Earth

Ecology-inspired mathematical models to understand social networks

The ease with which anyone can create online content for free, especially on social media, has led to superabundance of information being one of the defining characteristics of today's communication systems. This situation has resulted in increasingly intense competition for attention, which has become a scarce good. The researchers from the Complex Systems group (CoSIN3) at the UOC's Internet Interdisciplinary Institute (IN3) María José Palazzi and Albert Solé --professor at the Faculty of Computer Science, Multimedia and Telecommunications?--, led by Javier Borge, have participated in the design of an ecology-inspired mathematical model that makes it possible to break down and predict interaction patterns in a system as complex as the Twitter social network.

The model, published in the open access journal Nature Communications, is fundamentally based on two variables: the mutualistic (beneficial for both parties) relationship between users and hashtags, and competition for visibility, mirroring the situation of natural ecosystems with limited resources. According to the authors, this ecological framework "proposes a new and alternative way of understanding how Twitter works and can also be applied to other social media and communication ecosystems with similar characteristics."

The researchers considered various phenomena that went viral over the last nine years. One of the events was the 2012 UEFA European Football Championship, from which they recovered almost four million tweets from more than 1.3 million users, who used nearly 150,000 hashtags, from 19 June to 4 July 2012. The UOC research team also studied Twitter-based communication during the 2014 Hong Kong protests. From these demonstrations, they studied more than 800,000 tweets from almost 240,000 users, who wrote more than 30,000 possible hashtags from 27 September to 7 October. Another happening they analysed was the April 2015 Nepal earthquake, taking into consideration almost two million tweets from more than 810,000 users and contemplating more than 35,000 potential hashtags from 8 to 14 May of that year.

Parallels to the collaboration of flowers and pollinating insects

For decades, mathematical models have been applied to the fields of ecology and complex networks with the aim of describing the behaviour of natural systems to predict aspects such as the evolution of the abundance of species. Observing the behaviour of Twitter, the authors of the article identified similarities between some of these models and the characteristics of interactions on this social network. "Our intuition told us that Twitter users, understood in the abstract, compete for a limited resource (attention) in the same way as pollinating insects like bees compete for nectar. Hashtags, words and memes also compete to be the most used, in a similar way to how plants use their scents and colours to passively compete for the attention of insects," explained the authors.

Specifically, the new study adapts the type of mathematical models that have been used for more than 50 years in ecology to study natural mutualistic ecosystems (those in which species benefit from each other) to Twitter. "When a user chooses a hashtag, both agents benefit: the user because they believe it adequately expresses their desires and by using it they will obtain more attention, and the hashtag passively because it will be disseminated to more users, therefore reproducing the mutualistic relationship found between pollinators and plants. Our hypothesis was that if Twitter worked in a similar way to these ecosystems, we should be able to identify a certain correspondence and be able to predict the patterns according to which the social network is organized," they explained.

Two behaviour patterns: state of rest and collective attention

The results show that based on minimum ingredients (competition, mutual benefit and visibility maximization), this model makes it possible to capture and predict what actually happens. According to the researchers, Twitter has two basic patterns: when attention is fragmented, the system is structured like "a modular network, that is, organized into different groups according to the interests of the users around certain themed hashtags." But when there is an exceptional or viral event, which may be any extraordinary news story, such as elections, an earthquake or a TV show, "every user turns their attention to that phenomenon and themed communities disappear, entering what we have termed the nested state." In these cases, discussion centres around a small group of users who generate and use a large number of hashtags that are adopted by practically all the participants in the network. Once interest in the event wanes, the system returns to its normal modular condition: the state of rest.

One of the key aspects of this approach is that it is a simple model, given that with very few parameters it is capable of capturing the fundamental ingredients that drive the emerging patterns observed in Twitter and, moreover, it is "neutral" with respect to the users. That is, "the model does not need to assume anything about people's motives, biases or moods or about hashtag formats. The model's sole assumption is that both the users and the hashtags are in alignment with a subject of preference, which is why it works regardless of the communication event being analysed," stressed the researchers.

A model that can be adapted to other social media

The researchers indicate that this new ecological approach opens the door to modelling other social media and communication systems, as long as "there is competition for attention, through words or even images, as would be the case of Instagram." In this sense, the team that participated in the study aims to continue investigating this framework and is considering future lines of research, such as the possibility of using these models to intervene in communication events. "In the same way that ecologists use their models to try to intervene in ecosystems to, for example, prevent the extinction of a certain species, our idea is to conduct theoretical research into the conditions under which these communication events gain strength or wither away with a view to possible future intervention. For example, to make certain pernicious conversations or hashtags, such as those produced in fake news bubbles, disappear," concluded the authors.

Credit: 
Universitat Oberta de Catalunya (UOC)

New research will improve safety and quality of Heparin

image: Dr Andrew Hook in the lab

Image: 
University of Nottingham

A new method to analyse the blood thinning drug Heparin has been developed that can pinpoint contaminants more accurately and quickly, providing greater quality control and safety.

An interdisciplinary team from the University of Nottingham's Schools of Pharmacy and Medicine have used the latest chemical imaging technology to identify contaminants in Heparin at the nanoscale, a discovery that manufacturers could use to improve the quality and safety of this widely used anticoagulant drug. The research has been published in Communications Chemistry.

Heparin is naturally occurring glycosaminoglycan (GAG) but is also widely used widely as a medication. It is often used as an anticoagulant (blood thinner) before and after surgery but is also used in kidney dialysis and in blood processing. Pharmaceutical-grade heparin is derived from mucosal tissues of pig intestines or cow lungs. The majority of Heparin is made in China and in 2008 there were a number of deaths and illnesses caused by a contaminated batch. Continuing problems with the supply chain remain a concern.

Using a state-of-the-art chemical imaging technique called Time of Flight Secondary Ion Mass Spectrometry (ToF-SIMS) the researchers developed a new analytical approach that is more than 100 times more sensitive at detecting contaminants in Heparin, whilst also being faster and requiring less material to analyse. This technique blasts high-energy beams of positive ions at the sample's surface to produces secondary ions. These ions are then accelerated into a time-of-flight analyser and where their mass can be measured. The spectrum of ions provides a detailed measurement of the sample's chemical make-up.

Dr Andrew Hook from the School of Pharmacy led the research and said: "Heparin is particularly susceptible to contamination, commonly from other glycosaminoglycans and as they are all very similar chemically it is difficult to tell them apart using traditional analysis techniques. Whilst there are safety measures in place already to prevent contamination we saw room for improvement and using the ToF-SIMS techniques we were able to create a faster and more sensitive method for analysing Heparin that can be achieved with a very small amount of sample material."

Professor of Stem Cell Glycobiology, Cathy Merry adds: "There are many real risks to the heparin supply chain, not least of which are the increasing prevalence of animal viruses. The previous heparin crisis was linked to a reduction in the supply of porcine heparin following an outbreak of swine flu. There is a real risk this will happen again and there is now even tighter control on the international trade in animals so it is even more likely that vast numbers of animals could be destroyed if there's another outbreak. There's also been a huge drive to create synthetic heparin and, although this is still a way off, when it is available there will still be a need for a rapid, sensitive comparative technique to characterise the drug heparin which this technique can provide."

This new technique is scalable for commercial use with the ability to analyse large numbers of samples at a time.

Dr Hook continues; "It is critical that safety measures are as accurate and sensitive as possible. This technique will be a cost-effective way for manufacturers to take their safety and quality control to the next level. We are also looking at how this technique could be adapted to diagnose GAG based disorders that are typically difficult to diagnose like Hunter's Syndrome."

Credit: 
University of Nottingham

Artificial intelligence identifies the tiger mosquito from photos in the Mosquito Alert

Researchers from Mosquito Alert (who belong to CEAB-CSIC, CREAF and UPF) together with researchers from the University of Budapest have shown that an artificial intelligence algorithm is capable of recognizing the tiger mosquito (Aedes albopictus) in the photos sent by Mosquito Alert users.

The results of the study published in Scientific Reports have been obtained by applying deep learning technology or deep learning, an aspect of artificial intelligence that seeks to emulate the way of learning of humans and that has previously been used in the health field to interpret medical images (X-rays of patients with COVID19 to detect pneumonia, or facial features to detect heart disease, among others). Deep learning needs a lot of training data for the machine to learn.

John Palmer: "The initial idea is to get the machine to classify the simplest photos, and leave the task of identifying the most problematic images that require consensus to the experts".

In the case of the Mosquito Alert app, these images have been sent by the public and labeled by the project experts as "tiger mosquito" or "no tiger mosquito" for years. Specifically, the study used 7,168 classified photographs of mosquitoes that the project participants had sent between 2015 and 2019. After training, the algorithm has been able to correctly classify 96% of the photographs of this insect.

"The initial idea is to get the machine to classify the simplest photos, and leave the task of identifying the most problematic images that require consensus to the experts. As the artificial system learns from the classifications of the experts, we will be able to expand the range of automatically cataloged species ", explains John Palmer, UPF researcher and co-director of Mosquito Alert.

More predictability

This milestone can mark a before and after in the surveillance and monitoring of the tiger mosquito and other mosquitoes capable of transmitting diseases. "We are training a social immune system against these mosquitoes. The faster the threat is detected, the faster it can be acted upon ", comments Frederic Bartumeus, co-director of Mosquito Alert and ICREA researcher at CEAB-CSIC and CREAF. On the one hand, the citizen science of Mosquito Alert allows anyone to be part of this new social immune system and contribute a massive number of photos of mosquitoes, on the other, artificial intelligence allows, to accelerate the classification process of the received photos and thus help public health experts make better and faster decisions about mosquito management.

"In times of greatest need, such as in the months of greatest mosquito activity or in a context of epidemiological crisis, artificial intelligence can help us so that the system can absorb a greater amount of information, controlling its quality at all times, which it is key if the data is to be used for decision-making in public health ", adds Frederic Bartumeus.

Automating saves lives

The presence of the tiger mosquito in Spain poses a threat to public health. Millions of people are affected by its presence and are exposed to the risk of transmitting diseases such as dengue or chikungunya. In Europe, the tiger mosquito has been implicated every year since 2007 in small locally transmitted outbreaks of these viral diseases for which no vaccines are available. The only preventive measure is to control the mosquitoes that transmit them. Assessing the risk and the necessary action measures to mitigate it requires having accurate information on tiger mosquito populations, a costly and laborious task that requires manual placement and inspection of traps and their subsequent analysis in the laboratory where the insects are identified. A methodology that is not feasible to cover large geographic areas.

Mosquito Alert's citizen science methods, which allow anyone to report the presence of a mosquito through a mobile application available on Android and iOS, is an alternative that makes it easy to cover large geographic areas throughout the mosquito season. Since 2015, the initiative receives thousands of photographs every year that help estimate the abundance of mosquitoes. However, this large volume of photographs continues to be classified by visual examination by expert entomologists, a task that requires time and years of experience. Integrating artificial intelligence into this process can speed up classification and thus develop near-real-time hazard maps that improve tiger mosquito management.

Roger Eritja, CREAF scientist and Mosquito Alert entomological director, clarifies the limitations of artificial intelligence: "It will take time until a machine can have the same capacity as an expert eye, especially for other less characteristic species than the tiger mosquito. In Spain, 62 species of mosquitoes have been described, many of which currently cannot be classified from an image, but must be examined under a microscope. In some other cases, even a genetic analysis is required to identify them ".

Credit: 
Universitat Pompeu Fabra - Barcelona

Emergence of a new heteronanostructure library

Organizing functional objects in a complex, sophisticated architecture at the nanoscale can yield hybrid materials that tremendously outperform their solo objects, offering exciting routes towards a spectrum of applications. The development in synthetic chemistry over past decades has enabled a library of hybrid nanostructures, such as core-shell, patchy, dimer, and hierarchical/branched ones.

Nevertheless, the material combinations of these non-van der Waals solids are largely limited by the rule of lattice-matched epitaxy.

A research team led by professor YU Shuhong at the University of Science and Technology of China (USTC) has reported a new class of heteronanostructures they term axial superlattice nanowires (ASLNWs), which allow large lattice-mismatch tolerance and thus vast material combinations. The research article entitled "One-Dimensional Superlattice Heterostructure Library" was published in Journal of the American Chemical Society on May 12th.

To achieve the predictable, high-precision synthesis of a library of ASLNWs, they designed an axial encoding methodology that enables regiospecificity for chemoselective transformation.

They started from a predesigned, reconfigurable nanoscale framework, and then chemically decoupled the adjacent sub-objects by exploiting the reaction thermodynamics and kinetics. In this way, they achieved a library of nine distinct ASLNWs with in principle numerous geometric derivatives.

By regulating the reaction selectivity, they were capable of on demand programming the compositions, dimensions, crystal phases, interfaces, and periodicity in ASLNWs. Thanks to such high-level control, they finally achieved superior photocatalytic performances using optimized ASLNWs.

The results sheds new lights on creating high-order nanostructures with increased complexity and improved functions, which would show significant impacts on a broad range of applications in solar energy conversion and optoelectronics.

Credit: 
University of Science and Technology of China

No-one knew if lymph vessel cells bear cilia; turns out, they're indispensable for health

The primary cilium, an antenna-like subcellular structure ('organelle') protruding from the outside of many types of vertebrate cells, has an important but previously overlooked role in guiding the growth of lymphatic vessels, shows a new study. The authors show for the first time that mouse and human lymphatic endothelial cells (LECs) - which make up the inner and outer lining of lymphatic vessels - use primary cilia. They find that LEC primary cilia may direct the growth of a functional lymphatic network, not only during prenatal development, but also throughout life during inflammation and wound healing and in response to cancer. They show that mice in which the formation of primary cilia in LECs is prevented develop lymphatic vessels that are locally overgrown, suggesting that signals received by primary cilia may guide proper lymphatic vessel growth patterns. These results, published today in the open access journal Frontiers in Cell and Developmental Biology, have implications for human medicine.

"The first images were so exciting! LECs do have primary cilia and they are clearly important for patterning growth. The finding of a new regulatory 'hub' on LECs means that the way we think about how and what kind of signals are received by these cells has fundamentally changed. Targeting the assembly of cilia by the cell or their ways of signaling could allow us to control or stimulate lymphatic vessel growth in new ways," says corresponding author Dr Darci M. Fink, an assistant professor at the Department of Chemistry and Biochemistry of South Dakota State University.

Lymphangiogenesis continues throughout life

The lymphatic vessel system of vertebrates consists of hundreds of lymph nodes connected by a network of vessels spread throughout the body. Lymphatic vessels play a crucial role in health and homeostasis: they facilitate immune cell traffic during inflammation, drain excess fluid from the space between cells to lymph nodes and return it - clear of pathogens - to the bloodstream, and absorb fat molecules as an energy source. They first sprout during embryonic development, but 'lymphangiogenesis', the growth of new lymphatic vessels, continues throughout life in an adaptive response to the microenvironment, in particular during inflammation and wound healing. Faulty lymphangiogenesis can cause edema, impaired wound healing, chronic inflammation, and tumor progression.

"Primary cilia are such an essential part of the function of many cell types, including those that form other tube-like structures like blood vessels, breast ducts, and kidney tubules. Now we can add lymphatic endothelial cells to that list. Understanding exactly how primary cilia govern LEC movement, division, and tube formation and how to exploit these mechanisms is the next exciting challenge," says Fink.

First, Fink and colleagues used microscopy to show that in tissue from healthy mice, primary cilia on LECs can protrude either from the outside of lymphatic vessels or face the interior cavity. The incidence of primary cilia is also particularly high on LECs at the tips of growing lymphatic vessels, where guiding cues are received. These findings suggest that LECs might use their cilia to interact with the microenvironment inside as well as outside lymphatic vessels, for example sensing flow or the presence of soluble signaling molecules.

Disturbed prenatal development of lymph vessels after genetic knockout of IFT20

Next, the authors used a well-established genetic 'cut-and-paste' tool (called Cre-Lox recombination) to create a new transgenic line of mice, in which the key gene IFT20 - necessary for the molecular assembly of cilia and transport of proteins as 'ciliary cargo' - can be deactivated ('knocked out'). As predicted, the majority of LECs from these mice lacked a primary cilium. The embryos showed significant edema, and the lymphatic vessels of the embryos were dilated and improperly branched, became surrounded by excess smooth muscle and inappropriately contained red blood cells. These results mean that the presence of a functional cilium on embryonic LECs is necessary for the healthy prenatal development of the first lymphatic vessels.

Primary cilia are necessary for optimal lymphangiogenesis during disease

Finally, Fink's group studied the importance of primary cilia for guiding lymphangiogenesis in adult mice, during inflammation, wound healing and tumor growth. To cause localized acute or recurrent inflammation, they used the so-called cornea inflammation bioassay where small synthetic sutures are inserted (under anesthetic and continuous pain control) in the cornea of the eye. This procedure is known to stimulate LECs present in lymphatic vessels at the edge of the cornea to sprout, divide, and migrate toward the inflamed area, forming new lymphatic vessels. As predicted, this process was faulty in IFT20-knockout mice, where the network of new vessels became overgrown: too dense and with too many branches. The authors conclude that in the absence of primary cilia, lymphangiogenesis in response to disease is poorly regulated and results in new lymphatic vessels that aren't properly patterned.

"The striking overgrowth of lymphatic vessel seen after the loss of primary cilia points to the key role of cilia in coordinating the physiology of LECs with their microenvironment. The challenge now is to identify the signals sensed by lymphatic cilia. Across eukaryotic organisms, cilia are known to use a wide range of signals such as small molecules, peptides, physical forces, osmotic changes, and light, so in principle lymphatic cells have many options for sensing," concludes coauthor Prof Gregory J. Pazour, University of Massachusetts Medical School.

Credit: 
Frontiers

Probiotics associated with fewer respiratory symptoms in overweight and older people

Bethesda, MD (May 14, 2021) -- Daily probiotic use was associated with fewer upper respiratory symptoms in overweight and older people, according to a study that suggests a potential role for probiotics in preventing respiratory infections. The study was selected for presentation at Digestive Disease Week® (DDW) 2021.

"This is not necessarily the most intuitive idea, that putting bacteria into your gut might reduce your risk of respiratory infection," said Benjamin Mullish, MD, a lead researcher on the study and clinical lecturer in the Division of Digestive Diseases, Imperial College London, England, "but it's further evidence that the gut microbiome has a complex relationship with our various organ systems. It doesn't just affect how our gut works or how our liver works, it affects aspects of how our whole body works."

Researchers re-analyzed detailed daily diaries of 220 patients who participated in an earlier double-blind placebo-controlled study on probiotics and weight loss. Reviewing the entries for common symptoms of upper respiratory infection, including cough, sore throat and wheezing, researchers found that participants who took probiotics during the six-month study had a 27 percent lower overall incidence of upper respiratory tract symptoms compared to the placebo group. The effect was largest among participants who were aged 45 years or older, as well as those with obesity.

People with obesity are at higher risk for respiratory infections. Previous research has shown that probiotics reduce upper respiratory infections in healthy adults and children, but little data exists on this vulnerable population of older, overweight and people with obesity.

"These findings add to growing interest in the gut-lung axis -- how the gut and the lungs communicate with each other," Dr. Mullish said. "It's not just the gut sending out signals that affect how the lungs work. It works in both directions. It adds to the story that changes in the gut microbiome can affect large aspects of our health."

The researchers did not measure immune response, only respiratory symptoms. Future randomized clinical trials could help identify the mechanisms related to the reduction in respiratory symptoms and explore the possible impact of probiotics on the immune system, Dr. Mullish said.

DDW Presentation Details

Dr. Mullish will present data from the study, "Daily probiotic use is associated with a reduced rate of upper respiratory tract symptoms in overweight and obese people," abstract 739, on Sunday, May 23, at 1:16 p.m. EDT. For more information about featured studies, as well as a schedule of availability for featured researchers, please visit http://www.ddw.org/press.

Credit: 
Digestive Disease Week

Mammals can use their intestines to breathe

Rodents and pigs share with certain aquatic organisms the ability to use their intestines for respiration, finds a study publishing May 14th in the journal Med. The researchers demonstrated that the delivery of oxygen gas or oxygenated liquid through the rectum provided vital rescue to two mammalian models of respiratory failure.

"Artificial respiratory support plays a vital role in the clinical management of respiratory failure due to severe illnesses such as pneumonia or acute respiratory distress syndrome," says senior study author Takanori Takebe (@TakebeLab) of the Tokyo Medical and Dental University and the Cincinnati Children's Hospital Medical Center. "Although the side effects and safety need to be thoroughly evaluated in humans, our approach may offer a new paradigm to support critically ill patients with respiratory failure."

Several aquatic organisms have evolved unique intestinal breathing mechanisms to survive under low-oxygen conditions using organs other than lungs or gills. For example, sea cucumbers, freshwater fish called loaches, and certain freshwater catfish use their intestines for respiration. But it has been heavily debated whether mammals have similar capabilities.

In the new study, Takebe and his collaborators provide evidence for intestinal breathing in rats, mice, and pigs. First, they designed an intestinal gas ventilation system to administer pure oxygen through the rectum of mice. They showed that without the system, no mice survived 11 minutes of extremely low-oxygen conditions. With intestinal gas ventilation, more oxygen reached the heart, and 75% of mice survived 50 minutes of normally lethal low-oxygen conditions.

Because the intestinal gas ventilation system requires abrasion of the intestinal muscosa, it is unlikely to be clinically feasible, especially in severely ill patients--so the researchers also developed a liquid-based alternative using oxygenated perfluorochemicals. These chemicals have already been shown clinically to be biocompatible and safe in humans.

The intestinal liquid ventilation system provided therapeutic benefits to rodents and pigs exposed to non-lethal low-oxygen conditions. Mice receiving intestinal ventilation could walk farther in a 10% oxygen chamber, and more oxygen reached their heart, compared to mice that did not receive intestinal ventilation. Similar results were evident in pigs. Intestinal liquid ventilation reversed skin pallor and coldness and increased their levels of oxygen, without producing obvious side effects. Taken together, the results show that this strategy is effective in providing oxygen that reaches circulation and alleviates respiratory failure symptoms in two mammalian model systems.

With support from the Japan Agency for Medical Research and Development to combat the coronavirus disease 2019 (COVID-19) pandemic, the researchers plan to expand their preclinical studies and pursue regulatory steps to accelerate the path to clinical translation.

"The recent SARS-CoV-2 pandemic is overwhelming the clinical need for ventilators and artificial lungs, resulting in a critical shortage of available devices, and endangering patients' lives worldwide," Takebe says. "The level of arterial oxygenation provided by our ventilation system, if scaled for human application, is likely sufficient to treat patients with severe respiratory failure, potentially providing life-saving oxygenation."

Credit: 
Cell Press

Earth's oldest minerals date onset of plate tectonics to 3.6 billion years ago

image: Zircons studied by the research team, photographed using cathodoluminescence, a technique that allowed the team to visualize the interiors of the crystals using a specialized scanning electron microscope. Dark circles on the zircons are the cavities left by the laser that was used to analyze the age and chemistry of the zircons.

Scientists led by Michael Ackerson, a research geologist at the Smithsonian's National Museum of Natural History, provide new evidence that modern plate tectonics, a defining feature of Earth and its unique ability to support life, emerged roughly 3.6 billion years ago. The study, published May 14 in the journal Geochemical Perspective Letters, uses zircons, the oldest minerals ever found on Earth, to peer back into the planet's ancient past.

The team tested more than 3,500 zircons, each just a couple of human hairs wide, by blasting them with a laser and then measuring their chemical composition with a mass spectrometer. These tests revealed the age and underlying chemistry of each zircon. Of the thousands tested, about 200 were fit for study due to the ravages of the billions of years these minerals endured since their creation.

Image: 
Michael Ackerson, Smithsonian.

Scientists led by Michael Ackerson, a research geologist at the Smithsonian's National Museum of Natural History, provide new evidence that modern plate tectonics, a defining feature of Earth and its unique ability to support life, emerged roughly 3.6 billion years ago.

Earth is the only planet known to host complex life and that ability is partly predicated on another feature that makes the planet unique: plate tectonics. No other planetary bodies known to science have Earth's dynamic crust, which is split into continental plates that move, fracture and collide with each other over eons. Plate tectonics afford a connection between the chemical reactor of Earth's interior and its surface that has engineered the habitable planet people enjoy today, from the oxygen in the atmosphere to the concentrations of climate-regulating carbon dioxide. But when and how plate tectonics got started has remained mysterious, buried beneath billions of years of geologic time.

The study, published May 14 in the journal Geochemical Perspectives Letters, uses zircons, the oldest minerals ever found on Earth, to peer back into the planet's ancient past.

The oldest of the zircons in the study, which came from the Jack Hills of Western Australia, were around 4.3 billion years old--which means these nearly indestructible minerals formed when the Earth itself was in its infancy, only roughly 200 million years old. Along with other ancient zircons collected from the Jack Hills spanning Earth's earliest history up to 3 billion years ago, these minerals provide the closest thing researchers have to a continuous chemical record of the nascent world.

"We are reconstructing how the Earth changed from a molten ball of rock and metal to what we have today," Ackerson said. "None of the other planets have continents or liquid oceans or life. In a way, we are trying to answer the question of why Earth is unique, and we can answer that to an extent with these zircons."

To look billions of years into Earth's past, Ackerson and the research team collected 15 grapefruit-sized rocks from the Jack Hills and reduced them into their smallest constituent parts--minerals--by grinding them into sand with a machine called a chipmunk. Fortunately, zircons are very dense, which makes them relatively easy to separate from the rest of the sand using a technique similar to gold panning.

The team tested more than 3,500 zircons, each just a couple of human hairs wide, by blasting them with a laser and then measuring their chemical composition with a mass spectrometer. These tests revealed the age and underlying chemistry of each zircon. Of the thousands tested, about 200 were fit for study due to the ravages of the billions of years these minerals endured since their creation.

"Unlocking the secrets held within these minerals is no easy task," Ackerson said. "We analyzed thousands of these crystals to come up with a handful of useful data points, but each sample has the potential to tell us something completely new and reshape how we understand the origins of our planet."

A zircon's age can be determined with a high degree of precision because each one contains uranium. Uranium's famously radioactive nature and well-quantified rate of decay allow scientists to reverse engineer how long the mineral has existed.

The aluminum content of each zircon was also of interest to the research team. Tests on modern zircons show that high-aluminum zircons can only be produced in a limited number of ways, which allows researchers to use the presence of aluminum to infer what may have been going on, geologically speaking, at the time the zircon formed.

After analyzing the results of the hundreds of useful zircons from among the thousands tested, Ackerson and his co-authors deciphered a marked increase in aluminum concentrations roughly 3.6 billion years ago.

"This compositional shift likely marks the onset of modern-style plate tectonics and potentially could signal the emergence of life on Earth," Ackerson said. "But we will need to do a lot more research to determine this geologic shift's connections to the origins of life."

The line of inference that links high-aluminum zircons to the onset of a dynamic crust with plate tectonics goes like this: one of the few ways for high-aluminum zircons to form is by melting rocks deeper beneath Earth's surface.

"It's really hard to get aluminum into zircons because of their chemical bonds," Ackerson said. "You need to have pretty extreme geologic conditions."

Ackerson reasons that this sign that rocks were being melted deeper beneath Earth's surface meant the planet's crust was getting thicker and beginning to cool, and that this thickening of Earth's crust was a sign that the transition to modern plate tectonics was underway.

Prior research on the 4 billion-year-old Acasta Gneiss in northern Canada also suggests that Earth's crust was thickening and causing rock to melt deeper within the planet.

"The results from the Acasta Gneiss give us more confidence in our interpretation of the Jack Hills zircons," Ackerson said. "Today these locations are separated by thousands of miles, but they're telling us a pretty consistent story, which is that around 3.6 billion years ago something globally significant was happening."

This work is part of the museum's new initiative called Our Unique Planet, a public-private partnership, which supports research into some of the most enduring and significant questions about what makes Earth special. Other research will investigate the source of Earth's liquid oceans and how minerals may have helped spark life.

Ackerson said he hopes to follow up these results by searching the ancient Jack Hills zircons for traces of life and by looking at other supremely old rock formations to see if they too show signs of Earth's crust thickening around 3.6 billion years ago.

Credit: 
Smithsonian

Fibre-optics used to take the temperature of Greenland Ice Sheet

image: Fibre-optic cable (red) installed in 1 km deep borehole drilled on Store Glacier in Greenland

Image: 
Poul Christoffersen and RESPONDER team

Scientists have used fibre-optic sensing to obtain the most detailed measurements of ice properties ever taken on the Greenland Ice Sheet. Their findings will be used to make more accurate models of the future movement of the world's second-largest ice sheet, as the effects of climate change continue to accelerate.

The research team, led by the University of Cambridge, used a new technique in which laser pulses are transmitted in a fibre-optic cable to obtain highly detailed temperature measurements from the surface of the ice sheet all the way to the base, more than 1000 metres below.

In contrast to previous studies, which measured temperature from separate sensors located tens or even hundreds of metres apart, the new approach allows temperature to be measured along the entire length of a fibre-optic cable installed in a deep borehole. The result is a highly detailed profile of temperature, which controls how fast ice deforms and ultimately how fast the ice sheet flows.

The temperature of ice sheets was thought to vary as a smooth gradient, with the warmest sections on the surface where the sun hits, and at the base where it's warmed by geothermal energy and friction as the ice sheet grinds across the subglacial landscape toward the ocean.

The new study found instead that the temperature distribution is far more heterogenous, with areas of highly localised deformation warming the ice further. This deformation is concentrated at the boundaries between ice of different ages and types. Although the exact cause of this deformation remains unknown, it may be due to dust in the ice from past volcanic eruptions or large fractures which penetrate several hundred metres below the surface of the ice. The results are reported in the journal Science Advances.

Mass loss from the Greenland Ice Sheet has increased sixfold since the 1980s and is now the single largest contributor to global sea-level rise. Around half of this mass loss is from surface meltwater runoff, while the other half is driven by discharge of ice directly into the ocean by fast flowing glaciers that reach the sea.

In order to determine how the ice is moving and the thermodynamic processes at work within a glacier, accurate ice temperature measurements are essential. Conditions on the surface can be detected by satellites or field observations in a relatively straightforward way. However, determining what is happening at the base of the kilometre thick ice sheet is far more challenging to observe, and a lack of observations is a major cause of uncertainty in projections of global sea-level rise.

The RESPONDER project, funded by the European Research Council, is addressing this problem using hot-water drilling technology to bore through Sermeq Kujalleq (Store Glacier) and directly study the environment at the base of one of Greenland's largest glaciers.

"We normally take measurements within the ice sheet by attaching sensors to a cable that we lower into a drilled borehole, but the observations we've made so far weren't giving us a complete picture of what's happening," said co-author Dr Poul Christoffersen from the Scott Polar Research Institute who leads the RESPONDER project. "The more precise data we are able to gather, the clearer we can make that picture, which in turn will help us make more accurate predictions for the future of the ice sheet."

"With typical sensing methods, we can only attach about a dozen sensors onto the cable, so the measurements are very spaced out," said first author Robert Law, a PhD candidate at the Scott Polar Research Institute. "But by using a fibre-optic cable instead, essentially the whole cable becomes a sensor, so we can get precise measurements from the surface all the way to the base."

To install the cable, the scientists had to first drill through the glacier, a process led by Professor Bryn Hubbard and Dr Samuel Doyle from Aberystwyth University. After lowering the cable into the borehole, the team transmitted laser pulses in the cable, and then recorded the distortions in the scattering of light in the cable, which vary depending on the temperature of the surrounding ice. Engineers at Delft University of Technology in the Netherlands and geophysicists at the University of Leeds assisted with data collection and analysis.

"This technology is a big advance in our ability to record spatial variations in ice temperature over long distances and at really high resolution. With some further adaptations, the technique can also record other properties, such as deformation, at similarly high resolution," said Hubbard.

"Overall, our readings paint a picture that's far more varied than what current theory and models predict," said Christoffersen. "We found temperature to be strongly influenced by the deformation of ice in bands and at the boundaries between different types of ice. And this shows there are limitations in many models, including our own."

The researchers found three layers of ice in the glacier. The thickest layer consists of cold and stiff ice which formed over the last 10,000 years. Below, they found older ice from the last ice age, which is softer and more deformable due to dust trapped in the ice. What surprised the researchers the most, however, was a layer of warm ice more than 70 metres thick at the bottom of the glacier. "We know this type of warm ice from far warmer Alpine environments, but here the glacier is producing the heat by deforming itself," said Law.

"With these observations, we are starting to better understand why the Greenland Ice Sheet is losing mass so quickly and why discharge of ice is such a prominent mechanism of ice loss," said Christoffersen.

One of the major limitations in our understanding of climate change is tied to the behaviour of glaciers and ice sheets. The new data will allow the researchers to improve their models of how the Greenland Ice Sheet is currently moving, how it may move in the future, and what that this will mean for global sea-level rise.

The research was funded in part by the European Union.

Credit: 
University of Cambridge

Glaciologists measure, model hard glacier beds, write slip law to estimate glacier speeds

image: Researchers measure the topography of an exposed glacier bed at Castleguard Glacier in the Rocky Mountains of Alberta, Canada.

Image: 
Photo by Keith Williams, contributed by Christian Helanow.

AMES, Iowa - The field photos show the hard, rough country that some glaciers slide over: rocky domes and bumps in granite, rocky steps and depressions in limestone. The glacier beds dwarf the researchers and their instruments. (As do the high mountains pictured on the various horizons.)

During their trips to glacier beds recently exposed by retreating glaciers in the Swiss Alps (Rhone, Schwarzburg and Tsanfleuron glaciers) and the Canadian Rockies (Castleguard Glacier), four glaciologists used laser and drone technology to precisely measure the rocky beds and record their very different contours.

The researchers turned the measurements into high-resolution digital models of those glacier beds. Then they went to work with manageable but representative subunits of the models to study how glaciers slide along the bedrock base.

"The simplest way to say it is we studied the relationship between the forces at the base of the glacier and how fast the glacier moves," said Neal Iverson, a professor of geological and atmospheric sciences at Iowa State University and the study leader.

Small force changes, big speed changes

The resulting glacier "slip law" developed by the team describes that "relationship between forces exerted by ice and water on the bed and glacier speed," Iverson said. And that slip law could be used by other researchers to better estimate how quickly ice sheets flow into oceans, drop their ice and raise sea levels.

In addition to Iverson, the study team included Christian Helanow, a postdoctoral research associate at Iowa State from 2018 to 2020 and currently a postdoctoral researcher in mathematics at Stockholm University in Sweden; Lucas Zoet, a postdoctoral research associate at Iowa State from 2012 to 2015 and currently an assistant professor of geoscience at the University of Wisconsin-Madison; and Jacob Woodard, a doctoral student in geophysics at Wisconsin.

A grant from the National Science Foundation supported the team's work.

Helanow is the first author of a paper just published online by Science Advances that describes the new slip law for glaciers moving on bedrock.

Helanow's calculations - based on a computer model of the physics of how ice slides over and separates locally from rough bedrock - and the resulting slip law indicate that small changes in force at the glacier bed can lead to big changes in glacier speed.

Measuring to inches

The researchers used two methods to collect high-resolution measurements of the topographies of recently exposed rock glacier beds. They used ground-based lidar mapping technology to take detailed 3D measurements. And, they sent up drones to photograph the beds from various angles, allowing detailed plotting of topography to a resolution of about 4 inches.

"We used actual glacial beds for this model, in their fully 3D, irregular forms," Iverson said. "It turns out that is important."

Previous efforts used idealized, 2D models of glacier beds. The researchers have learned such models are not adequate to derive the slip law for a hard bed.

"The main thing we've done," Helanow said, "is use observed, rather than idealized, glacier beds to see how they impact glacier sliding."

A universal slip law?

The work follows another slip law determined by Zoet and Iverson that was published in April 2020 by the journal Science.

There are a few key differences between the two: The first slip law accounts for the motion of ice moving over soft, deformable ground, while the second addresses glaciers moving over hard beds. (Both bed types are common beneath glaciers and ice sheets.) And, the first is backed by experimental data from a laboratory device that simulates slip at the bed of a glacier, rather than being based on field measurements of former glacier beds and computer modeling.

Even so, the two slip laws ended up having similar mathematical forms.

"They're very similar - whether it's a slip law for soft beds or hard beds," Iverson said. "But it's important to realize that the processes are different, the constants in the equations have quite different values for hard and soft beds."

That has the researchers thinking ahead to more numerical analysis: "These results," they wrote, "may point to a universal slip law that would simplify and improve estimations of glacier discharges to the oceans."

Credit: 
Iowa State University

Researchers pinpoint possible way to prevent permanent hearing loss caused by cancer drug

image: University of Alberta researcher Amit Bhavsar is leading a team that has identified a receptor in cells that could be key to preventing permanent hearing loss in childhood cancer survivors who are being treated with the drug cisplatin.

Image: 
William Au

University of Alberta scientists have identified a receptor in cells that could be key to preventing permanent hearing loss in childhood cancer survivors who are being treated with the drug cisplatin. The researchers believe by inhibiting the receptor, they may be able to eliminate toxic side-effects from the drug that cause the hearing loss.

Cisplatin is an incredibly effective chemotherapeutic when it comes to treating solid tumours in children, contributing to an 80 per cent overall survival rate over five years, according to U of A researcher Amit Bhavsar, an assistant professor in the Department of Medical Microbiology & Immunology. The problem has always been with the side-effects. Nearly 100 per cent of patients who receive higher doses of cisplatin show some degree of permanent hearing loss. The ability to prevent this side-effect would dramatically improve the quality of life of childhood cancer survivors after they recover from the disease.

As Bhavsar explains, many researchers look at cisplatin's damaging side-effects from the angle of genetics, trying to determine underlying risk factors for hearing loss or examine how it works as a chemotherapeutic. A fair amount was known about the progression of hearing loss as a side-effect, but it was the initial spark--the instigating factor kicking everything off--that remained a mystery.

Bhavsar and his team thought outside the box and took things all the way back to the periodic table with their approach, getting some clues from the chemical composition of cisplatin itself and eventually identifying a particular receptor that was getting turned on.

The receptor in question is Toll-like receptor 4 (TLR4), which is involved in the body's immune response. TLR4 works by crossing the cell membrane, sticking a portion of itself outside the cell to sample the environment and to look for different signals that indicate damage or danger of some sort.

"It's a receptor that your body normally uses to detect when there's some sort of issue, like an infection. This receptor will turn on, and it'll start producing these signals that tell the cell it's under stress. Unfortunately in the case of cisplatin, those signals ultimately lead to the death of the cells responsible for hearing."

The cells affected by TLR4's signals are located within the cochlea of the ear, where they play a crucial role in hearing, translating vibrations in the ear into electrical impulses. Cisplatin also accumulates in the kidneys, but the difference is that it can be flushed out and diluted in that area of the body; in a closed system such as the ear, it accumulates and damages the cells.

"These cells don't renew. You really only get one shot and if they're gone, you're in trouble. The hearing loss is permanent," said Bhavsar.

The only way to prevent the damage is to stop the signals TLR4 produces that lead to the accumulation of cisplatin. To confirm the efficacy of inhibiting the TLR4 receptor, Bhavsar and his team looked at zebrafish models, with the help of Ted Allison, an associate professor in the Department of Biological Sciences and member of the U of A's Neuroscience and Mental Health Institute. They examined neuromasts, which are sensory cells within zebrafish that behave similarly to the human hair cells typically damaged by cisplatin. Bhavsar was able to prove that inhibiting TLR4 led to an inhibition of the damage on the sensory cells.

Bhavsar, a member of the Cancer Research Institute of Northern Alberta (CRINA), the Li Ka Shing Institute of Virology and the Women and Children's Health Research Institute (WCHRI), is collaborating with CRINA member Frederick West and Allison to refine an inhibitor that can disrupt this sampling process, removing the function that causes the toxic side-effect while still keeping the immune sensor function intact so patients don't become immunocompromised.

"It really does open the door for potential therapeutics," said Bhavsar.

The study, "Toll-like receptor 4 is activated by platinum and contributes to cisplatin-induced ototoxicity," was published in EMBO Reports. The work received support through operating grants from the Canadian Institutes of Health Research and the Stollery Children's Hospital Foundation through WCHRI, as well as funding from the Li Ka Shing Institute of Virology.

Credit: 
University of Alberta Faculty of Medicine & Dentistry

Heart attack recovery aided by injecting heart muscle cells that overexpress cyclin D2

image: "These results suggest that the cyclin D2-cardiomyocyte transplantation may be a potential therapeutic strategy for the repair of infarcted hearts," said study leader Jianyi "Jay" Zhang, M.D., Ph.D., the chair of Biomedical Engineering, a joint department of the UAB School of Medicine and the UAB School of Engineering.

Image: 
UAB

BIRMINGHAM, Ala. - In a large-animal study, researchers have shown that heart attack recovery is aided by injection of heart muscle cells derived from human induced pluripotent stem cell line, or hiPSCs, that overexpress cyclin D2. This research, published in the journal Circulation, used a pig model of heart attacks, which more closely resembles the human heart in size and physiology, and thus has higher clinical relevance to human disease, compared to studies in mice.

An enduring challenge for bioengineering researchers is the failure of the heart to regenerate muscle tissue after a heart attack has killed part of its muscle wall. That dead tissue can strain the surrounding muscle, leading to a lethal heart enlargement.

Heart experts thus have sought to create new tissue -- applying a patch of heart muscle cells or injecting heart cells -- to replace damaged muscle. Similarly, they have tried to stimulate division of existing heart muscle cells near the damaged area. This current study, led by researchers at the University of Alabama at Birmingham, shows progress in both goals.

After the experimental heart attack, heart tissue around the infarction site was injected with about 30 million bioengineered human cardiomyocytes that were differentiated from hiPSCs. These cells also overexpress cyclin D2, part of a family of proteins involved in cell division.

Compared to control human cardiomyocytes, the cyclin D2-cardiomyocytes showed enhanced potency to repair the heart. They proliferated after injection, and by four weeks, the hearts had less pathogenic enlargement, reduced size of dead muscle tissue and improved heart function.

Intriguingly, the cyclin D2-cardiomyocytes stimulated not only their own proliferation, but also proliferation of existing heart muscle cells around the infarction site of the pig heart, as well as showing angiogenesis, the development of new blood vessels.

"These results suggest that the cyclin D2-cardiomyocyte transplantation may be a potential therapeutic strategy for the repair of infarcted hearts," said study leader Jianyi "Jay" Zhang, M.D., Ph.D., the chair of Biomedical Engineering, a joint department of the UAB School of Medicine and the UAB School of Engineering.

This ability of the graft cyclin D2-cardiomyocytes to stimulate the proliferation of nearby existing heart cells suggested paracrine signaling, a type of cellular communication where a cell produces a signal that induces changes in nearby cells.

Exosomes -- small blebs or tiny vesicles that are released by human or animal cells and contain proteins and RNA from the cells that release them -- are one common form of paracrine signaling.

Zhang and colleagues found that exosomes that they purified from the cyclin D2-cardiomyocyte growth media indeed promoted proliferation of cultured cardiomyocytes. In addition, the treated cardiomyocytes were more resistant to programmed cell death, called apoptosis, induced by low oxygen levels. The exosomes also induced proliferation of various other cell types, including human umbilical vein endothelial cells, human vascular smooth muscle cells and 7-day-old rat cardiomyocytes that have almost undetectable proliferation.

Part of the cargo that exosomes carry are microRNAs, or miRNAs. These short pieces of RNA have the ability to interact with messenger RNA in target cells, and they are robust players of gene regulation in cells. Humans have more than 2,000 miRNAs with different RNA sequences, and these are thought to regulate a third of the genes in the genome.

So, the researchers documented which microRNAs were present in exosomes from the cyclin D2-overexpressing cardiomyocytes and in exosomes from non-overexpressing cardiomyocytes. As expected, they found differences.

Together, the exosomes from both types of cells contained 1,072 different miRNAs, and 651 were common to the two exosome groups. However, 332 miRNAs were found only in the cyclin D2-overexpressing cardiomyocytes, and 89 miRNAs were specific for the non-overexpressing cardiomyocytes. In preliminary work of characterizing the effects of specific miRNAs, one particular miRNA from the cyclin D2-overexpressing exosomes was shown to stimulate proliferation when delivered into rat cardiomyocytes.

"Thus, as the therapeutic potential of exosomes for improving cardiac function becomes more evident, combining an exosome-mediated delivery of proliferative miRNAs with transplantation of cyclin D2-overexpressing cardiomyocytes, or cell products, could become a new promising strategy for upregulating proliferation of the recipient cardiomyocytes and reducing cardiac fibrosis," Zhang said. "Altogether, our data suggest that cardiac cell therapy, involving cardiomyocytes with enhanced proliferation capacity, may become an efficacious future strategy for myocardial repair and prevention of congestive heart failure in patients with acute myocardial infarctions."

Credit: 
University of Alabama at Birmingham

Nanophotonics enhanced coverslip for phase imaging in biology

image: a The nanophotonics enhanced coverslip (NEC) adds phase imaging capability to a normal microscope coverslip, thereby shrinking bulky phase-imaging methods down to the size of a chip. The less than 200 nm thick design consists of a subwavelength spaced grating on top of an optically thin film, supported by a glass substrate. b Exemplary demonstration of phase-imaging of human cancer cells (HeLa cells) using the NEC. By placing the Petri dish containing the cell culture directly on top of the NEC, pseudo 3D images of the cells are created. The obtained images are similar to those obtained by the conventional phase-imaging technique of differential interference contrast (DIC) microscopy. In the reference image, recorded without the NEC, the cells are mostly invisible. c Use of the NEC device not only enabled visualization of the general shape of the cell, but also features inside of the cell nucleus (left). This was confirmed via comparison with images obtained via conventional DIC microscopy (middle) and fluorescence microscopy (right).

Image: 
by Lukas Wesemann, Jon Rickett, Jingchao Song, Jieqiong Lou, Elizabeth Hinde, Timothy J. Davis, and Ann Roberts

The ability to visualize transparent objects such as biological cells is of fundamental importance in biology and medical diagnostics. Conventional approaches to achieve this include phase-contrast microscopy and techniques that rely on chemical staining of biological cells. These techniques, however, rely on expensive and bulky optical components or require changing, and in some cases damaging, the cell by introducing chemical contrast agents. Significant recent advances in nanofabrication technology permit structuring materials on the nanoscale with unprecedented precision. This has given rise to the revolutionary field of meta-optics that aims to develop ultra-compact optical components that replace their bulk-optical counterparts as for example lenses and optical filters. Such meta-optical devices exhibit unusual properties for which they have recently drawn significant scientific interest as novel platforms for imaging applications.

In a new paper published in Light Science & Applications, a team of scientists, led by Professor Ann Roberts from the University of Melbourne node of the Australian Research Council Center of Excellence for Transformative Meta-Optical Systems have developed an ultra-compact, nanostructured microscope coverslip that allows the visualization of unstained biological cells. The device is referred to as a nanophotonics enhanced coverslip (NEC) since it adds phase-imaging capability to a normal microscope coverslip. In their study the researchers demonstrated that by simply placing biological cells on top of the NEC, high-contrast pseudo 3D images of otherwise invisible cells are obtained. The scientists used the example of human cancer cells (HeLa cells) to demonstrate the potential of this new phase-imaging method. The method not only enabled visualization of the general shape of the cancer cells but also made details of the cell nucleus visible. This capacity is crucial since the detection of changes in the structure of biological cells underpins the detection of diseases as for example in the case of malaria.

The version of the NEC presented in the publication differs from a normal coverslip through the addition of a thin-optical film and a nanometer spaced grating. The research team, however, envisage more complex variations of this concept to further extend the capabilities of the method to operation at different wavelengths and integration into highly-specialized optical imaging or microfluidic systems. In conclusion, this research has demonstrated an entirely new phase-imaging method that carries significant potential to be part of future biological imaging systems and mobile medical diagnostic tools.

The scientists summarize the potential of their phase-imaging method:

"We designed a nanostructured microscope coverslip that allows us to visualize otherwise transparent biological cells simply by placing them on top of the device and shining light through them. This is an exciting breakthrough in the field of phase-imaging, since our method requires neither the use of bulk-optical components, chemical staining or computational post processing as it is the case with conventional methods."
Prof. Roberts explained.

"The unavailability of medical diagnostic tools in many developing nations is regarded a reason for infectious diseases like malaria and tuberculosis to still be a leading cause of death. Our approach has significant potential to become an inexpensive, ultra-compact phase-imaging tool that could be integrated into smartphone cameras and other mobile devices to make mobile medical diagnostics broadly available."
Dr. Wesemann added.

Credit: 
Light Publishing Center, Changchun Institute of Optics, Fine Mechanics And Physics, CAS

New cellular atlas maps out healthy and cancerous breast tissue

image: Microscopic view of a mammary duct, which comprises part of the breast

Image: 
WEHI, Australia

Australian researchers have documented the diversity of cells in the human breast, explaining the relationship between healthy breast cells and breast cancer cells.

The research, which relied on expertise spanning from breast cancer biology through to bioinformatics, measured gene expression in single cells taken from healthy women and cancerous breast tissue, including tissue carrying a faulty BRCA1 gene. This enabled the researchers to create an 'RNA atlas' that details the different cells found in these tissues.

The atlas, which was described in EMBO Journal, will enable researchers to better understand the different cell types that constitute breast tissue and how these change during the development of cancer.

The research was undertaken by a team including Dr Bhupinder Pal, Dr Yunshun Chen and Dr François Vaillant, and led by Professor Jane Visvader, Professor Gordon Smyth and Professor Geoff Lindeman.

At a glance

A multidisciplinary team used single-cell transcriptomics to generate an RNA atlas that documents gene expression in different cells in healthy, pre-cancerous and cancerous human breast tissue.

The atlas reveals the changes that occur within the breast during key events, including cancer development and menopause.

The atlas is freely available to researchers around the world and is anticipated to be an important resource for breast cancer research.

Understanding single cells

The human breast is a complex tissue, comprising a wide range of cells including cells specialised for milk production and release, as well as fat cells and immune cells, Professor Visvader said.

"Different types of breast cancer arise from distinct precursor cells. However, breast cancer development can be impacted by other cells within the breast," she said. "This atlas provides a high-resolution view into the various cell types that make up breast tissue in different states and a blueprint for studying changes that lead to breast cancer."

Dr Pal, who is now a laboratory head at the Olivia Newton John Cancer Research Institute, said 'single-cell' technologies enabled the research team to isolate more than 340,000 individual cells from breast tissues donated by women and men and to measure the expression of different genes in these cells.

"Our studies included healthy, pre-cancerous and cancerous tissue, enabling us to study the differences between these tissues," he said

A diverse and changing landscape

The research revealed a wide variety of cell types are present in the human breast, Dr Chen said.

"Complex bioinformatic analysis was crucial for documenting the complex cellular landscape. For example, we found that the composition of a particular subset of cells in the breast was altered by menopause - a period of significant hormonal change within the body," he said.

The research also revealed many changes that occur within breast cancers, said Dr Vaillant.

"All the breast cancer types we studied displayed considerable diversity in their tumour cells, as well as in other cells found within the tumour. In particular, hormone-responsive cancers contained fewer dividing cells of a specific immune type, which could explain why many of these tumours are less responsive to anti-cancer immunotherapies."

A multidisciplinary effort

Single-cell RNA sequencing is a new technology that has revolutionised how researchers can study complex tissues such as the breast said Professor Smyth, joint head of WEHI's Bioinformatics division.

"Bioinformatics was critical for obtaining a global view of the diverse populations of cells within the different breast tissues we studied," he said. "Computational methods enabled the team to detect patterns and differences in gene expression in the different cells within the breast at unprecedented resolution."

Professor Visvader said the RNA atlas was the most comprehensive to-date for the human breast, and provided a framework for understanding the different cell types it can contain.

"This will be an invaluable resource for breast cancer researchers around the world. Our research also has important implications for not only understanding how breast cancers arise but also how cells in the surrounding environment contribute to their development, spread and response to treatment."

The research team would like to acknowledge the important role that tissue donors, the Victorian Cancer Biobank and kConFab played in this study.

The research was supported by the National Health and Medical Research Council, the Victorian Government, the National Breast Cancer Foundation, the Australian Cancer Research Foundation, Ian Potter Foundation, the Michael Heine Family Foundation, and the Qualtrough Cancer Research Fund.

Credit: 
Walter and Eliza Hall Institute

Health effects of prenatal exposure to 1994 genocide against the Tutsi in Rwanda

Twenty-seven years ago, more than 1 million Rwandans were killed during the genocide against the Tutsi in Rwanda from April 7 to July 4, 1994. It is estimated that 100,000 to 250,000 women were raped during the 100-day genocide, and that 10,000 children were born as a result. A new study finds that Rwandans who were conceived by mothers who survived the 1994 genocide against the Tutsi have poorer adult health outcomes than those who were conceived by Rwandan mothers living outside the country at that time. In addition, those who were conceived through genocidal rape have poorer adult health outcomes than those conceived by genocide survivors who were not raped. The findings are published in Social Science and Medicine.

The study was led by Glorieuse Uwizeye, a Rwandan genocide survivor and anthropology postdoctoral fellow of the Society of Fellows at Dartmouth. As a mental health nurse, in 2010, she started working with survivors of the genocide against the Tutsi, including women who were raped. "I was finding that these women's children who were born by genocidal rape, were kind of forgotten by everybody, including by policymakers and researchers," explains Uwizeye. "For these women, having children of perpetrators was an additional burden and this was a topic that was drawing little attention. She says, "It was then that I decided to shift my focus to working with Rwandan children who were conceived by genocidal rape. By studying their mental and physical health outcomes, I wanted to be able to write about their experience and be able to speak on their behalf with the hope that my research leads to the design of interventions that could mitigate these health effects of exposure in early life."

In March and April 2019, Uwizeye collected data from a total of 91 Rwandan men and women, who were 24-years old. There were three groups: 30 conceived by genocidal rape, 31 born of genocidal survivors not raped, and 30 born of women with neither exposure who left Rwanda before the genocide and returned afterwards (i.e. a control group). The participants were recruited from communities and organizations, including the Solidarity for the Development of Windows and Orphans to Promote Self-Sufficiency and Livelihoods (SEVOTA) and the Association of Genocide Widows Agahozo (AVEGA).

In Kinyarwanda, an official language of Rwanda, participants were asked a series of questions regarding their mental and physical health status. This included data on post-traumatic stress syndrome (PTSD), anxiety, depression, overall mental function, overall physical function, pain level, and interference with daily physical function. Demographic and socioeconomic information was also obtained, and prenatal exposure to genocide or genocidal rape or neither condition was noted. Data was also collected on adverse childhood experiences, including emotional, physical and sexual abuse; living in a household with violence and/or substance abusers; and exposure to community violence and resilience.

The findings demonstrate that participants conceived during the genocide had higher scores of depression, PTSD, pain intensity, and poorer mental health and physical function, than those not prenatally exposed to the genocide. Those who were born as a result of genocidal rape had poorer mental and physical health outcomes, including higher levels of depression, PTSD, and pain intensity and interference with daily function, than those who were exposed solely to the maternal stress of genocide. Both groups had more exposure to adverse childhood experience than the control group.

"Participants conceived by genocidal rape and who had high adverse childhood experiences had the worst adult health outcomes," explains Uwizeye. "Adverse childhood experiences appear to exacerbate health outcomes for those who were prenatally exposed to genocide."

"In the past, most research has just looked at prenatal environments in relation to adult health but has not considered this postnatal period," says co-author Zaneta Thayer, an assistant professor of anthropology at Dartmouth. "This research is important because it suggests that intervention at any point, even postnatally, can help reduce poor health following adverse prenatal exposures."

The research was part of Uwizeye's dissertation at the College of Nursing at the University of Illinois Chicago. "Glorieuse Uwizeye's work is essential to understanding the transgenerational impact of the genocide against the Tutsi and has major implications for ongoing sociopolitical violence around the world. It is not only the immediate survivors who are affected, but their children and even beyond," says senior author Julienne N. Rutherford, biological anthropologist and associate professor of Human Development Nursing Science at the College of Nursing at the University of Illinois Chicago, who served as Uwizeye's Ph.D. advisor. "Glorieuse Uwizeye, Zaneta Thayer and I plan to continue building on this research by working with these young adults as they age and start families of their own, to better understand how their early life experiences affect future generations."

Uwizeye and Thayer are currently studying ways to share their results with the participants in Rwanda. Thayer says, "As researchers, we have an ethical responsibility to communicate our findings back to the community, and we want to do that in a way that is thoughtful, informative and hopeful, not negative or pathologizing. We're looking forward to developing methods for dissemination and to working with community members and organizations on the ground to address these important health impacts."

Credit: 
Dartmouth College