Earth

In patients with bladder cancer, chemotherapy effectiveness is partially determined by the body's immune system response to the malignancy. This is the conclusion of research conducted by a team of scientists from Charité - Universitätsmedizin Berlin and the Berlin Institute of Health. The findings, which have been published in Science Translational Medicine*, can be used to predict treatment success and may increase survival in patients with bladder cancer.

Bladder cancer is one of the ten most common types of cancer in Germany, and one of the five most common cancers in men. Nationwide, the disease affects approximately 30,000 people a year. The risk of the cancer spreading (metastasizing) is particularly high once it invades the muscle layer inside the bladder wall. In patients with non-metastatic muscle-invasive bladder cancer, treatment usually consists of the surgical removal of the bladder. According to current professional guidelines, patients must undergo chemotherapy prior to surgery; they receive drugs which will target the cancer's fast-growing cells. The aim of this 'neoadjuvant' chemotherapy is to shrink the tumor prior to surgery in order to reduce the risk of recurrence and/or metastases. However, in more than fifty percent of patients, chemotherapy will not shrink the tumor. Not only do these people not benefit from neoadjuvant chemotherapy, they are losing valuable time - time during which the cancer can continue to grow and metastasize.

An international team of researchers led by Dr. Michael Schmück-Henneresse, a scientist at the Berlin Institute of Health Center for Regenerative Therapies (BCRT) as well as Charité's Institute of Medical Immunology and the Berlin Center for Advanced Therapies (BeCAT), has discovered a way to differentiate between patients who will benefit from chemotherapy and those who will not. The status of the patients' immune systems before the start of treatment was found to hold the key. Subsequent chemotherapy only proved effective if the cancerous tissue contained large quantities of two specific immune system components known as CXCL11 and CXCR3alt. "The process of measuring these two components in the laboratory is relatively straightforward and only requires the biopsy sample which is collected in order to diagnose the cancer," says Dr. Schmück-Henneresse. "This technologically simple method will make it possible to predict the likelihood of chemotherapy success in a specific patient at the point of diagnosis. If neoadjuvant chemotherapy is unlikely to be successful, one could dispense with this therapy altogether and directly move to the bladder cancer's surgical removal. This type of personalized approach would not only spare patients the side effects of an ineffective treatment, it would probably increase their chances of survival. However, our results will need to be confirmed by further, independent studies before we can get to a stage where CXCL11 and CXCR3alt measurements become standard in patients with bladder cancer."

As part of this research, the team studied tumor samples from 20 patients with muscle-invasive bladder cancer who had completed their chemotherapy treatment at Umeå University in Sweden. Dating back to before the start of treatment, the samples had been collected by Dr. Amir Sherif and his team during diagnostic cytoscopy procedures. The research group identified which immunological messengers were present in the biopsy tissue and which receptors (effectively the 'recipients' of these messengers) the immune cells inside the tumors were producing. For each of the components identified, they then tested whether there was a link between the quantities at which these were present and treatment success. Results confirmed this was the case for both the messenger substance CXCL11 and the receptor CXCR3alt. Chemotherapy only had an effect if the immune cell attractant CXCL11 was present at particularly high levels inside the tumor tissue and if specific immune system cells known as T cells produced the corresponding CXCR3alt receptor. The team subsequently examined their observations using existing data from 'The Cancer Genome Atlas'. Their comparison confirmed that, out of a total of 68 patients with bladder cancer who had received chemotherapy, patients whose tumor tissue contained large quantities of CXCL11 were more likely to survive.

"The signaling molecule CXCL11 attracts specific T cells into the tumor tissue, where it prompts them to proliferate and fight the cancer," explains the study's first author, Tino Vollmer, a doctoral student at Charité's Institute of Medical Immunology and scientist at the BCRT and BeCAT. "Chemotherapy appears to support the body's own fight against the tumor, possibly because the resulting degradation of cancerous tissue makes it easier for T cells to invade it." The immune system's effect on treatment outcome directly contradicts established scientific consensus, which posits that the effect of chemotherapy drugs is solely due to the ability of cancer cells to divide and replicate. "Along with other studies, our research demonstrates the importance of the immune system's active involvement in fighting the tumor," says Vollmer.

As a next step, the researchers plan to study whether cell therapy could be used to activate the T cells of patients whose immune systems show a weak response to their bladder cancer. To do this, the team wants to harvest T cells from affected patients, fit them with synthetic CXCR3alt receptors in the laboratory, and then reintroduce them into these patients. The researchers will also study the same approach in relation to the treatment of other cancers. Furthermore, they plan to advance the use of personalized chemotherapy in patients with bladder cancer. To achieve this, the researchers intend to test the predictive power of both immune system components (CXCL11 and CXCR3alt) using a process known as 'predictive validation', which will involve the study of independent groups of patients with muscle-invasive bladder cancer at various European hospitals. "Should the method's predictive reliability be confirmed, the analysis of a patient's immune status could become a routine tool to support decision-making in the treatment of bladder cancer," says Dr. Schmück-Henneresse.

Recently, the research team led by academician GUO Guangcan from the University of Science and Technology of China of the Chinese Academy of Sciences has made security analysis and improvement of source independent quantum random number generators with imperfect devices.

By studying the actual characteristics of the measurement devices of the source-independent quantum random number generation, the researchers pointed out that the security issues were caused by afterpulse, detection efficiency mismatching, poor sensitivity to photon number distribution in measurement devices, etc., and gave the corresponding solutions. The study was published in npj Quantum Information.

The source-independent quantum random number generation protocol is a new quantum random number protocol proposed in 2016. This protocol can generate secure random numbers under the condition that the light source is completely untrusted by monitoring the error code of the mutual unbiased basis corresponding to the base of the random number generation. It can simultaneously meet the requirements of security and high rate of random number generator, and has a very high devices loss tolerance.

However, the protocol has some security problems, such as the failure to consider the afterpulse problem of the detector, the mismatch of detection efficiency, the poor sensitivity of the detector to the distribution of light source and other characteristics, which impedes the application of this protocol.

In this study, the researchers presented a detector model containing these actual parameters, and then evaluated the impact of these problems on actual security. At the same time, aiming at the afterpulse problem, they gave the security random number information upper bound with the existence of eavesdropping.

To solve the problem of detection efficiency mismatch and poor detector sensitivity to the distribution of light source, the researchers proposed a method for monitoring the distribution of light source, and gave a bit rate formula based on the composable security with full consideration to the finite length effect.

This study has quantitatively analyzed the security problem caused by imperfect measurement devices in source-independent quantum random number systems and given the corresponding solutions, which provides an important theoretical support for the realization of ultra-fast commercial source-independent quantum random number generator.

In the inaugural issue of the journal Nature Aging a research team led by aging expert Linda P. Fried, MD, MPH, dean of Columbia University Mailman School of Public Health, synthesizes converging evidence that the aging-related pathophysiology underpinning the clinical presentation of phenotypic frailty (termed as "physical frailty" here) is a state of lower functioning due to severe dysregulation of the complex dynamics in our bodies that maintains health and resilience. When severity passes a threshold, the clinical syndrome and its phenotype are diagnosable. This paper summarizes the evidence meeting criteria for physical frailty as a product of complex system dysregulation. This clinical syndrome is distinct from the cumulative-deficit-based frailty index of multimorbiditys. The paper is published online here.

Physical frailty is defined as a state of depleted reserves resulting in increased vulnerability to stressors that emerges during aging independently of any specific disease. It is clinically recognizable through the presence of three or more of five key clinical signs and symptoms: weakness, slow walking speed, low physical activity, exhaustion and unintentional weight loss.

The authors of this Perspectives article integrate the scientific evidence of physical frailty as a state, largely independent of chronic diseases, that emerges when the dysregulation of multiple interconnected physiological and biological systems crosses a threshold to critical dysfunction that severely compromises homeostasis, or stability among the body's physiological presses. The physiology underlying frailty is a critically dysregulated complex dynamical system. This conceptual framework implies that interventions such as physical activity that have multisystem effects are more promising to remedy frailty than interventions targeted at replenishing single systems.

Fried and colleagues then consider how this framework can drive future research to optimize understanding, prevention and treatment of frailty, which will likely preserve health and resilience in aging populations.

"We hypothesized that when Individual physiological systems decline in their efficiency and communication between cells and between systems deteriorate, this results in a cacophony of multisystem dysregulation which eventually crosses a severity threshold and precipitates a state of highly diminished function and resilience, physical frailty," said Fried, who is also director of the Robert N. Butler Columbia Aging Center.

"The key insight is simply that one's physiological state results from numerous interacting components at different temporal and spatial scales (e.g., genes, cells, organs) that create a whole unpredictably more than the parts," observes Fried.

For example, Fried notes that physical frailty prevalence and incidence has been linked to the interconnected dynamics of three major systems, altered energy metabolism through both metabolic systems, including glucose/insulin dynamics, glucose intolerance, insulin resistance, alterations in energy regulatory hormones such as leptin, ghrelin, and adiponectin, and through alterations of musculoskeletal systems function, including efficiency of energy utilization and mitochondrial energy production and mitochondrial copy number. Notably, across these systems, both energy production and utilization are abnormal in those who are physically frail.

The aggregate stress response system and its subsystems are also abnormal in physical frailty. Specifically, inflammation is consistently associated with being frail, including significant associations with elevated inflammatory mediators such as C-reactive protein, Interleukin 6 (IL-6, and white blood cells including macrophages and neutrophils, among others, in a broad pattern of chronic, low-grade inflammation. Each of these three systems mutually regulate and respond to the others in a complex dynamical system.

The authors recommend that multisystem fitness is needed to maintain resilience and prevent physical frailty, including macro-level interventions such as activities to improve physical activity or social engagement; the latter, apart from contributing to psychological well-being, also can increase physical and cognitive activity.

"There is strong evidence that frailty is both prevented and ameliorated by physical activity, with or without a Mediterranean diet or increased protein intake," noted Fried.

"These model interventions to date are nonpharmacologic, behavioral ones, emphasizing the potential for prevention through a complex systems approach."

"This work, conducted under the leadership of Dr. Linda Fried, is the culmination of nearly two decades of research characterizing the pathophysiology of the frailty syndrome. It should pave the way for further elucidating the underlying mechanisms of frailty pathogenesis," said Ravi Varadhan, PhD, PhD, Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University, and a co-author. "The paper postulates that energetics - the totality of the processes involved in the intake, utilization, and expenditure of energy by the organism - is the key driver of frailty. Testing this hypothesis would be an important area of future research in aging."

Researchers from the University of Cambridge, the University of Milan and Google Research have used machine learning techniques to predict how proteins, particularly those implicated in neurological diseases, completely change their shapes in a matter of microseconds.

They found that when amyloid beta, a key protein implicated in Alzheimer's disease, adopts a highly disordered shape, it actually becomes less likely to stick together and form the toxic clusters which lead to the death of brain cells.

The results, reported in the journal Nature Computational Science, could aid in the future development of treatments for diseases involving disordered proteins, such as Alzheimer's disease and Parkinson's disease.

"We are used to thinking of proteins as molecules that fold into well-defined structures: finding out how this process happens has been a major research focus over the last 50 years," said Professor Michele Vendruscolo from Cambridge's Centre for Misfolding Diseases, who led the research. "However, about a third of the proteins in our body do not fold, and instead remain in disordered shapes, sort of like noodles in a soup."

We do not know much about the behaviour of these disordered proteins, since traditional methods tend to address the problem of determining static structures, not structures in motion. The approach developed by the researchers harnesses the power of Google's computer network to generate large numbers of short trajectories. The most common motions show up multiple times in these 'movies', making it possible to define the frequencies by which disordered proteins jumps between different shapes.

"By counting these motions, we can predict which states the protein occupies and how quickly it transitions between them," said first author Thomas Löhr from Cambridge's Yusuf Hamied Department of Chemistry.

The researchers focused their attention on the amyloid beta peptide, a protein fragment associated with Alzheimer's disease, which aggregates to form amyloid plaques in the brains of affected individuals. They found that amyloid beta hops between widely different states millions of times per second without ever stopping in any particular state. This is the hallmark of disorder, and the main reason for which amyloid beta has been deemed 'undruggable' so far.

"The constant motion of amyloid beta is one of the reasons it's been so difficult to target - it's almost like trying to catch smoke in your hands," said Vendruscolo.

However, by studying a variant of amyloid beta, in which one of the amino acids is modified by oxidation, the researchers obtained a glimpse on how to make it resistant to aggregation. They found that oxidated amyloid beta changes shape even faster than its unmodified counterpart, providing a rationale to explain the decreased tendency for aggregation of the oxidated version.

"From a chemical perspective, this modification is a minor change. But the effect on the states and transitions between them is drastic," said Löhr.

"By making disordered proteins even more disordered, we can prevent them from self-associating in aberrant manners," said Vendruscolo.

The approach provides a powerful tool to investigate a class of proteins with fast and disordered motions, which have remained elusive so far despite their importance in biology and medicine.

Scientists who highlighted the bug-busting properties of bacteria in Northern Irish soil have made another exciting discovery in the quest to discover new antibiotics.

The Traditional Medicine Group, an international collaboration of scientists from Swansea University, Brazil and Northern Ireland, have discovered more antibiotic-producing species and believe they may even have identified new varieties of antibiotics with potentially life-saving consequences.

Antibiotic resistant superbugs could kill up to 1.3 million people in Europe by 2050 - the World Health Organisation (WHO) describes the problem as "one of the biggest threats to global health, food security, and development today".

The search for replacement antibiotics to combat multi-resistance has prompted researchers to explore new sources, including folk medicines focusing on environments where well-known antibiotic producers like Streptomyces can be found.

The Traditional Medicine Group discovered that soil used in ancient Irish folk medicine in the West Fermanagh scarplands contains several species of these antibiotic producing organisms. This area of caves, alkaline grassland and bog is scattered with many remnants of previous Neolithic habitation.

One of the research team, Dr Gerry Quinn, a previous resident of Boho, County Fermanagh, has been aware of the healing traditions of the area for many years. Several years ago, an analysis of the soil there led to the team discovering a previously unknown strain of bacteria effective against four of the top six hospital superbugs that are resistant to antibiotics, including MRSA.

Since then, their research has continued but given local religious sensitivities and the self-limiting nature of the original site, the group relocated their search to another area of the West Fermanagh scarplands that retained the essential alkaline nature of the grasslands whilst also providing a link to traditional folk medicine.

Dr Paul Facey, one of the lead researchers from Swansea University said: "The fact that traditional medicine is incorporated in many local folk tales led us to believe that there was a good possibility of finding strong antibiotic producing organisms in other locations in these limestone hills."

The group discovered that their latest finding was able to express an even wider range of antimicrobial activity than their previous discovery.

The results of this study have now been published in MDPI Applied Microbiology and the DNA sequence has been deposited in the American national collection.

Antibiotic tests performed by Dr Quinn, Simms Adu, from Ulster University, and Swansea University's Nada Alharbi reveal that Streptomyces sp. CJ13 inhibits the growth of multi-resistant organisms such as:

Gram negative Pseudomonas aeruginosa, a common opportunistic pathogen associated with chronic lung infections in cystic fibrosis patients;

MRSA, a common opportunistic pathogen often resistant to many antibiotics;

Anaerobic bacteria, usually found in deep wounds, which cause serious infections; and

Candida, a yeast species often overlooked in mixed bacterial infections.

The group has yet to chemically identify the compounds responsible for antibiotic activity but preliminary analysis indicates there are genetic similarities to other known antibiotic production genes.

Even though the antibiotic genes found in Streptomyces sp. CJ13 are not identical to template antimicrobials, it raises the interesting possibility that these could be new varieties of antibiotics.

Given the significant contributions made by Streptomyces to the fields of cancer and anti-viral therapies, team member Hamid Bakshi added: "We are confident in the great potential of our most recent discovery to provide many interesting discoveries."

By feeding arctic ground squirrels special diets, researchers have found that omega-3 fatty acids, common in flax seed and fish oil, help keep the animals warmer in deep hibernation.

A University of Alaska Fairbanks-led study fed ground squirrels either a diet high in omega-3s or a normal laboratory diet, and measured how the animals hibernated afterward. Researchers found that the omega-3 diet helped the animals hibernate a little warmer than normal without negatively affecting hibernation. The omega-3 diets also increased the amount of a heat-producing fat, called brown adipose tissue, the animals pack on.

The discovery could add more understanding about how hibernation works and why animals eat some types of foods. The study was published Jan. 14 in the journal Scientific Reports.

"Arctic ground squirrels have an innate ability to withstand harsh subzero temperatures for an incredible amount of time," says Monica Mikes, who at the time of the study was an undergraduate researcher at UAF and a scholar in the university's Biomedical Learning and Student Training program.

Mikes, who also co-designed the study, noted that the animals are able to take their body temperature below freezing. How hibernators regulate body temperature has fascinated researchers for over a century. The type of fat they eat might have something to do with that.

Recent studies have found that omega-3s can affect metabolism in nonhibernating animals. Since wild hibernators are known to eat diets rich in omega-3 foods, the researchers wanted to know if those animals benefited from eating those diets.

"Fat is incredibly important in hibernation," said lead author Sarah Rice, who was a Ph.D. student at UAF's Institute of Arctic Biology at the time of the study. "Not only do these animals live off their fat stores, but the more people study specific types of fat, the more they realize specific types of fat can help regulate and signal the body to do certain things."

Scientists know hibernators specifically seek out and store polyunsaturated fatty acids, known as PUFAs, prior to hibernation. While omega-6 PUFAs have been well-studied in hibernation and are known to reduce temperature, omega-3s have been less studied.

As arctic ground squirrels experience extreme cold in their natural dens, eating more omega-3s to help increase brown adipose tissue may help defend against extreme cold in the wild. Researchers in this study did not investigate which foods might provide ground squirrels in the wild with such omega-3s.

"People know eating omega-3s like fish oil is good for them. Apparently, squirrels may realize this too, and it may have specialized effects for hibernators," Rice said.

In a normal year, biologists Daniel Janzen and Winnie Hallwachs spend about six months in Costa Rica, where they conduct research and pursue conservation efforts in Área de Conservación Guanacaste (ACG), a World Heritage Site in the northwest that encompasses, a network of parks and preserves they helped establish in the 1980s and that has grown to more than 400,000 acres, including marine, dry forest, cloud forest, and rain forest environments.

In 2020 that is where the married couple was when the COVID-19 pandemic took hold of the world, and compelled them to extend their stay in the virus-free forest until the fall, when they felt safe enough to travel back to their other home in Philadelphia.

"With modern laptops and internet, we could watch the world go by from the safety of the forest," says Janzen, a biology professor in the School of Arts & Sciences.

The extra time in the forest gave them added time for reflection, some of the fruits of which appear in a piece published this week in the Proceedings of the National Academy of Sciences, part of a special issue on global insect decline.

Their contribution draws on data collected since the 1970s on insect abundance and diversity in the tropics, as well as on observations about climate change that go back even further. Although the ACG's protected status has effectively eliminated certain threats to biodiversity loss, such as fire, hunting, deforestation, and pesticide use, the creatures that dwell there are not exempt from what Janzen and Hallwachs call the "heterogenous blanket" of climate change effects.

"What we have seen and lived since the mid-1970s, unambiguously, in our Costa Rican tropical wild world is that the biomass and species richness of insect individuals and species, and their interactions with everything, are decomposing," they write.

To respond to this decline, the scientists have focused their efforts locally. Keeping track of the effects of climate change through consistent monitoring is essential, they say, but what even more critical is engaging the people who own the preserved land: all five million Costa Ricans, in this case. Janzen and Hallwachs are internationally known for their work on this front, having created a model in ACG that empowers and employs local people in conservation work and attempts to facilitate the movement of these processes throughout the national park system and abroad.

In their article, the researchers describe a new approach to expand on these successes: BioAlfa, a nationwide program designed to enlist Costa Ricans themselves in hands-on learning and research about their nation's wild ecosystems. The initiative's name comes from the Spanish for bioliterate, "bioalfabetizado."

"The tradition in tropical countries is that when you want to know something about the biology of your country, expeditions from the North come and do studies of one sort or another and then they take the information home with them," Janzen and Hallwachs say. "What we said is, 'Look, you're capable of doing this all yourselves. You can find all the bugs and the plants and the birds and everything in your own country and, in the process, learn about them.'"

Measuring climate's toll

Janzen and Hallwachs never intended to explicitly study climate change. But its effects have been impossible to ignore. They note that in the 1980s cloud cover was a constant presence over the aptly named cloud forests of ACG, shrouding peaks like Volcán Orosí and Volcán Cacao. Yet the cloud layer shrank by the 1990s and now,many days pass with no cloud cover whatsoever. The result is a drying of forest ecosystems to the detriment of insects and other wildlife that thrive in damp leaf litter and moist conditions, to say nothing of the drying waterways that used to adequately irrigate flatland crops and other development.

The ACG now experiences far more days of temperatures that approach and exceed 90 degrees Fahrenheit than it did in past decades. In addition, a prolonged dry season and greater irregularities in rainfall amount and timing compound the stresses on the biodiversity that lives there. Essentially all tropical organisms use weather cues to guide their lives, and when these change and fracture everyone takes a hit.

Janzen and Hallwachs note that these climatic perturbations have extracted a price on insect biodiversity, a bellwether for impacts on the food web bottom to top. In their report, they compare photos from moth surveys--conducted at night by using a bright light to attract moths to a light-colored sheet, where they can be counted--that indicate a dramatic drop in both moth numbers and species diversity since the 1980s.

Looking at a different types of insects, they say that, despite a constant search effort by ACG's on-the-ground staff of trained and experienced neighbor researchers, the overall number of caterpillars found during regular surveys has fallen in half since 2005, a clear sign of decline.

Supporting this finding, when caterpillars are found, they are now less likely to be parasitized by another insect species. About a fifth of caterpillars were found parasitized in 1985; that has fallen to just 5% in recent years. While this may be a good thing for individual caterpillars, it's a worrying sign overall. Because parasites are hyperspecialized to associate with particular caterpillar species, Janzen says that this lack of parasitized caterpillars suggests that caterpillar numbers are so few that the parasites are unable to locate their desired species and maintain their populations.

"When caterpillar density goes down, the parasites go extinct faster," Janzen says. "So now you've lost that carnivore. And you repeat that a thousand times, 10,000 times."

Being 'kind to the survivors'

Mitigating climate change can be an overwhelming task, and Janzen says that "little guys"--like the economically-small but biodiversity-big country of Costa Rica--are unlikely to make a big-picture impact, except by example. In his eyes, it's essential for small tropical nations to focus energy on creating the conditions that enable the survivors of climate change to maintain a foothold. And that is where BioAlfa comes in.

While international conservation groups contribute money to preserve land in lush, biodiverse locales, such as ACG, the researchers argue that gaining buy-in from all levels of the owners of that preserved land, rather than outsiders who may never step foot in the country, is a necessary ingredient in tropical conservation.

"Charismatic vertebrates, tourist snapshots, and marketable big tree trunks are not even 0.001% of tropical biodiversity," Janzen and Hallwachs write. "The millions to billions of species, and billions of wild interactions still viable, are largely invisible without bioliteracy."

That's why underscoring bioliteracy is the foundation of BioAlfa. The Penn scientists' vision is that, just as elementary school children are taught to read, they should also be taught about the biodiversity around them, and not just in a classroom but by going on the land and learning by doing. And like reading, this knowledge becomes something one takes into whatever social sector becomes home.

This enhanced bioliteracy would then feed back into conservation, they say. Not only might a greater understanding of ecosystems among Costa Ricans translate into greater appreciation but concrete results by using biodiversity information wherever they are. Specifically, Janzen and Hallwachs want to expand the practice of having local researchers carry out their DNA barcoding work, in which species are identified by sequencing stretches of their genetic material.

While the Costa Rican government has committed to the idea of BioAlfa, fully fleshing it out over 10 years will take an estimated $100 million, a hefty sum that Janzen and Hallwachs hope can come from both international governmental and private sources.

"Right now Costa Rica has the political permission for this project, but it also needs the financial permission," says Janzen.

For their part, the couple continues to plug away at building their biodiversity inventory and studies in ACG, while sharing their successes at international meetings (for now virtually), hoping that other tropical nations will follow in their footsteps, protecting land to, in the words of their scientific paper, "be kind to the survivors" of climate change.

As soon as they're vaccinated for the coronavirus, Janzen and Hallwachs plan to be back on the ground in Costa Rica, continuing to pursue that goal.

When the Thomas Fire raged through Ventura and Santa Barbara counties in December 2017, Danielle Touma, at the time an earth science researcher at Stanford, was stunned by its severity. Burning for more than a month and scorching 440 square miles, the fire was then considered the worst in California's history.

Six months later the Mendocino Complex Fire upended that record and took out 717 square miles over three months. Record-setting California wildfires have since been the norm, with five of the top 10 occurring in 2020 alone.

The disturbing trend sparked some questions for Touma, who is now a postdoctoral researcher at UC Santa Barbara's Bren School for Environmental Science & Management.

"Climate scientists knew that there was a climate signal in there but we really didn't understand the details of it," she said of the transition to a climate more ideal for wildfires. While research has long concluded that anthropogenic activity and its products -- including greenhouse gas emissions, biomass burning, industrial aerosols (a.k.a. air pollution) and land-use changes -- raise the risk of extreme fire weather, the specific roles and influences of these activities was still unclear.

Until now. In the first study of its kind, Touma, with fellow Bren School researcher Samantha Stevenson and colleagues Flavio Lehner of Cornell University and the National Center for Atmospheric Research (NCAR), and Sloan Coats from the University of Hawaii, have quantified competing anthropogenic influences on extreme fire weather risk in the recent past and into the near future. By disentangling the effects of those man-made factors the researchers were able to tease out the roles these activities have had in generating an increasingly fire-friendly climate around the world and the risk of extreme fire weather in decades to come.

Their work appears in the journal Nature Communications.

"By understanding the different pieces that go into these scenarios of future climate change, we can get a better sense of what the risks associated with each of those pieces might be, because we know there are going to be uncertainties in the future," Stevenson said. "And we know those risks are going to be expressed unequally in different places too, so we can be better prepared for which parts of the world might be more vulnerable."

Warm, Dry and Windy

"To get a wildfire to ignite and spread, you need suitable weather conditions -- you need warm, dry and windy conditions," Touma said. "And when these conditions are at their most extreme, they can cause really large, severe fires."

Using state-of-the-art climate model simulations available from NCAR, the researchers analyzed the climate under various combinations of climate influences from 1920-2100, allowing them to isolate individual effects and their impacts on extreme fire weather risk.

According to the study, heat-trapping greenhouse gas emissions (which started to increase rapidly by mid-century) are the dominant contributor to temperature increases around the globe. By 2005, emissions raised the risk of extreme fire weather by 20% from preindustrial levels in western and eastern North America, the Mediterranean, Southeast Asia and the Amazon. The researchers predict that by 2080, greenhouse gas emissions are expected to raise the risk of extreme wildfire by at least 50% in western North America, equatorial Africa, Southeast Asia and Australia, while doubling it in the Mediterranean, southern Africa, eastern North America and the Amazon.

Meanwhile, biomass burning and land-use changes have more regional impacts that amplify greenhouse gas-driven warming, according to the study -- notably a 30% increase of extreme fire weather risk over the Amazon and western north America during the 20th century caused by biomass burning. Land use changes, the study found, also amplified the likelihood of extreme fire weather in western Australia and the Amazon.

Protected by Pollution?

The role of industrial aerosols has been more complex in the 20th century, actually reducing the risk of extreme fire weather by approximately 30% in the Amazon and Mediterranean, but amplifying it by at least 10% in southeast Asia and Western North America, the researchers found.

"(Industrial aerosols) block some of the solar radiation from reaching the ground," Stevenson said. "So they tend to have a cooling effect on the climate.

"And that's part of the reason why we wanted to do this study," she continued. "We knew something had been compensating in a sense for greenhouse gas warming, but not the details of how that compensation might continue in the future."

The cooling effect may still be present in regions such as the Horn of Africa, Central America and the northeast Amazon, where aerosols have not been reduced to pre-industrial levels. Aerosols may still compete with greenhouse gas warming effects in the Mediterranean, western North America and parts of the Amazon, but the researchers expect this effect to dissipate over most of the globe by 2080, due to cleanup efforts and increased greenhouse gas-driven warming. Eastern North America and Europe are likely to see the warming and drying due to aerosol reduction first.

Southeast Asia meanwhile, "where aerosols emissions are expected to continue," may see a weakening of the annual monsoon, drier conditions and an increase in extreme fire weather. risk.

"Southeast Asia relies on the monsoon, but aerosols cause so much cooling on land that it actually can suppress a monsoon," Touma said. "It's not just whether you have aerosols or not, it's the way the regional climate interacts with aerosols."

The researchers hope that the detailed perspective offered by their study opens the door to more nuanced explorations of the Earth's changing climate.

"In the broader scope of things, it's important for climate policy, like if we want to know how global actions will affect the climate," Touma said. "And it's also important for understanding the potential impacts to people, such as with urban planning and fire management."

A keen sense of smell is a powerful ability shared by many organisms. However, it has proven difficult to replicate by artificial means. Researchers combined biological and engineered elements to create what is known as a biohybrid component. Their volatile organic compound sensor can effectively detect odors in gaseous form. They hope to refine the concept for use in medical diagnosis and the detection of hazardous materials.

Electronic devices such as cameras, microphones and pressure sensors enable machines to sense and quantify their environments optically, acoustically and physically. Our sense of smell however, despite being one of nature's most primal senses, has proven very difficult to replicate artificially. Evolution has refined this sense over millions of years and researchers are working hard to catch up.

"Odors, airborne chemical signatures, can carry useful information about environments or samples under investigation. However, this information is not harnessed well due to a lack of sensors with sufficient sensitivity and selectivity," said Professor Shoji Takeuchi from the Biohybrid Systems Laboratory at the University of Tokyo. "On the other hand, biological organisms use odor information extremely efficiently. So we decided to combine existing biological sensors directly with artificial systems to create highly sensitive volatile organic compound (VOC) sensors. We call these biohybrid sensors."

Takeuchi and his team essentially grafted a set of olfactory receptors from an insect into a device that feeds certain odors to the receptors and also reads how the receptors respond to these odors. Analysis of electrical signals from the olfactory receptors indicates what molecules triggered the signals. This method yields great sensitivity and is possible thanks to the way the receptors are physically bound within lipid bilayers. In previous experiments such a method has limited the way odors can be delivered to the receptors, but the team created an efficient solution to this problem too.

"The receptors react to molecules in a liquid droplet, so one of the main challenges was to make a device to transplant molecules from their air into these droplets," said Takeuchi. "We designed and fabricated microscale slits underneath where the droplet passes to force this exchange of molecules. By introducing the gas into the microslit, we were able to increase the probability of contact between the gas and the droplet and transfer target molecules to the fluid efficiently."

With this system, the researchers were able to detect traces of the chemical octenol, also called mushroom alcohol, which is known to attract mosquitoes, in the breath of a test subject. Not only that but the VOC sensor could detect concentrations on the order of parts per billion. This is about a thousand times less than the sensitivity of a dog's nose but it is an impressive achievement nonetheless and has inspired the team to keep innovating.

"I would like to expand upon the analytical side of the system by using some kind of AI. This could enable our biohybrid sensors to detect more complex kinds of molecules," said Takeuchi. "Such refinements might help in our goals to not only measure hazardous materials and environmental hazards but maybe even early stages of diseases from patients' breath and body odor."

Without immediate and drastic intervention, humans face a "ghastly future" -- including declining health, climate devastation, tens of millions of environmental migrants and more pandemics -- in the next several decades, according to an international team of 17 prominent scientists.

In a paper published Jan. 13 in the journal Frontiers in Conservation Science, the researchers cite more than 150 scientific studies and conclude, "That we are already on the path of a sixth major extinction is now scientifically undeniable."

Among the paper's co-authors is Daniel Blumstein, a UCLA professor of ecology and evolutionary biology and member of the UCLA Institute of the Environment and Sustainability.

Because too many people have underestimated the severity of the crisis and have ignored experts' warnings, scientists must continue speaking out, said Blumstein, author of the 2020 book "The Nature of Fear: Survival Lessons from the Wild" -- but they also must avoid either sugarcoating the overwhelming challenges or inducing feelings of despair.

"Without fully appreciating and broadcasting the scale of the problems and the enormity of the solutions required, society will fail to achieve even modest sustainability goals, and catastrophe will surely follow," he said. "What we are saying is frightening, but we must be both candid and vocal if humanity is to understand the enormity of the challenges we face in creating a sustainable future."

The Earth has experienced five mass extinctions, each accounting for a loss of more than 70% of all species on the planet. The most recent was 66 million years ago. Now, the paper reports, projected temperature increases and other human assaults on the environment mean that approximately 1 million of the planet's 7 million to 10 million species are threatened with extinction in the coming decades.

Blumstein said that level of damage could occur within the next several decades; an extinction affecting as many as 70% of all species -- like the earlier mass extinctions cited in the paper -- could potentially occur within the next few centuries.

One of the major trends discussed in the paper is the explosive growth of the planet's human population. There are now 7.8 billion people, more than double the Earth's population just 50 years ago. And by 2050, the figure is likely to reach 10 billion, the scientists write, which would cause or exacerbate numerous serious problems. For example, more than 700 million people are starving and more than 1 billion are malnourished already; both figures are likely to increase as the population grows.

Population growth also greatly increases the risk for pandemics, the authors write, because most new infectious diseases result from human-animal interactions, humans live closer to wild animals than ever before and wildlife trade is continuing to increase significantly. Population growth also contributes to rising unemployment and, when combined with a hotter Earth, leads to more frequent and intense flooding and fires, poorer water and air quality, and worsening human health.

The authors write that there is a "near certainty that these problems will worsen over the coming decades, with negative impacts for centuries to come" and that the adverse global trends are obvious.

"Humanity is running an ecological Ponzi scheme in which society robs nature and future generations to pay for short-term economic enhancement today," said Paul Ehrlich, a Stanford University professor emeritus of population studies and a co-author of the study.

The paper elucidates issues that have been publicized over the past few years by many activists, including the Swedish 18-year-old Greta Thunberg, Time magazine's 2019 person of the year. Blumstein said Thunberg has been absolutely right about the urgency of the dangers we face.

The authors also write the severity of the threats should transcend political tribalism, but so far they haven't -- and they're skeptical about when or if change can occur. "[M]ost of the world's economies are predicated on the political idea that meaningful counteraction now is too costly to be politically palatable. Combined with financed disinformation campaigns in a bid to protect short-term profits, it is doubtful that any needed shift in economic investments of sufficient scale will be made in time," the paper reads.

Said Ehrlich: "While it is positive news that President-elect Biden intends to reengage the U.S. in the Paris Climate accord within his first 100 days of office, it is a minuscule gesture given the scale of the challenge."

The paper suggests concrete changes that could help avert catastrophe. Among them: completely and rapidly ending the use of fossil fuels, strictly regulating markets and property acquisition, reigning in corporate lobbying and empowering women. But it also acknowledges that humans' innate "optimism bias" has led some to ignore the warnings about our planet's future.

"By the time we fully comprehend the impact of ecological deterioration, it will be too late," Blumstein said.

The descendants of regular wild-type bacteria can evolve to survive for a long time on metallic copper surfaces that would usually kill them within a few minutes. An international research team led by Martin Luther University Halle-Wittenberg (MLU) and the Bundeswehr Institute of Microbiology was able to produce these tiny survivalists in the lab and has been able to study them more closely. The team reports on its findings in Applied and Environmental Microbiology.

Bacterial infections are usually treated with antibiotics. However, in recent decades many pathogenic bacteria have developed an increasing tolerance to common drugs. So-called multidrug-resistant bacteria are of particular concern as they can no longer be combated with most antibiotics. Copper surfaces - for example on door handles - are a good weapon to fight these germs. "Copper surfaces are a sure-fire way to kill bacteria. Most bacteria die within minutes after landing on a copper surface," explains Professor Dietrich H. Nies, a microbiologist at MLU. Copper is a vital trace element for bacteria - but only in very small quantities. On the copper surfaces, however, the bacteria are literally flooded to death with copper ions because that they can no longer stave them off using their normal defence strategies.

Nies' research team wanted to find out if and how quickly two typical species of bacteria, Escherichia coli and Staphylococcus aureus, are theoretically able to adapt to survive on copper surfaces. The team therefore placed the bacteria on the surfaces for only a few minutes before returning them to a normal culture medium where they were allowed to recover. This process was repeated several times, with the survivors gradually being exposed to the deadly surface for longer and longer periods of time. Within three weeks, the researchers had produced bacteria that could survive for more than one hour on a copper surface. "Outside the laboratory, conditions are obviously not as ideal. But if copper surfaces are not cleaned regularly, insulating layers of grease can begin to form on them, which could produce a similar development over time," says Nies.

Using comprehensive genetic analyses, the team sought to understand why the bacteria no longer died on the surfaces. "We were unable to find a gene that made them resistant to the deadly effect of metallic copper surfaces," says Nies. Instead, the team observed a phenomenon among the surviving bacteria that was already known for quite some time, although in a slightly different manner: the bacteria's metabolism slowed down to a bare minimum and they fell into a kind of hibernation. Because most antibiotics aim to disrupt the metabolism of growing bacteria, they are almost completely ineffective against these special bacteria, which are also known as "persisters". "No matter how well an antibiotic works, there are always a handful of persisters in every generation," explains Nies. However, these are not considered antibiotic-resistant bacteria, because their offspring are once again susceptible to the drugs.

Normally only a tiny proportion of bacteria become persisters. However, in the case of the isolated bacteria, it was the entire population. Although they were able to grow just as fast as their predecessors, they were also able to rescue themselves by switching rapidly into an early state of persistence under adverse conditions. The scientists were concerned one additional thing they observed: "The bacteria also inherited this capability over 250 generations, even though the offspring had not come into contact with a copper surface," says Nies. The team therefore recommends that copper surfaces be cleaned regularly and thoroughly with special agents so that no persister bacteria can develop in the first place. At the same time, Nies points out that the use of copper surfaces is only one of many ways - including antibiotics - to effectively combat harmful bacteria.

Metal surfaces play a role as catalysts for many important applications - from fuel cells to the purification of car exhaust gases. However, their behaviour is decisively affected by oxygen atoms incorporated into the surface.

This phenomenon has been known for a long time, but until now it has not been possible to precisely investigate the role of oxygen in complex surfaces point by point in order to understand the chemical background at the atomic level. This has now been achieved at TU Wien in cooperation with a team from the Elettra Synchrotron in Trieste. It became possible to explain why in previous studies partly contradictory results had been obtained: the oxygen atoms are not distributed evenly, but settle down particularly easily in very specific places.

Precision measurements instead of average values

"It is a great challenge to examine a metal surface directly during catalysis," says Prof. Günther Rupprechter from the Institute of Materials Chemistry at TU Wien. "You can, of course, put the whole catalyst into a reactor and measure exactly which chemical products are produced - but you only get an average value. You can't know which sites on the catalyst contributed to the chemical reaction and in what way."

Another possibility is not to use a real catalyst, but a simple, highly clean, idealised piece of it - such as a tiny single crystal, with well-known properties, which you can then study under the microscope. In this case, you get precise, reproducible results, but they don't have much to do with practical applications.

The research group led by Günther Rupprechter and Yuri Suchorski therefore combined the advantages of both approaches. They use thin foils made of rhodium, which consist of small grains. On each grain, the surface atoms can be arranged differently. In one grain, they form a smooth, regular surface with the outer atoms all in exactly the same plane; next to it, the atoms may arrange themselves to form a more complicated structure consisting of many atomic steps.

The favourite places of oxygen atoms

It is precisely these steps that turn out to be crucial. "For the catalytic activity, the oxidation state of the catalyst plays a central role - i.e. whether oxygen attaches itself to the metal atoms or not," says Philipp Winkler, the first author of the paper. "In earlier experiments, we found that we were often dealing with a certain state between "oxidised" and "not oxidised" - a situation that is difficult to interpret."

However, this can be understood when one realises that not every grain of the rhodium foil is oxidised to the same degree. The oxidation starts preferably at corners, edges and steps - there it is particularly easy for the oxygen atoms to bind to the surface. Therefore, different grains with different surface structures are oxidised to different degrees.

Electron microscope and synchrotron in Trieste

This could be studied using a combination of highly developed technologies: "In a special electron microscope, the sample is irradiated with UV-light during the catalytic reaction and the resulting electron emission is registered with micrometre spatial resolution," explains Yuri Suchorski, "this allows us to determine exactly which grains of the rhodium foil are particularly catalytically active. The same sample is then examined again with a completely different microscope: grain by grain with X-rays at the synchrotron, obtaining very precise information about the surface oxidation of the sample."

If you combine both results, you can determine exactly which chemical behaviour is characteristic for particular structures. The key advantage: It is possible to examine the entire rhodium foil containing hundreds of different grains in a single experiment,. Instead of studying tiny single crystals separately, a sample containing many different structures used for catalysis is studied under real conditions, and information about the properties of these structures is obtained at once.

"This is an important step in catalysis research," Rupprechter emphasises. "We now no longer have to settle for just measuring an average value that inadequately describes the entire sample, but we can really understand in detail which atomic structures exhibit which effects. This will also make it possible to specifically improve important catalysts that are needed for many applications in energy and environmental technology."

Cardiovascular Innovations and Applications, publishes selected abstracts from the 31st Great Wall International Cardiology (GW-ICC) Conference, October 19 - 25, 2020
Beijing, January 13, 2021: Cardiovascular Innovations and Applications (CVIA), in its role as the official journal of the Great Wall International Cardiology Conference (GW-ICC), has published selected abstracts from the 31st GW-ICC. Abstracts are now online at https://www.ingentaconnect.com/content/cscript/cvia/2020/00000005/a00101s1/art00001

Co-Editors-in-Chief of CVIA Dr. C. Richard Conti, past president of the American College of Cardiology, and Dr Jianzeng Dong, Capital Medical University, Beijing, China commented that CVIA is delighted to be publishing the abstracts to support GW-ICC in its aims of leading the development of cardiovascular medicine in China, by introducing and promoting new concepts and technologies and strengthening and promoting cooperation amongst Chinese and international cardiology experts. Topics covered by the abstracts include basic and translational medicine, clinical research on cardiovascular diseases, cardiovascular-disciplinary research and cardiovascular prevention & rehabilitation.

PHILADELPHIA -- (Jan. 13, 2021) -- Scientists at The Wistar Institute discovered that Early Growth Response 1 (EGR1), a protein that turns on and off specific genes during blood cell development, inhibits expression of pro-inflammatory genes in macrophages. As part of their function to protect the body against pathogens, macrophages play a major role in initiation, maintenance, and resolution of inflammation. The discovery expands the understanding of how macrophages are set off and deactivated in the inflammatory process, which is critical in many normal and pathological conditions. These findings were published online in the journal Science Advances.

"By deepening the understanding of the role of EGR1, we shed light on the fundamental process of macrophage maturation, which is required for many aspects of the immune response including inflammation," said Alessandro Gardini, Ph.D., assistant professor in the Gene Expression & Regulation Program at The Wistar Institute and senior author on the study. "Our data suggest EGR1 acts as a master regulator of inflammation in macrophages."

Macrophages are specialized immune cells that eliminate foreign substances, cellular debris and cancer cells. Their multi-step maturation from progenitor cells in the bone marrow requires the concerted action of critical transcription factors that regulate expression of specific genes. EGR1 is one of these factors but its function remained elusive.

In response to tissue damage and infection, white blood cells of the immune system called monocytes can leave the bloodstream and infiltrate tissues, where they undergo an elaborate developmental program and mature into macrophages. Macrophages have the ability to "eat" pathogens, promote inflammation and elicit pathogen-specific immune responses.

The molecular mechanisms underlying this maturation process are not well defined. The same set of transcription factors acting in early monocyte development were thought to be involved in the conversion of monocytes to macrophages.

Gardini and colleagues used a model to recreate differentiation of monocytes to macrophages in vitro and performed a systematic genomic analysis of the role of EGR1 in this process. They found that EGR1 binds to different DNA regulatory regions in late-differentiating macrophages as opposed to progenitor cells differentiating into monocytes.

The lab previously uncovered a mechanism whereby EGR1 regulates gene expression in monocytes and macrophages by interacting with enhancers. These are short regulatory DNA sequences that, when bound by specific transcription factors, augment the expression of the associated genes.

In the new study, researchers found that EGR1 represses inflammatory enhancers in developing and mature macrophages, blunting their activation and the immune response.

"Our results suggest that the role of EGR1 in modulating inflammation may extend beyond development of blood cells and be relevant to the control of inflammation in health and disease conditions," said Avery Zucco, Ph.D., a postdoctoral researcher in the Gardini lab and co-first author of the study.

Research into the neuronal basis of emotion processing has so far mostly taken place in the laboratory, i.e. in unrealistic conditions. Bochum-based biopsychologists have now studied couples in more natural conditions. Using electroencephalography (EEG), they recorded the brain activity of romantic couples at home while they cuddled, kissed or talked about happy memories together. The results confirmed the theory that positive emotions are mainly processed in the left half of the brain.

A group led by Dr. Julian Packheiser, Gesa Berretz, Celine Bahr, Lynn Schockenhoff and Professor Sebastian Ocklenburg from the Department of Biopsychology at Ruhr-Universität Bochum describes the results in the journal Scientific Reports, published online on 13 January 2021.

In previous studies on the neuronal correlates of emotion processing, feelings were usually triggered in subjects by presenting certain images or videos in the laboratory. "It was unclear whether that really reflects how people experience and act out feelings," says Julian Packheiser. "Ultimately, emotions comprise not only the perception of feelings but also their expression."

Mobile EEG equipment enables measurements at home

This is why, in the current study, the researchers measured the brain waves of 16 couples in positive emotional situations in their own homes. A measurement of this kind would not be possible using conventional EEG systems as the movements created during kissing, cuddling or gesticulation produce artifacts in the data. "We have used a mobile EEG system that records not only brain waves but also the movement patterns of the subjects," explains Julian Packheiser. This allowed the team to control the artifacts in the data.

Positive situations, above all emotional situations involving kissing and talking, were associated with greater activity in the frontal areas of the left half of the brain. The study thus confirmed the results from laboratory investigations and what is known as the valence model of emotional lateralisation, which states that positive emotions tend to be processed in the left half of the brain and negative emotions in the right.

During the study, the researchers evaluated the EEG data in a certain frequency range, the alpha frequency band between 8 and 13 Hz and the beta frequency band between 13 and 30 Hz.