Tech

The sheer endless expanses of the oceans are hostile deserts -- at least from the perspective of a bacterium living in water. Tiny as it is, its chances of finding sufficient nutrients in the great mass of water would seem to be vanishingly small. However, as in other deserts, there are life-saving oases in the sea: for example, microorganisms find everything they need to live on the surfaces of aquatic plants and algae. Here, very different species can grow within the community of a biofilm, as it is called, where they exchange information and offer each other protection.

Jena microbiologists working with Prof. Christian Jogler have now discovered natural products in a newly discovered species of bacteria, with the help of which the microorganisms living in the water control the composition of such biofilms and cultivate them like a garden, in line with their own needs. The team from Germany and the Netherlands presents its results in the current issue of the journal Communications Biology (DOI:10.1038/s42003-020-0993-2).

Planctomycetes produce bioactive natural substances

The bacterium Stieleria maiorica is one of nearly 80 newly discovered species of bacteria, which the team from the University of Jena has been cultivating from fresh and saltwater samples from all over Europe and the USA, obtained in a large-scale collection. Stieleria maiorica is a member of the planctomycetes and was fished out of the Mediterranean Sea off the coast of Majorca. The researchers are particularly interested in such planctomycetes because they suspect that they contain bioactive natural products. And rightly so, as the Jena scientists have shown in their latest paper. Stieleria maiorica, for instance, produces a previously unknown group of chemical compounds, which were named "stieleriacine", after the bacterium.

"These are relatively small molecules, which are structurally similar to a group of known signal molecules that microorganisms use to communicate with each other," says Christian Jogler. "This led to the assumption that the newly discovered stieleriacines also act as signalling molecules in the broadest sense," adds Jogler, who is Professor for Microbial Interactions at the University of Jena.

Bacteria release antibiotics after chemical signal

The researchers have therefore been examining how other bacterial species react to the stieleriacines produced by planctomycetes. And they indeed discovered that species of Roseobacter react to the stieleriacine signal. Like planctomycetes, these microorganisms occur on aquatic plants and algae and compete with the planctomycetes for habitat and nutrients. The stieleriacines promote the growth of some Roseobacter species, while inhibiting others. What is more, those species that grow better as a result of the chemical signal also produce an antibiotic which they release into their environment. Roseobacter that are inhibited in their growth by the stieleriacines do not produce an antibiotic.

"This is a crucial advantage for the planctomycetes," says Prof. Jogler. "They themselves are resistant to the antibiotic. Other species of bacteria, however, which compete with the planctomycetes in the biofilm, are inhibited by the antibiotic." This gives the rather slow-growing planctomycetes the chance to compete with bacterial species which would otherwise have made things difficult for them. "One could say that planctomycetes use the Roseobacter for the 'heavy manual work' of adapting the composition of the biofilm to their own requirements and, like skilled gardeners, for regulating the growth of other species."

Signalling substances modulate composition of biofilms

However, for Prof. Jogler and his colleagues in the Cluster of Excellence "Balance of the Microverse" at Jena University, the planctomycetes are of interest not only as skilful underwater landscape gardeners. "The chemical signalling substances that the microorganisms use to communicate and to influence their environment could also be of use in infection research," says Jogler. If small molecules can be used to modulate the composition of biofilms, this could be used, for example, to prevent pathogenic microorganisms from settling on the surfaces of catheters or implants.

With the present study, the authors feel confirmed in their hypothesis that in the search for new active substances, and in particular for the new antibiotics that are so crucial, it is worth taking a look below the surface of the water. They are convinced that other natural substances with bioactive properties could still be found in the biofilms on aquatic plants and algae.

In the course of the COVID-19 pandemic, scientists are facing great challenges because they have to reorient, interrupt or even cancel research and teaching. A team of international scientists with participation from the University of Göttingen published an international appeal which highlights the precarious situation of many scientists and calls for a collective effort by the entire scientific community, especially those in leadership positions, to protect decades of effort to build an inclusive scientific community. Their letter appeared in Nature Ecology and Evolution.

The coronavirus pandemic poses major challenges in particular for those scientists who are dependent on fixed-term positions or temporary visas, who have more responsibility for administration or family care, or who belong to disadvantaged social groups, especially early career researchers. According to EU reports, women in research still earn 17% less than their male counterparts, even when carrying out the same functions, and data for minority groups is generally not available. The writers emphasise the consequences that this crisis will have on early career researchers; especially those from communities historically underrepresented in science, including minorities of all genders, women, researchers from the Global South, and persons with disabilities.

"The crisis not only endangers many scientific positions and international collaborations, but also the diversity that has demonstrably made research more productive and innovative. Current and long-term consequences of the pandemic will be harder to overcome for many scientists from developing countries, who often rely on access to short-term funding for their education and research," says co-author Carolina Ocampo-Ariza, PhD student from the Agroecology group, University of Göttingen. Diversity, equality and inclusion promote innovative perspectives that are as international as the current environmental problems and challenges. "It will require courageous action by the entire scientific community to develop solutions to threats such as global climate change and species extinction," emphasises Dr Bea Maas, first author of the letter and guest scientist at Agroecology Group, University of Göttingen.

In summary, the recommendations of the international team of scientists are as follows: "We call on the international scientific leadership in workplaces, institutions and offices to actively protect the decades of efforts to build an inclusive scientific community through improved gender equality measures, targeted funding and increased state aid". The authors emphasize that overcoming the acute and long-term challenges of this pandemic calls for a strong international scientific community that understands that diversity and equity are key in promoting resilient ecosystems as the cornerstones of human health and well-being.

A group of experts from the University of Seville has carried out a comparative study of the concentrations, both totals as well as fractions, of the metals found in sediment in the River Guadiamar in 2002 with those present in the same area in 2018. After this study, the researchers state that there has been an important fall in the total concentrations, and evolution of the metal fraction towards their more innocuous forms, so the environmental risk is much reduced.

"The samples were taken in the same locations and by the same research group twenty years after the Aznalcóllar mining accident that occurred in 1998", says the University of Seville professor and leader of the group, Esteban Alonso, who adds that, specifically, sediments were analysed from six locations on the River Guadiamar and its main tributaries, from the area of the Aznalcóllar mine to the gates of Doñana national Park.

The samples taken were pre-treated using trituration, sifting and freeze-drying, to determine the concentration of the following metals: aluminium (Al), cadmium (Cd), copper (Cu), iron (Fe), manganese (Mn), lead (Pb) and zinc (Zn). Then, the sequential extraction method of the SMTP (European Commission Measurements and Testing Programme) was used, modified to extract four different metal fractions; interchangeable, reducible, oxidable and residual. The measurements were taken at the Radioisotope General Research Service (Servicio General de Investigación de Radioisótopos) at the University of Seville, and for estimating the risks carried by the metal concentrations found in the sediments, the Potential Ecological Risk Index (PERI) was used and the Sediment Quality Guide (SQG).

The risk coefficients calculated for the year 2002 showed an extreme risk with very high values for Cd, Pb and Zn n the whole area of study with the exception of the waters upstream of the mine. In 2018, according to the data obtained, the risk had descended and moderated at the majority of the sample locations.

"Despite the serious environmental consequences of the Aznalcóllar mining, it has been shown that measures taken after the disaster were effective in improving the quality of the waters of the River Guadiamar and its main tributaries in relation to the dumping of acid waters and pyrite muds. It is necessary, in any case, in such a sensitive area, due to its influence, among other things, on Doñana, to maintain the quality of the water and sediments by avoiding dumping and runoffs from still contaminated areas and by improving the purification of the urban waste waters that are released into the basin. In a parallel sense, it is vital to continue monitoring the evolution of the contamination by these metals, both in the water and in sediments, in the soil at the edge of the basin", the researcher states.

Nearly 13 kilometres per year: that is the rate at which the wintering area of Bewick's swans has shifted east over the past 50 years. It's a discovery with consequences for the conservation of this migratory species, writes a team of researchers led by the Netherlands Institute of Ecology (NIOO-KNAW) in Global Change Biology.

Why are Bewick's swans, a protected species, declining sharply in Ireland and Britain? And to a lesser extent also in the Netherlands, their main wintering area? "This decline in North-West Europe was not consistent with our data on breeding success and survival", says NIOO animal ecologist Rascha Nuijten. "That's why we started this research."

The first indication the researchers had, was that in Germany the number of wintering swans was actually increasing rather than declining. To find out more, an international team was formed that also included members from Estonia and the United Kingdom (Wildfowl & Wetlands Trust).

Between tundra and delta

Unlike their 'cousin' the mute swan, Bewick's swans migrate across great distances. They move between their breeding area in the Russian tundra and wintering grounds in North-West Europe and elsewhere.

"We found that both the time spent in the wintering grounds and the location of those wintering grounds changed significantly over the past fifty years", says Nuijten. "The time has been reduced - what we call 'short-staying' - and the area has shifted east, towards the breeding area: 'short-stopping'."

So what has triggered these changes? "We see a similar shift east in the 5°C temperature line across Europe in winter. This would suggest that the changes in the swans' wintering behaviour are driven by the warming of the climate."

Not so traditional after all

Instead of cosying up somewhere in Britain or the Netherlands, the average Bewick's swan is now spending winter in spots hundreds of kilometres more to the east - shortening the migratory journey to their breeding grounds considerably. Compared to 1970, the swans also arrive later and leave earlier. In total, the researchers estimate they have cut their 'winter holiday' short by almost nine weeks. Actually, 'holiday' is probably the wrong word: it's the time for recovering and fattening up before the all-important journey to their breeding grounds the next spring.

Should I stay or should I go? Nuijten now knows the answer: "We found out that individual swans are not changing the duration of their stay during their lifetime. So the observed shifts were caused by directional differences between generations." Distance is a different story, however. The researchers observed that swans can shorten the distance of their migration within their lifetime. "For a species that has the reputation of being traditional, that's an exciting discovery!"

Nature conservation

The researchers' findings suggest that Bewick's swans are, to an extent, able to adapt to climate change. What the observed changes mean for them in other times of the year is not yet clear. But it does have consequences for the optimal conservation and management of the species, says Nuijten.

"Some places have become much less important for the swans and other places much more. So when it comes to nature conservation and management, species dynamics - in relation to climate change for instance - need to be taken into consideration."

Scientists at RCSI University of Medicine and Health Sciences have developed a new biomaterial that has the potential to accelerate bone regeneration by promoting an immune response that encourages repair and lowers the risk of inflammation.

The study, conducted by researchers at RCSI Tissue Engineering Research Group (TERG) and AMBER, the SFI Research Centre for Advanced Materials and BioEngineering Research, is published in Acta Biomaterialia

The researchers have developed a technology that is a combination of nanoparticles and a collagen-based biomaterial called a scaffold, specifically designed by RCSI TERG that can be surgically implanted to aid bone tissue repair. The material allows for the delivery of a microRNA silencer, a molecule capable of influencing the way our cells function.

In laboratory conditions, researchers successfully demonstrated that damaged bone tissue is restored as the particular microRNA delivered by the biomaterial works to increase cells responsible for bone repair. The technology also assists in promoting a pro-repair immune system response, lowering the risk of inflammation and other complications.

"The results of our research are a promising step towards improving health outcomes for patients with fractures that fail to repair naturally or have degenerative bone diseases such as osteoporosis, although further pre-clinical and clinical trials are still required before the technology could be used to treat humans," said Dr Caroline Curtin, Lecturer in Anatomy and Regenerative Medicine at RCSI.

"We are confident that this biomaterial system will have several potential applications beyond bone repair, as it can be tailored to deliver other therapeutic molecules that address degenerated or diseased tissue in the body. At RCSI Tissue Engineering Research Group, we are exploring these possibilities through the development of similar methods to repair articular joints like the knee and hip, and attempting to apply the microRNA delivery systems to inhibit breast cancer cell growth and other novel research," said Prof. Fergal O'Brien RCSI Director of Research and Innovation, Professor of Bioengineering and Regenerative Medicine and Deputy Director of the SFI AMBER Centre.

The research, undertaken by first author Dr Irene Mencía Castaño, is supported by Science Foundation Ireland (SFI) Research Frontiers Programme, the Advanced Materials and Bioengineering Research (AMBER) Centre through SFI and the ERC under the European Commission's Horizon 2020 Framework Programme/ERC grant agreement.

A mysterious cloud containing radioactive ruthenium-106, which moved across Europe in autumn 2017, is still bothering Europe's radiation protection entities. Although the activity concentrations were innocuous, they reached up to 100 times the levels of what had been detected over Europe in the aftermath of the Fukushima accident. Since no government has assumed responsibility so far, a military background could not be ruled out.

Researchers at the Leibniz University Hannover and the University of Münster (both Germany) now found out that the cloud did not originate from military sources - but rather from civilian nuclear activities. Hence, the release of ruthenium from a reprocessing plant for nuclear fuels is the most conclusive scenario for explaining the incident in autumn 2017. The study has been published in the journal Nature Communications.

Background:

It is impossible to make a clear distinction between civilian and military sources solely based on measurements of radioactive isotopes of ruthenium. For the first time, researchers from the Institute of Radioecology and Radiation Protection at Leibniz University of Hannover and the Institute of Planetology at Münster University succeeded in quantifying stable ruthenium isotopes in air filters that were released with the radioactive ruthenium.

Within the scope of the study, the team left conventional scientific paths: "We usually measure ruthenium isotopes to study the formation history of Earth", says Prof. Thorsten Kleine from the University of Münster, adding that the methods originally developed to address research questions in planetology were instrumental in solving this mystery. The fact that the airborne ruthenium stemming from nuclear activities occurred in minuscule amounts and were diluted with natural stable ruthenium presented a significant challenge.

Through the clean chemical separation of ruthenium fractions from air filters and subsequent high-precision measurements via mass spectrometry, the researchers determined the ratio of stable ruthenium from the nuclear source. The ruthenium isotopic ratios found in the filter are consistent with the signature of a civilian source, in particular the signature of spent nuclear fuel from a nuclear power plant. A military background (such as the production of weapons-grade plutonium) can be ruled out.

Furthermore, high-precision measurements enabled the researchers to draw further conclusions. "The isotope signature discovered in the air filter exhibits no similarities with nuclear fuels of conventional Western pressurised or boiling water reactors. Instead, it is consistent with the isotope signature of a specific type of Russian pressurised water reactors - the VVER series. Worldwide, approximately 20 reactors of this type of VVER are currently operational", specifies Professor Georg Steinhauser from Leibniz University Hannover.

PITTSBURGH Research coauthored by team from the Department of Physics and Astronomy reveals that optical fields have the ability to modify electronic properties of a solid.

The paper, "Coherent multidimensional photoelectron spectroscopy of ultrafast quasiparticle dressing by light," describes how applying intense optical fields to electrons in metals can change how electrons flow between the ions. Researchers discovered applying optical pulses in the range of 10-14 seconds to a copper surface can change its electronic properties, for example, its electron conduction or optical reflection.

The paper was coauthored by Hrvoje Petek, the R.K. Mellon Professor of Physics and Astronomy, graduate students Andi Li and Zehua Wang and Marcel Reutzel of The University of Göttingen in Germany. It was published in Nature Communications in May.

The results answer questions about the nature of the electronic properties of solids that have only recently been anticipated, said Petek.

"It has long been known that one can apply strong optical fields and change electronic properties of atoms and molecules. This is called "dressing" of the electronic structure. Solids are much more dense than atoms, so it has not been clear whether applying a strong optical field would first damage the material or dress its electronic structure. The researchers found that metals are rather robust, and judicious application of optical fields will actually cause the dressing to occur," he said.

Petek said the results open the door for new areas of research and could introduce a range of new innovations by using light to control the properties of matter.

"One can think of how to apply such fields to create new properties of solids with potential applications in conventional electronics, quantum computing, or entirely new applications where one introduces light into solids to generate entirely new properties on very short time scales," he said. "Theorists have considered that such dressing could be used to study in a laboratory how black holes evaporate."

The team will next explore how to combine several different metals, along the lines of those found in electronic devices, to determine if it's possible to dress their electronic structure without causing damage.

A low-pressure system that developed in the Philippine Sea and tracked over the central Philippines has moved into the South China Sea and become a depression. NASA's Terra satellite provided an image of the newly formed storm.

Tropical Depression Nuri (also known as 02W) formed by 5 a.m. EDT (0900 UTC) after passing over Luzon, Philippines and moved into the South China Sea. On June 12, 2020, the Moderate Resolution Imaging Spectroradiometer or MODIS instrument that flies aboard NASA's Terra satellite provided a visible image of the newly developed Nuri. The image showed a cluster of thunderstorms surrounding the center of circulation and located between the Philippines and Hainan Island, China.

The Joint Typhoon Warning Center noted, "Animated enhanced infrared satellite imagery depicts discrete clusters of deep convection flaring around the periphery of a broad low-level circulation center. A microwave image indicates a broad weakly defined low level center with formative shallow banding [of thunderstorms] wrapping into the center."

By 11 a.m. EDT (1500 UTC), it was located approximately 329 nautical miles south-southeast of Hong Kong, China, near latitude 17.9 degrees north and longitude 116.8 degrees east. Maximum sustained winds were 30 knots (34.5 mph/55.5 kph) and strengthening is forecast. Nuri has tracked west northwestward at 13 knots (15 mph/24 kph).

The storm is forecast to make landfall to the southwest of Hong Kong, China on June 14.

Test samples collected by people who swabbed their own nasal passages yielded results for the COVID-19 virus that were as accurate as samples collected by a health care worker, according to a small study by researchers at the Stanford University School of Medicine.

The study was published June 12 in the Journal of the American Medical Association.

The 30 study participants, who previously had tested positive for COVID-19, collected their own samples at a drive-through testing site after watching a short video animation and reading a one-page document instructing them how to perform the swab. The nasal swab for the study is more comfortable to use than the long nasopharyngeal swab currently used to collect samples from the back of the nasal cavity.

Allowing people who suspect they may have COVID-19 to collect their own sample has many advantages. Sample-collection kits could be widely distributed, allowing more people to be tested. Those using the kit wouldn't have to travel to a testing site, negating the risk of transmission to health care workers and others with whom they interact in transit. Self-collection would also conserve supplies of personal protective equipment used by health care workers.

"There is an urgent need to increase our testing capacity to slow the overall spread of the virus," said Yvonne Maldonado, MD, professor of pediatric infectious diseases and of health research and policy. "A sample collection procedure that can safely and easily be performed by the patient in their own car or at home could reduce the exposure of health care workers and also allow many more people to submit samples for testing."

Maldonado is the senior author of the study, which was conducted in collaboration with Andra L. Blomkalns, MD, the Redlich Family Professor and professor and chair of emergency medicine, and Prasanthi Govindarajan, MD, associate professor of emergency medicine; senior research data analyst Jonathan Altamirano is the lead author.

Providing nasal swab instructions

The study participants had tested positive in March at Stanford Health Care for the virus that causes COVID-19. Maldonado and her team contacted each of them by phone at home and provided them with written instructions and a short video about how to collect a nasal swab.

They were asked to return to Stanford Health Care for drive-through testing. At that visit, they collected their own specimen by applying a nasal swab to both nostrils. Then, a physician collected two additional samples using a nasal swab and a swab applied to the back of the throat and the tonsils. All three samples were tested for the presence of the virus at the Stanford Clinical Virology Laboratory.

Of the 30 participants, 29 received identical results -- either positive or negative for the presence of the virus -- for the three samples. Eleven of the participants were positive, and 18 were negative. One person's self-collected swab at the drive-through site revealed the presence of the virus, whereas the two swabs collected by the physician tested negative.

The researchers were also interested in learning how long an infected person would test positive for the virus after they first experienced symptoms.

Twenty-three participants reported that they first experienced symptoms between four and 37 days prior to returning for the drive-through test. (The timing of symptom onset was unavailable for seven of the participants.) Of the 12 people who returned within two weeks after symptoms began, seven tested positive; of the 11 people who returned for testing more than two weeks after symptom onset, only two tested positive.

"It is critical for us to understand how long an infected person may remain infectious and what the pattern of transmission might be within their household," Maldonado said. "This information would help public health workers craft guidelines as to how long a person with COVID-19 should remain quarantined and when it is likely to be safe to interact again with family members and co-workers. Understanding the timeline of viral shedding will be particularly important for previously infected health care workers who are needed to care for other COVID-19 patients."

Researchers from North Carolina State University have developed a fundamentally new approach to DNA data storage systems, giving users the ability to read or modify data files without destroying them and making the systems easier to scale up for practical use.

"Most of the existing DNA data storage systems rely on polymerase chain reaction (PCR) to access stored files, which is very efficient at copying information but presents some significant challenges," says Albert Keung, co-corresponding author of a paper on the work. "We've developed a system called Dynamic Operations and Reusable Information Storage, or DORIS, that doesn't rely on PCR. That has helped us address some of the key obstacles facing practical implementation of DNA data storage technologies." Keung is an assistant professor of chemical and biomolecular engineering at NC State.

DNA data storage systems have the potential to hold orders of magnitude more information than existing systems of comparable size. However, existing technologies have struggled to address a range of concerns related to practical implementation.

Current systems rely on sequences of DNA called primer-binding sequences that are added to the ends of DNA strands that store information. In short, the primer-binding sequence of DNA serves as a file name. When you want a given file, you retrieve the strands of DNA bearing that sequence.

Many of the practical barriers to DNA data storage technologies revolve around the use of PCR to retrieve stored data. Systems that rely on PCR have to drastically raise and lower the temperature of the stored genetic material in order to rip the double-stranded DNA apart and reveal the primer-binding sequence. This results in all of the DNA - the primer-binding sequences and the data-storage sequences - swimming free in a kind of genetic soup. Existing technologies can then sort through the soup to find, retrieve and copy the relevant DNA using PCR. The temperature swings are problematic for developing practical technologies, and the PCR technique itself gradually consumes - or uses up - the original version of the file that is being retrieved.

DORIS takes a different approach. Instead of using double-stranded DNA as a primer-binding sequence, DORIS uses an "overhang" that consists of a single-strand of DNA - like a tail that streams behind the double-stranded DNA that actually stores data. While traditional techniques required temperature fluctuations to rip open the DNA in order to find the relevant primer-binding sequences, using a single-stranded overhang means that DORIS can find the appropriate primer-binding sequences without disturbing the double-stranded DNA.

"In other words, DORIS can work at room temperature, making it much more feasible to develop DNA data management technologies that are viable in real-world scenarios," says James Tuck, co-corresponding author of the paper and a professor of electrical and computer engineering at NC State.

The other benefit of not having to rip apart the DNA strands is that the DNA sequence in the overhang can be the same as a sequence found in the double-stranded region of the data file itself. That's difficult to achieve in PCR-based systems without sacrificing information density - because the system wouldn't be able to differentiate between primer-binding sequences and data-storage sequences.

"DORIS allows us to significantly increase the information density of the system, and also makes it easier to scale up to handle really large databases," says Kevin Lin, first author of the paper and a Ph.D. student at NC State.

And once DORIS has identified the correct DNA sequence, it doesn't rely on PCR to make copies. Instead, DORIS transcribes the DNA to RNA, which is then reverse-transcribed back into DNA which the data-storage system can read. In other words, DORIS doesn't have to consume the original file in order to read it.

The single-stranded overhangs can also be modified, allowing users to rename files, delete files or "lock" them - effectively making them invisible to other users.

"We've developed a functional prototype of DORIS, so we know it works," Keung says. "We're now interested in scaling it up, speeding it up and putting it into a device that automates the process - making it user friendly."

Scientists at St. Jude Children's Research Hospital, UCSF Benioff Children's Hospitals and Baylor College of Medicine are investigating how to best treat hemophagocytic lymphohistiocytosis (HLH), a rare immune disorder. Their work, appearing as an advance online publication today in Blood, details how combining two drugs may be a good treatment for HLH.

"For the last 20 years, treatment for HLH has remained a combination of the drugs dexamethasone and etoposide," said co-senior author Kim Nichols, M.D., of St. Jude Oncology. "But we know that many patients either do not respond to this regimen or later relapse, so we dug into the biology to come up with a different treatment strategy."

In HLH, the immune system becomes over-activated and immune cells produce cytokines, which are chemicals released into the bloodstream to try to recruit and activate additional immune cells. Patients with HLH can experience a cytokine storm syndrome where so many cytokines start circulating that they feed upon themselves to further drive immune activation.

There are several cytokines elevated in HLH patients. Some of these cytokines bind to receptors on the cell's surface. When that happens, those receptors recruit and activate Janus kinases (JAKs), which are signaling molecules.

A new strategy emerges

Previous research by Nichols revealed that the JAK1/2 inhibitor ruxolitinib had a positive effect in mouse models of HLH. By inhibiting the JAK/STAT pathway, ruxolitinib interferes with cytokine communication. Nichols and her team wanted to better understand the mechanism behind this and investigate whether any particular cytokine was more important to inhibit.

"We wanted to know whether any of the cytokines that are elevated in HLH contribute to dexamethasone resistance, and if so, whether blocking the signaling of these cytokines might reverse treatment resistance," said co-first author Katherine Verbist, Ph.D., of St. Jude Oncology.

The researchers' work in cell lines and mouse models determined that of all the cytokines elevated in HLH, interleukin-2 is critically important to driving resistance to dexamethasone. Interleukin-2 is produced by activated T cells and promotes their survival. The researchers showed that by blocking the effect of interleukin-2, the T cells can be re-sensitized to and destroyed by dexamethasone.

The researchers found that the combination of dexamethasone and ruxolitinib was significantly more effective in quelling the signs of HLH in animal models compared to treatment with either drug alone. The study provides additional evidence to support testing the combination through a clinical trial.

"We were able to take lessons learned from our studies of pediatric leukemia, which is also often treated with dexamethasone, and apply them to our study of cytokines in HLH," said co-senior author Michelle Hermiston, M.D., Ph.D., of UCSF Benioff Children's Hospitals. "Like in leukemia, we were able to show that a specific cytokine signaling through the JAK pathway could promote resistance to treatment."

When drought reshuffles the green-up of habitats that mule deer migrate across, it dramatically shortens the annual foraging bonanza they rely on.

That is the main finding of a new University of Wyoming study, which shows the benefits of migration are likely to decrease for mule deer and other migratory herbivores as drought becomes more common due to ongoing climate change.

Drought reduces the availability of key food resources by shortening the duration of spring green-up -- and altering the progression of the "green wave" across the landscape.

The study was conducted by a team of researchers working with lead author Ellen Aikens, a 2019 graduate of the Wyoming Cooperative Fish and Wildlife Research Unit at UW. The paper was published this week in Global Change Biology, a leading journal documenting the biological effects of global change.

"This research shows that climate change can alter the underlying distribution of food resources by compressing the time when optimal forage is available, which reduces the benefit of migration," Aikens says. "This work highlights an emerging threat to migratory mule deer and likely many other migratory species."

Aikens' analysis combined 19 years of drought data going back to 2001, with a 2013-15 GPS dataset of mule deer migrations in the Wyoming Range.

In a wet year, the study found that mule deer have access to newly sprouted springtime plants during an extended period, up to 120 days. That's a full four months when snow is melting, and runoff is saturating the soil and causing forage plants such as sticky purple geranium to emerge.

Deer get a significant portion of their forage benefit for the entire year by following this green wave of plants, which, in wet years, progresses in an orderly fashion from low-elevation winter ranges to summer ranges in the high mountains.

Previous work by Aikens has shown that mule deer are experts at "surfing the green wave" across the landscape. Their movements allow them to always be in the right place at the right time to consume plants at their peak green-up, when they are protein-rich and easy to digest.

Access to green-up provides mule deer their best chance to recover from harsh winters and to replenish lost body fat. They need sufficient fat to rear young and survive the coming winter.

In dry years, the green wave sweeps across the landscape in about half the time, roughly 60 days, the researchers found.

In essence, the good times don't last as long.

Although deer surf these altered green waves as best they can, they only have half the time -- only two months -- to eat plants at peak forage quality.

The researchers found that drought also makes for more patchy migration routes, where the green-up does not occur in sequence from low to high elevation. Patterns of green-up in dry years were quicker, less wave-like and, consequently, provided less of a foraging benefit to migrating mule deer.

One thing that didn't change in drought years was the remarkable ability of deer to move and track plants at the highest nutritional value. Deer "surfed" right along with these same peak waves of plant growth in wet years and in dry years. Even in drought, there was no "trophic mismatch," a situation where migration timing is mismatched with food resources.

Though researchers hoped to find that some migration routes were buffered from drought effects -- perhaps those that traverse shady north-facing slopes -- they found such routes did not exist. Instead, the best migration routes that produced the most abundant forage and the longest duration of green-up in wet years also were the most severely impacted by drought.

"This is a globally important study, because the findings ought to be relevant across the temperate landscapes of North America and Europe," says Matthew Kauffman, director of the Wyoming Cooperative Fish and Wildlife Research Unit and a co-author of the study.

"This study has revealed an underappreciated mechanism by which climate change is altering green-up and making migration less profitable for ungulates," Kauffman says. "We are identifying a new threat for migrating ungulates, which will likely worsen as climate change continues."

Researchers at Carnegie Mellon University have developed a method for self-assembling nanostructures with gamma-modified peptide nucleic acid (γPNA), a synthetic mimic of DNA. The process has the potential to impact nanomanufacturing as well as future biomedical technologies like targeted diagnostics and drug delivery.

Published this week in Nature Communications, the work introduces a science of γPNA nanotechnology that enables self-assembly in organic solvent solutions, the harsh environments used in peptide and polymer synthesis. This holds promise for nanofabrication and nanosensing.

The research team, led by Assistant Professor of Mechanical Engineering Rebecca Taylor, reported that γPNA can form nanofibers in organic solvent solutions that can grow up to 11 microns in length (more than 1000 times longer than their width). These represent the first complex, all-PNA nanostructures to be formed in organic solvents.

Taylor, who heads the heads the Microsystems and MechanoBiology Lab at Carnegie Mellon, wants to leverage PNA's "superpowers." In addition to its higher thermal stability, γPNA retains the ability to bind to other nucleic acids in organic solvent mixtures that would typically destabilize structural DNA nanotechnology. This means that they can form nanostructures in solvent environments that prevent formation of DNA-based nanostructures.

Another property of γPNA is that it is less twisted than the double helix of DNA. The result of this difference is that the "rules" for designing PNA-based nanostructures are different than the rules for designing structural DNA nanotechnology.

"As mechanical engineers, we were prepared for the challenge of solving a structural design problem, Taylor said. "Due to the unusual helical twist, we had to come up with a new approach for weaving these pieces together."

Because the researchers in Taylor's lab seek to use dynamic shape change in their nanostructures, they were intrigued to discover that morphological changes - like stiffening or unraveling - occurred when they incorporated DNA into the γPNA nanostructures.

Other interesting characteristics that the researchers want to explore further include solubility in water and aggregation. In water, these current nanofibers tend to clump together. In organic solvent mixtures, the Taylor lab has demonstrated that they can control whether or not structures aggregate, and Taylor believes that the aggregation is a feature that can be leveraged.

"These nanofibers follow the Watson-Crick binding rules of DNA, but they appear to act more and more like peptides and proteins as PNA structures grow in size and complexity. DNA structures repel each other, but these new materials do not, and potentially we can leverage this for creating responsive surface coatings," said Taylor.

The synthetic γPNA molecule has been perceived as a simple DNA mimic having desirable properties such as high biostability and strong affinity for complementary nucleic acids.

"We believe through this work, we could additionally adjust this perception by highlighting the ability of γPNA to act as both - as a peptide mimic because of its pseudopeptide backbone and as a DNA mimic because of its sequence complementarity. This change in perception could allow us to understand the multiple identities this molecule can leverage in the world of PNA nanostructure design," said Sriram Kumar, a mechanical engineering Ph.D. candidate and the first author on the paper.

Although PNA is already being used in groundbreaking gene therapy applications, there is still a lot to learn about this synthetic material's potential. If complex PNA nanostructures can someday be formed in aqueous solutions, Taylor's team hopes that additional applications will include enzyme-resistant nanomachines including biosensors, diagnostics, and nanorobots.

"PNA-peptide hybrids will create a whole new toolkit for scientists," Taylor said.

The researchers used custom gamma modifications to PNA that were developed by Danith Ly's lab at Carnegie Mellon. Future work will investigate left-handed γPNAs in the nanomanufacturing process. For future biomedical applications, left-handed structures would be of particular interest because they would not pose a risk of binding to cellular DNA.

Advances in transportation technology -- e-scooters and bike share, Lyft & Uber, and autonomous vehicles -- are beginning to have profound impacts on cities. New mobility is changing not only how we travel, but also urban form and development itself. In the near future, we can expect differences in what public transit looks like, the layout of cities, and the places we spend our time. In turn, these changes will likely have additional effects on land use, street design, parking, housing, equity, and municipal finance. Will cities be ready to meet these changes? Rather than be swept along in the wake of change, how can communities intelligently guide urban density, sprawl, vitality, economics and sustainability?

The latest report from the National Institute for Transportation and Communities (NITC), by Marc Schlossberg and Heather Brinton of the University of Oregon, is a guide for city staff and leadership on adopting local policy and code to respond to the emergence of these technologies and encourage their responsible use. For cities that are serious about climate change and social equity, these technological changes have enormous potential to address those issues - but it won't happen automatically. 

HOW CAN CITY STAFF USE THIS RESEARCH?

The final report "Matching the Speed of Technology with the Speed of Local Government: Developing Codes and Policies Related to the Possible Impacts of New Mobility on Cities" ( PDF) offers tools for any American community that is interested in updating local policy and code to meet the transportation realities of today. The report draws on existing best practices and presents new code language that can be used or adapted by local jurisdictions. Sections 5 and 6 of the final report offer code provisions for regulation of the built environment -- including curb management and off-street parking -- and regulation of new travel modes. These tools give flexibility to local leaders, allowing them to respond quickly and with intention to anticipated changes to the public right of way and urban land use.

LET COMMUNITY GOALS DRIVE MOBILITY DECISIONS

The first step for any city is to identify and articulate the community's goals and values for its public spaces--such as advancing equity, sustainability, community revitalization, and/or carbon reduction. Once those are defined, local governments can use these goals to guide how new technologies are regulated. For example, goals around equity can guide how shared mobility is deployed in the city, and climate goals may support reduction in TNC VMT, or electrification of fleets.The research identified eight key principles for cities to use as they refine their regulatory frameworks:Identify city goals, as stated above;Create a clear modal hierarchy within the city's priorities for its transportation modes;Require citywide compliance with city transportation policy;Identify the purpose of the right-of-way as public space instead of the purview of automobiles;Identify use of the specific functions of street types and zones;Utilize overlay zones to provide flexibility to adopt different management priorities without systemic code changes;Increase funding for non-automobile infrastructure and decrease funding for automobile infrastructure; andRequire data sharing as an essential part of new mobility infrastructure.

STRONGER POLICY RECOMMENDATIONS

Section 7 of the final report offers stronger policy suggestions that can help cities leapfrog into new patterns of development and decision making. For example, cities may wish to: 

Explicitly describe the right of wayDesignate 'curb zones' or 'curb lanes'
Add nimble flexibility to curb zone & other parking decisions 
Regulate bicycles and micromobility devices as one transportation mode
Rename bike lanes to be inclusive of other micromobility uses
Apply micromobility regulatory principles to all privately-owned vehicles
Apply TNC regulatory principles to all privately-owned vehicles
Prioritize pooled-ride for-hire vehicles
Regulate TNCs to meet sustainability goals

Accelerating and expanding the deployment of new technologies by actively promoting innovations that enhance safety and performance is a key goal of the U.S. DOT, and this research helps meet that goal by helping local governments steer new technology in the right direction.

CURRENT CRISIS: COVID-19 IMPACTS ON TRANSPORTATION

Immediately following the completion of this report, the COVID-19 pandemic began spreading, causing unprecedented  disruptions to people's mobility. Individual vehicle use and public transit experienced sharp declines at first. Use of individual vehicles are gradually rising, but transit continues to face lower ridership numbers. At first, bike share and e-scooter share systems experienced a large increase in ridership, and then a significant decline as public health warnings about the spread of COVID-19 became more urgent. Individually owned biking, however, has seen a significant increase and rates of walking, as streets have quieted with lower car use, are also going up. The public right of way - the street - has emerged as an important tool of local municipalities to address health, social, and economic challenges during a pandemic. Understanding how local policy and code can respond to disruptions (both short-term and long-term) can achieve better health, social, economic, and environmental outcomes as consistent with local values. So, while this report was completed just before the COVID-19 outbreak, its lessons and insights about matching the speed of local policy change with the speed of societal change is more important than ever.

Portland, Ore. (June 12, 2020) -- The Corrona® Psoriasis Registry, a joint collaboration between the National Psoriasis Foundation, NPF, and Corrona, LLC, the leading sponsor of registries in immune-mediated diseases, announces that studies from the registry will be presented at the American Academy of Dermatology Virtual Meeting Experience (AAD VMX) taking place June 12-14, 2020.

A total of 7 posters were accepted that highlight the breadth of real-world evidence collected in the Corrona Psoriasis Registry since its launch in 2015. The posters include studies of real-world prescribing patterns and regional variations, and in-depth characterization studies of patients prescribed recently approved biologic drugs. In addition, longitudinal studies reporting on improvements in patient reported outcomes such as quality of life and work productivity for biologic-treated patients will also be presented.

In support of the registry's objective to serve as the gold standard for real-world evidence generation in psoriasis on drug effectiveness and safety, Corrona also announces efforts to collect data on COVID-19 outcomes in patients enrolled in the registry.

"The Corrona registry has grown rapidly, enrolling over 11,000 patients in five years across 238 sites. It serves as a robust data source for understanding the impact of COVID-19 on our psoriasis and psoriatic arthritis patients, including the safety of advanced therapies. The outcome data collected for COVID-19 cases combined with the detailed treatment, comorbidity, and disease severity data captured by the registry will be useful to support characterization of risk among affected patients," noted Dr. Mark Lebwohl, professor and chairman, Kimberly and Eric J. Waldman Department of Dermatology, Icahn School of Medicine at Mount Sinai, chairman emeritus of the NPF Medical Board, and scientific co-director of the registry.

"The studies presented at this scientific meeting highlight the clinical depth and impact of real-world evidence studies generated by fit-for-purpose registries. We are incredibly grateful for our patients, investigators, and sites that directly contribute to generating timely clinical insights for the scientific community," said Dr. Jeff Greenberg, chief medical officer of Corrona.

Following is a list of accepted posters featuring Corrona Psoriasis Registry data:

-- Geographic variations in the use of biologic therapy for psoriasis in the Corrona Psoriasis Registry: A pilot analysis of 2018 data. Enos C, O'Connell K, Harrison R, McLean RR, Dube B, Van Voorhees AS.

-- Characterization of non-responders to IL-17 inhibitors in moderate-to-severe psoriasis patients enrolled in the Corrona Psoriasis Registry. Wu JJ, Lin T, Kearns DG, Chat VS, Litman HJ, Dube B, McLean RR.

-- Real-world disease severity of patients with psoriasis initiating brodalumab: findings from the Corrona Psoriasis Registry. Kimmel G, Lebwohl M, Gordon K, vonCsiky-Sessoms S, Cronin A, Jacobson A.

-- Real-World characteristics of patients with psoriasis initiating brodalumab: findings from the Corrona Psoriasis Registry. Armstrong A, Strober B, Drew S, Cronin A, Jacobson A.

-- Impact of guselkumab on quality of life and work productivity outcomes among patients with plaque psoriasis in the Corrona Psoriasis Registry. Armstrong AW, Duffin KC, Teeple A, Fitzgerald T, Rowland K, Uy JP, Gonzalez-Rivera T, McLean RR, Guo L, Shan Y, Van Voorhees AS.

-- Outcomes in ixekizumab initiators by prior biologic status in the Corrona Psoriasis Registry. Van Voorhees AS, Harrison RW, Burge R, Malatestinic WN, Zhu B, Atiya B, Murage MJ, McLean RR, Crabtree M, O'Brien J, Lockshin B.

-- Secukinumab significantly improves clinical and patient-reported outcomes up to 18 months of follow-up: real-world evidence from a US Psoriasis Registry. Bagel J, Behl A, Litman HJ, Medeiros RA, Guo N, Lebwohl M, Strober BE.

To learn more about the Corrona Psoriasis Registry, visit: https://www.corrona.org/registries/psoriasis.

Corrona provides real world evidence through syndicated registry data and analysis services, helping biopharmaceutical companies demonstrate the value of their products to clinicians, patients, payers, and regulators. Corrona operates six major autoimmune registries across the US, Canada and Japan, collecting data from over 500 participating investigator sites. In addition to supporting hundreds of manuscripts and abstracts, Corrona has supported post approval safety commitments for multiple advanced therapies approved for autoimmune conditions. Corrona is headquartered in Waltham, MA. Through its subsidiary Health iQ, Corrona has access to a broad range of UK and international data sets across primary and secondary care, as well as deep relationships with the NHS, Public Health England, and leading UK academic institutions. The Company's HealthiVibe business complements and strengthens Corrona's strong presence in disease registries by providing market-leading expertise in supporting innovative, evidence-based patient engagement initiatives across the product lifecycle. Learn more at http://www.corrona.org, or via email at info@corrona.org.