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Scientists at the Centro Nacional de Investigaciones Cardiovasculares (CNIC) have discovered that neutrophils, the most abundant cells of the innate immune system, have many more functions in the body than previously thought. This finding suggests possible new treatments for many diseases, including cancer.

In a study published in the journal Cell, the research team demonstrate that neutrophils acquire new characteristics when they arrive in a tissue and that these specialized functions help to maintain organ health.

The cells of the immune system defend the body against external pathogens, providing protection against microorganisms that cause disease, while also helping to repair injuries such as wounds and bone fractures.

The different types of immune cells include lymphocytes and the cells of the innate immune system. "Lymphocytes produce antibodies or receptors that specifically target viruses or bacteria to build immunity against these pathogens. The cells of the innate immune system, on the other hand, provide a faster but nonspecific response that can sometimes trigger uncontrolled inflammation, as happens in the lungs of patients with severe COVID-19, for example," explained Dr Andrés Hidalgo, lead investigator on the study.

Every day, the marrow inside our bones produces immense quantities of neutrophils. These cells then enter the bloodstream and are distributed to almost all tissues of the body. Neutrophils have a short lifespan, living for less than 24 hours. For this reason, scientists believed that these cells had a very limited capacity to adapt to their environment and adopt new functions.

But in the Cell study, "we found that when neutrophils leave the circulation and migrate into tissues they acquire new, previously unknown properties", said Dr Hidalgo.

"What is fascinating is that neutrophils appear to acquire functions useful to the specific tissues in each organ. For example, we found that neutrophils in the lung acquire the ability to contribute to the formation of blood vessels, whereas neutrophils in the skin help to maintain the integrity of the cutaneous epithelium. This ability to change cell properties was identified in healthy individuals, which suggests that neutrophils participate in a great variety of normal functions in the body and are not limited to combating infection," said Dr Hidalgo.

Historically, scientists have viewed the innate immune system as a collection of cells with fixed, nonspecific responses. But in recent years, some researchers have found evidence that these cells can acquire highly specific functions. According to co-lead investigator and first author Iván Ballesteros, "this is particularly exciting because if we can define the mechanisms that control how these cells acquire new functions we will be able to design new treatments to exploit this plasticity of neutrophil responses for the benefit of patients."

In cancer, for example, tumors need to promote the generation of new blood vessels in order to grow. To block tumor growth, scientists therefore need to understand how tumors co-opt the plasticity of the immune system to promote the formation of these blood vessels. For Ballesteros, a major point of interest in the new study is that "the results show that neutrophil immune plasticity is not dependent on the presence of disease, suggesting that it has beneficial functions that sometimes get short-circuited in pathological settings."

Previous studies had already identified neutrophil heterogeneity in several diseases. Indeed, these neutrophil changes are prognostic markers in cancer and help to regenerate blood cells after bone marrow transplantation.

However, the mechanisms that establish neutrophil hyperplasticity are poorly understood, and the new results are a crucial step towards filling this knowledge gap. "Essentially, what we have demonstrated is that neutrophils, despite their sort lifespan, can change their function and that they do this when they enter tissues. The identification of these adaptations allows a better understanding of the roles of different immune cells in disease," explained Andrea Rubio, joint first author on the study and a bioinformatician at the CNIC.

A strategy for giving intermittent, high doses of the anti-cancer drug sunitinib is well-tolerated by patients with advanced cancer and increases concentrations of the drug in tumours, which is associated with improved survival, according to research to be presented at the 32nd EORTC-NCI-AACR [1] Symposium on Molecular Targets and Cancer Therapeutics, which is taking place online.

Patients with a range of advanced cancers, but particularly kidney cancer, neuroendocrine tumours in the pancreas and sarcomas in the digestive system (gastro-intestinal stromal tumours), can be treated with sunitinib - a drug that inhibits receptors on the surface of cancer cells called tyrosine kinases (TKs), which play an important role in the development and progression of tumours. It is currently registered at a dose of 50mg once a day. Although many patients respond well at first to the drug, they eventually develop resistance to it. Giving large daily doses of the drug in order to achieve higher concentrations in the tumour itself is also limited by serious toxic side-effects.

Dr Sophie Gerritse, from the Department of Medical Oncology at Radboud University Medical Center, Nijmegen, The Netherlands, said: "Unfortunately, durable clinical benefit from sunitinib is hampered by intrinsic and acquired drug resistance in all patients. We need to exploit the full potential of sunitinib and other TK inhibitors in order to increase their efficacy in cancers where they are already registered for use and to repurpose them for other types of cancer.

"We have already shown in a phase I trial that giving high dose intermittent sunitinib 300mg once a week or 700mg once every two weeks to patients with advanced tumours was safe, resulted in higher peak concentrations of the drug in blood plasma samples, compared with regular dosing, and it had promising clinical benefit. [2]

"In this most recent research, we evaluated whether high concentrations of sunitinib in the blood led to higher concentrations in the tumour and what the effect on patient outcomes might be."

Dr Gerritse and her colleagues collected and analysed blood samples from 82 patients in the phase I trial that was conducted at the Amsterdam University Medical Center between 2014 and 2018. The blood samples were taken before treatment with sunitinib and then several times after treatment began. On the seventeenth day after the start of treatment, they also took skin biopsies from 36 of these patients, and tumour biopsies from 22 out of the 36 patients. The analyses were performed in collaboration with Dr Nielka van Erp, also from Radboud.

"There are five important findings from this trial," said Dr Gerritse. "The maximum tolerated dose for sunitinib is 300mg once a week or 700 mg once every two weeks, with adverse effects comparable to the normal schedule of 50mg daily. With this schedule, we were able to create very high peaks of sunitinib concentrations in blood samples - up to 18 times higher than with daily doses of 50mg. We were also able to achieve very high concentrations of sunitinib in the tumour. However, we found that the maximum concentrations of sunitinib in blood plasma underestimated concentrations in the tumour by a factor of 19. In fact, there was no relationship between concentrations in the blood and skin with concentrations in the tumour.

"In this small group of 22 patients, we found a statistically significant relationship between the tumour concentrations achieved and overall survival and length of time before the cancer progressed. This is the first time it has been shown that high concentrations of sunitinib in the tumour, in contrast to concentrations in the blood, is associated with an improved clinical outcome for patients treated with high-dose intermittent sunitinib. This interesting finding has to be validated further in large clinical trials.

"Our findings have the potential to change the dose and schedule of multi-targeting TK inhibitors, like sunitinib, and thereby enhance their clinical efficacy. An important result in this study is that the concentration of sunitinib in the blood underestimates the corresponding concentration of the drug in the tumour."

Nearly half of the patients in this phase I trial had bowel cancer; other cancers included bile duct, breast, hormone and nervous system, pancreas, liver, head and neck, and ovary. Based on these results, the principal investigator of the study, Professor Henk Verheul from Radboud, has initiated two further phase II/III clinical trials: one for patients with advanced bowel cancer who will be dosed with 700mg sunitinib once every two weeks versus trifluridine/tipiracil (TAS-102), and one for patients with advanced, recurrent glioblastoma who will be dosed with 700mg sunitinib once every two weeks versus standard treatment with lomustine [3]. They are also researching other, potentially interesting TK inhibitors in the lab, using the intermittent high dose strategy.

Professor Emiliano Calvo is co-chair of the EORTC-NCI-AACR Symposium on behalf of the EORTC; he is Director of START Madrid Group in Madrid, Spain, and Director of Clinical Research at the START Madrid-Centro Integral Oncológico Clara Campal hospital in Madrid and he was not involved in the research. He commented: "The finding from this research that sunitinib concentrations in the blood do not correlate with concentrations in the tumour, and that these higher tumour drug concentrations are associated with clinical outcome, is fascinating and important. It makes a lot of biological sense, as, in the end, we are seeing what happens in the tumour, which is one step closer to the therapeutic target, than when we see blood drug concentration levels or, even further away, the drug dose that the patient is taking by mouth.

"It has the potential to transform the use of TK inhibitors and possibly other drugs as well, because when we speak about 'precision oncology', it is not only about the right drug for the specific patient and tumour but also choosing the right dose for each patient through methods like these. It would be interesting to know if this effect is also seen with other classes of anti-cancer drugs and, of course, to validate these data prospectively.

"The finding that intermittent high dose of sunitinib increased concentrations in the tumours and was associated with improved survival is also important as patients with these types of advanced cancers are urgently in need of optimised treatments, as sometimes the tumour progresses not due to primary resistance but, instead, due to insufficient drug levels in the patient to fight against his or her cancer."

Secondary forests play an important part in carbon capture because they tend to absorb a larger amount of carbon than they lose to the atmosphere. However, the size and average age of these often abandoned areas where vegetation grows back were unknown until now. In a study recently published in the journal Scientific Data, a group led by two researchers at Brazil’s National Institute for Space Research (INPE) quantified these variables and found that the estimated carbon uptake by secondary forests throughout Brazil offset 12% of the carbon emissions due to deforestation in the Brazilian Amazon alone in a 33-year period.

The study was supported by FAPESP via two projects. The first project began in 2017 and is led by Luciana Vanni Gatti. The second began in 2019 and is led by Luiz Eduardo Oliveira e Cruz de Aragão.

“The capacity of secondary forests to absorb carbon is known from studies that involve monitoring of areas in the field. Their average net carbon uptake rate in Neotropical regions is 11 times that of old-growth forests. However, the long-term dynamics of secondary forests in Brazil and worldwide is poorly understood,” said Aragão, one of the authors of the study, which was conducted at INPE as part of Celso H. L Silva Júnior’s PhD research.

This knowledge is fundamental to enable Brazil to achieve its Nationally Determined Contribution targets under the 2015 Paris Agreement. These include the restoration and reforestation of 12 million hectares of forest by 2030, he noted.

Age and size of secondary forests in each biome

The study calculated the increment in secondary forests that previously had anthropic cover (plantation, pasture, urban infrastructure, or mining) and their age, biome by biome. According to Aragão, secondary forest growth is not linear and correlates with age, so that it is important to establish the age of a forest in order to estimate its carbon uptake.

The data showed that a total of 262,791 square kilometers (km²) of secondary forests were recovered in Brazil between 1986 and 2018. This corresponds to 59% of the old-growth forest area cleared in the Brazilian Amazon between 1988 and 2019.

“The restored forests were located all over Brazil with the smallest proportion in the Pantanal [wetlands in the Center-West], accounting for 0.43% [1,120 km²] of the total mapped area. The largest proportion was in the Amazon, with 56.61% [148,764 km²]. The Caatinga [the semi-arid biome in the Northeast] accounted for 2.32% [6,106 km²] of the total area and had the youngest secondary forests – over 50% were between one and six years old,” Aragão said.

The Atlantic Rainforest ranked second by size of restored areas, with 70,218 km² (or 26.72% of the total), and had the oldest – over half were between and 12 years old.

Four steps

The researchers used the method implemented by the Google Earth Engine (GEE) and a time series of data from the Brazilian Annual Land-Use and Land-Cover Mapping Project (MapBiomas) starting in 1986. They created 131 reference maps for the 33 years between 1986 and 2018 covering secondary forests divided by biome. The raw material is available at doi.org/10.5281/zenodo.3928660 and github.com/celsohlsj/gee_brazil_sv.

Having excluded wetland areas, they executed the methodology in four steps. First, the 34 maps from MapBiomas were reclassified into binary maps, in which pixels representing forest areas were assigned the value “1” and pixels corresponding to other land uses and types of cover were assigned the value “0”. Mangroves and planted forests were excluded. Each pixel corresponded to an area of 30 meters by 30 meters.

Next, the increment in secondary forest areas was measured using the maps produced in the previous stage, pixel by pixel. “We established that secondary forests occurred when a pixel classified as anthropic cover in a given year was replaced by a pixel corresponding to forest cover in the following year,” Aragão said.

In the third stage, the researchers generated 33 more maps showing the size of secondary forests year by year. “To produce the map for 1987, for example, we added the secondary forest increment map for 1986 obtained in stage 2 to the increment map for 1987. The result was a map containing all secondary forest pixels for 1986 and 1987,” Aragão explained. “Given that the sequential sum of these maps resulted in pixels with values higher than ‘1’, to create binary maps showing the size of secondary forests in each year we reclassified the annual maps by assigning a weight of ‘1’ to pixels with values between 2 and 33, which corresponded to forest area size proper year by year. Pixels with the value ‘0’ were left unchanged.”

Finally, it remained to calculate the age of the secondary forests mapped. To do this they added together the annual secondary forest increment maps obtained in the previous stage. “We added maps in this manner until we obtained a map showing the age of secondary forest areas in 2018,” Aragão said, adding that the next step will be to establish secondary forest growth as a function of age. “We’ve submitted an article in which we describe this quantification.”

Emissions

Potential net carbon uptake by secondary forests in each Brazilian biome between 1986 and 2018 was calculated pixel by pixel, assuming an average linear net carbon uptake rate of 3.05 Mg C ha−1 yr−1 (megagrams per hectare per year) during the first 20 years of secondary forest succession, regardless of age. Zero net uptake was assumed after 20 years.

The Pantanal contributed least, accounting for 0.42% of secondary forest carbon uptake between 1986 and 2018. The Amazon biome contributed most, accounting for 52.21%. The study concluded that the estimated carbon uptake by all secondary forests in Brazil offset 12% of carbon emissions from deforestation in the Brazilian Amazon alone in the period 1988-2018.

For Aragão, however, land use must continue to change, especially in the Amazon. “The aggregate area of secondary forest can be seen not to have increased very much in proportion to the deforested area,” he said. “This is due to land use, especially in the Amazon. We have to change land use. Deforestation means loss of the other benefits of natural forests, which play an indispensable role in the hydrologic cycle and in the maintenance of biodiversity – far more so than secondary forest. They’re also more resilient to climate change.”

The new data can help Brazilian policymakers decide on ways to protect biodiversity and plan the use and protection of secondary forests. “They aren’t protected and provide important services. In fact, they typically suffer the most conversion in the land use cycle in the Amazon. Now we can see why they so urgently deserve to be protected,” Aragão said.

The article “Benchmark maps of 33 years of secondary forest age for Brazil” can be read at: www.nature.com/articles/s41597-020-00600-4.

Journal

Scientific Data

DOI

10.1038/s41597-020-00600-4

There is much debate surrounding the age of the Clovis -- a prehistoric culture named for stone tools found near Clovis, New Mexico in the early 1930s -- who once occupied North America during the end of the last Ice Age. New testing of bones and artifacts show that Clovis tools were made only during a brief, 300-year period from 13,050 to 12,750 years ago.

Michael Waters, distinguished professor of anthropology and director of the Center for the Study of the First Americans, along with Texas A&M anthropologist David Carlson and Thomas Stafford of Stafford Research in Colorado, have had their new work published in the current issue of Science Advances.

The team used the radiocarbon method to date bone, charcoal and carbonized plant remains from 10 known Clovis sites in South Dakota, Colorado, Pennsylvania, Ohio, Virginia, Montana and two sites in Oklahoma and Wyoming. An analysis of the dates showed that people made and used the iconic Clovis spear-point and other distinctive tools for only 300 years.

"We still do not know how or why Clovis technology emerged and why it disappeared so quickly," Waters said.

"It is intriguing to note that Clovis people first appears 300 years before the demise of the last of the megafauna that once roamed North America during a time of great climatic and environmental change," he said. "The disappearance of Clovis from the archaeological record at 12,750 years ago is coincident with the extinction of mammoth and mastodon, the last of the megafauna. Perhaps Clovis weaponry was developed to hunt the last of these large beasts."

Waters said that until recently, Clovis was thought to represent the initial group of indigenous people to enter the Americas and that people carrying Clovis weapons and tools spread quickly across the continent and then moved swiftly all the way to the southern tip of South America. However, a short age range for Clovis does not provide sufficient time for people to colonize both North and South America. Furthermore, strong archaeological evidence "amassed over the last few decades shows that people were in the Americas thousands of years before Clovis, but Clovis still remains important because it is so distinctive and widespread across North America," he said.

Waters said the revised age for Clovis tools reveals that, "Clovis with its distinctive fluted lanceolate spear point, typically found in the Plains and eastern United States, is contemporaneous with stemmed point-making people in the Western United States and the earliest spear points, called Fishtail points, in South America.

"Having an accurate age for Clovis shows that people using different toolkits were well settled into multiple areas of North and South America by 13,000 years ago and had developed their own adaptation to these various environments."

Waters noted that a new accurate and precise age for Clovis and their tools provides a baseline to try to understand the mystery surrounding the origin and demise of these people.

If you flew from the sea towards the land in the north slope of Alaska, you would cross from the water, over a narrow beach, and then to the tundra. From the air, that tundra would look like a landscape of room-sized polygonal shapes. Those shapes are the surface manifestations of the ice in the frozen ground below, a solidified earth known as permafrost.

Scientists long believed the solid permafrost extended offshore: from the tundra, below that narrow beach and below the seafloor declining at a gentle slope. They viewed that permafrost like solid brick, locking the subsurface--and the vast amounts of carbon it holds--in place.

But new research led by Micaela Pedrazas, who earned her masters at The University of Texas at Austin Jackson School of Geosciences working with Professor Bayani Cardenas, has upended that paradigm. They found permafrost to be mostly absent throughout the shallow seafloor along a coastal field site in northeastern Alaska. That means carbon can be released from coastline sources much more easily than previously thought.

The study was published in Science Advances on Oct. 23 with coauthors from the Jackson School and UT's Marine Science Institute.

Using a geophysical technique called electrical resistivity imaging, the researchers mapped the subsurface beneath Kaktovik Lagoon along the northeastern coast of Alaska over the course of three years.

The results were unexpected. The beach and seafloor were entirely ice-free down to at least 65 feet. On the tundra itself, ice-rich permafrost was detected in the top 16 feet, but below that, the subsurface their imaging mapped was also ice-free.

"This leads to a new conceptual model," Pedrazas said.

Permafrost is found in cold climates that remain frozen during the course of the year. Scientists have been tracking the impact of a warming climate on permafrost because as it melts, permafrost releases its stores of frozen carbon into the atmosphere as methane and carbon dioxide, contributing to climate change.

Permafrost studies have almost exclusively focused on the region beneath the tundra. Because it's not easy to work in such remote locations and under harsh weather conditions, the transition from sea to shore has been largely ignored.

"This study tells us that the coastline is much more complicated than we thought," said co-author Jim McClelland from UT's Marine Science Institute. "It opens up the possibility for routes of water exchange that we weren't thinking about."

Besides global considerations, the work has local impacts. The communities along the coast, most of whom are Inupiat, live on the permafrost. As the permafrost thaws, it accelerates coastal erosion, which carves away at the land on which homes and infrastructure stand. In the Kaktovik region, erosion can be as great as 13 feet per year.

"Their cultural heritage and their welfare is integrated and intricately linked to their environment," Cardenas said. "There's an immediate need to understand what's happening in these lagoons."

The new paradigm requires reimagining the coastal Arctic ecosystem as well. Liquid groundwater means that carbon and nutrients can move between the tundra and the lagoon. It also means that saltwater can move beneath the tundra, potentially affecting freshwater sources.

Paul Overduin, who wasn't involved in the research, but who studies permafrost at Alfred Wegener Institute Helmholtz Centre for Polar and Marine Research, said that this work is the first step in understanding permafrost's transition from sea to shore.

"As is often the case, when we start looking at something people don't know much about, you open up a whole bunch of questions that needed to be looked at," he said. "That's what's really exciting here."

Emissions from coal-fired power plants in China are fertilizing the North Pacific Ocean with a metal nutrient important for marine life, according to new findings from a USC-led research team.

The researchers believe these metals could change the ocean ecosystem, though it's unclear whether it would be for better or worse.

The study shows that smoke from power plants carries iron and other metals to the surface waters of the North Pacific Ocean as westerly winds blow emissions from Asia to North America. Peak measurements show that up to nearly 60% of the iron in one vast swath of the northern part of the ocean emanates from smokestacks.

"It has long been understood that burning fossil fuels alters Earth's climate and ocean ecosystems by releasing carbon dioxide into the atmosphere," said Seth John, lead author of the study and an assistant professor of Earth sciences at the USC Dornsife College of Letters, Arts and Sciences. "This work shows fossil fuel burning has a side effect: the release of iron and metals into the atmosphere that carry thousands of miles and deposit in the ocean where they can impact marine ecosystems."

"Certain metal deposits could help some marine life thrive while harming other life,'' he added. "There are inevitable tradeoffs when the ocean water's chemistry changes."

The study was published on Thursday in the Proceedings of the National Academy of Sciences. Researchers from USC, Columbia University, University of Washington, MIT and the University of Hawaii, among others, collaborated.

USC-led team confirms that ocean metals stem from China

While wind-blown mineral dust from deserts has long been considered an important source of iron to open ocean waters, the new study shows how manmade sources contribute important micronutrients that plankton and algae need. Moreover, the study shows how fossil fuel burning affects not only global warming but marine environments, too.

Previous studies have shown widely divergent estimates about how much iron is carried from various land-based sources to the ocean, especially from anthropogenic sources. Iron is a key limiting factor for marine productivity for about one-third of the world's oceans.

Instead, the USC-led research team measured metals in surface seawater. They focused on a remote part of the Pacific Ocean, hundreds of miles north of Hawaii and about midway between Japan and California. The region is downwind of industrial emissions in east Asia.

In May 2017, they boarded a research vessel and took water samples along a north-south transect at latitudes between 25 degrees and 42 degrees north. They found peak iron concentrations in about the middle, which corresponded with a big wind event over east Asia one month before. The peak iron concentrations are about three times greater than background ocean measurements, the study shows.

In addition, the scientists found elevated lead concentrations coincided with the iron hot spots. Other research has shown that most of the lead at the ocean surface comes from manmade sources, including cement plants, coal-fired power plants and metal smelters.

Moreover, the metals in the seawater samples bear telltale traces of Chinese industrial sources, the study says.

"When we collected samples in the ocean, we found that the iron isotope and lead isotope 'fingerprints' from seawater matched those of anthropogenic pollution from Asia," said Paulina Pinedo-Gonzalez, a USC post-doctoral scientist and study author who is now at the Lamont-Doherty Earth Observatory at Columbia University.

Finally, the scientists also ruled out upwelling from the deep ocean as a source of the metals by testing water samples at depth.

What does the abundance of metals mean for marine life?

The study has important implications for marine life in the ocean. The North Pacific notably lacks iron, a key micronutrient, so an influx of metals and other substances can help build the foundation for a new ecosystem -- a 'good news, bad news' outcome for Earth.

"Microscopic iron-containing particles released during coal burning impacts algae growth in the ocean, and therefore the entire ecosystem for which algae form the base of the food chain," John explained. "In the short term, we might think that iron in pollution is beneficial because it stimulates the growth of phytoplankton, which then take carbon dioxide out of the atmosphere as they grow to offset some of the carbon dioxide released during the initial burning process.

"However, it's totally unsustainable as a long-term geoengineering solution because of the deleterious effects of pollution on human health. Thus, the take-home message is perhaps a better understanding of an unintended side effect of coal burning and the ways in which that can impact ocean ecosystems thousands of miles away."

The presence of insecticides in streams is increasingly a global concern, yet information on safe concentrations for aquatic ecosystems is sometimes sparse. In a new study led by Colorado State University's Janet Miller and researchers at the United States Geological Survey, the team found a common insecticide, fipronil, and related compounds were more toxic to stream communities than previous research has found.

The study, "Common insecticide disrupts aquatic communities: A mesocosm to field ecological risk assessment of fipronil and its degradates in U.S. streams," is published Oct. 23 in Science Advances.

Fipronil is used in the U.S. for insect control on pets, structures, yards and crops. Most of the streams where fipronil compounds were found to exceed toxic levels were in the relatively urbanized Southeast region.

Miller said the insecticide is likely affecting stream insects and impairing aquatic ecosystems across the country at lower levels than previously thought. In addition, fipronil degrades into new compounds, some of which this study found to be more toxic than fipronil itself.

The research team also found delayed or altered timing of when these insects emerged from streams, which has implications for the connections between stream and land-based communities.

"The emerging insects serve as an important food source," Miller explained. "When we see changes, including a drop in emergence rates or delayed emergence, it's worrisome. The effects can reverberate beyond the banks of the stream."

In experimental settings that had a high concentration of fipronil, the researchers also saw a reduced number of insects that scrape or eat algae off the rocks, leading to an increase of algae in those streams.

Mimicking natural habitats

In this study, the research team studied the effects of fipronil compounds on aquatic macroinvertebrates, insects that live on the rocks and sediment of stream bottoms. Examples of these insects include mayflies, stoneflies and caddisflies. These creatures spend the larval life stage in streams as aquatic invertebrates, later emerging from streams as flying insects.

"These macroinvertebrates serve as an important food source for fish and other organisms while also playing an important role in nutrient cycling ," said Miller, an aquatic ecologist with the Colorado Natural Heritage Program, which is part of the Warner College of Natural Resources at Colorado State University.

As one part of the study, the research team built rock trays to mimic the invertebrate's habitat, and placed them in the Cache La Poudre River in northern Colorado. In these habitats, the macroinvertebrates colonized naturally with algae to mimic communities that exist in nature.

Next, the scientists moved the rock trays containing macroinvertebrates into the lab, mimicking a natural environment while also controlling temperature, light and water flow. The team then added a range of concentrations of the insecticide fipronil or one of four associated fipronil degradate compounds - sulfone, sulfide, desulfinyl and amide - and observed the effects on macroinvertebrates.

Scientists found these degradates to be as toxic, if not more so than fipronil. Yet Miller said there is generally a lack of data for the compounds.

Streams in southeast most affected by fipronil

As an additional prong of the research, Miller and the team applied results from the laboratory experiment to data from a large field study conducted by the United States Geological Survey that sampled streams across the U.S. in five major regions.

Miller said fipronil compounds were detected at unsafe concentrations in 16% of streams sampled across the U.S. and were most prevalent in streams of the Southeast region of the country. Scientists found fipronil compounds much less widespread in other regions, suggesting use patterns of the insecticide differ across the country.

"We found that 51% of sampled streams in the southeast revealed the presence of fipronil, while in the Pacific Northwest, we detected only around 9% of streams with the insecticide," she said.

Miller said that while the results are concerning, it's helpful to have this scientific-based evidence to share with the scientific community and regulating agencies.

"We hope our findings provide greater understanding of the prevalence of fipronil compounds across the country and the levels at which these compounds are harmful to stream health," she said.

New research from Edith Cowan University (ECU) has revealed that training one arm can improve strength and decrease muscle loss in the other arm - without even moving it.

The findings could help to address the muscle wastage and loss of strength often experienced in an immobilised arm, such as after injury, by using eccentric exercise on the opposing arm.

In eccentric exercises, the contracting muscle is lengthening, such as when lowering a dumbbell in bicep curls, sitting on a chair slowly or walking downstairs. Previous research has shown these exercises are more effective at growing muscle than concentric exercises, in which muscle are shortening such as when lifting a dumbbell or walking up stairs.

A new way of thinking

ECU's Professor Ken Nosaka in the School of Medical and Health Sciences was part of the international study and said that the findings challenge conventional rehabilitation methods and could improve outcomes for post-injury and stroke patients.

"I think this could change the way we approach rehabilitation for people who have temporarily lost the use of one arm or one leg," Professor Nosaka said.

"By starting rehab and exercise in the uninjured limb right away, we can prevent muscle damage induced by exercise in the other limb and also build strength without moving it at all."

The opposite effect

The study involved 30 participants who had one arm immobilised for a minimum of eight hours a day for four weeks. The group was then split into three, with some performing no exercise, some performing a mix of eccentric and concentric exercise and the rest performing eccentric exercise only.

Professor Nosaka said the group who used a heavy dumbbell to perform only eccentric exercise on their active arm showed an increase in strength and a decrease in muscle atrophy, or wastage, in their immobilised arm.

"Participants who did eccentric exercise had the biggest increase in strength in both arms, so it has a very powerful cross-transfer effect," he said.

"This group also had just two per cent muscle wastage in their immobilised arm, compared with those who did no exercise who had a 28 per cent loss of muscle.

"This means that for those people who do no exercise, they have to regain all that muscle and strength again."

Future of rehab

Professor Nosaka said he plans on expanding the research further into other arm muscles and movements.

"In this study we focused on the elbow flexors as this muscle is often used as a model to examine the effects of immobilisation on strength and size, and of course it is an important muscle for arm movement," he said.

"In the future, we hope to look at how eccentric exercise can help improve motor function, movement and fine muscle control, which is particularly important for stroke and rehabilitation patients."

Professor Nosaka also said this type of training is useful for athletes who can begin post-injury recovery sooner.

Our hunger for energy is insatiable, it even continues to rise with the increasing supply of new electronic gadgets. What's more, we are almost always on the move and thus permanently dependent on a power supply to recharge our smartphones, tablets and laptops. In the future, power sockets (at least for this purpose) could possibly become obsolete. The electricity would then come from our own clothes. By means of a new polymer that is applied on textile fibers, jackets, T-shirts and the like could soon function as solar collectors and thus as a mobile energy supply.

Making luminescent materials flexible

Materials capable of using indirect or ambient light for energy generation are already being used in the solar industry. These materials contain special luminescent materials and are called "Luminescent Solar Concentrators", or LSC for short. The luminescent materials in the LSC capture diffuse ambient light and transmit its energy to the actual solar cell, which then converts light into electrical energy. However, LSCs are currently only available as rigid components and are unsuitable for use in textiles because they are neither flexible nor permeable to air and water vapor. An interdisciplinary research team led by Luciano Boesel from the Laboratory for Biomimetic Membranes and Textiles has now succeeded in incorporating several of these luminescent materials into a polymer that provides precisely this flexibility and air permeability.

Well-known polymer with sophisticated properties

This new material is based on Amphiphilic Polymer Co-Networks, or APCN for short, a polymer that has long been known in research and is already available on the market in the form of silicone-hydrogel contact lenses. The special properties of the polymer - permeability to air and water vapor as well as flexibility and stability - are also beneficial to the human eye and are based on special chemical properties. "The reason we chose exactly this polymer is the fact that we are capable of incorporating two immiscible luminescent materials at the nano scale and let them interact with each other. There are, of course, other polymers, in which these materials could be integrated; but this would lead to aggregation, and the production of energy would thus not be possible», explains Boesel.

Bright solar concentrators for clothing

In collaboration with colleagues from two other Empa labs, Thin Films and Photovoltaics and Advanced Fibers, Boesel's team added two different luminescent materials to the gel tissue, turning it into a flexible solar concentrator. Just as on large-scale (rigid) collectors, the luminescent materials capture a much wider spectrum of light than is possible with conventional photovoltaics. The novel solar concentrators can be applied to textile fibers without the textile becoming brittle and susceptible to cracking or accumulating water vapor in the form of sweat. Solar concentrators worn on the body offer an immense benefit for the ever-increasing demand for energy, especially for portable devices.

Night-shift workers face an increased risk of obesity and diabetes, but the underlying reason for that has been a mystery. Now, University of Missouri School of Medicine researchers have found a potential cause for metabolic changes during night-shift work that creates confusion between cells in the body and the central clock in the brain.

"We hypothesized that the messages cells produce and send each other during night work are different than those sent during the day shift," said David Gozal, MD, the Marie M. and Harry L. Smith Endowed Chair of Child Health at the MU School of Medicine. "These messages come via microscopic packages called exosomes. Our study found these packages disrupt the synchronicity of the body's systems during night shifts and cause increased insulin resistance and other health issues."

Gozal and MU collaborator Abdelnaby Khalyfa, PhD, associate professor, studied 14 participants who were assigned to either a simulated day shift or night shift. After the participants spent three days on the simulated shift, researchers drew their blood every 3 hours, extracted the exosomes from the plasma and delivered them into naïve fat cells. The goal was to examine any potential changes to the fat cells and the key genes that affect metabolism. They found that exosomes taken from the night-shift participants reduced insulin sensitivity of the fat cells. They also discovered that those exosomes contained specialized gene regulators called microRNAs that shifted the internal clock of the fat cells.

"The cells in your body do not adjust as quickly as the central clock in the brain to shifts in sleep patterns," Gozal said. "So when night-shift workers abruptly shift back and forth to daytime hours on the weekend, the cells in the body continue to send messages to each other through exosomes that lag behind the central clock. It creates a condition called 'circadian misalignment,' which is associated with an increased risk for cancer, diabetes, cardiovascular disease and other illnesses."

Gozal believes using exosomes taken from the blood as a marker of circadian misalignment could play a key role in identifying treatments to prevent the long-term health complications of night-shift work.

"By sampling the blood of workers at different times of the day and examining their exosomes, we might be able to identify whether they are misaligned," Gozal said. "This could give us a lot of information about which workers are better suited to work night shift. And this discovery raises the possibility of developing personalized less risk-generating shift schedules and also gene-targeted therapeutic approaches to prevent the long-term health complications of night-shift work. "

FINDINGS

More women could potentially be spared an axillary lymph node dissection -- the surgical removal of 10-20 lymph nodes -- a procedure that causes disabling arm swelling in up to 25% of women, according to a UCLA study led by Dr. Maggie DiNome, chief of breast surgery at the David Geffen School of Medicine at UCLA.

The procedure is currently a standard part of surgical treatment for women with breast cancer that has spread to the lymph nodes to determine the extent of the cancer's spread. However, the team found that over 40% of women with lymph node involvement at diagnosis have only 1-3 positive nodes at surgery with the remainder of nodes removed being normal. The team also identified certain features of a patient's tumor -- tumor size, lobular histology and nodal metastasis size -- that can predict which patients may be suitable for omission of this procedure.

BACKGROUND

Most women with invasive breast cancer are recommended for axillary surgery at the time of their breast surgery. Axillary surgery is a staging procedure that helps determine whether breast cancer has spread outside of the breast. Cancer cells can travel directly through the bloodstream to distant organs (bones, lungs, liver, brain) or via the lymphatics. There currently is no blood test that is able to detect cancer cells in a meaningful way so physicians rely on the lymph nodes to determine whether cancer has started to spread.

METHOD

A retrospective review from 2010-2019 was conducted of women who had positive lymph nodes at the time of their breast cancer diagnosis and were treated with a complete lymph node dissection at surgery. The team evaluated this cohort for extent of lymph node involvement on final pathology and whether any variables existed that predicted for higher nodal stage. This group of women have notoriously been excluded from previous similar studies because of the assumption that these women had extensive spread of breast cancer to the lymph nodes.

IMPACT

As treatments improve outcomes for breast cancer, reducing the long-term effects of treatment becomes more important. Being able to identify women who can be spared an axillary lymph node dissection procedure would be a significant step in improving quality of life. The researchers say future studies to validate these identified predictors are an important next step.

New research shows how a combination of imagery from mobile phones, drones and satellites can be used to clamp down on banana threats. The images of varying resolutions are fed into a platform "trained" through machine learning to identify banana crops and analyze threats with 97% overall accuracy. The findings were published in the ISPRS Journal of Photogrammetry and Remote Sensing.

The research case studies, conducted in the Democratic Republic of Congo and Republic of Benin, have important implications for the 90 million people in East, West and Central Africa who rely on bananas and plantains as a primary food source. These mostly small-scale farmers are dependent on their cultivation for food, income and job security.

The increasing arrival and spread of serious diseases, fungal infections and viruses, due to climate change and land-use change among other factors, pose a serious food security threat. There are six major and devastating threats to banana, among them bunchy top disease (BBTD) and Xanthomonas wilt of banana (BXW).

"Threats are currently detected by experts in the field using cell phones," said Michael Gomez Selvaraj, a crop physiologist and co-author at the Alliance of Bioversity International and the International Center for Tropical Agriculture (CIAT). "But to track and detect diseases across huge tracts of land at country, district or village level, you need a platform that quickly detects threats."

Using a pixel-based classification system, first the researchers trained the model to detect banana plants on mixed-farm systems, where smallholder farmers grow many things on one piece of land. After 'learning' the patterns and algorithms of banana plants, the researchers then trained the platform to analyze physical symptoms of the six diseases, and the percentage threat.

Information about the severity of the specific threat and its spread can be sent to organizations or government authorities who can take immediate measures to clamp down on them. "Otherwise potential threats multiply quickly, for example, farmers may give infected crop stems to others, and, in the case of a virus, spread it around the country or district without knowing until it's too late," said Selvaraj.

Currently, most disease surveillance systems focus on a single-sensor based solution that cannot monitor larger landscapes through mobile phones or drones. This method combines field-level information captured by farmers or extension workers in the field, with satellite data to detect crop area, and drones deployed to analyze the exact threat and its intensity.

"We can now detect six major banana threats with speed and accuracy with our Tumaini mobile phone app," said Selvaraj. The database is free for farmers, organizations and governments to use, and has been downloaded from the Google App store 2,500 times.

"The next step is to find financial support to bring more partners together, so we can track more data over a wider area. The hope is to cover Africa, India, Australia and Latin America where bananas are a major crop and these threats are looming," he added.

Graham Thiele, the Director of the CGIAR Research Program on Roots, Tubers and Bananas, said: "We congratulate the team on this breakthrough research. It validates the use of aerial images for disease detection, potentially transforming our ability to assess threat impact."

The platform can also be used to track other pests, diseases or viruses for other threats where symptoms are visible. For example, to track the spread of fall armyworm, an invasive crop pest which can feed on 80 different crop species including maize, and affected 83% of maize farmers in Kenya, causing losses of 33%, and costing an estimated US$3.6 to $6.2 billion across the 12 countries in the region.

LA JOLLA, CA--When it comes to defeating cancer, some immune cells are mightier than others. But even the best-trained eye and today's advanced scientific tools have trouble discerning the most powerful tumor-fighting cells from the rest.

A new technique developed at Scripps Research by scientist Peng Wu, PhD, aims to change that--offering a new platform that could propel personalized cancer treatments that have been hindered due to the challenges of isolating the most useful immune cells in patients. The development is published October 22 in Cell.

"In many new and emerging personalized cancer therapies, the key to success is finding the sometimes-elusive T cells that are directly targeting the tumor, then creating more of those cells outside of patients' bodies and re-introducing them for tumor treatment," says Wu, associate professor in the Department of Molecular Medicine and senior author of the study. "With our simple method to detect and isolate tumor-reactive immune cells, my hope is that we can advance personalized immunotherapy treatments that are now either too costly or laborious to reach their potential."

The method is called FucoID, named after the enzyme fucosyltransferase that plays a starring role in "tagging" the surface of sought-after immune cells so they can be seen and captured. The enzyme is loaded onto dendritic cells, a type of immune cell that presents tumor-specific material to the desired T cells. When the cells interact, the enzyme transfers a tag to the tumor-fighting cells so scientists can detect them with a fluorescent probe and extract them from the sample.

In experiments involving mice, the approach successfully identified multiple types of so-called "tumor antigen-specific T cells," including CD4+ and CD8+ T cells that infiltrate tumors and attack from within. These cells are central to certain cancer immunotherapies--including checkpoint inhibitors and treatments known as adoptive TIL (tumor infiltrating lymphocyte) transfer therapies.

"This approach removes a significant barrier to studying tumor-specific T cells and will be immensely useful for both basic scientists and clinicians," says John Teijaro, PhD, associate professor in the Department of Immunology and Microbiology and co-author of the study.

"This study also highlights how the highly collaborative environment at Scripps Research fosters innovative solutions to intractable problems."

The FucoID process of isolating the appropriate cells takes only one day, compared with four or five weeks using current methods, according to Wu. "Once we isolate them, we can expand them into millions or billions of cells to construct a treatment or simply to study them," he says.

Having the ability to quickly take stock of these cells in a patient can also help doctors predict therapeutic success or treatment progress, he says. And doing any of these things faster than today's methods, which rely on bioinformatics or genetic manipulations, can make a big difference to patients.

Wu is now collaborating with clinicians at UC San Diego to use FucoID to isolate the desired T cells from human patient tumor samples, with the goal of eventually applying the platform to a clinical trial for a cancer treatment.

"We believe FucoID has potential to be translated to a clinical setting for the detection and isolation of tumor-reactive immune cells, ultimately paving the way for lowering the cost and accessibility of personalized cancer treatment," Wu says.

Policy changes can help to fight stigmas of multiracial Americans, one of the fasting growing minority groups in the United States according to a Rutgers University-led study.

Published in the journal Policy Insights from the Behavioral and Brain Sciences, the study finds that such stigmas may be combated by legitimizing multiracial identities. Despite the increasing prominence of multiracial celebrities and leaders such as Barack Obama, Meghan Markle, and Bruno Mars, many multiracial people are physically isolated from their peers, said lead author Diana Sanchez, a Rutgers professor of psychology.

"Multiracial people encounter unique challenges because they straddle multiple racial groups," said Sanchez. "Sen. Kamala Harris is Black and South Asian, yet social media outlets vary to the extent to which they recognize her multiracial background. This lack of recognition for multiracial populations is common as is the tendency for fellow monoracial group members like South Asian or Black Americans to have trouble including a multiracial person in their group."

Multiracial people who report frequent racial identity denial also indicate more depressive symptoms, more stress, impaired motivation, and lower self-esteem--compared with those who experience denial less frequently, according to research.

Multiracial people experience discrimination and everyday, often subtle, instances of these racist microaggressions that stem specifically from their identity -- such as being told that they cannot identify with certain racial identities or that they are not full members of their own racial communities.

The study suggests adopting policy changes that could increase population estimates that would allow for more for distribution of educational and health care resources and improve health care delivery for multiracial populations. Recommendations include:

Legitimizing multiracial identity by capitalizing the "M" in multiracial and adjusting guidelines that are set forth by, for example, the American Psychological Association and in writing style guides about race-appropriate language.

Being explicit about the consequences of listing a multiracial background on business loans and applications. There is a lack of transparency regarding how claiming a multiracial identity will affect eligibility.

Fully integrating check-all-that-apply racial measures for data collection. These have psychological benefits for multiracial people by recognizing and validating their identities.

Minority programs tailored to building community and facilitating positive racial socialization should integrate education for multiracial people by discussing how to respond to questions such as: "What are you?," "Are you sure your dad is really your dad?"

The U.S. Census 2020 marks the third assessment that allows residents to indicate belonging to more than one racial group. The 2010 U.S. Census data revealed that multiracial individuals represent one of the fastest growing minority groups in the United States, representing, at the time, roughly nine million Americans.

"Many people have argued that Harris's vice presidential nomination may be an opportunity to unite Black and South Asian communities who can jointly celebrate this candidacy, but we will first have to confront the issue that many have trouble with -- seeing multiracial people as legitimate members of their monoracial communities," said Sanchez.

Annals of Internal Medicine News
Below please find a summary and link(s) of new coronavirus-related content published today in Annals of Internal Medicine. The summary below is not intended to substitute for the full article as a source of information. A collection of coronavirus-related content is free to the public at http://go.annals.org/coronavirus.

Experts suggest establishing general clinical endpoints for evaluating efficacy in COVID-19 vaccine trials

Safe and effective vaccines are a critical component in the control of COVID-19. Several vaccine candidates to protect COVID-19 have entered or will soon enter large-scale, phase 3, placebo-controlled randomized clinical trials.

A group of industry, government, and academic researchers propose a general set of clinical endpoints to facilitate a harmonized evaluation and comparison of the efficacy of vaccine candidates. The authors note they considered the pros and cons of various endpoints for use as primary endpoints. Additionally, the authors recommend including asymptomatic infection as a study endpoint. Read the full text: https://www.acpjournals.org/doi/10.7326/M20-6169.