Earth

The 17 SDGs and 169 targets set out in the 2030 Agenda set the direction for countries around the world to work on sustainable development from 2015 to 2030. After more than four years, various countries have made a series of breakthroughs. However, recent reports indicate that, based on current progress, there is no guarantee that all goals will be achieved by 2030, and that more in-depth and rapid measures will be needed to advance the implementation of SDGs.

Faced with the above difficulties and challenges, people have explored countermeasures from multiple perspectives. However, due to the scale effect, a single country's plan may have a negative external impact on other countries. To overcome this, a new article by Bojie Fu and his research group from the Beijing Normal University, China, now proposes a systems approach, Classification-Coordination-Collaboration (3C), to promote the overall realization of SDGs.

Among the 3C constituents, classification refers to the assignment of objects to groups by considering their properties, grades, or other characteristics. This process can lay foundation for relational analysis, comparison and the joint management of objects. Coordination is a top-down management process. In SDG-oriented management, the purpose of coordination is not only to integrate the various components, but also to synchronize the functions of the various departments in order to achieve the SDGs with minimal effort. Finally, compared to coordination, collaboration is a bottom-up, as well as a top-down process; it can spontaneously occur through the initiatives of different individuals or organizations.

In this approach, each constituent interacts with one another. For example, the classification requires multi-stakeholders' coordination and collaboration, and classification can also enhance coordination and promote more efficient collaboration.

Hydrogen flames can propagate even with very little fuel, within surprisingly narrow gaps and can extend breaking up into fractal patterns. That is the unexpected physical behavior of this gas when it burns, which has been detected by a scientific team led by researchers from Universidad Carlos III de Madrid (UC3M). These results can help to improve the safety of Hydrogen-powered devices.

The study, published in the latest edition of the journal Physical Review Letters, details the results from experiments which have demonstrated that hydrogen flames can survive in more extreme conditions than previously thought. In this research, led by Fernando Veiga, Eduardo Fernández-Tarrazo and Mario Sánchez Sanz, from the UC3M Department of Thermal and Fluids Engineering, Daniel Martínez Ruiz from the Universidad Politécnica de Madrid (UPM), Mike Kuznetsov from the Karlsruhe Institute of Technology (Germany) and Joachim Grune from Pro-Science GmbH (Germany) have likewise participated.

"Our article shows that hydrogen flames are capable of propagating in very narrow spaces of a millimeter or so, creating an undesirable and dangerous situation," explained Fernando Veiga, one of the researchers who has carried out a large share of the experimental work.

Using hydrogen as a fuel can help to reduce carbon dioxide emissions, but its storage and transport can hold certain risks. In this study, researchers have empirically shown that the gas can burn in unexpected situations. For that purpose, the team tested dilutions of gaseous fuel in a space just a few millimeters wide and found that the hydrogen could burn steadily even when its concentration was only 5% in volume.

Fractal structures

Hydrogen flames are almost invisible to the naked eye and emit very little radiant heat, which makes them difficult to detect. To do so, the researchers used a special method to trace their movement and a high speed camera to track the path of the flames during their propagation. They confirmed that they form a fractal path as they propagate, that is, they adopt a geometric form whose basic structure is repeated on different scales. "The video recording reveals this fractal path, which precisely permits the flame efficient access to new fuel as it burns," Mario Sánchez Sanz pointed out.

Hydrogen constitutes a clean and efficient energy, and as such, energy generation technologies based on its use will significantly increase in the near future. Accordingly, "their design and safety protocol will have to take these new ways for propagation into consideration," observed Daniel Martínez Ruiz, professor at the ETSI Aeronáutica y del Espacio (The School of Aeronautics and Space Engineering) of the UPM.

These results can be useful for engineering teams that design hydrogen storage systems, who will need to take into account its extreme flammability, even in very narrow spaces. Hydrogen fuel cells are used as a source of energy in cars and motorcycles, for example. "A hydrogen leak and its accumulation in a confined space could lead to these types of flames," added Mario Sánchez Sanz.

According to the researchers, more studies of this type are needed to assess safety in relation to leaks in hydrogen-powered vehicles and other related devices. Above all, within today's context of needing to reduce greenhouse gas emissions and combat climate change, it seems imperative to accelerate development and use of hydrogen-based energy technologies.

Transcranial direct current stimulation, tDCS, is a promising treatment for conditions such as depression and addictive disorders. New evidence on the safety of transcranial direct current stimulation was recently offered by a new study showing that tDCS does not affect metabolism.

Transcranial direct current stimulation is a non-invasive method for modulating neuronal activity by introducing a small electric current into the brain via electrodes placed on the scalp.

"In earlier studies, transcranial direct current stimulation has been found to alter glucose metabolism and stress hormone levels, among other things. However, our study looked at more than 100 molecules and we didn't observe an effect on any of them," PhD student Aaron Kortteenniemi, the lead author of the study, from the University of Eastern Finland notes.

The study, conducted in collaboration between the University of Eastern Finland and the University of Helsinki, analysed 79 healthy, adult men. Half of them were given transcranial direct current stimulation, while the other half received placebo stimulation. Each study participant was given stimulation on five consecutive days, and their blood samples were taken for analysis three times over the course of the study.

"This was a surprising discovery, since earlier studies have shown that transcranial direct current stimulation affects glucose metabolism in such a way that researchers have even considered its potential in the treatment of diabetes," Kortteenniemi explains.

"Yet, our findings show that there are no clinically significant changes in the measured metabolite levels. This supports our current understanding of transcranial direct current stimulation as a safe treatment also when taking metabolism into consideration."

Transcranial direct current stimulation has also attracted interest in the treatment of conditions such as depression and addictive disorders. These diseases are significant both for individuals' quality of life and for national economies. In the future, transcranial direct current stimulation could open up new opportunities for treatment in situations where other forms of treatment are infeasible.

Researchers at Karolinska Institutet in Sweden show that different measures of psychopathology can be combined into a single factor, "p", which predicts the patient's prognosis and need of extra support. The general factor of psychopathology reflects the overall risk of adverse psychiatric outcomes with an accuracy equal to that currently used for intelligence, they report in a paper published in World Psychiatry.

"We found that a high p value could predict future adverse outcomes, such as a higher suicide risk, criminality or drug abuse," says Erik Pettersson, researcher at the Department of Medical Epidemiology and Biostatistics, Karolinska Institutet. "The relationship between a high p value and unfavourable future outcomes was just as strong as between a high score on intelligence tests and favourable outcomes."

The general factor of intelligence, g (also known as "general intelligence") has been used since the 1900s, when it was established that a person scoring high on one intelligence test also tends to score high on others. A person with a high g score is often good at mathematics, language and visualising three-dimensional forms. A high g score can also be linked to other favourable outcomes, such as a high level of education and a high score on scholastic aptitude tests.

The question the researchers sought to answer was if it is possible to combine different measures of psychiatric outcomes into a general factor of psychopathology and if so, if this "p" factor would have the same predictive validity as g.

First, using Swedish registries, the researchers studied incidences of psychiatric symptoms and diagnoses, as measured on different scales, amongst 900,000 adults, adolescents and children to ascertain the possibility of combining such measures into a single score. Statistical calculations revealed that individuals who scored high on one psychiatric scale also scored high on others, just as was observed with intelligence tests.

Secondly, the researchers compared how well the g and p factors could predict outcomes ten years into the future. Analysing data from over 400,000 Swedish men who took an intelligence test on enrolment into military service, they found that p predicted negative outcomes such as suicide, criminality and drug overdoses roughly as well as g predicted educational level and a university aptitude test score.

They now hope that the combined p value might help psychologists and psychiatrists better predict, for instance, a patient's future need for extra support. The current diagnostic system focuses much more on specific diagnoses than on the total number of symptoms.

"If two patients have the same diagnosis, such as depression, a high p value for one of them might signal that treatment with antidepressants should be combined with other forms of intervention, such as counselling," says Pettersson. "And a high p value for an individual with multiple psychiatric symptoms but without a specific psychiatric diagnosis can also be an argument for providing support and therapy."

Platelets not only play a key role in blood clotting, but can also significantly intensify inflammatory processes. This is shown by a new study carried out by scientists from the University of Bonn together with colleagues from Sao Paulo (Brazil). In the medium term, the results could open up new ways to treat autoimmune diseases. They have now been published in the renowned journal Cell Reports.

For a long time, the role of platelets appeared to be clear: in the event of an injury, they adhere to the wound and stick to each other to rapidly stop the bleeding. This wound closure mechanism works quickly and efficiently, but its protagonists were not considered to have any other functions.

For some years now, this picture has begun to change significantly: these tiny cells, each of which is about the size of an intestinal bacterium, are also believed to perform important functions in the immune system. The current study by the universities of Bonn and Sao Paulo supports this thesis: it shows that platelets ensure that the white blood cells (the leukocytes) secrete significantly more inflammatory messengers. "It is possible that this effect contributes to the often severe course of autoimmune diseases," explains Prof. Dr. Bernardo Franklin from the Institute of Innate Immunity at the University Hospital Bonn. "These are diseases in which the immune system attacks and destroys the body's own tissue."

In their study, the researchers focused on an important immune mechanism: the activation of the NLRP3 inflammasome. Inflammasomes are molecular machines that consist of a number of different proteins. Among other things, they are able to convert inactive inflammatory messengers into their active form. One of them is the interleukin 1 (IL-1). When cells secrete IL-1, they call on other immune cells to help and thereby trigger a strong inflammatory reaction. As this can also become dangerous for the body, the activity of the inflammasomes, and hence also the formation of IL-1, is strictly regulated.

"We have now been able to demonstrate that platelets interfere with this regulation," explains Dr. Lucas Ribeiro, first author of the study: "They cause certain white blood cells, the macrophages and neutrophilic granulocytes, to form more active inflammasomes." To do this, they apparently release a whole cocktail of substances that diffuse to the white blood cells. Once there, these ensure, among other things, that certain genes required for the construction of the inflammasomes are more frequently expressed. This effect does not require the platelets to make direct contact with the macrophages or granulocytes. Instead, they release their active substances into the environment, for example, into the blood.

"To prove that, we incubated human platelets in the laboratory and then filtered them off, so the platelet factor could be present in the culture medium," explains Dr. Ribeiro. "When we added this platelet medium to human white blood cells, the formation of inflammasomes and the IL-1 production were significantly boosted." Exactly which of the substances released by the platelets are responsible for this process is not yet known. However, the effect was supported by observations in human malaria patients: the more platelets they have, the higher the IL-1 concentration in their plasma. The researchers also experimentally reduced the number of platelets in mice. The animals then released significantly less IL-1 after being injected with inflammatory compounds.

As IL-1 promotes inflammation, the messenger substance can significantly worsen the course of autoimmune diseases. Nevertheless, Prof. Franklin is keen to speak up against a one-sided view of platelets as villains: they also intervene in other ways in the immune response, for example by preventing the development of life-threatening sepsis after an infection. Regardless of this, the results might pave the way to new therapies for diseases such as rheumatism or diabetes.

Single cell cultures do not tell the whole story

However, one important message of the current study is of a more general nature: isolated blood cells in culture often behave very differently than in their natural environment, where they communicate with numerous other cells. "Experiments in the test tube therefore do not provide complete insight into the processes happening in the body," emphasizes Prof. Franklin. "Still, most of research into inflammasomes are based on them, which is a fact we should rethink." After all, platelets may only reveal their additional immune functions in concert with white blood cells.

The ability to accurately detect changes in ecosystem biodiversity caused by human activity has long challenged environmental scientists and ecologists, but a new study, published in PNAS, has established new DNA-based methods that are effective for environmental assessment and monitoring.

Led by researchers from Environment and Climate Change Canada's Water Science and Technology Directorate and the Hajibabaei Lab at the University of Guelph, the study focused on at-risk wetlands in the Peace-Athabasca Delta (PAD) located in northern Alberta, Canada. The PAD is a large inland wetland complex threatened by encroachment from oil sands mining in the Athabasca watershed and hydroelectric dams in the Peace watershed.

"For more than a decade, we have been working closely with scientists from Environment and Climate Change Canada to develop and apply high-throughput DNA based biodiversity analysis for monitoring key ecosystems across Canada," said Dr. Mehrdad Hajibabaei, a co-author of the study, and a professor in the Department of Integrative Biology at the University of Guelph. "This study is a key contribution from this collaborative effort to bring cutting-edge genomics to ecological analyses."

Aquatic macroinvertebrates were sampled between 2011 and 2016 across a gradient of wetland flood frequency, applying both microscope-based morphological identification and DNA metabarcoding -- a method first introduced by Hajibabaei Lab in 2011. DNA metabarcoding involves sequencing environmental DNA (eDNA) to identify many organisms within the same environmental sample. By using multispecies occupancy models (MSOMS) -- a model used to assess biodiversity through species richness and interactions -- the study found that DNA metabarcoding detected a much broader range of biodiversity per sample compared to traditional morphological identification and was essential to identifying significant responses to flood and thermal regimes.

"By using massively parallel sequencing and advanced computational analysis, DNA metabarcoding overcomes critical chokepoints in biomonitoring," said Hajibabaei. "It allows processing large number of samples without the need of separating and sorting tiny larvae. It uses sequences from the DNA barcoding gene to make taxonomic identification often at a better resolution than achievable by morphological examination."

The study demonstrates that family-level occupancy masks high variation among genera and quantify the bias of barcoding primers on the probability of detection in a natural community. It also revealed that patters of community assembly were nearly random, suggesting a strong role of randomness in the dynamics of the metacommunity.

"Until now, our ability to make consistent and accurate identifications of the hundreds of species which comprise these hyper-diverse and dynamic communities has limited our ability to make broad statements about how resource developments are degrading critical goods and services needed by migratory birds and wildlife," said Dr. Donald Baird, federal scientist with Environment and Climate Change Canada. "These impacts can have knock-on consequences for local communities who rely on these critical habitats for food security," said Baird, who co-authored the study and is actively involved in monitoring wetlands in Alberta's oil sands region.

Simulations used in the study also demonstrated that metabarcoding was much more efficient, especially in a more precise taxonomic resolution, and provided the statistical strength required to detect change on a broader, landscape-level scale.

"Being able to demonstrate DNA metabarcoding as an effective tool in ecological analyses across space and time, and in critical ecosystems such as the Peace-Athabasca Delta, is an important stepping-stone for broader application of this approach," said Hajibabaei.

Hajibabaei is currently applying the study's DNA metabarcoding approaches to assess key watersheds across Canada in a new program called STREAM. Launched last year in partnership with World Wildlife Fund-Canada, Living Lakes Canada, Environment and Climate Change Canada, STREAM is establishing a nationwide network of community-based biomonitoring programs.

Researchers from Lingnan University of Hong Kong published a new paper in the Journal of Marketing that examines the role that facial attractiveness has in social selling.

The study forthcoming in the Journal of Marketing is titled "The Faces of Success: Beauty and Ugliness Premiums in Online Platforms" and is authored by Ling Peng, Geng Cui, Yuho Chung, and Wanyi Zheng.

Across C2C e-commerce platforms like eBay and Etsy, millions of social sellers pitch products of every imaginable category. Because trust is a key driver of online transactions between strangers, the first impression from the profile pictures of sellers, and specifically how attractive they are, makes a real difference. Unlike super models or celebrity endorsers, online sellers are mostly ordinary people who may be attractive, plain looking, or unattractive. How the facial attractiveness of these profile pictures affects sales is the question of a new study in the Journal of Marketing. Some of the findings are surprising.

The research team first used the homestay platform Airbnb as a data pool. For more than 17,000 Airbnb listings, the facial attractiveness of over 10,000 hosts was rated using their profile pictures. The annual occupancy rates of these listings were also noted. Hosts with attractive faces had a 6% higher annual occupancy rate than those with plain-looking faces (62% vs. 56%). Hosts with perfect faces had an occupancy rate as high as 22% more than those with plain-looking faces. So, everything being equal, good looks sell more. In other words, there is a "beauty premium."

As much as we would like to believe that we, as consumers, make rational decisions and are not affected by superficial factors, studies have repeatedly shown the opposite. We tend to make judgments of a person's sociability, competence, and credibility based on facial attractiveness. Specifically, people with attractive faces are perceived to have more of these positive qualities. Evolutionary psychology helps explain this beauty premium: attractive faces signal good genes and health for reproduction.

What about hosts on the other end of the spectrum--those with unattractive faces? While previous studies mostly compare attractive people with less attractive ones (i.e., the plain-looking and unattractive groups lumped together), this study separates these groups and find an "ugliness premium." Unattractive Airbnb hosts had a 4% higher annual occupancy rate on average compared with plain-looking hosts and the most unattractive hosts had as much as a 16% higher occupancy rate.

This second finding might appear counterintuitive. However, evolutionary theory can provide an answer here, too. It is widely believed that people engage in compensatory adaptation to leverage their advantages or compensate for their disadvantages. As such, unattractive people may compensate for their disadvantaged appearance by working harder to achieve similar results, leading to a perception of greater competence.

All in all, the extremely attractive and unattractive hosts have the most success. Results from studying another e-commerce site, 5miles, confirm the same pattern: Both attractive and unattractive sellers are likely to make a sale than their plain-looking counterparts. So, although a profile picture only occupies a small portion of a seller's product listing, loading a profile picture is not a task to be taken lightly. It has a non-negligible effect on purchases because consumers form instant impressions of people based on face perception.

Subsequent experiments indicate that we pay longer attention to both attractive and unattractive faces than plain-looking sellers. The amygdala, an almond-shaped region of our subcortical brain, directs our attention to unusual things, attractive or not. Moreover, attractive sellers are considered more sociable and competent than plain-looking people, especially when selling items relevant to appearance such as cosmetics and skin care products, whereas unattractive sellers are thought of only as more competent, especially when pitching technical products that require expertise, like electronics.

Interestingly, the beauty and ugliness premiums we observed were gendered. While the beauty premium is typically stronger for the opposite sex than for the same gender, we find this does not apply to women selling online--attractive female sellers do not have an edge over less attractive women in appealing to male buyers. Meanwhile, the ugliness premium is only true for male sellers facing female buyers, who may consider unattractive men more competent than the average Joe, perhaps perpetuating the stereotype of the tech-savvy nerd.

These novel findings give social sellers and e-marketers insight about how to leverage seller appearances in online selling. Peng explains that "While attractive sellers enjoy an advantage, especially for appearance-enhancing products, people without perfect facial symmetry and proportions should not shy away from displaying their true colors. Emphasizing expertise in technical products can boost their credibility and performance."

If you, like many others, have a plain look, you can do a few things to avoid the plainness penalty and boost your sales. In addition to a good quality photograph (i.e., in brightness and pixels), wearing make-up or a smile, or taking a photo from your best angle may help to enhance your attractiveness and avoid being too plain-looking to get attention or to make a sale.

The long-term effects of climate change suggests that the butterfly effect is at work on butterflies in the alpine regions of North America, according to a new study by University of Alberta scientists--and the predictions don't bode well.

"We often frame the effects of climate change directly onto a species as the future becoming either too hot, too dry, or too wet," explained Alessandro Filazzola, postdoctoral fellow in the Faculty of Science Department of Biological Sciences and lead author on the study. "However, climate change can have indirect effects such as through the food resources of a species. These effects are more likely to affect butterflies, because as caterpillars they often feed on one or a few plant species."

The researchers used climate change models to understand the effects of changing ecosystems on alpine butterflies in North America. The results show that alpine butterflies who have specialized diets, meaning that they feed on one or a few plants, are more vulnerable to climate change because of fluctuations in their food. On the other hand, butterflies that have diverse diets are less likely to be affected.

"The main outcome from this study is our improved ability to quantify the complex effects of climate change on ecosystems," said Filazzola, who conducted this work under the supervision of Professors Jens Roland and JC Cahill. "Understanding the effects of climate change on a species through its food items is very important for biological conservation--climate change is likely going to have complex effects that extend beyond single species mortality."

Models like the one used in this study provide a more holistic approach to understanding the way that a changing climate could affect entire ecosystems. "Using an approach that looks at the ecosystem level would improve our ability to mitigate biodiversity loss and maintain the delivery of ecosystem services such as pollination," added Filazzola.

A team of researchers from the Biology Centre Czech Academy of Sciences (Budweis, Czechia), MARUM - Center for Marine Environmental Sciences at the University of Bremen (Germany), and Max Planck Institute for Marine Microbiology (Bremen, Germany) have estimated that these chemoautotrophs recycle approximately 5 per cent of the carbon and phosphorus assimilated by marine algae and release terragrams (1012 g) of dissolved organics to the ocean interior each year. These findings are now published in the journal Science Advances.

The widespread success of marine thaumarchaea arises largely from their ability to convert trace concentrations of ammonia to nitrite, which gives them energy to fix carbon and produce new biomass in the absence of light. This process, termed nitrification, recycles the chemical energy originally derived from photosynthesis by marine algae and is an essential component of global nutrient cycling. Using a radiotracer approach, the collaborative research effort has now determined that archaea fix roughly 3 moles of carbon for every 10 moles of ammonia oxidized and this efficiency varies with cellular adaptations to phosphorus limitation. "Thaumarchaea are active throughout the ocean, and their vast numbers imply significant contributions to global cycles of carbon (C) and nitrogen (N)," says Travis Meador, who is lead author of the study and had received a grant by the German Research Foundation (Deutsche Forschungsgemeinschaft DFG) to perform this work during his time at MARUM. "Just how much carbon is fixed by nitrifiers is regulated by the amount of organic nitrogen (energy) that is created during photosynthesis, the physiological coupling of nitrification and carbon-assimilation, and also apparently their ability access to phosphorus (P)."

Let them eat ammonia

Ammonia in the ocean derives from the breakdown of organic matter produced by phototrophs in surface waters and is a valuable source of energy and nutrition for Eukarya, Bacteria, and Archaea alike. Culture studies of the thaumarchaeon Nitrosopumilus maritimus have previously revealed that the tiny cells (Ø = 0.17-0.22 μm) boast enzyme systems to achieve a high affinity for ammonia and the most energy-efficient C-fixation pathway in the presence of oxygen. "These adaptations make thaumarchaea the oceans' foremost energy recycler, allowing them to outcompete their bacterial counterparts and create a separate niche, particularly in the deep ocean where energy is limiting," Meador said. "Our colleagues have suggested that most organic N that is exported below the ocean's euphotic zone eventually fuels nitrification by thaumarchaea. While the global export flux has been investigated for several decades, there has been no empirical evidence to further couple archaeal ammonia oxidation to global rates of C-fixation, until now."

The need for P

In addition to their important contributions to chemical fluxes in the dark ocean chemical, thaumarchaea are actually more abundant in the euphotic zone, where the majority of organic matter is respired (to CO2 and ammonia). In fact, the highest accumulations of ammonia may be situated at the base of the euphotic zone, where heterotrophic bacteria feed on the sinking biomass produced in the warm, surface mixed-layer and below where water temperatures decrease rapidly with depth.

This zone, known as the thermocline, also experiences large fluctuations in the concentration and turnover time of another key nutrient, phosphate (P). The researchers thus questioned if thaumarchaeal access to phosphate may control their contributions to recycled production in the surface ocean.

Interrogating archaea with radioactivity

By introducing radiolabeled 14C-bicarbonate and 33P-phosphate to the culture medium, the authors could track the rates of C and P assimilated into N. maritimus cells and released as dissolved organic carbon and phosphorus (DOC and DOP) metabolites into culture media. Normalizing these rates to nitrification, the researchers generated the first estimates of C-, P-, DOC-, and DOP- yields for a marine archaeon.

Acquainting the models

The upshot of this work is that global rates of C-fixation by widely-distributed thaumarchaea are likely at least 3-fold higher than previously assumed. Also, C- and P-assimilation by marine archaea may now be modeled as directly proportional to the renowned remineralization ratio established by Alfred Redfield in the mid-20th century. The researchers further found that N. maritimus is apt at acquiring phosphate, but strategic increases in cellular phosphate affinity came at a cost of approximately 30 per cent reduction in C-fixation efficiency. These results may therefore explain the widely ranging values of specific nitrification rate observed across the surface ocean. Finally, Meador portends that "the release of chemosynthetically manufactured compounds by thaumarchaea is minor compared to the substantial reservoir of dissolved organic nutrients in the ocean, but it does represent a fresh flux of labile substrates throughout the ocean interior".

Announcing a new article publication for BIO Integration journal. In this review article the authors Jing Liu, Mengze Xu and Zhen Yuan from University of Macau, Macau SAR, China consider immunotherapy for the treatment of tumors.

This review outlines the features of the most difficult-to-treat and challenging cold tumors and potential approaches to transform "cold" tumors into "hot" tumors, because hot tumors are associated with a higher response rate to immunotherapy. The authors also summarize the current popular strategies for enhancing T cell trafficking, which may be helpful to provide an etiological basement for a more rational design of drug delivery systems and conquer drug-resistance during cancer therapy.

Immunotherapy for the treatment of tumors has become the most compelling strategy after targeted treatment, especially for lung cancer and melanoma, as well as some blood cancers. For most remaining types of tumors (e.g., pancreatic, colorectal, and breast cancers), abundant immunotherapeutic strategies in the forms of immune checkpoint blockade, cancer vaccines, and CAR-T therapies produce little effect. Furthermore, the immunoreactions induced by various types of cancer and even in individual patients, differ among the single therapeutic immune checkpoint inhibitors, whose pre-existing immunoreaction remains to be optimized for cancer immunotherapy. According to the density of the infiltrating lymphocyte subsets at the invasive margin or core of primary solid tumors, the tumors were classified into four grades using the immunoscore, which is complementary to the tumor node metastasis (TNM) staging system in providing a better prognosis of cancer patients in addition to the classification of immunogenic hot tumors and non-immunogenic cold tumors.

BIO Integration is a fully open access journal which will allow for the rapid dissemination of multidisciplinary views driving the progress of modern medicine.

As part of its mandate to help bring interesting work and knowledge from around the world to a wider audience, BIOI will actively support authors through open access publishing and through waiving author fees in its first years. Also, publication support for authors whose first language is not English will be offered in areas such as manuscript development, English language editing and artwork assistance.

DNA scientists investigating new marine life migration patterns in the Atlantic Ocean surfaced the genetic traces of species far from their usual southern homes.

A species of ray -- the Brazilian cownose ray, Rhinoptera brasiliensis, and the Gulf kingfish, Menticirrhus littoralis, have been turning up when the weather turns warm in New Jersey's Barnegat Inlet, about a two hour drive south of New York City.

The ray has never before been recorded in the US north of the Gulf of Mexico; the perch-like Gulf kingfish has never before been recorded north of Chesapeake Bay, Virginia, about 250 miles (400 km) to the south.

Led by Mark Stoeckle of The Rockefeller University and published in the journal Frontiers in Marine Science, the study involved drawing seawater twice monthly for two years and testing it for genetic material -- DNA contained in cells sloughed off the slimy, gelatinous outer coating of a fish as it swims, for example, in its excretions, in tissue fragments shed in combat with a predator, or after death or injury.

Dr. Stoeckle explains that DNA degrades and disperses within a few days of an animal's departure, but lingers in the water, despite currents and tides, long enough to detect a species' passing presence.

Over two years, from spring 2017 to spring 2019, sampling was conducted at a pair of Barnegat Inlet, NJ sites within a few miles of each other -- an outer shore to sample Atlantic Ocean waters, and inside a sheltered bay.

In 2010, a Census of Marine Life program, the Future of Marine Animal Populations (FMAP), forecast changes in diversity of marine species based on available habitat and anticipated changes in water temperature.

Jesse Ausubel, Director of the Program for the Human Environment at The Rockefeller University, and CoML's co-founder, says the Brazilian cownose ray or Gulf kingfish far north of its known range fits FMAP's prediction, while noting that other explanations remain possible. For example, the animals may have simply evaded New Jersey trawl nets for years.

With changes in the oceans owing to climate, chemical pollution, debris, noise, night-time illumination, and other factors, Mr. Ausubel stresses, "this study further establishes aquatic environmental DNA (eDNA) as an innovative, inexpensive, low-impact way to monitor marine life migrations, changing ranges, diversity and distribution."

Says Dr. Stoeckle: "Promising work is also underway to confirm a relationship between the concentration of a species' DNA in seawater and the abundance of that species in the water. If water samples can provide an index of the number or total weight of fish of a given species in a defined ocean area, that offers a potential leap forward for sustainable fisheries and ocean management, improving the rationality with which fish quotas are set and the quality and reliability of their monitoring around the world."

Tony MacDonald, Director of Monmouth University's Urban Coast Institute, which helped initiate the work, adds: "Censusing marine fish and other animals that move typically involves costly, time-consuming surveys with specialized equipment and personnel. eDNA science is granting humanity a very old wish: an easy way to estimate the distribution and abundance of diverse fish species and other forms of aquatic life in the dark waters of rivers, lakes, and seas."

Dr. Stoeckle, who has worked with high school and college students to study New York Harbor and the Hudson River, adds that "the collection process is simple enough for supervised schoolchildren or citizen scientists on any coast anywhere to help monitor the changing ranges of all marine life." Co-author Mithun Das Mishu joined the project when he was a sophomore at Hunter College.

After water is drawn, it is filtered to concentrate the DNA for extraction. The target segment of the DNA is amplified in a laboratory and then sent for "next-generation" sequencing, the result of which--a record of all the DNA sequences in the sample--is fed into computer software that counts the number of copies of each sequence and searches for matches in an online public reference library.

The New Jersey study, co-authored by Mishu and bioinformatics expert Zachary Charlop-Powers, detected bony fish species in consistent seasonal patterns. And they found a small number of species accounted for the great majority of DNA obtained.

Detection of rays and other cartilaginous marine species, meanwhile, was confined mostly to warmer months.

In addition to straining its genetic material from the water, researchers used DNA to identify the decayed remains of a Brazilian cownose ray washed ashore in the sampling area in August 2017.

The researchers also added to growing global databases the first DNA reference sequences for 31 regional species catalogued by New Jersey scientists from trawl surveys over the past 30 years.

Dr. Stoeckle's earlier studies of New York's East and Hudson Rivers revealed the presence or absence of several key fish species passing through those waters. The weekly data snapshots created a moving picture that largely reinforced and correlated with knowledge from years of fishnet trawls.

By conducting a series of tests over time, the work pioneered a novel way to record fish migration. eDNA has a goldilocks quality just right for research, Dr. Stoeckle notes: If it disappeared too quickly, sampling wouldn't tell us much; if it lingered too long, too much DNA would be in the water, undermining useful, timely insights.

Next steps include fine tuning calibrations, comparing eDNA "reads" and results with data from traditional surveys conducted with nets and sonar. Do 100 DNA "reads" indicate the presence of 1 fish or 10 fish?

Also to be determined: the rate at which different fish and other marine species shed DNA.

A new machine learning tool can calculate the energy required to make -- or break -- a molecule with higher accuracy than conventional methods. While the tool can currently only handle simple molecules, it paves the way for future insights in quantum chemistry.

"Using machine learning to solve the fundamental equations governing quantum chemistry has been an open problem for several years, and there's a lot of excitement around it right now," says co-creator Giuseppe Carleo, a research scientist at the Flatiron Institute's Center for Computational Quantum Physics in New York City. A better understanding of the formation and destruction of molecules, he says, could reveal the inner workings of the chemical reactions vital to life.

Carleo and collaborators Kenny Choo of the University of Zurich and Antonio Mezzacapo of the IBM Thomas J. Watson Research Center in Yorktown Heights, New York, present their work May 12 in Nature Communications.

The team's tool estimates the amount of energy needed to assemble or pull apart a molecule, such as water or ammonia. That calculation requires determining the molecule's electronic structure, which consists of the collective behavior of the electrons that bind the molecule together.

A molecule's electronic structure is a tricky thing to calculate, requiring the determination of all the potential states the molecule's electrons could be in, plus each state's probability.

Since electrons interact and become quantum mechanically entangled with one another, scientists can't treat them individually. With more electrons, more entanglements crop up, and the problem gets exponentially harder. Exact solutions don't exist for molecules more complex than the two electrons found in a pair of hydrogen atoms. Even approximations struggle with accuracy when they involve more than a few electrons.

One of the challenges is that a molecule's electronic structure includes states for an infinite number of orbitals going farther and farther from the atoms. Additionally, one electron is indistinguishable from another, and two electrons can't occupy the same state. The latter rule is a consequence of exchange symmetry, which governs what happens when identical particles switch states.

Mezzacapo and colleagues at IBM Quantum developed a method for constraining the number of orbitals considered and imposing exchange symmetry. This approach, based on methods developed for quantum computing applications, makes the problem more akin to scenarios where electrons are confined to preset locations, such as in a rigid lattice.

The similarity to rigid lattices was the key to making the problem more manageable. Carleo previously trained neural networks to reconstruct the behavior of electrons confined to the sites of a lattice. By extending those methods, the researchers could estimate solutions to Mezzacapo's compacted problems. The team's neural network calculates the probability of each state. Using this probability, the researchers can estimate the energy of a given state. The lowest energy level, dubbed the equilibrium energy, is where the molecule is the most stable.

The team's innovations made calculating a basic molecule's electronic structure simpler and faster. The researchers demonstrated the accuracy of their methods by estimating how much energy it would take to pull a real-world molecule apart, breaking its bonds. They ran calculations for dihydrogen (H2), lithium hydride (LiH), ammonia (NH3), water (H2O), diatomic carbon (C2) and dinitrogen (N2). For all the molecules, the team's estimates proved highly accurate even in ranges where existing methods struggle.

In the future, the researchers aim to tackle larger and more complex molecules by using more sophisticated neural networks. One goal is to handle chemicals like those found in the nitrogen cycle, in which biological processes build and break nitrogen-based molecules to make them usable for life. "We want this to be a tool that could be used by chemists to process these problems," Carleo says.

Carleo, Choo and Mezzacapo aren't alone in tapping machine learning to tackle problems in quantum chemistry. The researchers first presented their work on arXiv.org in September 2019. In that same month, a group in Germany and another at Google's DeepMind in London each released research using machine learning to reconstruct the electronic structure of molecules.

The other two groups use a similar approach to one another that doesn't limit the number of orbitals considered. This inclusiveness, however, is more computationally taxing, a drawback that will only worsen with more complex molecules. With the same computational resources, the approach by Carleo, Choo and Mezzacapo yields higher accuracy, but the simplifications made to obtain this accuracy could introduce biases.

"Overall, it's a trade-off between bias and accuracy, and it's unclear which of the two approaches has more potential for the future," Carleo says. "Only time will tell us which of these approaches can be scaled up to the challenging open problems in chemistry."

A Stanford research team has developed a way to boost the effectiveness of the insulin injections people with diabetes routinely take to control their blood sugar.

Led by materials scientist Eric Appel, the advance might enable patients with diabetes to take a double-acting shot that contains insulin in combination with a drug based on a second hormone, known as amylin. Amylin plays a synergistic role with insulin to control blood sugar levels after eating in a way that is more effective than insulin alone and mimics what occurs naturally with a meal.

While the amylin-based drug is already commercially available, it is estimated that less than 1 percent of patients with diabetes taking insulin therapy also take this complementary treatment because the two hormones - which work together seamlessly in the body - are too unstable to coexist in the same syringe.

"Taking that second injection with the insulin shot is a real barrier for most patients. Our formulation would allow them to be given together in a single injection or in an insulin pump," said Appel, senior author of a research paper published May 11 in Nature Biomedical Engineering.

The new technique involves a protective coating that wraps around insulin and amylin molecules and, for the first time, allows them to coexist in a single shot.

"This coating dissolves in the bloodstream, enabling these two important hormones to work together in a way that mimics how they function in healthy individuals," Appel said.

So far, the researchers have tested the wrapper's stability in the laboratory, and done preliminary experiments to see how their two-in-one injection works on the most advanced preclinical model - diabetic pigs. But, because both drugs are already on the market and the dual-drug formulation was tested in advanced models, Appel said the team need only demonstrate that their technique is nontoxic in humans to start trials in people, bringing this technology closer to market than most early-stage drugs.

Appel and his collaborators hope this approach could, one day, dramatically increase the use of amylin and lead to improved glucose management for the estimated 450 million people worldwide with either juvenile (type 1) diabetes or adult-onset (type 2) diabetes.

Although few patients with diabetes currently take the amylin-based drug after their insulin injection, those who do experience profound benefits, Appel said. Past clinical data shows that patients taking both lose weight and have better control over their blood sugar. Enhanced diabetes management can reduce the risk of serious health complications, such as renal failure, blindness, heart disease and amputations, all of which loom over anyone with diabetes.

If the wrapper approach makes it possible to combine insulin and amylin in one dose, this would offer patients with diabetes a convenient way to mimic their natural secretion in the human body. In non-diabetics, amylin is secreted from the same cells in the pancreas that produce insulin. Insulin improves the uptake of sugar by cells, removing it from the bloodstream.

For its part, amylin does three things to control blood sugar. First, it stops another hormone, glucagon, from telling the body to release additional sugar that has been stored in the liver. Second, it produces a sense of "fullness" at mealtimes that reduces food intake. Third, it actually slows the uptake of food by the body, reducing the typical spike in blood sugar after a meal. All three are a boon to diabetes care.

To make it possible to pair insulin and amylin in one syringe, the researchers developed a molecular wrapper made of polyethylene glycol, or PEG, a common nontoxic chemical used in everything from cosmetics to laxatives. The Stanford team used a new type of PEG that has a sort of molecular Velcro on the end, called cucurbituril-PEG or CB-PEG. The Velcro-like abilities of CB-PEG enable it to reversibly bind to both insulin and amylin separately, shielding the unstable portions of each molecule from breakdown. Once injected into the body, however, the drugs unbind from the CB-PEG and are free to act unhindered.

"CB-PEG is an entirely new chemical entity," Appel said.

In lab tests of stability, the researchers heated wrapped and unwrapped insulin to normal body temperature and shook it, a process known as stressed aging. They found that unprotected insulin was stable for just 10 hours in the test tube, but the "PEGylated" insulin was still fully active 100 hours later. Without the wrap, the dual-drug combo fails in just 3 hours.

More impressive, however, is that the co-formulation of PEGylated insulin and amylin remained stable for at least 100 hours, which could be a long enough shelf life to mean that the combination could be delivered by insulin pumps.

In animal studies, the researchers saw significant overlap of the activity of the dual-drug formulation, an important finding that indicates the approach is closely mimicking what happens in a healthy body - including a near-total suppression of glucagon, the hormone that tells the liver to release stored sugar, even though the person has just consumed a meal.

"We're excited about the results to say the least," Appel said. Appel has already filed for a patent on the technology.

When it comes to forming a lasting bond, our longing for a partner may be as important as--if not more important than--how we react when we're with them, suggests a surprising new brain imaging study published in the Proceedings of the National Academy of Sciences this week.

"In order to maintain relationships over time, there has to be some motivation to be with that person when you are away from them," said lead author Zoe Donaldson, an assistant professor of behavioral neuroscience at the University of Colorado Boulder. "Ours is the first paper to pinpoint the potential neural basis for that motivation to reunite."

The paper marks the latest discovery in Donaldson's years-long study of prairie voles, one of only about 3% to 5% of mammalian species (including humans) that tend to mate for life. By observing the behavior and brain activity of the monogamous rodents, she seeks to better understand what brain regions--down to the cellular level--drive the instinct to form lasting bonds.

Ultimately, the findings could be used to develop therapies for those with autism, severe depression and other disorders that make such emotional connections hard to come by. But right now, she said, the research also lends insight into why social distancing is so tough.

"We are uniquely hardwired to seek out close relationships as a source of comfort, and that often comes through physical acts of touch," she said.

For the study, Donaldson used tiny cameras and a cutting-edge technology called in-vivo-calcium imaging to spy on the brains of dozens of voles at three time points: when they were just meeting another vole; three days after they had mated; and 20 days after they had essentially moved in together. Researchers also observed the animals interacting with voles who were not their mates.

Previous brain imaging research in humans has shown altered brain activity in a region called the nucleus accumbens, the same reward center that lights up during heroin or cocaine use, when the research subjects held the hand of a romantic partner versus a stranger. So, at first, Donaldson's team assumed the voles' brain activity would be markedly different when they were huddling with their mate versus a random vole.

"Surprisingly, that is not what we found," she said.

Stranger or lover, the voles' brains looked basically the same when they were together.

It was only when the voles were away from their partner and running to meet them--imagine the classic romantic reunion-scene at the airport or the theme of any number of love poems--that a unique cluster of cells in the nucleus accumbens consistently fired up.

The longer the animals had been paired, the closer their bond became and the larger the glowing cluster of cells--dubbed the "partner approach ensemble"--on image screens.

Notably, a completely different cluster of cells lit up when the vole approached a stranger.

"This suggests that maybe the recruitment of these cells for this new purpose is important for forming and maintaining a bond," Donaldson said.

She suspects that brain chemicals like oxytocin, dopamine and vasopressin, which have been shown in both animal and human studies to play a role in fostering trust and closeness, are involved in the process. But she doesn't know for sure what that cluster of cells does.

It's also not clear whether the specific "neuronal code" associated with a desire to reunite in voles inspires the same emotion in people. More research is underway.

What the study does confirm is that monogamous mammals are uniquely hard-wired to be with others.

"These negative feelings so many of us are experiencing right now may result from a mismatch: we have a neuronal signal telling us that being with loved ones will make us feel better, while practical restrictions mean this need is going unmet," Donaldson said. "It's the emotional equivalent of not eating when we are hungry, except now instead of skipping a meal, we are slowly starving."

An interdisciplinary team of researchers at the Eli and Edythe Broad Center for Regenerative Medicine and Stem Cell Research at UCLA has developed a first-of-its-kind roadmap of how human skeletal muscle develops, including the formation of muscle stem cells.

The study, published in the peer-reviewed journal Cell Stem Cell, identified various cell types present in skeletal muscle tissues, from early embryonic development all the way to adulthood. Focusing on muscle progenitor cells, which contribute to muscle formation before birth, and muscle stem cells, which contribute to muscle formation after birth and to regeneration from injury throughout life, the group mapped out how the cells' gene networks -- which genes are active and inactive -- change as the cells mature.

The roadmap is critical for researchers who aim to develop muscle stem cells in the lab that can be used in regenerative cell therapies for devastating muscle diseases, including muscular dystrophies, and sarcopenia, the age-related loss of muscle mass and strength.

"Muscle loss due to aging or disease is often the result of dysfunctional muscle stem cells," said April Pyle, senior author of the paper and a member of the Broad Stem Cell Research Center. "This map identifies the precise gene networks present in muscle progenitor and stem cells across development, which is essential to developing methods to generate these cells in a dish to treat muscle disorders."

Researchers in Pyle's lab and others around the world already have the capacity to generate skeletal muscle cells from human pluripotent stem cells -- cells that have the ability to self-renew and to develop into any cell type in the body. However, until now, they had no way of determining where these cells fall on the continuum of human development.

"We knew that the muscle cells we were making in the lab were not as functional as the fully matured muscle stem cells found in humans," said Haibin Xi, first author of the new paper and an assistant project scientist in Pyle's lab. "So we set out to generate this map as a reference that our lab and others can use to compare the genetic signatures of the cells we are creating to those of real human skeletal muscle tissue."

To create this resource, the group gathered highly specific data about two different groups of skeletal muscle cells: those from the human body, ranging from the fifth week of embryonic development to middle age, and those derived from human pluripotent stem cells the researchers generated in the lab. They then compared the genetic signatures of cells from both sources.

The group obtained 21 samples of human skeletal muscle tissue from their UCLA collaborators and from colleagues at the University of Southern California and the University of Tübingen in Germany. For the pluripotent stem cell-derived muscle cells, the group evaluated cells created using their own unique method and the methods of several other groups.

The Pyle lab collaborated with the lab of Kathrin Plath, a UCLA professor of biological chemistry and member of the Broad Stem Cell Research Center, to conduct high-throughput droplet-based single-cell RNA sequencing of all of the samples. This technology enables researchers to identify the gene networks present in a single cell and can process thousands of cells at the same time. Leveraging the power of this technology and the Plath lab's bioinformatics expertise, the group identified the genetic signatures of various cell types from human tissues and pluripotent stem cells.

They next developed computational methods to focus on muscle progenitor and stem cells and mapped out their gene networks associated with every developmental stage. This enabled the group to match the genetic signatures found in the pluripotent stem cell-derived muscle cells with their corresponding locations on the map of human muscle development.

The group found that pluripotent stem cell-derived muscle cells produced by all the methods they tried resembled muscle progenitor cells at an early developmental state and did not align to adult muscle stem cells.

In addition to pinning down the true maturity of the lab-produced cells, this analysis also provided details about the other cell types present in skeletal muscle tissue across development and in populations derived from human pluripotent stem cells. These cells could play an essential role in muscle cell maturation and could be critical to improving methods to generate and support muscle stem cells in a dish.

"We found that some methods to generate muscle cells in a dish also produce unique cell types that likely support the muscle cells," said Pyle, who is also a member of the UCLA Jonsson Comprehensive Cancer Center. "And so now our questions are, what are these cells doing? Could they be the key to producing and supporting mature and functional muscle stem cells in a dish?"

Moving forward, Pyle and her colleagues will focus on harnessing this new resource to develop better methods for generating muscle stem cells from human pluripotent stem cells in the lab. She hopes that by focusing on the stem cell-associated gene expression networks and supportive cell types they identified, they can produce high-powered muscle stem cells that can be useful for future regenerative therapies.