Earth

DNA from 75-year old eradicated European malaria parasites uncovers the historical spread of one of the two most common forms of the disease, Plasmodium vivax, from Europe to the Americas during the colonial period, finds a new study co-led by UCL.

The research published in Molecular Biology and Evolution reports the genome sequence of a malaria parasite sourced from blood-stained medical microscope slides used in 1944 in Spain, one of the last footholds of malaria in Europe.

Malaria was a major disease throughout Europe since antiquity and was only eradicated in the region in the 20th century.

The international team, led by UCL, the Institute of Evolutionary Biology (IBE), Barcelona, and the University of Copenhagen, analysed microscopy slides from the 1940s that were obtained with permission from the medical collection of Dr Ildefonso Canicio, a Spanish malaria researcher from the early 1900s. The slides were used to diagnose patients suffering from malaria in Spain's Ebro Delta, where malaria was common until the 1960s.

By comparing the genetic data from the slides to a global dataset of modern P. vivax genomes, the researchers found that the eradicated European malaria parasites were genetically most similar to tertian (P. vivax) malaria strains currently found in the Americas, including Mexico, Brazil and Peru.

"Being able to obtain a full genome of extinct European Plasmodium vivax from these decades old slides allowed us to ask questions as to how malaria may have been affecting us centuries ago," said co-lead author Dr Lucy van Dorp (UCL Genetics Institute).

"We found a clear relationship with modern Central and South American strains, establishing historic links spreading disease between these continents."

Analysing a historical sample also enabled the researchers to estimate mutation rates, helping them to infer when the different regional strains of P. vivax malaria diverged from each other. They estimated the last common ancestor between the eradicated European strain and the ones still present in the Americas to the 15th century.

This divergence is in line with European colonists introducing tertian malaria into the Americas and suggests indigenous peoples of the Americas were not infected before their contact with Europeans. There is no reliable evidence of malaria in the Americas before colonial times, but there are historical accounts of tertian malaria in Europe as far back as classical Greece.

"We could date the age of the spread to the Americas to around the 15th century, which clearly points to an introduction of the disease following European contact," explained co-author Professor Francois Balloux (UCL Genetics Institute).

The researchers were also able to gain new insights into how infectious disease agents can develop resistance to treatments. The team found that the 1940s malaria sample already had some genetic mutations which are known to confer resistance to modern anti-malarial drugs, despite them not having been in use at the time.

The findings suggest drug resistance potential may have already existed in some past malaria strains, possibly due to the historical use of quinine (which has been used to treat malaria as well as other ailments), allowing the parasite to evade modern medications soon after their introduction.

Professor Carles Lalueza-Fox, paleogeneticist at the Institute of Evolutionary Biology (IBE, CSIC-UPF) in Barcelona who co-led the study, said he is excited by the prospect of historical genomes to help us understand malaria: "My initial motivation to study this ancient malaria strain is the fact that my father contracted malaria in 1938, while crossing the Ebro region with the Republican army during the Spanish Civil War."

"After realising the potential of old medical material to understand modern infectious diseases, I got hooked and we're currently sourcing more slides from medical and museum collections to understand where malaria emerged first and then spread to other regions of the world."

A new deep-learning algorithm can quickly and accurately analyze several types of genomic data from colorectal tumors for more accurate classification, which could help improve diagnosis and related treatment options, according to new research published in the journal Life Science Alliance.

Colorectal tumors are extremely varied in how they develop, require different drugs and have very different survival rates. Often, they are classified into subtypes based on analysis of gene expression levels.

"Disease is much more complex than just one gene," said Altuna Akalin, bioinformatics scientist who leads the Bioinformatics Platform research group at MDC's Berlin Institute of Medical Systems Biology (BIMSB). "To appreciate the complexity, we have to use some kind of machine learning to really make use of all the data."

To look at numerous features contained in genetic material, including gene expression, single point mutations and DNA copy-numbers, Akalin and PhD student Jonathan Ronen designed the Multi-omics Autoencoder Integration platform - "maui" for short.

How it works

Supervised machine learning typically requires human experts to label data and then train an algorithm to predict those labels. For example, to predict eye color from pictures of eyes, the researchers first feed the algorithm with pictures where eye color is labeled. The algorithm learns to identify different eye colors and can independently analyze new data.

In contrast, unsupervised machine learning does not involve training. A deep-learning algorithm is fed data without labels and sifts through it to find common patterns or representative features, which are called latent factors. For example, this kind of algorithm can process pictures of faces that are not labeled in any way, then identify key features, like eye colors, eyebrow shapes, nose shapes, smiles.

As a deep-learning platform, maui is able to analyze multiple "omics" datasets and identify the most relevant patterns or features, in this case, gene sets or pathways to colorectal cancer.

Reclassifying subtypes?

maui identified patterns associated with the four established subtypes of colorectal cancer, assigning tumors to subtypes with high accuracy. It also made an interesting discovery. The platform found a pattern that suggests one subtype (CMS2) might need to be split into two separate groups. The tumors have different mechanisms and survival rates. The team suggests further investigation to verify if the subtype is unique or perhaps representative of the tumor spreading. Still, it demonstrates the power of the platform to take all the data, rather than only the known genes associated with a disease, and produce deeper insights.

"Data science can handle complex data that is hard to handle other ways and makes sense of it," Akalin said. "You can feed it everything you have on the tumors and it finds meaningful patterns."

Faster, better

The program was not just more accurate, it also works much faster than other machine learning algorithms - three minutes to pick out 100 patterns, compared to the other programs that took 20 minutes and 11 hours.

"It is able to learn orders of magnitude more latent factors, at a fraction of the computation time," said Jonathan Ronen, first author of the research.

The team was actually surprised at how fast the system performs, especially because they did not have to use graphics cards that usually help speed up calculations. This shows how extremely well optimized, or efficient, the algorithm is, though they are continuing to find ways to further finetune the system.

Improving drug discovery

The team, which also included Bayer AG computational biologist Sikander Hayat, adapted their program to analyze cell lines taken from tumors and grown in labs for researching the effects of potential drug treatments. However, cell lines differ from real tumors in many ways on the molecular level. The team used maui to compare cell lines currently used for testing colorectal cancer drugs to see how closely they were related to real tumors. Nearly half of the lines were found to be more related to other cell lines than actual tumors. A handful were found to be the best lines most closely representing the different classes of CRC tumors.

While drug discovery research is moving away from cell lines, this insight could help maximize the potential impact of cell line research, and could be adapted for other types of genetic-based drug testing tools.

Google for tumors

Now that the deep-learning platform for colorectal cancer has been established, it could be used to analyze data for new patients.

"Think of this like a search engine," Akalin said.

A clinician could input the new patient's genetic data into maui to find the closest match to quickly and accurately classify the tumor. The platform could advise what drugs have been used on the closest matching tumors and how well they worked, thus helping to predict drug responses and survival outlook.

For now, this could take place in a research setting only after doctors have tried the established protocols. It is a long road for a test or system to be approved for clinical use, Akalin said. The team is exploring the potential for commercialization with the help of the Berlin Institute of Health's Digital Health Accelerator Program. They are also in the process of adapting maui for other types of cancers.

Many cellular processes involve patterned distributions of proteins. Scientists have identified the minimal set of elements required for the autonomous formation of one such pattern, thus enabling the basic phenomenology to be explored.

Many essential processes in living organisms require the self-organization of specific proteins into precise patterns within cells. For example, autonomous pattern formation is necessary for cell division, active locomotion and intra- and intercellular communication. The Min system in the bacterium Escherichia coli, which is responsible for defining the plane of cell division, is an iconic example of pattern formation. A group led by physicist Erwin Frey (Professor of Statistical and Biological Physics at Ludwig-Maximilians-Universitaet (LMU) in Munich) and Petra Schwille (Max Planck Institute for Biochemistry) has now identified the minimal set of structural motifs required for the operation of this system. This in turn has allowed them to develop a simplified model with which to investigate the phenomenology of biological pattern formation as a whole. Their findings appear in the online journal eLife.

Cell division in the rod-shaped bacterium E. coli is controlled by two proteins, named MinD and MinE. MinD undergoes modification in the cytoplasm, which causes it to bind to the cell membrane and recruit MinE, thus forming MinDE complexes. After some delay, MinE in turn detaches MinD from the membrane by removing the modification, thus releasing both proteins back into the cytoplasm. This cycle gives rise to intracellular distributions that oscillate back-and-forth in the cell cytoplasm. Ultimately a membrane-bound pattern emerges, which ensures that the plane of cell division is localized to the middle of the cell and not close to either of the poles. Because of its simplicity, this system has provided a valuable model for studying the basic mechanisms that underlie biological formation in general. In addition, the system can be reconstituted from the purified proteins, which allows one to identify the essential functional units and explore the effects of localized mutations on the pattern-forming process.

In the new study, the authors have further simplified this system and identified the minimal set of components required for correct pattern formation. They first created a bare-bones version of MinE by systematically deleting parts of the protein and testing the truncated forms for function. These experiments showed that the short amino-acid sequence which enables MinE to interact with MinD on the membrane and trigger loss of the modification is necessary but not sufficient to implement the process. By successively adding other segments of MinE to this sequence, they obtained several mutants that exhibited the ability to mediate various steps of the process. In addition to its MinD binding sequence, they found that the sequence required for binding of MinE to the cell membrane is also essential for pattern formation. Strikingly, however, analogous membrane-binding sequences from structurally related proteins can be substituted for this sequence.

"Based on these results, we developed a mathematical model that explains why these elements are required for MinE's function, and how they contribute to pattern formation. In addition, the model predicts how the pattern adapts to the shape of the cell," says Fridtjof Brauns, who is in Frey's team and, together with Jacob Halatek (a member of Frey's group) and Philipp Glock, a PhD student at the MPI for Biochemistry, joint first author of the new paper.

"With this model, one can now ask, irrespective of the specific protein system considered, what functional features must be present in order to make self-organization and pattern formation possible," says Frey. The new study thus constitutes a significant advance in the quest for a comprehensive understanding of protein-based pattern formation in biological systems.

The structure of an Organic Lake Phycodnavirus rhodopsin II (OLPVRII), which is a unique protein found in the genome of giant viruses, has been determined thanks to the work of MIPT graduates and PhD students. The paper was published in Nature Communications.

The study is the result of a collaboration that included many MIPT alumni. Dmitry Bratanov was among them. Dmitry, who currently works at the Institute of Complex Systems (ICS-6) at the Research Center Juelich, Germany, says that although viral rhodopsins were first discovered in the so-called giant viruses several years ago, their structure, function, and biological role have remained unclear until now.

A giant virus is a very large virus, the size of a typical bacterium. It is so big that it is visible under a light microscope. Giant viruses infect green algae, which produce oxygen and help maintain the natural ecological balance of the world's ocean. Therefore, giant viruses are of considerable research interest from an environmental perspective.

"In this work, we deciphered the high-resolution structure of OLPVRII, functionally characterized the protein, and showed that it forms pentamers not only in crystals but in lipid membranes as well," explains Dmitry. "This was no easy task. Numerous experiments had to be performed, for some of them we used sophisticated techniques and equipment. What we have achieved is the result of the hard and meticulous work of the international group of scientists."

This pentameric organization has previously been observed in some other rhodopsins, such as, for instance, in the light-driven sodium pump KR2. However, what makes the OLPVRII structure peculiar is that it has an unusual pore in the center (see figure 1). Its function remains unknown.

"We think that perhaps the pore acts as an ion channel, most probably for chloride ions," says Kirill Kovalev, a co-author of the paper and PhD student at MIPT.

Ion channels are proteins that create a passive pathway for ions to flow across the cell membrane. These channels are usually closed in the dark, meaning ions cannot move into or out of the cell. In the case of light-sensitive channels, they open in response to light absorption, which allows ions to flow down the concentration gradient. In other words, ions move in the direction that would even out the concentrations of ions inside and outside the cell.

A typical example of a light-sensitive channel is channelrhodopsin 2. It was found in the green alga Chlamydomonas reinhardtii and is widely used as an optogenetic tool. As for OLPVRII, the researchers think that this might be the first pentameric light-gated ion channel ever discovered, as suggested by the determined structure and molecular simulations.

"However, the channel activity of OLPVRII has yet to be demonstrated," notes Kirill Kovalev." We will continue our research and will definitely find out why this unusual rhodopsin was created by nature. Perhaps it helps the host continue to carry out its life-sustaining functions when a cell is infected by a virus, or maybe it is a sensor."

That said, studying the structure of the viral rhodopsin shed some light on how it functions. It was shown that OLPVRII, like most other rhodopsins, acts as a proton pump. This however is unlikely to be its principal function, the researchers say. Its main purpose has yet to be investigated and proved.

"If we prove that this viral rhodopsin is in fact an ion channel, it can become a great tool in optogenetics and biomedical applications," says paper co-author Valentin Gordeliy, who leads research groups at the Institute of Structural Biology in Grenoble and the Research Center Juelich. Valentin is also a research coordinator at MIPT's Research Center for Molecular Mechanisms of Aging and Age-Related Diseases.

The researchers say that the new tool will outperform all its counterparts thanks to the advantages of its pentameric structure: the ease with which you can genetically manipulate the properties of the protein and perhaps the high currents circulating through the central pore.

To have the priority right to utilize their invention, the authors of the paper have submitted a patent application for the use of the viral rhodopsin OLPVRII in the field of optogenetics.

Optogenetics is a branch of biophysics that uses light to control cells in a living organism. As has already been demonstrated, optogenetics can be applied to restore vision and hearing loss, help control movement in neurological patients, and treat those with Parkinson's and Alzheimer's disease.

According to Valentin Gordeliy, MIPT has all the necessary equipment required to conduct a detailed study of the functions of the viral rhodopsin. The group will continue their research into OLPVRII, which will be of great significance for biology, evolutionary science, optogenetics, and ecology.

CHICAGO --- The percentage of African ancestry in a person's genome determines the level that certain genes are expressed, called mRNA, according to a new Northwestern Medicine study. The discovery could offer insight into the different risk of diseases as well as a different response to medications in African Americans.

This is the first study to compare gene production between African Americans. Previous studies compared only black and white individuals.

"We know there is a difference between black and white. We asked, does 'the shade gray' matter? Apparently it does," said lead study author Minoli Perera, associate professor of pharmacology at Northwestern University Feinberg School of Medicine. "We continue to lump individuals into racial categories to determine what will work best in them as a group. But African Americans are not a monolithic group."

The study on gene expression in African Americans was published Nov. 25 in Genomic Medicine.

The research examined the gene products, or mRNA, in the liver, which metabolizes drugs. The gene production, or mRNA levels, indicate how much protein will be made for a gene in specific tissue. Proteins are the workers that carry out the biological functions in our body.

There were at least 28 genes whose expression (mRNA level) varied with the proportion of African Ancestry. These genes were linked to 220 diseases
or clinical outcomes such as coronary heart disease and triglyceride levels. Some of the identified genes that vary with African ancestry are related to drug metabolism (CYP2C19), renal disease (APOL1) and an important target for cancer therapy (VGEF.)

This study was done by isolating hepatocytes, the major cell type in the liver, from 60 African American livers. These living cells contain the genome of the donor.

For groups like African Americans and other "admixed" populations like Latinos, variability within the group may be important to how we interpret findings, Perera said.

"To have precision medicine may require understanding ancestry and not just the DNA sequence in these minority populations," she said.

The aim of the study is to add information on African Americans to the scientific sphere.

"These types of data are sorely missing in most of the public databases," Perera said. "If African Americans are not represented in these databases, the factors that are unique to them will never be considered for precision medicine or drug target discovery."

Ludwig-Maximilians-Universitaet (LMU) in Munich researchers report that a central component of the innate immune response is activated by two short RNAs which are produced by site-specific cleavage of a precursor RNA molecule - and both derivatives are generated by the same enzyme.

The innate immune system can be thought of as the frontline in the body's fight against invasive pathogens. Cells possess specialized receptors that can distinguish between RNAs derived from foreign cells - such as pathogenic bacteria and viruses - and 'native' RNAs. Recognition of the former then activates the appropriate immune response to eliminate the invaders. However, the molecular mechanisms that underlies this mode of detection has remained obscure. Now LMU immunologist Professor Veit Hornung, in collaboration with LMU chemist Professor Thomas Carell, has discovered that the activation of one of these receptors, called TLR8, is mediated by the binding of two specific RNA fragments, generated by degradation of foreign RNA - and that both breakdown products are generated by a single enzyme called RNase T2. The new findings appear in the leading journal Cell.

"Earlier work had suggested that foreign RNA molecules are not recognized as a whole, but must first be cut into smaller fragments before they can be recognized by the innate immune system," says Hornung. To explore the recognition process further, he and his colleagues specifically deleted the genes for individual RNases in a human cell model. They then asked how the loss of each of the RNases affected the activation of TLR8, which is known to be an important sensor of bacterial RNA in human cells. "We chose to work with a human cell model in this case, because the version of the receptor found in mouse acts in a different way," explains Wilhelm Greulich of Veit Hornung's research group, who is joint first author of the new study.

The team found that only the cells that lacked the gene for RNase T2 failed to trigger the TLR8 mediated response to bacterial RNA, clearly pointing to a central role of this enzyme in the activation of the receptor. Notably, RNase T2 has been highly conserved over the course of evolution. The enzyme is found in virtually all classes of organisms and its structure has remained largely unchanged. This high degree of conservation strongly indicates that it carries out an essential cellular function, and that this mechanism may also play a role in other species.

"We were able to identify the specific products of RNA cleavage by RNaseT2 using mass spectrometry," says Mirko Wagner, a member of Thomas Carell's team. These data revealed that the enzyme preferentially cleaves RNA molecules at defined nucleotide sequences leading to degradation products exclusively activating TLR8: uridine and a purine terminate RNA fragment. "Essentially, the receptor contains two distinct pockets, which have to be occupied for activation," Carell explains. One pocket accommodates uridine, and this interaction is ultimately responsible for receptor activation.

However, in a physiological context, activation depends on prior binding of the purine-terminated RNA fragment, which then allows the uridine to bind. "Activation is a two-step process, and RNase T2 provides the keys that trigger both steps," says Hornung. "We believe that, in the course of its evolution, the receptor has adapted to specifically recognize the degradation products of this enzyme."

Daily marijuana use during pregnancy may lead to an increased risk of low birth weight, low resistance to infection, decreased oxygen levels and other negative fetal health outcomes, according to a new study from a team of UNLV Medicine doctors.

In the latest issue of the Journal of Maternal-Fetal and Neonatal Medicine, physicians reviewed sonogram data from nearly 450 pregnant women who self-reported daily marijuana use. They found that daily cannabis use is associated with delayed fetal growth, which can put a baby at risk of certain health problems during pregnancy, delivery, and even after birth.

Those problems include low birth weight, hypoglycemia, low Apgar scores, among others, and in the most severe cases, delayed growth can lead to stillbirth. Physicians also found an increase in placental vascular resistance in both the second and third trimesters, which can "disrupt the necessary flow of oxygen rich blood through the placenta," and can lead to delayed growth.

"Recent data from JAMA (The Journal of the American Medical Association) indicates that marijuana use in pregnancy has doubled over the last 15 years and what's more alarming is that 70% of women believe there is minimal or no harm from using marijuana in pregnancy," said Dr. Bobby Brar, UNLV School of Medicine Resident Physician and a lead author of the study. "Our findings contribute to the growing body of evidence that fetal marijuana exposure may not be as safe as people think."

The physicians noted that the exposure to some chemical compounds that can be found in both tobacco and marijuana smoke may explain the growth abnormalities they observed. The compounds, known as polycyclic aromatic hydrocarbons, are present in both tobacco and marijuana smoke, but some studies have shown a higher concentration of these substances in secondhand marijuana smoke when compared to tobacco smoke, the physicians wrote.

It's likely that the exposure to the smoke, and not necessarily nicotine, which is found in tobacco, or THC, which is found in marijuana, is what leads to delayed fetal growth, the authors wrote.

While additional studies are needed to further understand the negative impacts of daily marijuana usage on fetal growth, the team of doctors said that cannabis use should be discouraged during pregnancy. The physicians embarked upon the research as recent legalization of marijuana across the country has increased overall use. Current reports estimate that about 16% of pregnant women engage in daily use.

Additionally, the researchers argue that patients should be screened throughout pregnancy for marijuana use and counseled appropriately on its potential effects, as well as strategies for cessation.

A research team led by Northwestern Engineering's Luis Amaral has developed an algorithmic approach for data analysis that automatically recognizes uninformative words -- known as stop words -- in a large collection of text. The findings could dramatically save time during natural language processing as well as reduce its energy footprint.

"One of the challenges in machine learning and artificial intelligence approaches is that you don't know which data is useful to an algorithm and which data is unhelpful," said Amaral, Erastus Otis Haven Professor of Chemical and Biological Engineering at the McCormick School of Engineering. "Using information theory, we created a framework that reveals which words are uninformative for the task at hand."

The trouble with stop words

One of the most common techniques data scientists use in natural language processing is the bag-of-words model, which analyzes the words in a given text without considering the order in which they appear. To streamline the process, researchers filter out stop words, those adding no context to the data analysis. Many stop word lists are manually curated by researchers, making them time consuming to develop and maintain as well as difficult to generalize across languages and disciplines.

"Imagine you analyze millions of blog posts and want to learn what topic each post addresses," said Amaral, who codirects the Northwestern Institute on Complex Systems. "You would typically filter out common words like 'the' and 'you,' which don't provide any background about the topic."

However, the majority of words that are not useful for that specific task depend on the language and the blog's particular subject area. "For a collection of blogs on electronics, for example, there are many words that could not enable an algorithm to determine whether a blog post is about quantum computing or semiconductors," he added.

An information theoretic framework

The research team used information theory to develop a model that more accurately and efficiently identifies stop words. Central to the model is a 'conditional entropy' metric that quantifies a given word's certainty of being informative. The more informative the word, the lower its conditional entropy. By comparing the observed and the expected values of conditional entropy, the researchers could measure the information content of specific words.

To test the model, the researchers compared its performance to common topic modelling approaches, which infers the words most related to a given topic by comparing them to other text in the data set. This framework produced improved accuracy and reproducibility across the texts studied, while also being more applicable to other languages in a straightforward manner. Additionally, the system achieved optimal performance using significantly less data.

"Using our approach, we could filter 80 percent or more of the data and actually increase the performance of existing algorithms for topic classification of text corpora," Amaral said. "In addition, by filtering so much of the data, we are able to dramatically reduce the amount of computational resources needed."

Beyond saving time, the filtering system could lead to long-term energy savings, combating the negative impact large-scale computing has on climate change.

A paper describing the work was published December 2 in the journal Nature Machine Intelligence. Amaral was a co-corresponding author on the paper along with Martin Gerlach, a postdoctoral fellow in Amaral's lab.

While the researchers' analysis was restricted to bag-of-words approaches, Amaral is confident that his system could be expanded to account for additional structural features of language, including sentences and paragraphs.

In addition, since information theory provides a general framework for the analysis of any sequence of symbols, the researchers' system could be applicable beyond text analysis, supporting pre-processing methods for analyzing audio, images -- even genes.

"We have begun applying this approach to the analysis of data from experiments measuring gene-specific RNA-molecules in individual cells as a way to automatically identify different cell types," Gerlach said. "Filtering uninformative genes -- think of them as "stop genes" -- is particularly promising to increase accuracy. Those measurements are much more difficult compared to texts and current heuristics are not nearly as well developed."

GRAND RAPIDS, Mich. (Dec. 2, 2019) -- Understanding how the brain processes sweet, bitter and umami tastes may one day help researchers design more effective drugs for neurological disorders.

Van Andel Institute scientists have for the first time revealed the near atomic-level structure of a calcium homeostasis modulator (CALHM), a type of protein that plays critical roles in processing taste stimuli and mitigating toxicity in brain cells. These proteins work by sensing chemical and electrical changes in their environment -- in the taste buds, for example -- and relaying the information back to the brain.

They also help regulate calcium concentrations and amyloid-beta protein levels in the central nervous system. Previous research has shown that abnormal changes in CALHMs -- and the resulting dysregulation of calcium or build-up of amyloid-beta -- can contribute to Alzheimer's disease, stroke and other neurological conditions.

"This is the first time we've been able to visualize one of these important proteins with such clarity. Until now, we didn't know what they looked like or how they worked," said Wei Lü, Ph.D., an assistant professor at VAI and co-corresponding author of the study, published in Nature. "Our molecular blueprint of calcium homeostasis modulator 2 lays the groundwork for understanding the broader family of CALHMs, which could inform therapeutic development down the road."

The shape of a protein is a key factor in how that protein carries out its function, much like how a specific key only works with a certain lock. In the case of CALHM2, the new images show drastic differences in its structure when it is in its open state versus its inhibited state, providing new insight into how the protein works in varying circumstances.

Importantly, the team also identified an area of the protein that would be an optimal drug target.

"Understanding CALHM2's structure is the first step in understanding exactly how these proteins function, how they impact neurological diseases and how they may be leveraged therapeutically," said Juan Du, Ph.D., an assistant professor at VAI and co-corresponding author of the study. "We look forward to broadening our studies, with the ultimate goal of developing novel medications for CALHM-related disorders."

The findings were made possible by VAI's state-of-the-art David Van Andel Advanced Cryo-Electron Microscopy Suite, which allows scientists to view some of life's smallest components in exquisite detail. VAI's most powerful microscope, the Titan Krios, can visualize molecules 1/10,000th the width of a human hair.

CHICAGO - A panel of medical professionals will discuss the public health impact of e-cigarette use, or "vaping," today during a session at the annual meeting of the Radiological Society of North America (RSNA).

E-cigarette use is on the rise. According to the Centers for Disease Control and Prevention (CDC), more than 9 million adults in the U.S. use e-cigarettes, and vaping has become especially popular among teens. The 2018 National Youth Tobacco Survey reported that in 2018 more than 3.6 million middle and high school students were using e-cigarettes.

E-cigarette inhalants, upon vaporization of the e-cigarette solution, contain potentially harmful toxic substances that can cause lung injury and, in some cases, inhibit vascular function.

In August, a multistate outbreak of lung disease associated with e-cigarette product use began in the United States. The situation is ongoing, and multiple substances and product sources are still under investigation by the CDC. However, most patients involved in the outbreak have reported using products containing tetrahydrocannabinol (THC). Therefore, the CDC recommends that people avoid e-cigarette products that contain THC.

"An outbreak of lung disease associated with vaping has developed recently throughout the U.S.," said Jeffrey S. Klein, M.D., RSNA Board Liaison for Publications and Communications and A. Bradley Soule and John P. Tampas Green and Gold Professor of Radiology at the University of Vermont College of Medicine in Burlington. "Radiographic and CT findings of diffuse pneumonitis have emerged as characteristic findings in affected patients and are included in the CDC case definition of vaping-induced lung injury.

"In our efforts to educate radiologists about this potentially fatal condition they may encounter in younger patients with acute respiratory symptoms, the RSNA has organized a special session at RSNA 2019 where experts will provide up-to-date information regarding key radiologic, pathologic and physiologic findings associated with this critical public health issue," he said.

Dr. Klein participated in calls with the CDC, as it worked with various medical specialty groups to investigate and identify potential causes of vaping-related lung injury. In September, Dr. Klein produced a brief educational video aimed at updating radiologists on this topic, so that they could be well positioned to assist in identifying cases.

For the session at RSNA 2019, Dr. Klein will be joined by Mark L. Schiebler, M.D., professor of cardiothoracic radiology at University of Wisconsin School of Medicine and Public Health - Madison, Travis S. Henry, M.D., associate professor of clinical radiology at the University of California, San Francisco, Seth J. Kligerman, M.D., associate professor of radiology and section chief of cardiothoracic imaging at the University of California, San Diego, Brandon Larsen, M.D., Ph.D., consultant and associate professor of laboratory medicine and pathology at Mayo Clinic in Scottsdale, Ariz., and Alessandra Caporale, Ph.D., post-doctoral researcher in the Laboratory for Structural, Physiologic and Functional Imaging at the University of Pennsylvania Perelman School of Medicine in Philadelphia.

The session will provide a brief introduction, followed by an exploration of the scope of the problem, description of imaging findings and histopathology associated with vaping-related lung injury, a presentation on how vaping affects the vascular system and a Q&A with the panelists.

After attending the session at RSNA 2019, radiologists and other medical professionals should have a greater understanding of the public health implications of the vaping-related lung injury outbreak in the U.S. They will also become familiar with common CT and X-ray findings associated with the condition, and how the pathology helps to define the possible causes of this disorder. Lastly, they will know more about vaping's impact on vascular function.

"As we learn more, RSNA will continue to keep radiologists informed on this important public health topic," Dr. Klein said.

"Special Interest: E-cigarette/Vaping-associated Lung Injury (EVALI)" (SPSI27) will be held Monday, Dec. 2, from 4:30 - 5:30 p.m.

Perovskite nanocrystals hold promise for improving a wide variety of optoelectronic devices - from lasers to light emitting diodes (LEDs) - but problems with their durability still limit the material's broad commercial use.

Researchers at the Georgia Institute of Technology have demonstrated a novel approach aimed at addressing the material's durability problem: encasing the perovskite inside a double-layer protection system made from plastic and silica.

In a study published Nov. 29 in the journal Science Advances, the research team describes a multistep process to produce encased perovskite nanocrystals that exhibit strong resistance to degradation in moist environments.

"Perovskite nanocrystals are highly susceptible to degradation, particularly when they come into contact with water," said Zhiqun Lin, a professor in the Georgia Tech School of Materials Science and Engineering. "This dual-shelled system offers two layers of protection while allowing each nanocrystal to remain a distinct and separate unit, achieving the maximum amount of surface area and other physical characteristics of the perovskite needed for optimizing optoelectronic applications."

The term perovskite refers to the crystal structure of the material, which is generally composed of three parts: two cations of different sizes and an anion in between. For decades, researchers have tested substituting various chemicals into the structure to achieve unique characteristics. In particular, perovskites containing halide compounds such as bromide and iodine can act as light absorbers and emitters.

For this study, which was supported by the Air Force Office of Scientific Research, the National Science Foundation, the Defense Threat Reduction Agency, and the Department of Energy, Lin's group worked with one of the most common halide configurations, which is formed from methylammonium, lead, and bromide.

Their process involves first forming star-shaped plastic molecules that could serve as "nanoreactors" by growing 21 polymer arms on a simple sugar molecule. Then, once precursor chemicals for the silica and perovskite nanocrystals are loaded onto the plastic molecule, several stages of chemical reactions produce the final system.

After the star-shaped plastic has played its role as a nanoreactor, the star-shaped components remain permanently attached, almost like hair, to the silica, which encases the perovskite. The hairs then serve as the first layer of protection, repelling water and preventing the nanocrystals from clumping together. The subsequent layer of silica adds further protection should any water get past the water-repelling plastic hair.

"Synthesis and applications of perovskite nanocrystals have been a rapidly evolving research field over the past five years," said Yanjie He, a coauthor of the paper and former graduate student at Georgia Tech. "Our strategy, based on a judiciously designed star-shaped plastic as a nanoreactor, enables unprecedented control in the crafting of high-quality perovskite nanocrystals with complex architecture, which is inaccessible in conventional approaches."

To test the material, the researchers coated glass substrates with a thin film of the encapsulated perovskites and conducted several stress tests, including immersing the entire sample in deionized water. By shining ultraviolet light upon the sample, they found that the photoluminescent properties of the perovskites never diminished during a 30-minute test. For comparison, the researchers also immersed unencapsulated perovskites in water and watched as their photoluminescence vanished in a matter of seconds.

Lin said the new method unlocks the possibility of tuning the surface characteristics of the dual-shelled nanocrystal to enhance its performance in a greater range of applications. The process of fabricating the new perovskite nanocrystals from the star-shaped plastic was also unique in that it employed low-boiling point solvents with low toxicity. Future research may center on developing different perovskite nanocrystal systems, including all-inorganic perovskites, double perovskites, and doped perovskites.

"We envision that this type of perovskite nanocrystal will prove very useful for creating durable optoelectronic devices for bioimaging, biosensors, photonic sensors, and radiation detection, as well as next generation LEDs, lasers, and scintillators," Lin said. "This is because these hairy perovskite nanocrystals carry unique advantages, including high defect tolerance, narrower emission bands, and high scintillation efficiency."

Burning of the rainforest in southwestern Amazonia (the Brazilian, Peruvian and Bolivian Amazon) may increase the melting of tropical glaciers in the Andes, according to a study in Scientific Reports.

Newton de Magalhães Neto and colleagues modelled the possible effect of biomass burning in the Amazon Basin on the Bolivian Zongo Glacier using data collected between 2000 and 2016 on fire events, the movement of smoke plumes, precipitation and glacier melting. They found that aerosols from biomass burning, such as black carbon, can be transported by wind to tropical Andean glaciers. There they are deposited in snow and have the potential to increase glacier melting as snow that is darkened by black carbon or dust particles reflects less light (reduced albedo).

Focusing their analyses on the years 2007 and 2010 when fire seasons were the most critical for the Amazon Basin, the authors investigated the snow albedo reduction due to black carbon alone and black carbon in the presence of previously reported quantities of dust. Their model showed that black carbon or dust alone had the potential to increase annual glacier melting by 3-4%; or by 6% when both were present. If dust concentrations were high, dust alone had the potential to increase annual melting by 11-13% and by 12-14% in the presence of black carbon. The findings suggest that the impact of Amazon biomass burning depends on the dust content in snow.

Pressure related to global food demand may result in further expansion of Brazilian agriculture and deforestation, resulting in enhanced black carbon and CO2 emissions that may impact Andean glaciers.

Many women in the WHO European Region, particularly those in their 40s, are diagnosed at a late stage of HIV infection when their immune system is already starting to fail. They are three to four times more likely to be diagnosed late than younger women.

According to data for 2018 released today by the European Centre for Disease Prevention and Control (ECDC) and the WHO Regional Office for Europe, women accounted for one-third of the 141 000 new HIV diagnoses in the Region, indicating that this population needs more attention in Europe's prevention and testing efforts.

The HIV epidemic in the Region is driven by a persistent problem with late diagnosis, and this affects 54% of known cases among women. Such proportions of late diagnoses are partly a result of relatively low HIV testing coverage and uptake in the Region, and are an indication that sexual risks, including HIV and other sexually transmitted infections, are not being adequately addressed with older adults.

Two-thirds (60%) of the HIV diagnoses among women in 2018 were in the age group 30-49 years old. Heterosexual sex was the most commonly reported HIV transmission mode (92%) among women in the Region.

Vytenis Andriukaitis, the European Commissioner for Health and Food Safety highlights: "Too many people living with HIV are still not aware of their status. The sooner women and men know of their HIV status, the sooner they can be put on antiretroviral treatment and halt transmission of HIV sexually. This makes a major difference in the lives of people living with HIV and those around them. It is all the more important, therefore, for public health services to support easy access to testing and fast linkage to care, especially for those at risk of HIV, in order to bring people faster to the stage where they are no longer infectious. We must all ramp up our efforts to halt and reverse the HIV epidemic in order to achieve our Sustainable Development Goals by 2030."

ECDC Director Dr Andrea Ammon stresses that "Women are generally diagnosed with HIV later than men and the older they are, the longer they live with undiagnosed HIV. We do not know why but it seems current systems and testing efforts in Europe are failing women and older adults". "One strategy to reach older adults is to diversify and complement HIV testing opportunities. One of the most significant factors that influences testing patterns among older adults is quite simple: actively offer an HIV test as a health service provider."

Dr Piroska Östlin, WHO Regional Director for Europe ad interim said: "Late diagnosis in women indicates that gender-sensitive counselling and testing, including information about sexual health, is not reaching this population. It's time to end the silence about sexual health, especially when it comes to HIV, and ensure that women are well informed and enabled to protect themselves. If we are to achieve universal health coverage, we need to improve prevention, treatment and care for women and reduce missed opportunities for testing those vulnerable to HIV in health facilities and in the community."

Countries in central Europe reported almost six times fewer diagnoses among women compared to men in 2018, and three times fewer diagnoses among women than men were reported in the European Union and European Economic Area (EU/EEA). The only exception is the eastern part of the Region, where there is a more even distribution between women and men, and where 86% of the almost 50 000 cases among women were reported in 2018.

Improving testing so treatment can reach those who need it

Early diagnosis of HIV allows people to start HIV treatment sooner, which in turn increases their chances of living a long and healthy life. In addition, it reduces the risk of transmitting HIV to others, since effective treatment results in an undetectable viral load, meaning that the virus can no longer be transmitted to others.

Enhanced strategies and systems, making HIV testing more widely available and user-friendly, are required to ensure early diagnoses. The WHO consolidated guidelines on HIV self-testing and partner notification and ECDC's evidence-based guidance on integrated testing for HIV and viral hepatitis recommend innovative approaches that include self-testing and community-based testing by lay providers as part of overall HIV testing services.

Enhanced strategies to diagnose women earlier include:

- increasing awareness among women and health-care providers;

- offering counselling and testing services adapted to the needs of women;

- notifying partners of men who are diagnosed with HIV;

- providing HIV testing based on specific health conditions, such as other sexually transmitted infections, viral hepatitis, tuberculosis or certain cancers;

- providing testing and treatment services in the community, closer to populations in need

Kanazawa, Japan - Hematopoietic stem cells (HSCs) are multipotent cells that can develop into every type of blood cell in the body. They can also be used in medical research to understand and treat blood-based diseases. Zebrafish (Danio rerio) are used to study HSCs, particularly in the field of developmental biology, but the research in the adult animal is often limited because stem cells are difficult to purify in this species. Researchers at Kanazawa University and their collaborators now describe a purification scheme that allows these elusive zebrafish HSCs to be collected.

"Zebrafish are a great system to study how hematopoietic cells function in normal development and their role in disease," says lead researcher Isao Kobayashi. "Much of their biology mirrors what we see in humans, and with zebrafish there's the added benefit of having quite a few experimental tools at our fingertips, including live cell imaging and comparative analysis among vertebrates. Unfortunately, it's proven challenging to effectively isolate HSCs from this species, and this has been a major impediment to the field."

HSCs are highly abundant in the kidneys of adult zebrafish (unlike in humans, where HSCs are found in bone marrow). The challenge is separating them from other cells found in kidneys. Cell separation usually involves a purification technique called flow cytometry, where cells are sent in single file through a tube and hit with a laser beam. The machine (a flow cytometer) then sorts the cells based on how they reflect or scatter light.

In the study, published in Scientific Reports, the researchers created a strain of zebrafish that makes two light-emitting proteins, one green (Green Fluorescent Protein, GFP) and one red (mCherry), that can be sensed and sorted by a flow cytometer. Each fluorescent protein in this zebrafish strain was regulated by the genes related with blood cells, but the cells having both fluorescent proteins were limited in HSCs. By color coding the cells with two distinct blood cell markers, the team was able to purify cells that show hallmark signs "stemness" - like the ability to self-propagate and differentiate into other types of blood cells.

So, what might the successful isolation of HSCs in zebrafish mean for the field of stem cell research?

"When HSCs were finally purified in mice, the research community learned an enormous amount about how and where stem cells self-renew and differentiate to form blood cells," says co-author Mao Kondo. "We're very hopeful that this might spur a similar proliferation of research in zebrafish. In addition to some experimental advantages in zebrafish, we found that zebrafish HSCs share many key genes in common with HSCs in mammals. This suggests that mechanistic discoveries in zebrafish could have direct implications for understanding blood diseases in humans and for developing new medical treatments."

Ceria (CeO2)-based materials are widely used in industries such as catalysis, fuel cells, gas sensors, and particularly lie at the heart of the three-way catalysts (TWCs) as the Ce ions can easily switch between Ce4+ and Ce3+ driven by oxygen chemical potential. Compared with their counterparts, one-dimensional (1D) ceria nanomaterials are more reactive. Because they are usually synthesized under unusual conditions, and some reactive crystal planes may be obtained.

Activity of ceria nanomaterials at high temperature is closely associated with the changes of morphology, structure and chemical states at the microscopic scale. Significant sintering of ceria nanoparticles at high temperature or the transition from cubic structure to hexagonal structure will degrade the chemical activity of ceria nanoparticles. Moreover, defects of cerium oxide at high temperature are of great significance for the applications.

Very recently, Professor Xuedong Bai's group in Institute of Physics, Chinese Academy of Science studied the defect dynamics in ceria nanowires under heating by in situ aberration-corrected TEM. The defects appear and grow up while elevating temperature, and then grow into regular rhombic or hexagon shapes at 1023K. Much needed atomic-level structural detail at the defect interface is also provided. Although the defects are generated due to high temperature (up to 1023K), the structure of cubic fluorite remains unchanged and more reactive sites are introduced. This work provides a useful insight into designing ceria-based catalyst and ionic conductors.