Tech

Development of the immune system varies according to age, location and anaemia

image: Phase III clinical trial in Mozambique

Image: 
ISGlobal

Age and geographical location have the strongest influence on immune composition and vaccine responses, with anaemia having a considerable effect, according to a study co-led by the Barcelona Institute for Global Health (ISGlobal), an institution supported by "la Caixa", the Babraham Institute and the Swiss Tropical and Public Health Institute, in collaboration with the Manhiça Health Research Center (CISM). The results, published in Science Translational Medicine, will help improve the efficacy of early childhood vaccines in low-income countries.

The first years of life are key for the development of the immune system. During this period, the ability to respond to vaccines is reduced, and the susceptibility to infectious diseases is increased. This is particularly relevant in low-income countries, where malnutrition and other environmental factors may also play a role.

In this study, an international team co-led by ISGlobal researcher Carlota Dobaño, sought to identify the factors that shape the immune system during the first years of life. To do so, they analysed blood samples from children in Mozambique and Tanzania that participated in the phase 3 clinical trial for the RTS,S malaria vaccine. Specifically, they studied the immune phenotype - i.e. the percentage of different cell types that make up the immune system - over a 32-month period.

The immune profile depends on age and location

The results show that the immune system composition changes considerably during early childhood, with a progressive increase in dendritic cells and memory T and B cells - key elements for a strong immune response. These changes are observed over short periods of time (21 months), in contrast with the long-term stability observed in the adult. Comparison with a cohort of Dutch children suggests that this "maturation" of the immune system occurs faster in sub-Saharan Africa. "This could be due to a higher exposure to certain pathogens from early life," explains Gemma Moncunill, ISGlobal researcher and study co-author.

Anaemia can reduce vaccine responses

The authors also observed immune profile differences between both African countries: the Mozambican cohort had a more activated profile than the Tanzanian cohort, which was associated with a better response to the RTS,S vaccine. A detailed analysis of the samples indicated that this difference could be due to low haemoglobin levels.

Experiments performed by the Babraham Institute confirmed that iron deficiency reduces the development of antibody-secreting cells in vitro. "Our results suggest that iron deficiency can impair the development of adaptive immunity in anaemic children," says Dobaño.

"These findings indicate that the optimal age to vaccinate infants and children may vary according to the vaccine and the location," she adds. "This will help us design more effective vaccination strategies and maximise the benefits for this particularly vulnerable population in low income countries."

Credit: 
Barcelona Institute for Global Health (ISGlobal)

Viruses and cancer -- systematic overview published

Scientists from the German Cancer Research Center systematically investigated the DNA of more than 2,600 tumor samples from patients with 38 different types of cancer to discover traces of viruses - which they found in 13 percent of the samples studied. The researchers also identified mechanisms that the pathogens use to trigger carcinogenic mutations in the DNA. The work is part of the Pan-Cancer Analysis of Whole Genomes (PCAWG), an initiative launched by the International Cancer Genome Consortium (ICGC).

The World Health Organization (WHO) estimates that more than 15 percent of all cancers are directly or indirectly attributable to infectious pathogens. The International Agency for Research on Cancer (IARC) in Lyon has classified 11 different pathogens - viruses, bacteria, and worms - as carcinogenic agents and estimates that one in ten cancers is linked to viruses. Throughout the world, a total of 640,000 cancers each year are caused by human papillomaviruses (HPV) alone.

A new paper has now been published by an international team of genome researchers led by Peter Lichter from the German Cancer Research Center (DKFZ) to provide a precise overview of which viruses play a role in which cancers. The researchers also looked for viruses that have not previously been associated with carcinogenesis or even ones that were completely unknown. "The issue of which viruses are linked to cancer is highly relevant in medicine," explained Marc Zapatka from DKFZ, the lead author of the present study. "Because in virus-related cancers, real prevention is possible: If a carcinogenic virus is identified, there is a chance of avoiding infection with a vaccine and hence to prevent cancer developing."

The current work is part of the Pan-Cancer Analysis of Whole Genomes (PCAWG), a consortium of more than 1,300 researchers who have teamed up to establish which genetic mutations or patterns of DNA mutations play a role in several types of tumors. For this meta-analysis, they carried out a comprehensive bioinformatic analysis of the sequencing data of more than 2,600 tumor genomes from 38 different types of cancer.

The DFKZ team discovered traces of a total of 23 different virus types in 356 cancer patients. As expected, the known viral drivers of tumor initiation and growth were the most common: The genome of Epstein-Barr viruses (EBV), which are known to cause a number of different types of cancer, in particular lymphomas and gastric and nasopharyngeal carcinomas, was found in 5.5 percent of the cancer genomes investigated. Hepatitis B virus (HBV) DNA was found in 62 of the 330 cases of liver cancer.

The researchers primarily found human papillomaviruses, most commonly HPV16, in cervical carcinomas (in 19 of 20 cancer cases investigated) and in head and neck tumors (in 18 of 57 cases).

They were able to rule out a connection with the cancers as highly unlikely for some of the virus types detected. Thus adenoviruses and baculoviruses are often used as research tools in the field of molecular biology, for example, so the sequences found were probably due to contamination.

In a few cases, the team found other viruses already known to cause cancer, such as a retrovirus in kidney carcinoma. Other pathogens were occasionally found in tumors of the tissue type that they normally infect, such as cytomegaloviruses in gastric cancer. Despite thorough bioinformatic analysis, the researchers have not found any completely unknown viruses, however.

In some of the tumors linked to HPV and EBV, the researchers observed that the characteristic driver mutations that the cells of these cancer types normally depend on for growth were missing: The presence of the virus presumably supports malignant cell degeneration through other factors.

Viral integration into the host genome was found as as the most important mechanism that leads to mutations caused by viruses, particularly HVB and papillomaviruses. "We often observed integration of HPV DNA into the telomerase promoter: This genetic switch steers production of the 'immortality enzyme' telomerase and is mutated in many types of cancer. We have now shown that viral integration can also lead to activation of this genetic switch and can thus immortalize the cells," Marc Zapatka explained.

The DKFZ researchers identified cellular defense against viruses as another key mechanism that leads to mutations in the DNA of infected cells: The cell uses its APOBEC proteins to attack the DNA of dangerous viruses - but this often leads to mutations of the cell's own genome too. As a result, cervical cancer and head and neck tumors may arise following HPV infection, for example.

"When analyzing the whole cancer genome, we discovered traces of viruses in considerably more tumors than in earlier studies that were based on investigating the RNA only. Nevertheless, we were not able to confirm the common speculation that other, as yet unknown viruses are associated with cancer," remarked principal investigator Peter Lichter, summarizing the results of the study. "However, in many cases we now have a clearer idea of how the pathogens cause malignant mutations in cells."

Credit: 
German Cancer Research Center (Deutsches Krebsforschungszentrum, DKFZ)

A close-up look at mutated DNA in cancer cells

image: MDC scientists Julia Markowski (left), Roland Schwarz (center) and Matthew Robert Huska (right) all contributed to the paper.

Image: 
Felix Petermann, MDC

No two tumors are alike. That's why two people with the same kind of cancer can react very differently to the same medicine. In one the tumor gets smaller, in another the degenerated tissue remains unaffected. Usually this is due to genetic variations in the individual cancer cells.

In order to understand these variations in detail and better adapt therapies to the individual needs of patients in the future, an international team of more than 1,500 scientists - the Pan-Cancer Analysis of Whole Genomes (PCAWG) consortium - decided several years ago to trace the common mutation patterns in the genomes of about 3,000 cancer patients. The donated tissue samples included tumors of the liver, pancreas, brain, and 17 other organs.

PCAWG researchers used data from the International Cancer Genome Consortium (ICGC) and The Cancer Genome Atlas (TCGA) for their project. Participants in those groups had already completely sequenced the genomes and transcriptomes, that is the entire set of RNA molecules, of 1,188 degenerated tissue samples.

Regulatory sequences of DNA were also decoded

"Thanks to PCAWG, not only have the parts of genomes containing the blueprints for proteins from such a large number of patient samples been studied for the first time, but so have the regulatory sequences of DNA that control the expression of genes," says Dr. Roland Schwarz, head of the Evolutionary and Cancer Genomics Group at the Max Delbrück Center for Molecular Medicine (MDC) in the Helmholtz Association. Schwarz is one of seven senior authors of the study in the current issue of Nature. This publication is the main paper of PCAWG Working Group 3 "Integration of Transcriptome and Genome." Two scientists from Schwarz's own research group at the Berlin Institute for Medical Systems Biology (BIMSB) at the MDC - Dr. Matthew Robert Huska and Julia Markowski - also contributed to the paper.

"In our work, we and our colleagues systematically studied a variety of RNA alterations and identified mutations on the DNA level that cause these RNA alterations," Schwarz explains. Cancer-specific alterations on the RNA level have long been known. "Genes often get overexpressed in tumors, causing the formation of more RNA," says Schwarz. "Or there are gene fusions or modifications in splicing, an important step in the formation of RNA." In total, the PCAWG publishes more than 20 studies simultaneously in Nature, Nature Genetics, Nature Communications, Nature Biotech and Communications Biology.

Structural alterations in the genome play a decisive role

Until now, however, it has been rather unclear which DNA mutations are caused by the known RNA alterations. The work done by Schwarz and 49 other researchers has filled a significant gap in geneticists' understanding of carcinogenesis.

"An especially important focus of our work at the MDC has been on the interplay between selective DNA mutations and structural alterations, such as gene copy number variants," Schwarz reports. "Our cells normally contain two inherited copies of each and every chromosome, a maternal and a paternal allele." In cancer cells, the number of copies is often much higher, or entire segments of the genome have gone missing."

Using high-performance computers and cloud computing, Schwarz and his team have found out that such alterations in copy number play a decisive role in the altered gene expression of cancer cells. "By analyzing the DNA sequences of the entire genome, we have been able to accurately determine how copy number variants work together with point mutations - and what influence this in turn has on the expression of a specific parental allele," Schwarz explains.

Every one of a cell's three billion base pairs can mutate

Schwarz hopes that the work he and his colleagues are doing will significantly improve our understanding of gene regulation in tumors. "Our study will certainly lay the foundation for further research that will help us to become more familiar with the genetic heterogeneity of tumors," he says.

For the fact is that every single one of the approximately three billion base pairs contained in a human genome could theoretically mutate. "To find out how cells actually degenerate, we have to distinguish between significant and insignificant mutations," Schwarz says. And that's only possible with a large number of tumor samples. And with a large number of dedicated researchers, such as we see united in the PCAWG consortium. The main paper the group plans to publish will certainly be of major interest.

Credit: 
Max Delbrück Center for Molecular Medicine in the Helmholtz Association

Crystal-stacking process can produce new materials for high-tech devices

MADISON, Wis. -- The magnetic, conductive and optical properties of complex oxides make them key to components of next-generation electronics used for data storage, sensing, energy technologies, biomedical devices and many other applications.

Stacking ultrathin complex oxide single-crystal layers -- those composed of geometrically arranged atoms -- allows researchers to create new structures with hybrid properties and multiple functions. Now, using a new platform developed by engineers at the University of Wisconsin-Madison and the Massachusetts Institute of Technology, researchers will be able to make these stacked-crystal materials in virtually unlimited combinations.

The team published details of its advance Feb. 5 in the journal Nature.

Epitaxy is the process for depositing one material on top of another in an orderly way. The researchers' new layering method overcomes a major challenge in conventional epitaxy -- that each new complex oxide layer must be closely compatible with the atomic structure of the underlying layer. It's sort of like stacking Lego blocks: The holes on the bottom of one block must align with the raised dots atop the other. If there's a mismatch, the blocks won't fit together properly.

"The advantage of the conventional method is that you can grow a perfect single crystal on top of a substrate, but you have a limitation," says Chang-Beom Eom, a UW-Madison professor of materials science and engineering and physics. "When you grow the next material, your structure has to be the same and your atomic spacing must be similar. That's a constraint, and beyond that constraint, it doesn't grow well."

A couple of years ago, a team of MIT researchers developed an alternate approach. Led by Jeehwan Kim, an associate professor in mechanical engineering and materials science and engineering at MIT, the group added an ultrathin intermediate layer of a unique carbon material called graphene, then used epitaxy to grow a thin semiconducting material layer atop that. Just one molecule thick, the graphene acts like a peel-away backing due to its weak bonding. The researchers could remove the semiconductor layer from the graphene. What remained was a freestanding ultrathin sheet of semiconducting material.

Eom, an expert in complex oxide materials, says they are intriguing because they have a wide range of tunable properties -- including multiple properties in one material -- that many other materials do not. So, it made sense to apply the peel-away technique to complex oxides, which are much more challenging to grow and integrate.

"If you have this kind of cut-and-paste growth and removal, combined with the different functionality of putting single-crystal oxide materials together, you have a tremendous possibility for making devices and doing science," says Eom, who connected with mechanical engineers at MIT during a sabbatical there in 2014.

The Eom and Kim research groups combined their expertise to create ultrathin complex oxide single-crystal layers, again using graphene as the peel-away intermediate. More importantly, however, they conquered a previously insurmountable obstacle -- the difference in crystal structure -- in integrating different complex oxide materials.

"Magnetic materials have one crystal structure, while piezoelectric materials have another," says Eom. "So you cannot grow them on top of each other. When you try to grow them, it just becomes messy. Now we can grow the layers separately, peel them off, and integrate them."

In its research, the team demonstrated the efficacy of the technique using materials such as perovskite, spinel and garnet, among several others. They also can stack single complex oxide materials and semiconductors.

"This opens up the possibility for the study of new science, which has never been possible in the past because we could not grow it," says Eom. "Stacking these was impossible, but now it is possible to imagine infinite combinations of materials. Now we can put them together."

The advance also opens doors to new materials with functionalities that drive future technologies.

"This advance, which would have been impossible using conventional thin film growth techniques, clears the way for nearly limitless possibilities in materials design," says Evan Runnerstrom, program manager in materials design in the Army Research Office, which funded part of the research. "The ability to create perfect interfaces while coupling disparate classes of complex materials may enable entirely new behaviors and tunable properties, which could potentially be leveraged for new Army capabilities in communications, reconfigurable sensors, low power electronics, and quantum information science."

Credit: 
University of Wisconsin-Madison

Bumblebees carry heavy loads in economy mode

video: Bumblebees can fly while carrying up to their own weight in nectar. A new study shows they can do this by increasing wingbeat frequency or with an energy-efficient economy mode. High-speed video shows a bee flying in a test chamber with extra weight added from a piece of solder wire.

Image: 
Combes lab, UC Davis.

Bumblebees are the big lifters of the insect world, able to fly back to the hive with almost their own bodyweight in nectar on board. A study published Feb. 5 in Science Advances shows how they do it - and that bees can show more flexibility in behavior than you might expect from a bumbling insect.

"They can carry 60, 70 or 80 percent of their body weight flying, which would be a huge load for us just walking around," said researcher Susan Gagliardi, a research associate in the College of Biological Sciences at the University of California, Davis. "We were curious to see how they do it and how much it costs them to carry food and supplies back to the hive."

Gagliardi and Stacey Combes, associate professor in the Department of Neurobiology, Physiology and Behavior, measured the energy expended by bumblebees flying in a specially designed chamber (an emptied snowglobe). They attached small pieces of solder wire to the bees to adjust their weight.

"We have the bees in a little chamber and we measure the carbon dioxide they produce. They are mostly burning sugar so you can tell directly how much sugar they are using as they are flying," Gagliardi said.

They also used high-speed video to examine wing beats and movements.

Bumblebees fly in a very different way to aircraft, Combes said. While air flows smoothly over an aircraft wing or rotor blade, bees move their wings at a high angle to the air generating vortices that curl round the wing. This produces much more lift than smooth airflow, but it is unstable as the vortices quickly break down. Bees are able to sustain flight by moving their wings very rapidly.

Two modes of flight

Because bumblebees fuel flight from the nectar they are carrying, they should get lighter as they fly and use less energy. To their surprise, Combes and Gagliardi found that the bees could actually use less energy per unit load when they were more heavily laden.

"They get more economical in flying the more heavily loaded they are, which doesn't make any sense in terms of energetics," Combes said.

Looking closely, the researchers found that bumblebees have two different ways to cope with increasing loads. They always increase stroke amplitude (how far the wings flap) when they are more heavily loaded, but this isn't enough to support the extra weight on its own. To make up the difference, bees can increase wingbeat frequency, which generates more lift and increases energetic cost.

But bees also have an alternative, subtly different flying mode that allows them to carry heavier loads while expending less energy than when they increase flapping frequency.

It's not yet clear exactly what this "economy mode" involves, Combes said, although it may involve a change in how the wing rotates to reverse direction between strokes. But it is something the bees can chose to do, or not.

"It turns out to be a behavioral choice they are making in terms of how they support the load," Combes said. When bees are lightly loaded or rested, they are more likely to increase wingbeat frequency. When they are more heavily loaded, they switch to the mysterious economy mode, producing enough force to support the load with only a small increase, or even a decrease, in flapping frequency.

Economy and stability

If the bees can save energy while flying, why don't they use this economy mode all the time? It's not clear, but it may be that high wingbeat frequency has performance advantages, for example in maintaining stability in turbulent air or avoiding obstacles, Combes said.

The work has prompted a shift in how Combes sees insects, she said.

"When I started in this field there was a tendency to see them as little machines, we thought they'll flap their wings one way when carrying zero load, another way when they're carrying 50 percent load and every bee will do it the same way every time," she said. "This has given us an appreciation that it's a behavior, they choose what to do. Even the same bee on a different day will pick a new way to flap its wings."

Credit: 
University of California - Davis

Novelty speeds up learning thanks to dopamine activation

Brain scientists led by Sebastian Haesler (NERF, empowered by IMEC, KU Leuven and VIB) have identified a causal mechanism of how novel stimuli promote learning. Novelty directly activates the dopamine system, which is responsible for associative learning. The findings have implications for improving learning strategies and for the design of machine learning algorithms.

Novelty and learning

A fundamental type of learning, known as associative learning, is commonly observed in animals and humans. It involves the association of a stimulus or an action with a positive or negative outcome. Associative learning underlies many of our every-day behaviors: we reward children for doing their homework, for example, or limit their TV time if they misbehave.

Scientists have known since the 1960's that novelty facilitates associative learning. However, the mechanisms behind this phenomenon remained unknown.

"Previous work suggested that novelty might activate the dopamine system in the brain. Therefore we thought that dopamine activation might also promote associative learning." says Prof. Sebastian Haesler, who led the study.

Sniffing out novelty

To demonstrate that novelty indeed activates dopamine neurons, the researchers exposed mice to both new and familiar smells.

"When mice smell a novel stimulus, they get very excited and start sniffing very rapidly. This natural, spontaneous behavior provides a great readout for novelty perception." explains Dr. Cagatay Aydin, postdoc in the group of Sebastian Haesler. With the mouse experiments, the team confirmed dopamine neurons were activated by new smells, but not by familiar ones.

In a second step, the mice were trained to associate novel and familiar smells with reward.

"When we specifically blocked dopamine activation by novel stimuli in only a few trials, learning was slowed down. On the other hand, stimulating dopamine neurons during the presentation of familiar stimuli accelerated learning." says Joachim Morrens, PhD student in the group.

The value of novelty

The findings demonstrate that dopamine activation by novel stimuli promotes learning. They further provide direct experimental support for a group of theoretical frameworks in computer science, which incorporate a 'novelty bonus' to account for the beneficial effect of novelty. Incorporating such a bonus can speed up machine learning algorithms and improve their efficiency.

From a very practical perspective, the results remind us to break our routine more often and seek out novel experiences to be better learners.

Credit: 
VIB (the Flanders Institute for Biotechnology)

An end-to-end general framework for automatic diagnosis of manufacturing systems

image: Summary of classification and regression results of ten manufacturing data sets.

Image: 
©Science China Press

The manufacturing sector is envisioned to be heavily influenced by artificial intelligence-based technologies with the extraordinary increases in computational power and data volumes.

Data-driven methods use sensor data, such as vibration, pressure, temperature, and energy data to extract useful features for diagnosis and prediction. A central challenge in manufacturing sector lies in the requirement of a general framework to ensure satisfied diagnosis and monitoring performances in different manufacturing applications.

In a new research article published in the Beijing-based National Science Review, Prof. Ye Yuan from the School of Artificial Intelligence and Automation and Prof. Han Ding from the State Key Laboratory of Digital Manufacturing Equipment and Technology, Huazhong University of Science and Technology, jointly proposed an end-to-end diagnostic framework that can be used in diverse manufacturing systems. This framework exploits the predictive power of convolutional neural network to automatically extract hidden degradation features from noisy time-course data. The proposed framework has been tested on ten representative data sets drawn from a wide variety of manufacturing applications. Results reveal that the framework performs well in examined benchmark applications and can be applied in diverse contexts, indicating its potential use as a critical corner stone in smart manufacturing.

Considering that the potential time dependency existing among the reconstructed samples, this paper uses three standard cross-validation methods (random subsets, contiguous block, and independent sequence) to evaluate the performance of the framework. This paper also interprets how the CNN model learns from temporal manufacturing data and the robustness of the proposed framework is also discussed.

Credit: 
Science China Press

A 3D study of a tiny beetle that attacks the fruits of coffee reveals details of its anatomy and secret life that can help fight this pest

image: Professor Javier Alba-Tercedor with Ignacio Alba-Alejandre in the laboratory.

Image: 
UGR Divulga

Scientists from the University of Granada (UGR), belonging to the Department of Zoology, have provided new data on Hypothenemus hampei, a tiny beetle of just over a millimeter in size that is known as 'the coffee berry borer', because it attacks coffee berries digging tunnels with cameras in which they lay eggs.

This insect is responsible for the greatest pests that exist in coffee, and to date its hidden life within coffee berries was little known. The Microtomography Unit of the Department of Zoology of the University of Granada, which is led by Professor Javier Alba-Tercedor, has revealed secret, and until now unknown, aspects of tunnel construction strategies, and how to exploit the fruit. They have also been able to study in detail the structures and organs of this small insect.

After suffering a metamorphosis, the larvae of this beetle become pupae that give rise to adults of both sexes. The males copulate with their sisters, who once fertilized leave the fruit and spread the plague. To avoid the toxicity of coffee, interestingly, these small insects have symbiont microorganisms in their digestive tract that degrade caffeine.

Thanks to the dissemination of the spectacular achievements made with microtomography, Dr. Fernando Vega, a well-known scientist from the Department of Agriculture in Maryland (United States) who has been working with this pest for many years, contacted the University of Granada for collaboration. Thus, as part of the doctoral thesis of Ignacio Alba-Alejandre, the UGR researchers have obtained new and revealing data on this tiny beetle species.

Females generally drill a single entrance tunnel. The microtomography has revealed that the entrance tunnel does not have a rectilinear trajectory, but is zigzag, and the founder female is placed plugging the entrance with the back of the body. This hinders the rapid entry of potential enemies.

The same defensive pattern as at the gates of the Alhambra

"Interestingly, this strategy has been used throughout history to protect fortresses and castles. For example, the entrance doors of the Alhambra in Granada follow this same pattern", says Alba-Tercedor. In addition, the larvae do not deplete the fruit by eating and drilling new random tunnels, but instead follow an organized pattern by first depleting one side of the coffee bean, and always starting at the outermost part, and then the other grain of the fruit. If it is difficult to imagine how such a small animal has developed such complex construction behavior and mastery throughout evolution, it is even more astonishing to contemplate the complex internal anatomy with the different organs. "pay attention, for instance, existing sexual differences, such as those that exist in the configuration of the digestive system according to sex: the male, who is smaller, has a greater number of convolutions in his digestive tract so that, maintaining the length of absorption of tubes, the digestive tract can fit in a short-smaller body than the female, "says the UGR professor.

In addition, as the life of the males is less risky and complex (since they do not leave the fruit of the coffee cherry in which they were born), it has reduced wings (and therefore lack the necessary muscles) and their brains are smaller and differently shaped in relation to females.

The insects have a respiratory system, called the tracheal system, composed of a complex network of tubes that, starting from small external holes, are branching into smaller and smaller tubes, reaching diameters of just one thousandth of a millimeter, in order to carry Oxygen to each cell. Given its small size, it is difficult to be able to highlight this complicated network of tubes either by classical dissections techniques, or even by using microtomographic techniques.

Despite this, the research team at the University of Granada has been able to develop a technique that needs to scan the insects immediately after immobilizing them (sacrificing or anesthetizing them) and then rebuilding the air-filled space inside the tracheal tubes

The anatomy of an insect

Thanks to this, scientists have been able to reconstruct the tracheal system of these insects for the first time and describe and name many of the branches that for the layman would be a circulatory system. The total length of tubes is 73 times the length of the animal. If we transpose this to a human scale, then a 175 cm long insect (the average height for American males47) would have 123 m of tracheal tubes (longer than a football or soccer field). The circulatory system of insects is barely reduced to a heart that pumps hemolymph (blood) and from which an anterior and a posterior aorta (which has also been studied).

"The novelty of the study lies in being the first time that with microtomography the entire anatomy of an insect is reconstructed, being the smallest studied with this technique, so this achievement constitutes itself a great scientific advance", highlights the UGR researcher. But in addition, the images, videos and 3D models obtained by scientists, which can be viewed on any mobile device (smartphones / tablets), represent a great help in teaching entomology and of interest to the general public.
These findings have been published in recent months in different works in the prestigious journal Scientific Reports of Nature.

This collaboration of the UGR researchers is not the first one they get thanks to the scientific dissemination of their work. Thus, his articles on honey bees inspired in 2019 to create works of art for a humanoid robot, named Ai-Da developed in Oxford, and Professor Alba-Tercedor also participated in the scanning of beetles that appear in the film 'Blade Runner 2049', which in 2017 won the Oscar for the best visual effects

Credit: 
University of Granada

Waterbug from european rivers found in the Iberian Peninsula

image: The new study confirms this water insect as part of the Iberian fauna.

Image: 
Ekkerhardt Wachmann

Aphelocheirus aestivalis, a waterbug found in mid and high sections of well-oxygenated and preserved rivers in the European continent, has been found for the first time in Catalonia (Spain) -specifically in rivers Ter and Llobregat- according to an article published in the journal Limnetica. This discovery confirms the presence of this insect from the Aphelocheiridae family in the Iberian Peninsula and enables the incorporation of a new family of Heteroptera in the Catalan fauna.

The new study is led by the lecturer Marta Goula, from the Department of Evolutionary Biology, Ecology and Environmental Sciences of the Faculty of Biology and the Biodiversity Research Institute (IRBio) of the University of Barcelona. Other authors included in the new study are the experts from the Freshwater Ecology, Hydrology and Management (FEHM) research group of the UB Narcís Prat, Cesc Múrria and Pau Fortuño, Marcos Roca-Cusachs (UB-IRBio) and Laia Jiménez, Núria Sellarès and Marc Ordeix, from the Center for the Study of Mediterranean Rivers (CERM) of the University of Vic-Central University of Catalonia.

With this new finding on the species in the Catalan water systems, researchers can complete the current map of the peninsular distribution of the Aphelocheiridae family, which was so far represented by two endemic species -A. murcius and A. occidentalis- described in other autonomous communities of Spain. Actually, the previous scientific bibliography noted that citations of A. aestivalis in the Iberian Peninsula could be wrong, and will probably correspond to any of the already described endemisms or to others yet to be described.

The new specimens of this waterbug -an insect with a high habitat specificity- were found in in two sections of the river Llobregat and the Ter that were spaced thirty-six kilometers. According to the study, these insects show some differences in male internal genital structures compared to other specimens that were found in other European areas. The restricted and fragmented distribution of the species together with its biological requirements - mainly a good ecological quality of water systems- are factors that put in danger its future conservation and require to take urgent measures to preserve the natural habitat, experts warn.

The findings of A. aestivalis show the research effort made on ecology and biology of water ecosystems carried out for more than twenty-five years by the experts from the Freshwater Ecology, Hydrology and Management (FEHM) research group of the UB and CERM of UVic-UCC in the water basins of the rivers Llobregat and Ter.

Credit: 
University of Barcelona

Nanoparticles produced from burning coal result in damage to mice lungs

image: Associate professor of inflammatory disease Irving Coy Allen.

Image: 
Virginia Tech

Virginia Tech scientists have discovered that incredibly small particles of an unusual and highly toxic titanium oxide found in coal smog and ash can cause lung damage in mice after a single exposure, with long-term damage occurring in just six weeks.

The tests were headed by Irving Coy Allen, a professor with the Virginia-Maryland College of Veterinary Medicine, with collaborators from across Virginia Tech and researchers at the University of Colorado, the University of North Carolina at Chapel Hill, East Carolina University, and East China Normal University in Shanghai. The findings were recently published in the scientific journal Frontiers in Immunology.

Watch video: https://video.vt.edu/media/Nanoparticles+produced+from+burning+coal+may+be+toxic+to+humans/1_z4706e5b

They follow 2017 findings by Virginia Tech geoscientist Michael Hochella that burning coal -- when smoke is not captured by high-end filters currently found in U.S. power plants -- emits tiny particulates known as titanium suboxide nanoparticles into the atmosphere. Such nanoparticles were found by Hochella's team of scientists in ash collected from the city streets, sidewalks, and in ponds and bays near U.S. and Chinese cities.

Using mouse models in a lab setting, these tiniest of nanoparticles -- as small as 100 millionths of a meter -- entered the lungs after being inhaled. Once inside the lungs, the nanoparticles encountered macrophages, the lungs' defensive cells that trap and remove foreign materials. Typically, these cells protect the lungs from pathogens, such as bacteria and viruses. But against these nanoparticles, the macrophages falter.

"They can't break the titanium nanoparticles down, so the cells begin to die, and this process recruits more macrophages. These processes begin a feedback loop with each round of dying cells concentrating around the nanoparticles," said Allen, a member of the Department of Biomedical Sciences and Pathobiology. "The dying, nanoparticle-containing cells then begin making deposits in the lungs and these deposits cause problems. We begin seeing negative impacts on lung function, and basically the lungs fail to continue to work correctly."

In what Allen calls a "striking find," his team discovered negative effects after only one exposure to the toxic nanoparticles. Long-term damage from the deposits can appear in as little as six weeks, raising concerns for highly polluted cities. "We realized if someone is living near a power plant, or near one of these coal burning sources, they wouldn't be exposed to a single dose, they'd be exposed to this daily," he said. "We also did not see lung clearance after a week, so when these things are in your lungs they are staying there, and they are staying there for an extended period of time."

More so, damaged lungs can lead to higher susceptibility to virus or bacterial infection, and could worsen symptoms associated with asthma or chronic obstructive pulmonary disease (COPD).

However, the exact effects of these toxic nanoparticles on humans, other animals, vegetation, and water systems are not known and demand further study by international researchers, Allen said.

"Mouse and human lungs are functionally similar, but anatomically different in a variety of subtle ways," Allen added. "While the studies done in this paper are commonly utilized to model airway disorders in people, more direct clinical data are necessary to fully understand the human impact of exposure to these nanoparticles."

The titanium suboxide nanoparticles -- called Magnéli phases by researchers -- were once thought rare, found on Earth in some meteorites, from a small area of certain rocks in western Greenland, and occasionally in moon rocks. However, Hochella, working with other researchers in 2017, found that these nanoparticles are in fact widespread globally from the burning of coal.

According to the earlier study, published in Nature Communications, nearly all coal contains small amounts of the minerals rutile or anatase, both "normal," naturally occurring, and relatively inert titanium oxides. But when burnt, these minerals convert to titanium suboxide. The nanoparticles then become airborne if the power plant is not equipped with high-tech particle traps, such as those in the United States. For countries without strict regulations, the nanoparticles can float away in air currents locally, regionally, and even globally, Hochella said. (He added that the United States first started using electrostatic precipitators on coal stacks in the 1920s.)

Early biotoxicity studies by Hochella's group with zebra fish embryos showed signs of negative biological impact from the nanoparticles, suggesting potential harm to humans. Now, with this study, the odds of toxicity to humans are much greater. "The problem with these nanoparticles is that there is no easy or practical way to prevent their formation during coal burning," said Hochella, University Distinguished Professor Emeritus of Geosciences with the Virginia Tech College of Science, upon the earlier study's release two years ago.

Hochella and his team came across the titanium suboxide nanoparticles quite by accident while studying the downstream movement of a 2014 coal ash spill in the Dan River of North Carolina. The group later produced the same titanium suboxide nanoparticles when burning coal in lab simulations. This potential health hazard builds on established findings from the World Health Organization: More than 3.3 million premature deaths occurring worldwide per year due to polluted air, and in China alone, 1.6 million premature deaths are estimated annually due to cardiovascular and respiratory injury from air pollution.

This raises multiple questions: Are the nanoparticles absorbed through the body by other means, such as contact with eyes or skin? Can they find their way into vegetation - including food - though soil? If so, what are the implications on the gastrointestinal tract? Are they present in drinking water? If a mouse experiences long-term damage at six weeks, what does that pose for humans who breathe the air?

Allen urges that testing move to human-focused studies.

"We've identified a unique pollutant in the environment, and we've shown there's a potential health concern for humans, so that gives us a biomarker that we can monitor more closely," he said. "We should begin looking at these particulates more closely as we become more aware of the hazards these nanoparticles pose. These are questions that need to be asked."

That path, while obvious, may not be so simple, ethically or politically. Scientists can't expose human test subjects to coal smog or ash and the toxic nanoparticles. Therefore, a likely scenario: scientists could study these particles in human lung tissue from lung biopsies and clinical specimens. However, many clinicians have been reluctant to take part in this effort in many of the countries at the most risk. Allen said one reason may be the sensitivity that these countries hold toward air-quality issues.

Credit: 
Virginia Tech

Protein could offer therapeutic target for breast cancer metastasis

LEXINGTON, Ky. (Feb. 5, 2020) - A new study by University of Kentucky Markey Cancer Center researchers suggests that targeting a protein known as heat shock protein 47 (Hsp47) could be key for suppressing breast cancer metastasis.

Metastasis is when cancer cells spread from the primary tumor to surrounding tissues and distant organs in the body and is the primary cause for breast cancer mortality. It is estimated that metastasis is responsible for about 90% of breast cancer deaths.

The study, led by Markey researcher Ren Xu, associate professor in the UK College of Medicine's Department of Pharmacology and Nutritional Sciences, found that Hsp47, a protein that assists with collagen production, plays a role in breast cancer metastasis.

Xu and co-author Gaofeng Xiong analyzed DNA/RNA generated from human breast cancer tissue, which showed that increased production of Hsp47 was linked to metastasis in triple-negative breast cancer. About 10-20% of breast cancers are classified as triple-negative, which is considered to be more aggressive and have a poorer prognosis than other types of breast cancer.

The results suggest that targeting Hsp47 could be a promising strategy to block cancer cell-platelet interaction and cancer colonization in secondary organs for triple-negative breast cancer patients, says Xu.

"If we can find a way to target this pathway with therapeutics we could block this process and therefore inhibit metastasis," Xu said.

Xu says another benefit of the study is the potential that Hsp47 could serve as a prognosis or biomarker of metastasis since it is often amplified in the genes of metastatic breast cancer tissue.

The study was published in PNAS and was supported by funding from the National Cancer Institute.

Credit: 
University of Kentucky

Colossal oysters have disappeared from Florida's 'most pristine' coastlines

image: Prehistoric oysters from Crystal River are 55% larger than modern oysters.

Image: 
University of South Florida

TAMPA, Fla. (February 5, 2020)- Hundreds of years ago, colossal oysters were commonplace across much of Florida's northern Gulf Coast. Today, those oysters have disappeared, leaving behind a new generation roughly a third smaller - a massive decline that continues to have both economic and environmental impacts on a region considered by many to be the last remaining unspoiled coastlines in the Gulf.

The loss of these colossal oysters is at the center of new research from an interdisciplinary team of scientists at the University of South Florida. Led by Integrative Biology PhD student Stephen Hesterberg, School of Geosciences faculty member Gregory Herbert, PhD, and Anthropology faculty member Thomas Pluckhahn, PhD, researchers utilized prehistoric oyster shells, excavated from archaeological sites near Crystal River, Florida to measure how much oyster size has changed in the area and learn more about the factors that have led to it. The intent is to better understand the habitats of the distant past to help inform the conservation efforts of today.

"Most policy makers and conservationists working in this area are only considering the last 50 years - when we first began actively monitoring these habitats," said Herbert. "Using archaeological data, our work shows that what these systems looked like 100 or 1,000 years ago matters for conservation efforts now."

The region researchers explored is of significant importance, particularly within the oyster industry. Crystal River is within Florida's 'Big Bend' region and is considered one of the last remaining pristine coastal zones with natural oyster fisheries in the United States. However, because this work illustrates huge changes there that were previously unrecognized, researchers now believe the region may not be as pristine as once thought.

"We've been altering the environment in Florida for a lot longer than the 1950's. So, if we don't look at a longer time scale, we might be missing the root causes of why fisheries and marine environments in our state are beginning to collapse," Hesterberg said.

While the loss of large oysters in these coastal regions may not seem like cause for concern, biologists say the ripples caused by their disappearance have had large-scale repercussions. On the one hand, there's the economic impact to an industry that generates hundreds-of-millions-of-dollars annually and relies upon adult oysters of a minimum size to harvest.

There are also environmental concerns. In nature, large animals of all species are uniquely important in terms of their ecological function. Large oysters, for example, have an exponentially greater role in reproductive output and water filtration compared to smaller oysters. Having more offspring helps oyster reefs recover faster after mass mortality events from storms or natural enemies. Slower rates of water filtration mean that estuary waters downstream from oysters are now increasingly muddy, leading to less sunlight penetration and reduced growth of seagrass, a hugely important habitat for a variety of fish.

Researchers also utilized isotopic geochemistry to study the chemical elements within prehistoric and modern oyster shells. This technique allowed them to gain a better understanding of the biological changes that have led to a roughly 2.6 inch decrease in maximum size.

The team found that the lifespan of modern oysters is shorter by about one year compared to their ancestors and that their current rate-of-growth is slower. In an ideal world, restoring Florida's oyster habitats would mean restoring conditions that lead to longer-lived, faster-growing oysters. If that's not possible, the authors add, the filtration rates of prehistoric oyster reefs might still be restored by increasing oyster numbers or densities.

USF researchers hope these new insights can help change the perspective of the current state of Florida's coastal habitats and, in turn, have significant impacts on the direction of conservation and restoration efforts already underway.

Credit: 
University of South Florida

First-of-its-kind study examines toll of nuclear war on world's oceans

A nuclear war, even a relatively contained conflict, wouldn't just have devastating consequences for life on land. It could also take a toll on the oceans, according to recent research led by the University of Colorado Boulder and Rutgers University.

The new study, published recently in the journal Geophysical Research Letters, explores a previously unknown link: How a clash between modern nuclear powers might shift the chemistry of the world's seas.

"The impacts are huge," said Nicole Lovenduski, lead author and an associate professor in the Department of Atmospheric and Oceanic Sciences (ATOC) at CU Boulder.

Lovenduski and her colleagues discovered that the smoke generated by the detonation of nuclear warheads could shift patterns of ocean acidification across the globe--and rob those waters of the building blocks that many organisms, like corals, need to build their hardy exteriors.

"This result is one that no one expected," said Brian Toon, a coauthor of the study and an ATOC professor. "In fact, few people have previously considered the impact of a nuclear conflict on the ocean."

Acidity falling

The findings stem from a long-running effort led by Toon and Alan Robock of Rutgers to better understand the potential, and sometimes hidden, costs of nuclear war.

Until recently, most research on the topic only explored those costs on land.

Lovenduski and her colleagues wanted to go deeper. To do that, the team examined a series of possible nuclear conflicts of various magnitudes. They included a hypothetical war between India and Pakistan. Even this regional conflict could wind up lofting huge amounts of black carbon high in Earth's atmosphere, causing the globe to cool.

"A lot of things would change in the oceans once you dim the lights," said Lovenduski, also of the Institute of Arctic and Alpine Research (INSTAAR) at CU Boulder. "The way the water moves in the ocean, for example, is sensitive to how much heat it gets from the atmosphere."

Her group followed those changes using detailed computer simulations called global climate models.

They discovered that the fallout would come in two stages. Soon after a nuclear war, or as little as one year later, the acidity of the world's oceans would likely dip. Such a shift is important, Lovenduski said, because ocean acidification has been ramping up in recent decades--the result of humans pumping large quantities of carbon dioxide gas into the air.

Losing calcium

Organisms living in the ocean, however, wouldn't be in the clear yet.

That's because roughly three to five years after the bombs fell, something else would happen in the seas: The world's salt water would begin to suck up more carbon dioxide from the air. Lovenduski explained that it's akin to how you can keep your Diet Coke bubbly for longer by putting it in the fridge.

"Cold liquids hold more gas than warm liquids," Lovenduski said.

That Diet Coke effect would tip the balance of ocean chemistry. Supplies of carbonate in the oceans would shrink, removing the key ingredient that corals use to maintain their reefs and oysters use to maintain their shells.

"It makes me question whether organisms could adapt to such a change," Lovenduski said. "We're already questioning whether they can adapt to the relatively slower process of man-made ocean acidification, and this would happen much more abruptly."

She said it's too soon to say for sure what the fate of shelled critters in the oceans would be if nuclear war broke out. Study coauthor Holly Olivarez, however, noted that the impact of such a conflagration has parallels with the toll of more natural global disasters: major volcanic eruptions.

"Using global climate models to look at these extreme circumstances allows scientists to see Earth processes from different vantage points," said Olivarez, a graduate student in INSTAAR.

Lovenduski hopes that her group's findings will bring more attention to the wide-ranging devastation that would follow a nuclear exchange. There's no such thing, she said, as a minor nuclear war.

"I hope this study helps us to gain perspective on the fact that even a small-scale nuclear war could have global ramifications," she said.

Credit: 
University of Colorado at Boulder

Focus on context diminishes memory of negative events, researchers report

image: U. of I. psychology professors Sanda and Florin Dolcos explore emotional-regulation strategies that promote psychological health.

Image: 
Photo by L. Brian Stauffer

CHAMPAIGN, Ill. -- In a new study, researchers report they can manipulate how the brain encodes and retains emotional memories. The scientists found that focusing on the neutral details of a disturbing scene can weaken a person's later memories - and negative impressions - of that scene.

The findings, reported in the journal Neuropsychologia, could lead to the development of methods to increase psychological resilience in people who are likely to experience traumatic events - like soldiers, police officers or firefighters. Those plagued by depression or anxiety might also benefit from this kind of strategy, the researchers said.

"We were interested in different properties of memories that are typically enhanced by emotion," said Florin Dolcos, a professor of psychology at the University of Illinois at Urbana-Champaign who led the study with psychology professor Sanda Dolcos. "The idea was to see whether by engaging in an emotional-regulation strategy we can influence those types of memory properties."

There are two categories of memory retrieval. A person may recall a lot of details about an event or experience, a process the researchers call "recollection." Or an individual may have a sense of familiarity with the subject matter but retain no specifics.

"We and others showed a while ago that emotion tends to boost our memories," Florin Dolcos said. "We have also known that emotion specifically boosts recollected memories."

This memory-enhancing quality of emotion is useful, but it can be problematic for those who recall - again and again - the details of a disturbing or traumatic event, he said.

"Negative memories could lead to clinical conditions such as post-traumatic stress disorder, where something that is really traumatic stays with specific details in people's minds," he said.

In the study, 19 participants had their brains scanned while they looked at photos with negative or neutral content - a bloody face or a tree, for example - superimposed on a neutral background. Functional MRI signaled which brain areas were activated during the task. An eye-tracker recorded where participants looked.

Before each photo, participants were asked to focus their attention either on the foreground or on the background of the image. After viewing it for four seconds, they rated how negatively the photo made them feel (not at all, very, or somewhere in between).

Participants returned to lab three to five days later to view the same photos - and a few new ones. They were asked to indicate whether the images were entirely new; familiar, but with no remembered specifics; or recollected in more detail.

Not surprisingly, when they focused on the foreground of photos with negative content, participants rated the photos as more negative. When they focused instead on the neutral backgrounds of photos with negative content, they still evaluated the photos as negative, but rated them less negatively. They also retained fewer detailed memories of the negative photos a few days later, the team found.

"This is the first example that we know of that focusing on the context of an emotional event while it is occurring can directly influence memory formation in the moment - and one's recall of the event a few days later," Sanda Dolcos said.

The fMRI scans revealed that brain regions known to be associated with emotional memory formation were most active when participants focused on the foregrounds of negative photos. Brain activity differed, however, when participants focused on the backgrounds of negative images.

"The background-focus condition was associated with decreased activity in the amygdala, hippocampus and anterior parahippocampal gyrus," the researchers wrote. These brain regions play a role in encoding memory and processing emotional information. A statistical analysis "also showed that reduced activity in these regions predicted greater reduction in emotional recollection."

"It might seem counterintuitive that we are looking for ways to reduce people's memories," Sanda Dolcos said. "Usually, people are interested in improving their memories. But we are finding that strategies like this, that can be employed when we are exposed to certain distressing situations, can help a lot."

Florin and Sanda Dolcos are affiliates of the Beckman Institute for Advanced Science and Technology at the U. of I.

Credit: 
University of Illinois at Urbana-Champaign, News Bureau

Controlling light with light

The future of computation is bright -- literally.

Researchers from the Harvard John A. Paulson School of Engineering and Applied Sciences (SEAS), in collaboration with researchers at McMaster University and University of Pittsburgh, have developed a new platform for all-optical computing, meaning computations done solely with beams of light.

"Most computation right now uses hard materials such as metal wires, semiconductors and photodiodes to couple electronics to light," said Amos Meeks, a graduate student at SEAS and co-first author of the research. "The idea behind all-optical computing is to remove those rigid components and control light with light. Imagine, for example, an entirely soft, circuitry-free robot driven by light from the sun."

These platforms rely on so-called non-linear materials that change their refractive index in response to the intensity of light. When light is shone through these materials, the refractive index in the path of the beam increases, generating its own, light-made waveguide. Currently, most non-linear materials require high-powered lasers or are permanently changed by the transmission of light.

Here, researchers developed a fundamentally new material that uses reversible swelling and contracting in a hydrogel under low laser power to change the refractive index.

The hydrogel is composed of a polymer network that is swollen with water, like a sponge, and a small number of light-responsive molecules known as spiropyran (which is similar to the molecule used to tint transition lenses). When light is shone through the gel, the area under the light contracts a small amount, concentrating the polymer and changing the refractive index. When the light is turned off, the gel returns to its original state.

When multiple beams are shone through the material, they interact and affect each other, even at large distances. Beam A could inhibit Beam B, Beam B could inhibit Beam A, both could cancel each other out or both could go through -- creating an optical logic gate.

"Though they are separated, the beams still see each other and change as a result," said Kalaichelvi Saravanamuttu, an associate professor of Chemistry and Chemical Biology at McMaster and co-senior author of the study. "We can imagine, in the long term, designing computing operations using this intelligent responsiveness."

"Not only can we design photoresponsive materials that reversibly switch their optical, chemical and physical properties in the presence of light, but we can use those changes to create channels of light, or self-trapped beams, that can guide and manipulate light," said co-author Derek Morim, a graduate student in Saravanamuttu's lab.

"Materials science is changing," said Joanna Aizenberg, the Amy Smith Berylson Professor of Materials Science at SEAS and co-senior author of the study. "Self-regulated, adaptive materials capable of optimizing their own properties in response to environment replace static, energy-inefficient, externally regulated analogs. Our reversibly responsive material that controls light at exceptionally small intensities is yet another demonstration of this promising technological revolution."

This research was published in the Proceedings of the National Academy of Sciences. It was co-authored by Ankita Shastri, Andy Tran, Anna V. Shneidman, Victor V. Yashin, Fariha Mahmood, Anna C. Balazs. It was supported in part by the US Army Research Office under Award W911NF-17-1-0351 and by the Natural Sciences and Engineering Research Council, Canadian Foundation for Innovation.

Credit: 
Harvard John A. Paulson School of Engineering and Applied Sciences