

Image: 
C. Kersten, GEOMAR

In their model simulations, climate researchers always have to make compromises. Even with the largest computers available worldwide, they can only reproduce the real world to a limited extent. Depending on the application, simplifications have to be made in the spatial resolution, but also in the physical processes represented by the model. While model experiments over periods of months to a few years can often still be made with high spatial resolution, integrations over centuries to millennia can only be performed at coarser resolution. In the past, models were developed for a specific purpose. Now, GEOMAR Helmholtz Centre for Ocean Research Kiel presented a flexible model kit, called FOCI (Flexible Ocean and Climate Infrastructure). It is based on the Earth system model of the Max Planck Institute for Meteorology in Hamburg and has been modified with the NEMO ocean model, in order to represent small-scale processes in the oceans at higher resolution.

"In FOCI we combine decades of expertise in ocean and climate modelling at GEOMAR. The new system enables the investigation of new questions such as the influence of the stratospheric ozone hole on the circulation in the Southern Ocean or the impact of the Gulf Stream on atmospheric processes", explains Professor Dr. Katja Matthes from the Maritime Meteorology Research Unit at GEOMAR.

"With the new system, we can investigate many different research questions on ar range of time scales", Professor Dr. Arne Biastoch, head of the Ocean Dynamics Research Unit at GEOMAR, points out. "We initially performed a set of standardised basic tests with the FOCI system", the oceanographer continues. "We had to find out whether the model system is capable of reproducing the observed climate and the present ocean circulation. Only if we are confident that the system can successfully simulate the present conditions within limited error bands it can be used to investigate unknown phenomena or for the predictions of future climate conditions". The results, which have been published in the international journal Geoscience Model Development, are very promising. "In particular, our special know-how in operating the ocean model regionally at very high resolution improves the results considerably and reduces, for example, common model errors such as deviations in sea surface temperatures in the Gulf Stream system", says Professor Biastoch. FOCI also enables configurations which were previously impossible at spatial resolutions of up to one kilometre in the ocean.

The basic experiments carried out so far include a control run over 1,500 years with pre-industrial greenhouse gas concentrations and several experiments covering the period from 1850 to the present day, for which observational data are available for verification. "The current results are very encouraging", says Katja Matthes. The system will be further improved and used for various questions to study natural climate fluctuations, but also anthropogenic climate change. "From our point of view, FOCI is the ideal system for GEOMAR to simulate small-scale processes in the ocean, interactions between stratosphere and troposphere as well as biogeochemical processes in the ocean. It also allows us to carry out complex projects such as a large number of model simulations over several decades with a reasonable amount of computing time", Professor Matthes concludes.

Credit: 
Helmholtz Centre for Ocean Research Kiel (GEOMAR)

Wet wipes and sanitary products found to be microplastic pollutants in Irish waters

image: From left, Dr Liam Morrison of NUI Galway with PhD student Ana Mendes and Maynooth University graduate student Oisín Ó Briain at Grattan beach near Galway City.

Image: 
Aengus McMahon

Researchers from Earth and Ocean Sciences and the Ryan Institute at NUI Galway have carried out a study on the contribution of widely flushed personal care textile products (wet wipes and sanitary towels) to the ocean plastic crisis.

Dr Liam Morrison led the study, which showed that sediments adjacent to a wastewater treatment plant are consistently strewn with white microplastic fibres that are comparable to those from commercially available consumer sanitary products (wet wipes and sanitary towels). The article has been published in the international journal Water Research and was co-authored by NUI Galway PhD student Ana Mendes and Maynooth University graduate Oisín Ó Briain.

In most studies to date, white fibres are likely underestimated, because of the commonly used filtration procedure to capture microplastic fibres as filters are commonly white, making visual identification of microscopic white fibres against a white background difficult. This is significant given the global growth of non-woven synthetic fibre products and their ubiquity in wastewater.

Speaking today, President of NUI Galway, Professor Ciarán Ó hÓgartaigh said: "Our University has made sustainability a strategic priority, and for the world to address climate change, we have a duty to examine the behaviour of individuals and corporations that can help our planet. This research highlights the need for us to adapt our behaviours and tackle the ubiquity of plastic in so many products."

An urban rural gradient involving three locations from Galway City (close to Mutton Island and adjacent to a wastewater treatment plant) to counties Clare (Bell Harbour) and Mayo (Bellacragher) were investigated in this study. The total number of fibres found near Mutton Island was 6083 microplastics fibres per kilogram of sediment, while the rural sites had much lower levels (Bell Harbour, 1627 and Bellacragher 316). The total number of white fibres was 5536, 788, and 265 per kilogram of sediment for Mutton Island, Bell harbour and Bellacragher respectively. Incredibly, 91% of microplastic fibres at Mutton Island are likely derived from wet wipes and sanitary towels.

Lead researcher of the study, Dr Liam Morrison from Earth and Ocean Sciences and Ryan Institute at NUI Galway, said: "COVID-19 may have brought its own challenges for the oceans including the increased use of disinfectant wipes during the pandemic which potentially may end up as microplastic fibres in the sea. It is widely known that microplastics can act as vectors for contaminants including bacteria and viruses and are potentially harmful for public health and marine life."

The nearby intertidal zone at Mutton Island is prone to the accumulation of high volumes of washed-up sewage-derived debris on a frequent basis. Excessive microplastic loading in sediments in December 2017 was likely induced by heavy precipitation episodes during a south-westerly storm front. Elevated debris loading on this occasion may result from combined sewer overflows, where excessive input of drainage water exceeds wastewater treatment effluent capacity and is released untreated in the overflow. Dr Morrison said: "This was significant in the context of climate change, where we are likely to see increased rainfall events and flooding."

While most microplastics may be removed by the wastewater treatment process, combined sewage overflows associated with periods of heavy rainfall give rise to the release of sewage waste containing wipes and sanitary towels, impacting on public health and the environment. Combined sewer overflows and the subsequent shoreline deposition of sanitary waste have not previously been thoroughly investigated as a source of white microplastic fibres in the marine environment. The study found that wet wipes and sanitary towels are a source of unaccounted white microplastic fibres in the marine environment and not all flushable wipes are biodegradable. In fact 50% of the wipes labelled "flushable" in this study were shown to contain microplastics. The lack of regulation for hygiene and sanitary products results in a failure to identify the plastic composition of these materials. This demonstrates the consequences of misleading labelling of non-woven textile personal care products.

The samples of sanitary-related macro debris (wipes and sanitary towels) collected from the intertidal zone near Mutton Island in Galway City following a heavy rainfall event were mostly comprised of the plastic polyethylene terephthalate (PET), with only a quarter of the samples analysed presenting as a mix of PET and cellulose, and over 80% of the wipes in the shoreline waste were identified as non-flushable due to their polymer composition following the International Water Services Flushability Group and non-woven textile industry guidelines (INDA/EDANA, 2018; IWSFG, 2018).

Given the global distribution and projected growth of the non-woven textile industry (as non-woven textiles form the base material of many sanitary products), this is a concern. European production of non-woven textiles for hygiene and sanitary products exceeded one million tonnes in 2016 alone and these products frequently cause blockages in sewage systems globally, incurring significant technical and financial costs to wastewater utilities.

These products are a consistent feature of global plastic pollution surveys and in comparison, microplastic fibres from clothing are generally coloured or multi-coloured. To date the role of these white microplastic fibres as significant components of wastewater effluent remained poorly understood. The quantities of wet wipes washing up on beaches in the UK has increased 400% in the last decade (Marine Conservation Society, 2019*).

Dr Morrison added: "There is a need for increased public awareness of microplastic pollution in the environment and human behaviour should shift away from the inapt disposal of sanitary products down the toilet and instead divert to alternative land-based waste management."

Credit: 
University of Galway

A blue spark to shine on the origin of the Universe

image: Artistic representation of the new fluorescent molecule that can shed light on the elusive nature of neutrinos.

Image: 
UPV/EHU

Why is our Universe made of matter? Why does everything exist as we know it? These questions are linked to one of the most important unsolved problems in particle physics. This problem is that of the nature of the neutrino, which could be its own antiparticle, as argued by the unfortunate Italian genius Ettore Majorana almost a century ago. If this were so, it could explain the mysterious cosmic asymmetry between matter and antimatter.

Indeed, we know that the Universe is made almost exclusively of matter. However, the Big Bang theory predicts that the early Universe contained the same amount of matter and antimatter particles. This prediction is consistent with the "small Big Bangs" that form in proton collisions at CERN's giant LHC accelerator, where a symmetrical production of particles and antiparticles is always observed. So, where did the antimatter of the early Universe go? A possible mechanism points to the existence of heavy neutrinos that were its own antiparticle, and therefore, could decay into both matter and antimatter. If a second phenomenon occurs, called violation of charge and parity (that is, if the neutrino slightly favors in its decay the production of matter over that of antimatter), then it could have injected an excess of the first over the second. After all the matter and antimatter in the Universe were annihilated (with the exception of this small excess), the result would be a cosmos made only of matter, of the leftovers from the Big Bang. We could say that our Universe is the remnant of a shipwreck.

It is possible to demonstrate that the neutrino is its own antiparticle by observing a rare type of nuclear process called neutrinoless double beta decay (bb0nu), in which concurrently two neutrons (n) of the nucleus are transformed into protons (p) while two electrons (e) are emitted out of the atom. This process can happen in some rare isotopes, such as Xenon-136, which has in its nucleus 54 p and 82 n, in addition to 54 e when is neutral. The NEXT experiment (directed by J.J. Gómez-Cadenas, DIPC and D. Nygren, UTA), located in the underground laboratory of Canfranc (LSC), looks for these decays using high pressure gas chambers.

When a Xe-136 atom undergoes spontaneous bb0nu decay, the result of the process is the production of a doubly charged ion of Barium-136 (Ba2+); with 54 e and a nucleus made of 56 p and 80 n; and two electrons (Xe à Ba2+ + 2e).

So far, the NEXT experiment has focused on observing these two electrons, whose signal is very characteristic of the process. However, the bb0nu process that is meant to be observed is extremely rare and the signal that is expected is of the order of one bb0nu decay per ton of gas and year of exposure. This very weak signal can be completely masked by background noise due to the ubiquitous natural radioactivity. However, if in addition to observing the two electrons, the barium ionized atom is also detected, the background noise can be reduced to zero, since natural radioactivity does not produce this ion. The problem is that observing a single ion of Ba2+ in the midst of a large bb0nu detector is technically so challenging that until recently it was considered essentially unfeasible. However, a number of recent works, the latest of which has just been published in the journal Nature, suggest that the feat may be feasible after all.

The work, conceived and led by the researchers F.P. Cossío, Professor at the University of the Basque Country (UPV/EHU) and Scientific Director of Ikerbasque, and J.J. Gómez-Cadenas, Professor Ikerbasque at the Donostia International Physics Center (DIPC), includes an interdisciplinary team with scientists from DIPC, the UPV/EHU, Ikerbasque, the Optics Laboratory of the University of Murcia (LOUM), the Materials Physics Center (CFM, a joint center CSIC-UPV/EHU), POLYMAT, and the University of Texas at Arlington (UTA). Gómez-Cadenas has pointed out that "the result of this interdisciplinary collaboration that combines, among other disciplines, particle physics, organic chemistry, surface physics and optics, is a clear example of the commitment that DIPC has recently shown to developing new research lines. The purpose is not only to generate knowledge in other fields, different from the centre's usual ones, but also to look for hybrid grounds and create interdisciplinary projects that, in many cases, like this one, can be the most genuine".

The research is based on the idea, proposed by one of the authors of the article, the prestigious scientist D. Nygren (inventor, among other devices of the Time Projection Chamber technology applied by many particle physics experiment, including NEXT). In 2016, Nygren proposed the feasibility to capture Ba2+ with a molecule capable of forming a supramolecular complex with it and to provide a clear signal when this occurs, thus yielding a suitable molecular indicator. Nygren and his group at UTA then went into designing "on-off" indicators, in which the signal of the molecule is highly enhanced when a supra-molecular complex is formed. The group led by Cossío and Gómez-Cadenas has followed a different path, designing a fluorescent bicolor indicator (FBI) which combines a large intensity enhancement and a dramatic color shift when the molecule captures Ba2+. The synthesis of FBI was done under the direction of DIPC researcher I. Rivilla. If an FBI molecule with no barium is illuminated with ultraviolet light, it emits fluorescence in the range of green light, with a narrow emission spectrum of about 550 nm. However, when this molecule captures Ba2+, its emission spectrum shifts towards blue (420 nm). The combination of both features results in a spectacular enhancement of the signal, thus making it very suitable for a future Ba2+ detector.

It is interesting to note that the experimental multiphoton microscopy systems used in the LOUM by P. Artal's group for the green/blue spectral detection are based on those developed previously for imaging the cornea of the human eye in vivo. This is an example of interlacing the use of a unique technology in the world for biomedical applications on a fundamental problem of particle physics. "The effort to combine basic science and new instrumental implementations is essential to open new research avenues to answer the many questions that we scientists ask ourselves every day," says J.M. Bueno, Professor of Optics at LOUM.

As Cossío has explained, "the most difficult task in the chemical part of the work was to design a new molecule that would meet the strict (almost impossible) requirements imposed by the NEXT experiment. This molecule had to be very bright, capture barium with extreme efficiency (bb0nu is a very rare event and no cation could be wasted) and emit a specific signal that would allow the capture to be detected without background noise. In addition, the chemical synthesis of the new FBI sensor had to be efficient in order to have enough ultra-pure samples for installation within the detector. The most rewarding part was to check that, after many efforts by this multidisciplinary team, actually our specific and ultra-sensitive FBI sensor worked as planned".

Besides the design and characterization of FBI, the paper offers the first demonstration of the formation of a supramolecular complex in dry medium. This landmark result has been achieved preparing a layer of FBI indicators compressed over a silica pellet and evaporating over such a layer a salt of barium perchlorate. Z. Freixa, Ikerbasque Professor at the UPV/EHU says, with a smile: "the preparation of FBI on silica has been a quick-but-not-so-dirty solution for this proof of concept. A bit of home alchemy". The vacuum sublimation experiment was done by the CSIC scientist at CFM C. Rogero and her student P. Herrero-Gómez. Rogero, an expert in physics of surfaces says: "it was one of those Eureka moment, when we realized that we had in my lab just the tools to carry on the experiment. We evaporated the perchlorate and got FBI shinning in blue almost at the first attempt"

The next step of this research project is the construction of an FBI based sensor for the detection of the neutrinoless double beta decay or bb0nu, for which Gomez-Cadenas, F. Monrabal from DIPC and D. Nygren and collaborators at UTA are developing a conceptual proposal.

This work is a significant advance towards building a future "barium-tagging" NEXT experiment to look for noise-free bb0nu events through the identification of the two electrons and the barium atom produced in the reaction. This experiment would have a great potential to find out if the neutrino is its own antiparticle, which could lead to answer fundamental questions about the origin of the Universe.

Credit: 
University of the Basque Country

Dimethylsulfoniopropionate concentration in coral reef invertebrates

image: Coral nursery ground of the InterContinental Moorea Resort & Spa (Moorea, French Polynesia)

Image: 
Dr Isis Guibert

New research highlights the effect of benthic assemblages on the sulfur metabolism of coral and giant clam species. The research was conducted at CRIOBE and ENTROPIE research units, with the collaboration of the Swire institute of Marine Science of The University of Hong Kong (SWIMS, HKU), Paris-Saclay UVSQ University, The Cawthron Institute (New Zealand) and The University of French Polynesia. The findings were recently published in the journal Scientific Reports.

To better understand how benthic species assemblages could influence their respective fitness, the researchers created artificial benthic assemblages using two coral species (Pocillopora damicornis and Acropora cytherea) and one giant clam species (Tridacna maxima) and measured the dimethylsulfoniopropionate (DMSP) concentration in each species using Nuclear Magnetic Resonance (NMR) spectroscopy. DMSP, produced in large quantities in coral reefs, is a key compound that plays a central role in the marine sulfur cycle and climate regulation as major precursor of the volatile compound Dimethylsulfide (DMS). While DMSP has been found in terrestrial and marine organisms, only few species are able to produce it, among them marine algae such as dinoflagellates and corals. Numerous ecological studies have focused on DMSP concentrations in corals, which led to the hypothesis that increases in DMSP levels might be a general response to stress.

"We submitted our different assemblages of one, two or three co-occurring species to a thermal stress and measured the DMSP concentration in each species. Interestingly, we demonstrated that the concentration of DMSP in A. cytherea and T. maxima is modulated according to the complexity of species assemblages", explains Dr Isis Guibert.

Coral and giant clams are holobionts living in association with symbiotic algae, Symbiodiniaceae, as well as a large bacterial community. Both, Symbiodiniaceae and bacteria are able to produce DMSP. To determine whether giant clams might also contribute to DMSP production, the team explored transcriptomes of T. maxima for genes encoding enzymes involved in the DMSP biosynthesis. "For the first time, we revealed the existence of homologous genes involved in DMSP production in giant clam genome" said Dr Gaël Lecellier, who supervised the study. "Taken together, our results suggest that DMSP concentration in the holobiont is influenced by their neighboring species, modifying the metabolism of the sulfur pathway". The findings of this study offer new perspectives for future global sulfur cycling research.

Credit: 
The University of Hong Kong

An environmental warning system to monitor the coast

Researchers at the University of Seville Marine Biology Laboratory, working in the research team of Dr. José Carlos García Gómez, have demonstrated the usefulness of using the SBPQ (Sessile Bioindicators Permanent Quadrats) methodology to detect potential shifts in coastal areas. This technique acts a warning of incidents of a local nature, such as water pollution from poorly treated urban wastewater discharges; or of a more global nature, which become evident by monitoring climate change through species that are sensitive to temperature increases; or incidents caused by the intrusion of potential invasive species.

The first step in applying the SBPQ methodology is to select areas where sensitive native species are present and live in their adult form attached to the rocks (sessile), such as corals and sponges. These species have are unable to escape or relocate if environmental conditions deteriorate, meaning they can be used as environmental sentinels. To do this, the evolution over time of their presence in specific enclaves is monitored closely so that it is possible to detect changing circumstances if they begin to disappear. This early detection of environmental impacts in the coastal environment enables researchers to locate the source of the impact and, potentially, to correct it swiftly when the first signs of change are observed.

These conclusions flow from data collected over a ten year period (2005-2014), making this study one of the longest in the field of pre-coral and coral reefs. Long-term series are key to establishing trends and solving many unanswered questions around developments in ecosystems and possible changes to them. The study, published in the scientific journal PloS One, sought to confirm the validity and usefulness of the SBPQ methodology by focusing on a ten-year historical series which it was designed to test.

Furthermore, the researchers were able to confirm the hypothesis that in very stable and biostructured, high diversity beds, coral reef communities are very stable and tend not to vary over time unless disturbed by environmental factors that change the system. For ten years no change was recorded in the presence/absence of the monitored indicator species or in their abundances on the monitored fixed surfaces, meaning that, in that period of time no change--at least no change of significance--occurred leading to lethal or maladaptive effects on selected sensitive organisms in native biota.

Further research, also using the SBPQ method, led to the detection in 2015 of the invasive Asian algae Rugulopteryx okamurae (although not yet formally declared as such) in the Strait of Gibraltar. Its presence was detected for the first time in the area associated with pre-coral enclaves of high stability, spatial structure and associated biodiversity, which are very sensitive to environmental changes in the system. In this case, researchers from the University of Seville Marine Biology Laboratory tentatively linked this shift to global warming, since the invasion of the species occurred in 2015, coinciding with the highest peak in surface water temperature on the Andalusian coast in the period between 2000 and 2017. These considerations were reflected in another recent article by the team led by Dr. García Gómez, published in the scientific journal Science of The Total Environment (STOTEN).

The Strait of Gibraltar is an especially interesting area to test the usefulness of the SBPQ methodology as it presents coral habitats in pristine waters, especially in the Estrecho Natural Park, featuring excellent indicator species which are highly sensitive to environmental changes.

Based on the results obtained, the researchers underscored the importance of promoting a network to monitor environmental impacts in the coastal environment, tracking invasive species and monitoring global warming in the western Mediterranean. "But perhaps the most important thing about the SBPQ methodology is that it is a tool for social participation that reaches out to diving clubs and centres who want to get involved, under scientific supervision, in the underwater environment to monitor our coastal ecosystems," says Professor José Carlos García Gómez, director of the University of Seville Marine Biology Laboratory. "It is a tool that aims to fit into the recent world trend of Citizen Science, which has shown engagement with the conservation of underwater nature". It is a promising line of research developed by the University of Seville to transfer research results and social innovation in the field of marine biology.

The study was conducted thanks to financing from various European projects, the Network of Northern Mediterranean Protected Areas (Med-PAN), the RAC/SPA (Activity Centre for Special Protected Areas), the Department of the Environment of the Andalusian Regional Government (now CAGPyDS), the Port Authority of Seville (APS), the CEPSA Foundation and Red Eléctrica de España. The Port Authority of Algeciras (APBA) is currently studying the idea of including the waters around its facilities in the research project for the long term.

Credit: 
University of Seville

Tracking down cryptic peptides

image: Schematic representation of the formation and presentation of cryptic peptides.

Image: 
Rudolf Virchow Center / University of Wuerzburg

Almost all cells of the human body present fragments of cellular proteins on their surface, so-called human leukocyte antigens or HLA peptides, which play an important role in the immune response. If the immune system detects foreign HLA peptides, such as viral peptides on a virus-infected cell or mutated peptides on a tumour cell, T-cells eliminate the corresponding cell. The entirety of the HLA peptides presented on a cell is referred to as the cell´s immunopeptidome.

New approach enables comprehensive analysis for the first time

Besides the usual HLA peptides, there are also cryptic HLA peptides. These are derived from specific RNA sequences that do not contain information for a specific protein as is usually the case. Over the last few decades, only a few cryptic HLA peptides have been identified because they are very small and are quickly degraded in the cells. On the other hand, efficient computer algorithms for the analysis were lacking.

In a completely new approach, the Würzburg scientists have now combined several analytical methods that are particularly suitable for small peptides. "Using a novel bioinformatics method developed by us, for the first time we were able to identify thousands of cryptic HLA peptides in the immunopeptidomes of a wide variety of tumors such as melanoma and breast cancer," explains Dr. Andreas Schlosser, research group leader at the Rudolf Virchow Center at Julius-Maximilians-Universität (JMU) Würzburg in Bavaria, Germany.

The new bioinformatics approach is based exclusively on data from mass spectrometry, a method for determining the mass of molecules such as Peptides. This makes it possible to systematically and comprehensively determine the cryptic HLA peptides. In addition, it was possible to clarify on which cells and to what extent cryptic peptides are present: "We were able to show that cryptic HLA peptides make up a significant part of the immunopeptidomes of tumors," explains Prof. Dr. Florian Erhard, group leader at the JMU Institute of Virology.

Effective points of attack for the immune system

It was already known from individual studies that cryptic peptides can trigger autoimmune reactions such as in diabetes type 1 as well as immune responses against tumor cells. The new analyses provide evidence that certain cryptic HLA peptides are exclusively found on tumour cells. Such tumour-specific cryptic HLA peptides might thus prove to be worthwhile target structures for cancer immunotherapies. Scientists at the University of Würzburg and the University Hospital of Würzburg are already examining a selection of the identified peptides to determine whether they are suitable as targets for cancer immunotherapy.

Virus-infected cells also present cryptic HLA peptides that could be used as a target structure for vaccines. With their new method, the researchers thus have an effective tool in hand to learn more about the general function and formation of cryptic peptides. "We hope that our bioinformatics approach will provide us with a better understanding of autoimmune reactions as well as immune reactions against tumour cells and virus-infected cells," says Schlosser.

Credit: 
University of Würzburg

Lack of damage after secondary impacts surprises researchers

image: A map showing crystallographic orientation of a region that originally contained a void, which was then subjected to a second shock loading (the shock wave passed from the bottom to the top of the image). The void has been recompacted with enough energy to not only reach a fully dense state, but drive recrystallization at the interface, as demonstrated by the thin band of very small grains.

Image: 
David Jones

WASHINGTON, June 23, 2020 -- When a material is subjected to an extreme load in the form of a shock or blast wave, damage often forms internally through a process called spall fracture.

Since these types of intense events are rarely isolated, research is needed to know how damaged materials respond to subsequent shock waves -- a piece of armor isn't much use if it disintegrates after one impact.

To the surprise of researchers, recent experimentation on spall fracture in metals found that, in certain cases, there was an almost complete lack of damage with only a thin band of altered microstructure observed. Usually, under these sorts of conditions, the material would contain hundreds of small voids and cracks.

In an article for the Journal of Applied Physics, published by AIP Publishing, researchers from Los Alamos National Laboratory narrowed down exactly why the expected damage was missing.

"Conflicting hypotheses were suggested for the lack of damage. Was there some sort of strengthening occurring, so that damage never nucleated, or was the damage recompacted to a fully dense state by some other loading?" said author David Jones. "By splitting the experiment into two phases -- damage formation and recompaction -- we could determine which hypothesis was correct."

Materials experiencing shock damage at high strain rates from a sudden impact will exhibit significantly different behavior compared to their response under standard, low-rate mechanical testing.

The researchers used gas-gun flyer-plate impact experiments to first damage samples, and then impact these samples a second time to see how the shock wave interacts with the damage field, which had not been done before. They found a shock stress of just 2 to 3 gigapascal actually recompacted a damaged copper target and created a new bond where the once broken surfaces were brought back together.

"This research, where careful experiments are used to isolate the strength and damage response of a material under shock loading, helps to reveal how microstructure plays a key role in dynamic response," said Jones.

The authors hope the future of shock physics research will involve next-generation free electron X-ray lasers, a game-changing tool.

"Being able to image in real time these micrometer-scale, microsecond-duration damage events in metals will be a paradigm shift in shock physics diagnostics," said Jones.

Credit: 
American Institute of Physics

Getting real with immersive sword fights

image: Computer Scientists at the University of Bath have found a solution to the challenges of creating realistic VR sword fights, and it's called Touché.

Image: 
Christof Lutteroth

Sword fights are often the weak link in virtual reality (VR) fighting games, with digital avatars engaging in battle using imprecise, pre-recorded movements that barely reflect the player's actions or intentions. Now a team at the University of Bath, in collaboration with the game development studio Ninja Theory, has found a solution to the challenges of creating realistic VR sword fights: Touche - a data-driven computer model based on machine learning.

Dr Christof Lutteroth, who created Touche with colleague Dr Julian Padget and EngD student Javier Dehesa, said: "Touche increases the realism of a sword fight by generating responsive animations against attacks and eliminating non-reactive behaviour from characters.

"Using our model, a game character can anticipate all possible fight situations and react to them, resulting in a more enjoyable and immersive game experience."

The unpredictability of user actions presents a major conundrum for designers of VR games, explained Dr Lutteroth, who is a senior lecturer in Computer Science, director of Real and Virtual Environments Augmentation Labs (REVEAL) and co-investigator at the Centre for the Analysis of Motion, Entertainment Research and Applications (CAMERA). "VR games offer new freedom for players to interact naturally using motion, but this makes it harder to design games that react to player motions convincingly," he said.

He added: "There are different expectations for screen-based video games. With these, a player presses 'attack' and their character displays a sequence of animations. But in a VR game, the player input is much harder to process."

The Touche framework for VR sword fighting simplifies the necessary technical work to achieve a convincing simulation. It eliminates the need for game designers to add layer upon layer of detail when programming how a character should move in a particular situation (for instance, to block a particular sword attack). Instead, actors wearing motion capture equipment are asked to perform a range of sword fighting movements, and Touche builds a model from these movements. The virtual version of the actor is able to react to different situations in a similar fashion to a flesh-and-blood fighter. Game designers can then fine-tune this model to meet their needs by adjusting high-level parameters, such as how skilled and aggressive the game character should be. All this saves game developers a lot of time and leads to more realistic results.

For the Bath study, 12 volunteers were asked to take part in two three-minute sword fights: for the first fight, they used technology that is currently available and for the second, they used Touche. Touche had a strong positive effect on realism and the perceived sword fighting skills of game characters. Feedback from participants pointed to a convincing preference for Touche, with current sword fights being described as 'unresponsive' and 'clumsy' by comparison.

"Based on this, we are convinced that Touche can deliver more enjoyable, realistic and immersive sword fighting experiences, presenting a more skilled and less repetitive opponent behaviour," said Dr Lutteroth. "I'm convinced this framework is the future for games - not only for sword fighting but also for other types of interaction between game characters. It will save developers a lot of time."

Javier Dehesa Javier, who is based at the Centre for Digital Entertainment, interviewed game developers who had tested this new technology. He said: "Developers see the Touche framework as an important practical step in the industry towards data-driven interaction techniques. We could see this technology appear in commercial games very soon."

Touche: Data-Driven Interactive Sword Fighting in Virtual Reality is published by CHI '20: Proceedings of the 2020 CHI Conference on Human Factors in Computing Systems.

Video to accompany press release: https://vimeo.com/430682565

Credit: 
University of Bath

New compressor delivers above-terawatt 1.5-cycle pulses at kilohertz repetition rate

image: The inset shows the measured shape and beam profile of the 1.5-cycle pulses.

Image: 
MBI

Researchers at the Max Born Institute for Nonlinear Optics and Short Pulse Spectroscopy (MBI) have reached a new milestone in few-cycle pulse generation, breaking a 10-year-old record and achieving 1.5-optical-cycle-long laser pulses with 1.2 terawatt peak power by a new high-energy hollow fiber compressor beamline. The intense pulses will be used to generate intense attosecond harmonic radiation for nonlinear XUV spectroscopy studies.

In order to shed light on complex charge transfer mechanisms during the formation of a chemical bond or in biologically relevant processes, one needs tools with exceptional temporal resolution in the attosecond (10^-18 s) realm. Single attosecond light pulses can be generated in the extreme ultraviolet (XUV) spectral range by focusing intense few-cycle laser pulses encompassing only a few oscillations of the electric field onto noble gas atoms, using the process called high-harmonic generation (HHG). However, the conversion efficiency is low, yielding very weak attosecond pulses, insufficient for nonlinear spectroscopic applications. In order to create more intense isolated attosecond pulses, high-energy, near infrared, few-cycle driving laser pulses are required.

Now, researchers at the MBI have made a big step forward in the energy scaling of the driver pulses. The group succeeded to spectrally broaden and subsequently compress pulses of a titanium sapphire laser, which emits at a wavelength of 790 nm, to 3.8 fs duration (1.5 optical cycles) at an energy of 6.1 mJ, which is unprecedented at kilohertz repetition rate. Thus the peak power of the pulses exceeds the terawatt (> 10^12 W) level. This result breaks a 10-year-old record achieved at RIKEN [1].

In order to achieve these results, a new 8.2 meter long compressor beamline was built around a 3.75 meter long, stretched flexible hollow-core fiber (SF-HCF) where spectral broadening took place as a result of nonlinear interaction between the intense light pulses and helium atoms admitted into the capillary. The spectrally broadened pulses were then compressed by a set of chirped mirrors and characterized by an in-line dispersion scan device that was directly placed into the vacuum beamline that is constructed for subsequent high-harmonic generation and XUV experiments. The new HCF compressor is an up-scaled version of a device that was recently developed in the framework of an international collaboration with participation of the MBI [2].

Credit: 
Forschungsverbund Berlin

Scientists create program that finds synteny blocks in different animals

image: Scientists developed a software tool that makes it possible to quickly and efficiently find similar parts in the genomes of different animals, which is essential for understanding how closely related two species are, and how far they have evolved from their common ancestor. The research was published in Giga Science.

Image: 
Dmitry Lisovsky, ITMO.NEWS

Modern genetics implies working with immense amounts of data which cannot be processed without the help of complex mathematical algorithms. For this reason, the task of developing special processing programs is no less important for bioinformatics specialists than that of genomic sequencing of specific animals. An international team of scientists that included researchers from ITMO University developed a software tool that makes it possible to quickly and efficiently find similar parts in the genomes of different animals, which is essential for understanding how closely related two species are, and how far they have evolved from their common ancestor. The research was published in GigaScience.

There are millions of biological species on planet Earth, and this diversity is laid down on the genetic level. Animals' anatomy, size, color patterns and habits are defined by their genes. Then again, the diversity of genes themselves is not that great: by today, scientists have only identified about over 20,000. Therefore, species are different in not only the sets of genes they have but also in how their genes are arranged. In the language of comparative genomics, this is called synteny, i.e. the arrangement of genes and regulatory elements.

"Let's take a gorilla and a chimpanzee as an example," says Ksenia Krasheninnikova, a researcher and engineer at ITMO University. "These two species have the same set of genes, but their regulatory elements and genome mutations create slightly different orders which results in differences between these primates."

Therefore, for the purposes of understanding how close two species are from the evolutionary standpoint, scientists need to know not just their genes but also how they are arranged in a chromosome, and how many common genome fragments, or synteny blocks, as geneticists call them, there are. Then again, looking for them manually is impossible: the amount of data is just too big. Genomes of mammals consist of millions and billions of base pairs, which makes processing without big data technologies next to impossible. For this reason, scientists create programs of their own that make it possible to solve this new category of tasks which has emerged in the course of the development of this science. And this is what the research team that included scientists from ITMO's Laboratory of Genomic Diversity did.

The new software tool was named halSynteny. According to its authors, it can search for synteny blocks better and faster than other programs developed for this purpose. What's more, halSynteny works with data in two standard and well-documented formats.

"Our goal was to create an algorithm that could be easily applied to accessible data," says Ksenia, who is the first author of this research. "Some of the approaches to the identification of synteny sequences are based on annotating genes in advance; our method is different. We don't use any additional annotation. We use the alignment method, when different parts of one genome are aligned by their degree of similarity with parts of another genome. This way, we can identify homogeneous parts, parts that are of the same origin."

The program makes it possible to speed up the computations by over two times in comparison with SatsumaSynteny2, another popular tool. Such high efficiency was attained by implementing a mathematically effective algorithm using C++.

The proposed method and software tool were tested by comparing cat and dog genomes.

"We showed that large fragments of cat chromosomes and some fragments of dog chromosomes unite in synteny blocks, which means that they've evolved from similar chromosomes of a common ancestor. And this can be used as a basis for making conclusions about their evolutionary process. Previous research in the field of "wet" biology demonstrated that cats' genome changed less from the genome of their common ancestor in comparison with that of dogs. This can be seen in comparison with other species that are not part of the carnivora order. The results that we got confirm these conclusions and make them more accurate. This means that in some specific part, the genome of a cat and the species taken for comparison is similar, and in dogs, it is rearranged."

In future, this algorithm will be used in other research in the field of comparative genomics that takes place at ITMO University.

Credit: 
ITMO University

Nearly 70% of patients make personal or financial sacrifices to afford medications

video: Beyond industry and survey data, the 2020 Medication Access Report also includes filmed interviews with patients and caregivers who share their personal experiences with common medication access challenges, and how these challenges have impacted their lives.

Image: 
CoverMyMeds

COLUMBUS, Ohio, June 23, 2020 -- Nearly 70 percent of patients have made personal or financial sacrifices to afford prescribed medications1 according to new research released by CoverMyMeds, highlighting the impact of one of the most common medication access challenges. The 2020 Medication Access Report, and corresponding Prescription Decision Support, Electronic Prior Authorization, Specialty Patient Support and COVID-19 sub-reports, investigate healthcare barriers that impede access to prescriptions, contribute to increased provider burden and motivate patient consumerism. The report also examines the impact of the COVID-19 pandemic on healthcare and assesses how the market is responding to these challenges with tools that inform medication decisions, streamline administrative tasks and support remote healthcare. Click here to access the full report.

"Navigating the patient journey can be complex, especially for patients who encounter significant barriers--such as medication cost, clinical requirements and enrollment processes--to obtain their prescription," said Eric Weidmann, MD. Chief Medical Officer of eMDs. "The complexity of obtaining access to medications can also take a toll on providers who are faced with increasingly burdensome administrative tasks, especially during the pandemic. As a practicing physician, I appreciate the benefits of technology to help streamline many traditionally-manual processes, inform my conversations with patients and support my prescribing decisions."

Key takeaways from the 2020 Medication Access Report include:

The COVID-19 pandemic has caused millions of Americans to face healthcare insecurity:

As of June 5, 2020, 44 million people -- over a quarter of the U.S. workforce -- had filed for first-time unemployment benefits since March 2020, when much of the U.S. economy began to shut down in response to the pandemic. This is six times the number of claims during the peak of the Great Recession.2

When asked what medication barriers their patients are experiencing due to COVID-19, 30 percent of providers said their patients are unable to pay for prescriptions.3

Since the beginning of COVID-19, more than 20 percent of patients said they've used a cash price program to help afford medications.4

The COVID-19 pandemic fast-tracked adoption of many healthcare technologies, but there is still room for growth.

Prior to COVID-19, only 11 percent of patients used telehealth services.5 Now, 67 percent say they are more likely to use telehealth services moving forward.4

Despite increased utilization, over 30 percent of providers said lack of integration within EHR and privacy concerns were challenges they faced with telemedicine.3

80 percent of providers surveyed listed patients' lack of technology skills as a telemedicine challenge.3

Many Americans face medication access challenges, such as affordability barriers and manual processes that can delay care:

When patients cannot afford their prescriptions, 29 percent admit to abandoning their medications while 52 percent seek affordability options through their physician, a labor-intensive process which creates additional work for the provider and can delay the patient's time to therapy.1

55 percent of patients reported delays in time to therapy due to a prescribed medication requiring prior authorization.1

82 percent of patients say they spent at least one hour or more making multiple phone calls to track down needed information to begin specialty therapies.1 As a result of this time-consuming administrative work, nearly one in 10 patients reported waiting eight weeks or more to receive their first dose of therapy.1

"The 2020 Medication Access Report uses industry statistics, market research and new survey data to highlight critical barriers that can limit patients' access to medications," said Miranda Gill MSN, RN, NEA-BC, Senior Director, Provider Services and Operations at CoverMyMeds. "The report also highlights important strides in creating innovative solutions that help patients overcome many of these disruptive obstacles. However, there needs to be more widespread adoption and collaboration across the healthcare industry to see the true benefits of these solutions: streamlining inefficiencies which can help improve patients' health outcomes."

The 2020 Medication Access Report is published by CoverMyMeds, part of McKesson Prescription Technology Solutions, with an advisory board of leaders from BestRx, Blue Cross Blue Shield North Carolina, Cerner Corporation, eMDs, Express Scripts, Horizon Government Affairs, Humana, National Alliance of State Pharmacy Associations, National Council for Prescription Drug Programs, National Patient Advocate Foundation, OptumRx, Orsini Healthcare, RelayHealth Pharmacy Solutions, RxCrossroads and University of Virginia Health System.

To view the full 2020 Medication Access Report, click here.

Sources

1 - CoverMyMeds Patient and Provider Surveys, 2020
Survey based on responses from 1,000 patients and 400 providers.

2 - Unemployment Insurance Weekly Claims, Department of Labor, 2020

3 - CoverMyMeds Provider COVID-19 Survey, 2020
Survey based on responses from 3,000 providers.

4 - CoverMyMeds Patient COVID-19 Survey, 2020
Survey based on responses from 500 patients.

5 - Telehealth: A quarter-trillion-dollar post-COVID-19 reality?, McKinsey & Company, 2020

Credit: 
CoverMyMeds

CAR T cell therapy: potential for considerable savings

Chimeric antigen receptor (CAR) T cell therapy is a new and in some cases highly effective form of immunotherapy to treat certain types of cancer of the blood and lymph system. This promising treatment comes at a cost, however: The manufacturers charge up to EUR 320,000 for the production of immune cells for a single patient. By determining the fixed and variable costs involved, researchers from the German Cancer Research Center (DKFZ) established that cellular immunotherapy could be produced at a scientific institution such as DKFZ at around a tenth of the cost.

For several years now, physicians have been achieving considerable success using an innovative form of immunotherapy in patients with certain types of cancer of the blood and lymph system: The treatment involves harvesting immune cells (T cells) from the patient and modifying them outside the body to make them more effective in attacking the malignant leukemia cells. To do so, the researchers equip the cells in the laboratory with a specific receptor protein. This chimeric antigen receptor (CAR) recognizes a protein molecule as a target structure that is formed by every cancer cell in certain types of leukemia. The CAR T cells are subsequently propagated and transferred back to the patient - where they hunt down malignantly transformed leukemia cells, sometimes with spectacular success.

Two commercial CAR T cell products have been approved to treat patients with acute lymphoblastic T cell leukemia and non-Hodgkin lymphomas such as diffuse large cell B cell lymphoma. They are only used if other treatment options have failed. The treatment is often effective: two years after treatment, 40 to 60 percent of patients have not relapsed.

This promising and highly individualized treatment comes at a cost, however: In Germany, the manufacturers charge up to EUR 320,000 for the production of CAR T cells for a patient. "CAR T cell therapy is still only feasible in a few cancer patients, but this treatment approach will hopefully be able to be extended to other types of cancer. There is considerable concern that our health care systems will not be able to meet the costs of this potential increase in the number of patients," Michael Schlander, a health economist at DKFZ, explained.

As an alternative to the two CAR T cell products developed by large pharmaceutical companies, many research institutions, including DKFZ, hope to manufacture the therapeutic cells themselves. For the first time, health economist Schlander, immunologist Stefan Eichmüller and their team of researchers at DKFZ have now listed in detail the costs incurred by an academic institution in producing CAR T cell therapies.

The fixed and variable costs included setting up a clean room, laboratory materials, equipment, and all salaries and non-wage labor costs for the specially trained laboratory staff. As expected, the calculated costs were heavily dependent on the capacity utilization rate of the fully automated production system for the cells. The researchers based their calculations on different scenarios, including a maximum annual capacity utilization rate of the machine with 18 CAR T cell products.

Under these conditions, DKFZ could produce a CAR T cell product to treat a patient for less than EUR 60,000. "That would be only about a fifth of the price that the companies charge. And we can cut these costs even further by a considerable amount," Michael Schlander explained, adding that the greatest savings could be made if several of the automated production machines were operated at the same time. An alternative method of transferring the genes for the chimeric receptor could further reduce the production costs to as little as around EUR 33.000 Euro - a tenth of the current commercial price.

Quite apart from these direct savings, the patients would benefit from decentralized CAR T cell production too: "Without the time needed to send the patient's blood and the finished cell therapy, we can provide the treatment within 12 to 14 days - a considerable reduction compared with the three- to four-week waiting time for the commercial products. Patients might then need less chemotherapy and would spend less time in hospital, which would lead to further savings," remarked immunologist Stefan Eichmüller.

The analysis did not take account of the cost of license fees. Michael Schlander and Stefan Eichmüller hope that the present study will also encourage the manufacturing companies to review their current pricing policy for CAR T cell therapies.

Credit: 
German Cancer Research Center (Deutsches Krebsforschungszentrum, DKFZ)

A bacterial toxin turning cells into swiss cheese

image: Researchers from Kanazawa University developed a novel tool to study how the innate immune system fights bacterial toxins. They purified the pore-forming toxin Monalysin from a bacterial culture, and structurally and functionally characterized the purified toxin to show how it functions at the molecular level. This study could help understand the mechanisms underlying the interactions between host defense and microbial invaders.

Image: 
Kanazawa University

Kanazawa, Japan - Although the innate immune system is the front line of defense against microbial infections, the complex mechanisms of innate immunity are incompletely understood. In a new study, researchers from Kanazawa University synthesized and characterized the bacterial toxin Monalysin to enable the study of how the innate immune system and toxin-producing bacteria interact with each other.

The innate immune system detects microbial infections through sensing either microbial molecules (pathogen-associated molecular patterns, or PAMPs) or host signaling molecules that are released from damaged host cells (damage-associated molecular patterns, or DAMPs). The bacterium Pseudomonas entomophila has been utilized as a tool to study the mechanisms of DAMPs in the gut. P. entomophila infects insects and damages intestinal cells using a pore-forming toxin called Monalysin. Monalysin is secreted as an inactive pro-toxin, which is then activated by certain proteins called proteases. Although the fruit fly, Drosophila, protects itself from activation of the pro-toxin by building a physical barrier against proteases, it can still take damage upon exposure to the toxin.

"Activated Monalysin forms pores in the plasma membrane of host cells, resulting in cell death, so it is important for the host to prevent its activation," says corresponding author of the study Takayuki Kuraishi. "We wanted to purify and functionally characterize Monalysin from P. entomophila to develop a tool that could help us understand how the host and bacteria that produce pore-forming toxins interact."

To achieve their goal, the researchers cultured P. entomophila and purified pro-Monalysin from their lysates. By reacting the purified toxin with Drosophila cells, the researchers confirmed its toxic effect when cell viability dropped significantly as more pro-Monalysin was added to the cells. To confirm that purified Monalysin forms pores, the researchers added activated Monalysin onto a chip covered with a lipid bilayer, similar to the plasma membrane of cells. By measuring the electrical current resulting from ion passage through the formed pores, the researchers showed that Monalysin forms pores around 0.7-1nm in diameter. To analyze the structural composition of Monalysin, the researchers then turned to atomic force microscopy (AFM), which provides high-resolution images by touching the surface with a sensitive mechanical probe. Using AFM, the researchers showed that eight Monalysin molecules came together to form pores in the plasma membrane. By combining AFM with high-speed imaging, the researchers then demonstrated that activated Monalysin preferentially inserted into the edge of the plasma membrane, suggesting that highly curved parts of membranes are the sites of their action.

"These are striking results that show how Monalysin functions at the molecular level," says Kuraishi. "Our findings could help understand how the innate immune system fights off bacteria that produce pore-forming toxins."

Credit: 
Kanazawa University