Earth

Researchers from Tallinn University of Technology, Grete Raba, Signe Adamberg, and Kaarel Adamberg showed that an acidic environment enhances the production of butyric acid from apple pectin by faecal bacterial consortia - microbiota. Pectin is a dietary fibre abundant in apples, berries, fruits, and vegetables. Pectin is used in jellies and desserts. As human digestive enzymes are not able to degrade pectin, it is metabolized by the microbes of the large intestine. The main conclusions of the research, published in FEMS Microbiology Letters, was the importance of environmental acidity (pH) on the composition and metabolism of colon bacteria. The colonic pH is, however, strongly related to one's diet.

Fibre-rich diets that contain plenty of whole-grain products, vegetables, fruits and berries, support the formation of beneficial metabolic products by colon bacteria. One of the well-known metabolites, butyric acid, provides energy and nutrients to gut epithelial cells, thus, protecting the host against inflammation and infections. Moreover, dietary fibres improve the gut transit rate (movement of the chyme through intestine) and control the pH of the intestine. The colonic pH of a healthy person remains between 6 - 7, whilst elevated (more basic pH > 7 - 8) pH is associated with several gut diseases such as irritable bowel syndrome or colon cancer.

Scientists at Tallinn University of Technology studied the effect of pH between 6 and 8 on the composition and metabolism of complex faecal microbial consortium in vitro. The experiments showed that the growth of butyric acid producing bacteria (Faecalibacterium prausnitzii and Coprococcus comes) was significantly enhanced in an acidic environment (pH 7.5), typical for fibre-deficient diets, the microbial composition resembled those characteristic to disease states: elevated numbers of protein-degrading bacteria with production of a higher content of potentially harmful substances. It was seen that certain bacteria clearly preferred higher acidities, whilst others preferred more basic environments. Some taxa however, have superior adaptability and can grow in a wide range of pH.

The dynamics of bacterial consortium is largely controlled by availability of substrates. In the current research, the specific effect of pectin was studied, however, real food contains a mixture of several dietary fibres with various effects on colon microbiota.

As an important outcome the authors observed significant effect of acidity on the dynamics of mucin degrading bacteria. Mucin is the main component of the mucous layer that covers the intestinal epithelial cells. The continuous secretion of mucins functions as a protective layer between blood circulation and the intestine. Certain colon bacteria can degrade mucin as an energy source. Thus, the numbers of mucin-degrading bacteria should be controlled to maintain an effective protection function.

In addition to the effect of acidity, the changes of the bacterial consortia were studied under two different dilution rates, simulating fast and slow colonic transit rates. The main differences observed was the increased abundance of methane producing species at slow dilution rate, that has been shown to occur in the case of colon cancer. In turn, the fast dilution rate supported the growth of the bacteria that produce butyric acid.

The study by Grete Raba, Signe Adamberg, and Kaarel Adamberg confirms the importance of pH as a key factor to control the growth and metabolism of colon microbiota.

This information is important for nutritionists as well as for further in vitro studies and diagnostics of gut health. Measuring the faecal pH as a fast and cheap, though underscored method, gives valuable information on the nutrition and health status of a person. Fruits, berries and vegetables that contain pectin are essential for good gut health.

WASHINGTON, June 28, 2021 -- Ancient Rome's emperors did some pretty bizarre stuff -- bursting into uncontrollable fits of laughter, appointing a horse as a priest, dressing in animal skins and attacking people ... the list goes on. Why were they acting that way? Well, it might have been lead poisoning. In this week's episode, we unwrap the possibility that lead caused the Roman Empire's collapse: https://youtu.be/4k7CvSiomlA.

Allabogdanite was first reported in the early 2000s from the Onello - a small iron meteorite recovered from the gold placer at the Bolshoi Dolguchan River in Eastern Yakutia. Chemically, the mineral belongs to phosphides - the compounds containing phosphorus in a negative oxidation state. It was named in honour of the crystallographer Alla Bogdanova. Since that, allabogdanite was identified in several iron meteorites. The recent discovery at the Dead Sea is the first confirmation of the mineral on Earth. Allabogdanite was detected in the course of a systematic study of terrestrial phosphides from the Dead Sea region.

'Our research included the experiments on phase transitions of terrestrial allabogdanite at high pressure and high temperature at the DESY synchrotron light source in Germany,' said Sergey Britvin, the main author of the article, Professor in the Department of Crystallography at St Petersburg University. 'It has been found that terrestrial allabogdanite could be formed at pressures exceeding 25 gigapascals that corresponds to ca. 250 kbar. Such high pressures on Earth can be attained during catastrophic collisions with large meteorite impactors, or at the Earth's mantle conditions, at a depth of more than 500 kilometres. However, the discovery of terrestrial allabogdanite is associated with the surface rocks of the Hatrurim Formation (also known as the Mottled Zone) in the Negev Desert in Israel. This is the area where natural cyclophosphates have been recently discovered.'

Professor Sergey Britvin added that the discovery of allabogdanite in the historical region of the South Levant in the Middle East raises many questions related to the formation conditions of surficial rocks in this region.

Despite the fact that allabogdanite was discovered in meteorite almost 20 years ago, it was only in 2008 that it was shown that the mineral belongs to the indicators of high pressure. The results of current research evidence that terrestrial allabogdanite is a metastable high pressure phase. It was formed as a result of transformation from another mineral - barringerite, and was preserved under normal conditions as a result of quenching - an abrupt release of temperature and pressure.

'This way excludes the possibility of allabogdanite formation as an intermediate phase from the elements under atmospheric pressure. This, in turn, raises a number of key questions regarding the origin of rocks in the Mottled Zone. Until now, no evidence for the large meteorite collisions or the rocks having Earth's mantle origin has been found in the South Levant. However, such evidence might have been 'erased' from the Earth's surface as a result of later processes of geological erosion. The discovery of allabogdanite justifies the necessity of further research in this direction,' said Professor Sergey Britvin.

COLUMBUS, Ohio -- Mountaintop glacier ice in the tropics of all four hemispheres covers significantly less area -- in one case as much as 93% less -- than it did just 50 years ago, a new study has found.

The study, published online recently in the journal Global and Planetary Change, found that a glacier near Puncak Jaya, in Papua New Guinea, lost about 93% of its ice over a 38-year period from 1980 to 2018. Between 1986 and 2017 the area covered by glaciers on top of Kilimanjaro in Africa decreased by nearly 71%.

The study is the first to combine NASA satellite imagery with data from ice cores drilled during field expeditions on tropical glaciers around the world. That combination shows that climate change is causing these glaciers, which have long been sources of water for nearby communities, to disappear and indicates that those glaciers have lost ice more quickly in recent years.

The two datasets allowed the researchers to quantify exactly how much ice has been lost from glaciers in the tropics. Those glaciers are "the canaries in the coal mines," said Lonnie Thompson, lead author of the study, distinguished university professor of Earth Sciences at The Ohio State University and senior research scientist at Ohio State's Byrd Polar and Climate Research Center.

"These are in the most remote parts of our planet--they're not next to big cities, so you don't have a local pollution effect," Thompson said. "These glaciers are sentinels, they're early warning systems for the planet, and they all are saying the same thing."

The study compared changes in the area covered by glaciers in four regions: Kilimanjaro in Tanzania, the Andes in Peru and Bolivia, the Tibetan Plateau and the Himalayas of Central and South Asia, and ice fields in Papua, New Guinea, Indonesia. Thompson has led expeditions to all these glaciers and recovered ice cores from each. The cores are long columns of ice that act as timelines of sorts for the regions' climates over centuries to millennia. As snow falls on a glacier each year, it is buried and compressed to form ice layers that trap and preserve the chemistry of snow and whatever is in the atmosphere, including pollutants and biological material such as plants and pollen. Researchers can study those layers and determine what was in the air at the time the ice formed.

One image taken in 2019 of the top of Huascarán, the highest tropical mountain in the world, shows ice retreating upslope and exposing the rock beneath. Analyses performed by researchers at the University of Colorado showed that the area of the glacier ice on top of that mountain decreased by nearly 19% from 1970 to 2003. In 2020, the surface area of the Quelccaya Ice Cap, the second-largest glaciated area in the tropics, had decreased by 46% from 1976, the year Thompson drilled the first ice core from its summit.

Around the time of Thompson's first expedition, NASA launched the first version of its Landsat mission. Landsat is a collection of satellites that photograph Earth's surface and has been in operation in various forms since 1972. It offers the longest continuous space-based record of Earth's land, ice and water.

"We are in this unique position where we have ice core records from these mountaintops, and Landsat has these detailed images of the glaciers, and if we combine those two data sets, we see clearly what is happening," Thompson said.

Glaciers in the tropics respond more quickly to climate change and as they exist in the warmest areas of the world, they can survive only at very high altitudes where the climate is colder. Before Earth's atmosphere warmed, the precipitation there fell as snow. Now, much of it falls as rain that causes the existing ice to melt even faster.

"You're not sustaining the ice at the highest elevations anymore," said co-author Christopher Shuman, associate research professor at the University of Maryland-Baltimore County and associate research scientist at NASA Goddard Space Flight Center in Maryland. "It's this interplay between the warm air lower down melting away the margins of the ice fields while the very highest elevations are still cold enough to get a certain amount of snowfall, but not enough to sustain the ice cap to the dimensions it once was."

That could have profound repercussions for people who live near those glaciers.

The study details the story of one community near the Quelccaya Ice Cap, and the aftermath of a flood caused by massive amounts of ice that fell from the glacier into a nearby glacial lake. The flood destroyed fields that one farming family had spent years cultivating and so frightened the family that they moved four hours away from the community to start a new life in the city.

In Papua New Guinea, the ice has cultural significance for many of the indigenous people who live near the ice fields, as they consider the ice to be the head of their god. Thompson believes the ice fields there will disappear entirely within two or three years.

It is too late for those glaciers, Thompson said, but not too late to attempt to slow the amount of carbon dioxide and other greenhouse gases emitted into the atmosphere, which are causing the planet to warm.

"The science doesn't change the trajectory we're on -- regardless of how clear the science is, we need something to happen to change that trajectory," he said.

A new study has found baby coral reef fishes can outpace all other baby fishes in the ocean.

Lead author Adam Downie is a PhD candidate at the ARC Centre of Excellence for Coral Reef Studies at James Cook University (Coral CoE at JCU).

Mr Downie said when considering aquatic athletes, young coral reef fishes shine: they are some of the fastest babies, swimming around 15-40 body lengths per second.

As a comparison, herring babies swim up to two body lengths per second, and the fastest human in the water, Olympic gold medalist Michael Phelps, can only swim 1.4 body lengths per second.

"We found the swimming performance in baby fishes relates to whether they ultimately associate with a reef or not," Mr Downie said.

"When they're a baby searching for a new reef to call home, a reef fish has to navigate the open ocean and its currents. To be successful at this they need a higher swimming capacity than other non-reef fishes."

"We think that, over evolutionary time, habitat association shaped the swimming performance in the early life stages of these marine fishes," said co-author Dr Peter Cowman, also from Coral CoE at JCU and Senior Curator of Biosystematics from Queensland Museum's Project DIG.

"In our study, we compared more than 200 marine fish species across their 150 million years of shared ancestry. We found baby fishes that settle onto a reef later in life, whether tropical or temperate, have evolved to grow larger muscles and swim faster than their non-reef relatives," Dr Cowman said.

The reef fish babies develop these muscles as well as their organs very quickly--all signs of great athletes. Other fishes--such as the herring, which remains in the open ocean for its whole life--don't have these attributes.

"These tiny creatures aren't just passive particles floating around in the ocean," said co-author Associate Professor Jodie Rummer, also from Coral CoE and the College of Science and Engineering at JCU. "They are finely tuned athletes."

"Swimming machinery forms early in a fish's life--and some just do it bigger, faster and better than others."

In another recent study, Mr Downie also found the health of the reef that baby reef fishes choose to call home could affect their athletic performance. Settling on degraded coral reefs may require extra energy for these young fishes, which could then compromise their growth, swimming and other vital activities.

"While reef fishes may be exceptional swimmers in early life, the condition of their home can have huge impacts on their performance--and likely their ability to develop into healthy adults," Mr Downie said.

Coral reefs worldwide are degrading due to climate change, pollution, boat traffic, sediment run-off and coastal development.

"As the global damage to coral reefs persists, future populations of reef fishes are at risk," Dr Rummer said.

"Compromising the health of baby fishes compromises the health of adult populations and therefore entire marine ecosystems," she said.

"There are around 17,000 known marine fish species," Mr Downie said. "They are an important part of any functioning marine ecosystem--not to mention crucial for fisheries, which support nearly half of the world's human population."

"Our findings show how important it is to urgently reduce the human impact on these fragile species and ecosystems," he said.

"Healthy reefs mean healthy fish and a healthy planet."

HUNTINGTON, W.Va. - According to researchers at Marshall University, a maternal diet rich in Omega-3 fatty acids protects from breast cancer development in offspring. In a new study recently published by Frontiers in Cell and Developmental Biology, researchers noted a significant difference in mice from mothers that were fed a diet rich in canola oil, compared with mothers fed a diet rich in corn oil. A maternal Omega 3-rich diet affected genome-wide epigenetic landscape changes in offspring and potentially modulated gene expression patterns.

Dr. Ata Abbas, a former postdoctoral research fellow in Marshall's Department of Biological Sciences, headed a research team under the leadership of Dr. Philippe Georgel in the College of Science. Research was done in the Cell Differentiation and Development Center at Marshall as part of a collaborative effort with the Joan C. Edwards School of Medicine's Department of Biochemistry and Microbiology, under the leadership of Dr. W. Elaine Hardman.

Researchers noticed a three-week delay in mortality in mice whose mothers were fed canola oil versus corn oil. The early delay in mortality was significantly different, but the ultimate overall survival rate was not. Eventually, all the mice developed tumors, but the ones fed canola oil had tumors that were slower-growing and smaller than the mice fed corn oil. Translated to human time scale, the duration of the protective effect linked to the maternal diet would be equivalent to several months (Sengupta et al., 2016).

This study is among a body of work done by Marshall University scientists and others looking at the link between Omega-3 fatty acids and reduced incidence of various types of cancer including, but not restricted to, Chronic Lymphocytic Leukemia and Diffuse Large B-Cell Lymphoma.

"The issue of parental diet and inter-generational transmission has become an important field of research; however, the mode of action often remains partially elusive," said Georgel, a professor in the Department of Biological Sciences at Marshall. "The MU research group focused on 'epigenetic' aspects of trans-generational transmission to explain the reported role of Omega-3 fatty acids. Epigenetics involves changes in gene expression which are not linked to changes in genetic sequences. These results have the potential to promote the design of simple changes in diet which would allow for reduced onset of various types of cancer, not only for the individuals using that diet but also for their offspring."

PULLMAN, Wash. - A research team led by Washington State University has created a computer model to understand how plants store energy in the thylakoid membrane, a key structure to photosynthesis in plant leaves.

The team confirmed the accuracy of the mathematical model with lab experiments. Their work was recently published in the journal Nature Plants.

"We provided an important piece to the overall puzzle of plant metabolism," said Helmut Kirchhoff, a professor in WSU's Institute of Biological Chemistry and leader of the team who made this discovery. "If we integrate our model into the bigger picture, it may provide a good path for how to improve plants for certain environments."

Plants convert sunlight into usable energy through photosynthesis, but constantly adjust where and how they store the self-made energy based on light level, temperature, moisture and other factors.

Figuring out how plants make these adjustments could improve our understanding of how they perform in the field and help develop new plants that can withstand rising temperatures from climate change.

Kirchhoff and his collaborators' findings could have broad implications and benefits in years to come, as their model is integrated with others to learn more about how exactly photosynthesis works.

Energy conversion from sunlight and energy storage happens in specialized thylakoid membranes in chloroplasts in leaves.

"It functions like a battery," Kirchhoff said. "In leaves, plants pump protons from one side of the thylakoid membrane to the other generating a gradient of positive and negative charges."

To regulate this energy storage, ion channels control the fluctuation in amount of energy available, he said.

Understanding this complex process could be the key to feeding people around the world on a warming planet.

"Photosynthesis is very powerful," Kirchhoff said. "If it's not controlled, it can produce too much energy, which creates dangerous molecules that can kill a plant. Engineering plants with better photosynthetic control would mean those plants could survive in sunnier, warmer conditions."

The scientists shined a variety of lights on leaves and measured the changes in absorption and fluorescence.

"We illuminate leaves with different light intensities to create excited states in pigments," Kirchhoff said. "The leaf then changes its absorption and fluorescence properties that we measure, telling us what is going on in the leaf."

Oncotarget published "Predicting clinical outcomes using cancer progression associated signatures" which reported somatic mutation signatures are an informative facet of cancer aetiology, however they are rarely useful for predicting patient outcome.

The aim of this study is to evaluate the utility of a panel of 142 mutation-signature–associated metrics for predicting cancer progression in patients from a ‘TCGA PanCancer Atlas’ cohort.

Cancer specific machine learning models were built using the output from the P142 panel to predict patient Progression Free Survival status as either “High PFS” or “Low PFS”.

Models accurately predicted PFS status for several cancer types, including adrenocortical carcinoma, glioma, mesothelioma, and sarcoma.

In conclusion, the P142 panel of metrics successfully predicted cancer progression status in patients with some, but not all cancer types analyzed.

The P142 panel of metrics successfully predicted cancer progression status in patients with some, but not all cancer types analyzed.

Dr. Mamrot from The GMDx Group Ltd as well as The Monash University said, "Cancer is a leading cause of human mortality worldwide and the incidence of cancer is expected to rise as our average life expectancy increases."

Furthermore, the accumulation of specific deaminase-associated mutations in a patient can provide valuable information on how the cancer has developed, and in specific cases provide information on the rate of progression of the disease and likely response to specific treatments.

Antecedent research has shown that, when combined with the codon-context of the targeted motifs for both cytosine and adenosine deaminases as described by Lindley, deaminase-associated mutation signatures can be used to stratify patients with high-grade serous ovarian cancer into long-term and short-term survivors.

This is the first application of these deaminase-associated metrics for predicting cancer progression and patient outcomes.

The aim of this study is to evaluate the efficacy of a panel of 142 deaminase-associated metrics for predicting the rate of cancer progression in patients selected from The Cancer Genome Atlas PanCancer Atlas cohort.

The P142 metrics evaluated in this study are defined and described in Supplementary Table

1. The authors hypothesize that the P142 markers associated with AID/APOBEC and ADAR deamination and codon reading frame context can be used to predict cancer progression for patients with a range of different cancer types.

The Mamrot Research Team concluded in their Oncotarget Research Output, "we have identified a correlation between cancer patient outcomes and changes in metrics associated with deaminase mutagenesis in some, but not all, cancer types investigated. Potential molecular explanations for this observation are based on our evolving understanding of dysregulated deaminase DNA mutagenesis, disrupted DNA-RNA repair pathways and subsequent aberrant protein production. Further investigation using prospective, purpose-designed studies would likely improve the efficacy of machine learning models and provide a more accurate evaluation of the potential utility of this approach. This study provides a basis for further development of biomarker panels based on metrics associated with deaminase mutagenesis for predicting cancer progression and patient outcome."

HAMILTON, ON June 28, 2021 -- Researchers at McMaster University have developed a promising new cancer immunotherapy that uses cancer-killing cells genetically engineered outside the body to find and destroy malignant tumors.

The modified "natural killer" cells can differentiate between cancer cells and healthy cells that are often intermingled in and around tumors, destroying only the targeted cells.

The natural killer cells' ability to distinguish the target cells, even from healthy cells that bear similar markers, brings new promise to this branch of immunotherapy, say members of the research team behind a paper published in the current issue of the journal iScience, newly posted on the PubMed database.

The experimental treatment is an alternative to chimeric antigen receptor T-cell therapy, or CAR-T, which received FDA approval in 2017. The engineered T-cells used in CAR-T therapy are highly effective against some blood-borne cancers but cannot distinguish between cancerous and non-cancerous cells, so while they offer important benefits, they are not uniformly applicable to all forms of cancer. In patients with solid tumors, the T-cells can cause devastating, even lethal side effects.

The team behind the research wanted a treatment with the same power as CAR-T, but which could be used safely against solid-tumor cancers. They first propagated natural killer cells taken from the blood of patients with breast cancer. Such cells perform a similar function to T-cells in the immune system.

The researchers then genetically modified them to target specific receptors on cancer cells, successfully testing the CAR-NK cells in the laboratory on tumor cells derived from breast cancer patients

"We want to be able to attack these malignancies that have been so resistant to other treatments," says lead author Ana Portillo, a PhD candidate in the Department of Medicine. "The efficacy we see with CAR-NK cells in the laboratory is very promising and seeing that this technology is feasible is very important. Now, we have much better and safer options for solid tumors."

"These CAR-NK cells are a little bit smarter, in a way, in that they only kill the enemy cells and not good cells that happen to have the same marker," says Ashkar, Portillo's supervisor and a Professor of Medicine at McMaster. "These cells have a sober second thought that says, 'I recognize this target, but is this target part of a healthy cell or a cancer cell?' They are able to leave the healthy cells alone and kill the cancer cells."

Portillo and Ashkar's 12 co-authors, most associated with McMaster's Department of Medicine and its Immunology Research Centre, include McMaster's Bindi Dhesy-Thind (Associate Professor, Oncology), who provided blood samples from patients being treated for breast cancer in her clinical practice at Hamilton Health Sciences' Juravinski Cancer Centre.

"These are very exciting results, as to date the benefits of immunotherapy in breast cancer have lagged behind that of other malignancies," she said. "These engineered CAR-NK cells are an important step towards having a viable immunotherapy option in this large group of patients."

Ashkar says there is good reason to believe the technology would have a similar effect on solid tumors associated with lung, ovarian and other cancers.

The next step in moving the therapy toward clinical use is to conduct human trials, which the researchers are now arranging.

What The Study Did: Researchers looked at whether age-related hearing impairment among older adults is associated with poorer and faster decline in physical function and reduced walking endurance.

Authors: Pablo Martinez-Amezcua, M.D., Ph.D., M.H.S., of the Johns Hopkins Bloomberg School of Public Health in Baltimore, is the corresponding author.

To access the embargoed study: Visit our For The Media website at this link https://media.jamanetwork.com/

(doi:10.1001/jamanetworkopen.2021.13742)

Editor's Note: The article includes conflict of interest disclosures. Please see the article for additional information, including other authors, author contributions and affiliations, conflict of interest and financial disclosures, and funding and support.

RICHLAND, Wash.--Earth bears many signs of human influence, from warming that exceeds pre-industrial temperatures to a rising sea. Add to that list, now, the human influence on the timing of Earth's water cycle, revealed by a new study led by researchers at the U.S. Department of Energy's Pacific Northwest National Laboratory.

The research, published this week in the journal Nature Climate Change, peels back layers of climatological noise to uncover a clear signal: from 1979 to 2019, increases in greenhouse gases and reductions in human-generated aerosols triggered an approximate four-day delay in seasonal rainfall over tropical land and the Sahel. The lag could mean delayed crop production, exacerbated heat waves, and worsened wildfires, among other consequences.

"The global warming we've seen has already been attributed to human activities with high confidence," said atmospheric scientist Ruby Leung, who coauthored the study. "But, historically, we have not been very successful in pinpointing the footprint of human activity in the hydrological cycle. This study shows that, yes, the later onset of monsoon rainfall, paired with future warming projected by climate models, has already emerged."

More moisture

Ironically, the rain delay is caused by an increasingly moist atmosphere. As greenhouse gases warm Earth's surface, more water vapor makes its way into the atmosphere. This added moisture boosts the amount of energy needed to heat the atmosphere as spring transitions to summer, which can shift the timing of rainy seasons.

"When there is more water vapor in the atmosphere, it becomes more ocean-like," said Earth scientist and first author Fengfei Song. "And we know the ocean takes longer to warm up than the atmosphere. More moisture means it will take longer for the atmosphere to absorb energy and produce rainfall."

Human-generated aerosols, like the particulates produced from burning fossil fuels, tend to reflect sunlight. These cool the atmosphere and undercut the warming trend caused by greenhouse gases.

But, as aerosol concentrations continue to decline from efforts to improve air quality, some of that cooling effect is lost, which escalates both warming and the delay of monsoon rainfall in recent decades, according to the study.

If aerosol concentrations continue to decline and greenhouse gas concentrations continue to rise, the delay will extend in the future, said Leung. The study's authors project that, by the end of the century, the rainy season could be further delayed by more than five days over northern tropical land and more than eight days over the Sahel.

"For monsoon regions, like India, with an agrarian economy," said Leung, "a delayed onset of summer rainfall could devastate crop production and jeopardize the livelihood of large populations, unless farmers recognize and adapt to the long-term changes amidst the highly variable monsoon onset date."

What is the hydrological cycle?

Most of Earth's water lies within the ocean. Sunlight heats the sea, and some of that water rises from the surface as vapor. That water vapor, along with water transpired from plants and water evaporated from soil, can condense and produce clouds and rainfall when it encounters rising air.

Rising air currents are strongest in the tropics, where solar radiation is strongest. Gaze upon our planet from space and you'd see the product of these strong, moisture-rich air currents: Earth's signature rain band, vigorous with storms and showers, encircling the planet about its middle.

As seasons shift and the Sun migrates between hemispheres, the rain band moves. When the band reaches land, it marks the onset of the monsoon season, delivering ample water supply for both tropical forests and the large populations that live within and near them.

In a world made warmer by human activity, a more moisture-laden atmosphere stores more energy, delaying the movement of the rain band and the onset of monsoon rainfall.

A signal among noise

Researchers first projected the rain delay through climate modeling roughly a decade ago. Being able to point to the delay within the observational record, however, proved challenging. One does not simply measure global precipitation; the difficulty, said Leung, is twofold.

First, disentangling human-caused influence from the day-to-day or year-to-year variability in Earth's climate is arduous work. Think of trying to pinpoint a single voice's signature audio wave in a recording filled with background chatter.

"Temperature and precipitation aren't the same each year," said Leung. "There's a huge amount of variability."

The second challenge stems from data collection. Where the historical record of global temperature is long-standing, data-rich, and directly measured, the record of global precipitation is relatively short and saddled by uncertainty.

Satellites measure global precipitation indirectly by detecting energy reflected by clouds and raindrops, which imbues a degree of uncertainty. Widespread satellite use began in the late 1970s, leaving a record of only several decades.

Uncovering the delay signal buried in the noise of climatic variability came as global precipitation data became increasingly available and climate models grew more robust. By using eight observational data sets paired with 243 simulations made through multiple models, the study's authors were finally able to show that rainfall had indeed delayed in spring in the northern hemisphere.

Much of the seasonal shift came as a result of post-World War II economic development that brought increased greenhouse gas emissions and, subsequently, a reduction of aerosol emissions beginning in the 1980s, according to the study. Human activity was not the only driver behind the delay, however. Decadal sea surface temperature variability, among other factors, may have also contributed to the seasonal shift.

Babies are generally poorer at seeing and recognizing objects than adults because of their immature visual abilities. However, a study published in the journal Proceedings of the National Academy of Sciences (PNAS) on June 23 reported that, in some circumstances, infants younger than 7 months old can perceive objects that older infants and adults cannot. This surprising result demonstrates the distinct mechanisms of visual perception between young infants and adults.

We can generally recognize an object, even if it is presented for a very brief time. However, if another object appears immediately following the first object, the perception on the first object is impaired such that we do not notice its existence. This perceptual phenomenon, called "visual backward masking," is used in vision science to study how visual perception is processed in the brain. Interestingly, this phenomenon occurs even if the second object does not spatially overlap the first object, such as a contour or four dots surrounding the object.

The occurrence of this phenomenon is assumed to be due to a disruption of "feedback processing." When we see something, visual information is serially processed from lower to higher visual areas in the brain in a bottom-up manner. However, top-down feedback processing, in which visual signals are sent back from higher to lower areas, also plays a critical role in visual perception. Visual backward masking is thought to occur owing to interference with feedback processing.

"We applied backward masking to infants aged 3-8 months to examine the development of feedback processing," says Yusuke Nakashima, a postdoctoral fellow at Chuo University in Tokyo and the study's lead author. "Recent studies in vision science revealed the importance of feedback processing in visual perception, but its development is poorly understood."

To test whether backward masking occurs in infants, the researchers presented images of faces on a computer screen and measured the length of time that infants spent looking at them. As infants tend to look longer at faces, researchers can test whether infants perceive faces by measuring their looking time. The faces were presented in two ways. In one condition, a face was followed by a mask image, in which infants would not see the face if backward masking occurred. In another condition, nothing appeared after the face; thus, infants would be able to see the face.

The researchers found that infants aged 7-8 months could not see faces followed by the mask, indicating that backward masking occurred, similar to adults. In contrast, infants aged 3-6 months could perceive faces even when the faces were followed by the mask image, indicating that masking did not occur and that younger infants could see faces that older infants could not.

"These results suggest that feedback processing is immature in infants younger than 7 months," says Nakashima. "That is, younger infants do not have feedback processing that backward masking should interfere, and thus, masking is ineffective for them." The results of the study demonstrated that the mechanisms for visual perception change drastically in the second half of the first year of life, from the bottom-up system to the system incorporating top-down processing.

The results also showed that objects that can be perceived in early infancy become imperceptible during development. "This might seem counterintuitive," says Masami Yamaguchi, a professor at Chuo University. "Instead, important visual abilities would be acquired by the maturation of feedback processing."

For example, feedback processing is essential for robustly perceiving ambiguous visual images, such as occluded objects. "Younger infants whose feedback processing is immature might perceive the external world ambiguously," says Yamaguchi. "In return for susceptibility to visual masking, we acquire the ability to robustly perceive ambiguous visual scenes."

In 2021 Acta Pharmaceutica Sinica B (APSB) is celebrating its 10th anniversary. The journal was founded with the goal of creating a global high-level forum centred around drug discovery and pharmaceutical research/application. APSB was included by Chemical Abstracts in 2011, accepted by PubMed Central in 2015, indexed by Science Citation Index in 2017 and has evolved to become one of the most important international journals in the field of pharmaceutical sciences.

Volume 11, issue 6 is a special issue marking the beginning of a series of celebratory events for the 10-year anniversary of the journal. The issue includes 8 review articles and 13 research articles covering wide-ranging topics from disease targets (such as cancers, metabolic diseases, and infectious diseases) to basic science subjects (such as pharmacology and pharmaceutics). Many of the articles are written by authors that have been frequent contributors to the journal, and the topics highlight some of the most important issues in pharmaceutical sciences today. In addition to this special issue, other invited review articles are in the works, which will appear in various journal issues in 2021. Additionally, several other, more focused, special issues are forthcoming, covering such topics as "drug- and xenobiotic-induced liver toxicity," "drug target and drug development for Alzheimer's disease," "antiviral drug discovery and pharmacology," and "novel peptides and peptidomimetics in drug discovery."

Featured papers in this issue are:

A comprehensive review of integrative pharmacology-based investigation: A paradigm shift in traditional Chinese medicine by authors Haiyu Xu, Yanqiong Zhang, Ping Wang, Junhong Zhang, Hong Chen, Luoqi Zhang, Xia Du, Chunhui Zhao, Dan Wu, Feng Liu, Hongjun Yang and Changxiao Liu (https://doi.org/10.1016/j.apsb.2021.03.024). This review focuses on the presentation of the novel concept and the main research contents, methodologies and applications of integrative pharmacology-based traditional Chinese medicine.

Preclinical efficacy against acute myeloid leukaemia of SH1573, a novel mutant IDH2 inhibitor approved for clinical trials in China by authors Zhiqiang Wang, Zhibo Zhang, Yong Li, Li Sun, Dezhen Peng, Danyu Du, Xian Zhang, Luwei Han, Liwen Zhao, Ligong Lu, Hongzhi Dud, Shengtao Yuan and Meixiao Zhan (https://doi.org/10.1016/j.apsb.2021.03.005). This study comprehensively evaluated SH1573, a novel mIDH2 inhibitor, in terms of pharmacodynamics, pharmacokinetics, and toxicological properties, which made this drug enter phase I clinical trials successfully.

Corilagin inhibits SARS-CoV-2 replication by targeting viral RNA-dependent RNA polymerase by authors Quanjie Li, Dongrong Yi, Xiaobo Lei, Jianyuan Zhao, Yongxin Zhang, Xiangling Cui, Xia Xiao, Tao Jiao, Xiaojing Dong, Xuesen Zhao, Hui Zeng, Chen Liang, Lili Ren, Fei Guo, Xiaoyu Li, Jianwei Wang and Shan Cen (https://doi.org/10.1016/j.apsb.2021.02.011). The authors report that RAI-S-37 (corilagin) acts as a non-nucleoside inhibitor of SARS-CoV-2 RdRp, binds directly to RdRp, effectively inhibits the polymerase activity in both cell-free and cell-based assays, fully resists the proofreading activity and potently inhibits SARS-CoV-2 infection in vitro.

Homo-PROTAC mediated suicide of MDM2 to treat non-small cell lung cancer by authors Shipeng He, Junhui Ma, Yuxin Fang, Ying Liu, Shanchao Wu, Guoqiang Dong, Wei Wang and Chunquan Sheng (https://doi.org/10.1016/j.apsb.2020.11.022). The authors demonstrate for the first time "suicide" cleavage of MDM2: a homo-PROTAC strategy possessing effective in vitro and in vivo antitumor activities. The approach may offer an opportunity to overcome the bottleneck of the dose-related adverse effects of MDM2?P53 inhibitors in the development of clinical anticancer agents.

Other articles published in the issue include:

Editorials

Celebratory message from the Editor-in-Chief on the 10th anniversary of APSB
Jian-dong Jiang
https://doi.org/10.1016/j.apsb.2021.05.025

A message from the Co-Editor-in-Chief
Xinxin Ding
https://doi.org/10.1016/j.apsb.2021.05.026

Reviews

Role of CD8+ T lymphocyte cells: Interplay with stromal cells in tumor microenvironment
Qin Xie, Jian Ding, Yi Chen
https://doi.org/10.1016/j.apsb.2021.03.027

The role of ALDH2 in tumorigenesis and tumor progression: Targeting ALDH2 as a potential cancer treatment
Hong Zhang, Liwu Fu
https://doi.org/10.1016/j.apsb.2021.02.008

The Ca2+-activated chloride channel ANO1/TMEM16A: An emerging therapeutic target for epithelium-originated diseases?
Yani Liu, Zongtao Liu, KeWei Wang
https://doi.org/10.1016/j.apsb.2020.12.003

Nature?s marvels endowed in gaseous molecules I: Carbon monoxide and its physiological and therapeutic roles
Xiaoxiao Yang, Wen Lu, Christopher P. Hopper, Bowen Ke, Binghe Wang
https://doi.org/10.1016/j.apsb.2020.10.010

The disruption of protein-protein interactions with co-chaperones and client substrates as a strategy towards Hsp90 inhibition
Michael A. Serwetnyk, Brian S.J. Blagg
https://doi.org/10.1016/j.apsb.2020.11.015

Insight into chemical basis of traditional Chinese medicine based on the state-of-the-art techniques of liquid chromatography-mass spectrometry
Yang Yu, Changliang Yao, De-an Guo
https://doi.org/10.1016/j.apsb.2021.02.017

Extracellular vesicle activities regulating macrophage- and tissue-mediated injury and repair responses
Qian Hu, Christopher J. Lyon, Jesse K. Fletcher, Wenfu Tang, Meihua Wan, Tony Y. Hu
https://doi.org/10.1016/j.apsb.2020.12.014

Original articles

Identification of ferroptosis as a novel mechanism for antitumor activity of natural product derivative a2 in gastric cancer
Ying Liu, Zan Song, Yajie Liu, Xubin Ma, Wang Wang, Yu Ke, Yichao Xu, Dequan Yu, Hongmin Liu
https://doi.org/10.1016/j.apsb.2021.05.006

Notoginsenoside Ft1 acts as a TGR5 agonist but FXR antagonist to alleviate high fat diet-induced obesity and insulin resistance in mice
Lili Ding Qiaoling Yang, Eryun Zhang, Yangmeng Wang, Siming Sun, Yingbo Yang, Tong Tian, Zhengcai Ju, Linshan Jiang, Xunjiang Wang, Zhengtao Wang, Wendong Huang, Li Yang
https://doi.org/10.1016/j.apsb.2021.03.038

Mitochondrial protein IF1 is a potential regulator of glucagon-like peptide (GLP-1) secretion function of the mouse intestine
Ying Wang, Jiaojiao Zhang, Xinyu Cao, Yaya Guan, Shuang Shen, Genshen Zhong, Xiwen Xiong, Yanhong Xu, Xiaoying Zhang, Hui Wang, Jianping Ye
https://doi.org/10.1016/j.apsb.2021.02.002

LIX1-like protein promotes liver cancer progression via miR-21- 3p-mediated inhibition of fructose-1,6-bisphosphatase
Jie Zou, Xiaoyun Zhu, Dejuan Xiang, Yanqiu Zhang, Jie Li, Zhigui Su, Lingyi Kong, Hao Zhang
https://doi.org/10.1016/j.apsb.2021.02.005

HYD-PEP06 suppresses hepatocellular carcinoma metastasis, epithelial-mesenchymal transition and cancer stem cell-like properties by inhibiting PI3K/AKT and WNT/β-catenin signaling activation
Wei Tian, Jiatong Li, Zhuo Wang, Tong Zhang, Ying Han, Yanyan Liu, Wenfeng Chu, Yu Liu, Baofeng Yang
https://doi.org/10.1016/j.apsb.2021.03.040

Can remdesivir and its parent nucleoside GS-441524 be potential oral drugs? An in vitro and in vivo DMPK assessment
Jiashu Xie, Zhengqiang Wang
https://doi.org/10.1016/j.apsb.2021.03.028

From Vietnamese plants to a biflavonoid that relieves inflammation by triggering the lipid mediator class switch to resolution
Tran Thi Van Anh, Alilou Mostafa, Zhigang Rao, Simona Pace, Stefan Schwaiger, Christian Kretzer, Veronika Temml, Carsten Giesel, Paul M. Jordan, Rossella Bilancia, Christina Weinigel, Silke Rummler, Birgit Waltenberger, Tran Hung, Antonietta Rossi, Hermann Stuppner, Oliver Werz, Andreas Koeberle
https://doi.org/10.1016/j.apsb.2021.04.011

New guaiane-type sesquiterpenoid dimers from Artemisia atrovirens and their antihepatoma activity
Lihua Su, Xintian Zhang, Yunbao Ma, Changan Geng, Xiaoyan Huang, Jing Hu, Tianze Li, Shuang Tang, Cheng Shen, Zhen Gao, Xuemei Zhang, Ji-Jun Chen
https://doi.org/10.1016/j.apsb.2020.12.006

Effect of paracellular permeation enhancers on intestinal permeability of two peptide drugs, enalaprilat and hexarelin, in rats
David Dahlgren, Tobias Olander, Markus Sjöblom, Mikael Hedeland, Hans Lennernäs
https://doi.org/10.1016/j.apsb.2020.12.019

Extensive expansion of the chemical diversity of fusidane-type antibiotics using a stochastic combinational strategy
Xiaojun Song, Jianming Lv, Zhiqin Cao, Huiyun Huang, Guodong Chen, Takayoshi Awakawa, Dan Hu, Hao Gao, Ikuro Abe, Xinsheng Yao
https://doi.org/10.1016/j.apsb.2020.12.007

Short communication

Development of a highly-specific 18F-labeled irreversible positron emission tomography tracer for monoacylglycerol lipase mapping
Zhen Chen, Wakana Mori, Jian Rong, Michael A. Schafroth, Tuo Shao, Richard S. Van, Daisuke Ogasawara, Tomoteru Yamasaki, Atsuto Hiraishi, Akiko Hatori, Jiahui Chen, Yiding Zhang, Kuan Hu, Masayuki Fujinaga, Jiyun Sun, Qingzhen Yu, Thomas L. Collier, Yihan Shao, Benjamin F. Cravatt, Lee Josephson, Ming-Rong Zhang, Steven H. Liang
https://doi.org/10.1016/j.apsb.2021.01.021

Scientists from within the Antibody and Vaccine Group at the University of Southampton have gained novel insights into how an important class of immune receptors called tumour necrosis factor receptors (TNFR) are activated.

The work, published in the journal Communications Biology, investigates a class of receptors present on immune cells called TNFR. These receptors, such as CD40, 4-1BB and OX40, are key in helping the immune system fight pathogens and cancer cells. Accordingly, antibody drugs which are designed to specifically target and activate these receptors (called agonists) have been developed for cancer treatment.

The mechanism by which these receptors are activated on the cell surface is important for designing optimal drug formats; however, to date it is not fully understood. Previous work showed that receptor clustering, redistribution of receptors dispersed over the cell surface into localised clusters, is essential for TNF receptor activation, and it is commonly believed that larger clusters induce more potent activation.

The current study, led by Dr Ben Yu and Professor Mark Cragg at the Centre for Cancer Immunology, with colleagues across the University and at ONI UK, employed a set of unique reagents developed at Southampton targeting CD40, 4-1BB and OX40, as well as a new super-resolution microscopy acquired through funding from from the Mark Benevolent Fund, to address how differential receptor clustering mediates receptor activity.

Results from the study confirmed that TNF receptor activation absolutely requires receptor clustering but interestingly, disproved the commonly held belief that larger clusters induce more receptor activation. Rather, the study finds that agonists that induced smaller clusters - but with higher receptor density - mediated better TNF receptor activity than those which induced larger clusters.

In addition to receptor size, the study reveals that one of the most potent antibody agonists targeting CD40 induced a novel rod-shaped clustering structure, which could potentially explain the super-agonistic nature of that antibody. These findings add significant insight into how TNF receptors cluster to mediate immune activation and will help guide future development of therapeutic antibodies targeting TNF receptors.

To make computer chips, technologists around the world rely on atomic layer deposition (ALD), which can create films as fine as one atom thick. Businesses commonly use ALD to make semiconductor devices, but it also has applications in solar cells, lithium batteries and other energy-related fields.

Today, manufacturers increasingly rely on ALD to make new types of films, but figuring out how to tweak the process for each new material takes time.

Part of the problem is that researchers primarily use trial and error to identify optimal growth conditions. But a recently published study — one of the first in this scientific field — suggests that using artificial intelligence (AI) can be more efficient.

In the ACS Applied Materials & Interfaces study, researchers at the U.S. Department of Energy’s (DOE) Argonne National Laboratory describe multiple AI-based approaches for optimizing the ALD processes autonomously. Their work details the relative strengths and weaknesses of each approach, as well as insights that can be used to develop new processes more efficiently and economically.

“All of these algorithms provide a much faster way of converging to optimum combinations because you’re not spending time putting a sample in the reactor, taking it out, doing measurements etc. as you typically would today. Instead you have a real-time loop that connects with the reactor,” said Argonne principal materials scientist Angel Yanguas-Gil, a co-author of the study.

Cutting edge, but with challenges

In ALD, two different chemical vapours, known as precursors,  adhere to a surface, adding a thin layer of film in the process. This all happens inside a chemical reactor and is sequential: one precursor is added and interacts with the surface, then any excess of it is removed. Afterwards the second precursor is introduced then later removed, and the process repeats itself. In microelectronics, the ALD thin film might be used to electrically insulate nearby components in nanoscale transistors.

ALD excels at growing precise, nanoscale films on complex, 3D surfaces such as the deep and narrow trenches patterned into silicon wafers to manufacture today’s computer chips. This has motivated scientists worldwide to develop new thin film ALD materials for future generations of semiconductor devices. 

However, developing and optimizing these new ALD processes is challenging and labor-intensive. Researchers have to consider many different factors that can alter the process, including:

The complex chemistries between the molecular precursors
Reactor design, temperature and pressure
The timing for each dose of their precursors

In an effort to find ways of overcoming these challenges, Argonne scientists evaluated three optimization strategies — random, expert system and Bayesian optimization — the latter two utilizing different AI approaches. 

Set it and forget it

Researchers evaluated their three strategies by comparing how they optimized the dosage and purge times of the two precursors used in ALD. Dosage time refers to the time period when a precursor is added to the reactor, while purge time refers to the time needed to remove excess precursor and gaseous chemical products.

The goal: Find the conditions that would achieve high and stable film growth in the shortest time. Scientists also judged the strategies on how quickly they converged on the ideal set of timings using simulations that represented the ALD process inside a reactor.

Linking their optimization approaches to their simulated system let them measure film growth in real time after each cycle, based on the processing conditions their optimization algorithms generated.

“All of these algorithms provide a much faster way of converging to optimum combinations because you’re not spending time putting a sample in the reactor, taking it out, doing measurements, etc., as you would, typically. Instead you have a real-time loop that connects with the reactor,” said Argonne Principal Materials Scientist Angel Yanguas-Gil, a co-author of the study.

This set up also made the process automatic for the two AI approaches by forming a closed-loop system.

“In a closed-loop system, the simulation performs an experiment, gets the results, and feeds it to the AI tool. The AI tool then learns from it or interprets it in some way, and then suggests the next experiment. And this all happens without human input,” said Noah Paulson, a computational scientist at Argonne and the lead author.

Despite some weaknesses, the AI approaches effectively determined the optimal dose and purge timings for different simulated ALD processes. This makes the study among the first to show that thin-film optimization in real time is possible using AI. 

“This is exciting because it opens up the possibility of using these types of approaches to rapidly optimize real ALD processes, a step that could potentially save manufacturers precious time and money when developing new applications in the future,” concluded Jeff Elam, a senior chemist at Argonne and co-author.