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Male grave goods for grave 53 at Collegno. Applying a comprehensive analysis of genetic, historical, and archeological factors in two 6th-century barbarian cemeteries, researchers have gleaned new insights into a key era known as the Migration Period that laid the foundation for modern European society. Spanning the 4th to 8th centuries, this epoch followed the decline of the Western Roman Empire and was a time of major socioeconomic and cultural transformation in Europe. However, despite more than a century of scholarly work by historians and archaeologists, much about the period still remains unknown or is hotly debated, as reliable written accounts are lacking. A paper, published today in Nature Communications, seeks to shed new light on how these communities were formed, how people lived, and how they interacted with the local populations they supposedly came to dominate. The international team of geneticists, historians, and archaeologists led by Professor Patrick Geary of the Institute for Advanced Study and Professor Krishna Veeramah of Stony Brook University in the U.S., Professor Johannes Krause of the Max Planck Institute for the Science of Human History in Jena, Germany, and Professor David Caramelli of the University of Florence in Italy, have for the first time sequenced the genomes of entire ancient cemeteries -- one in Hungary and one in Italy. This research provides the clearest picture yet of the lives and population movements of communities associated with the Longobards, a barbarian people that ruled most of Italy for more than two hundred years after invading from the Roman Province of Pannonia (modern-day Hungary) in 568 C.E. The team's data from the Hungarian cemetery, Szólád, almost doubles the number of ancient genomes obtained from a single ancient site to date. This in-depth genomic characterization allowed the team to examine the relationship between the genetic background of the community and the archaeological material left behind. Professor Patrick Geary, of the Institute for Advanced Study, a senior author of the paper said, "Prior to this study, we would not have expected to observe such a strong relationship between genetic background and material culture. This appears to suggest that these particular communities contained a mix of individuals with different genetic backgrounds, that they were aware of these differences, and that it likely influenced their social identity." A somewhat surprising result was that in both cemeteries, individuals buried with elaborate grave goods, like swords and shields for the men and beaded necklaces and broaches for the women, tended to have a genetic ancestry associated with modern northern and central Europeans today, while grave goods in individuals with more southern European-looking genomes were much less abundant. The individuals with abundant grave goods also tended to consume more protein rich diets. "What we have presented in this study is a unique cross-discipline framework for the future," added Geary, "uniting experts from different disciplines to reinterpret and reconcile historical, genomic, isotopic, and archaeological evidence to enhance our knowledge of the past, compile new information on how populations move, how culture is transmitted, how to better understand identity, and new ways of understanding the complexity, heterogeneity, and malleability of Europe's population in the past and the present." The approach also allowed researchers for the first time to reconstruct comprehensive genealogies of the people who were buried in these cemeteries, finding that family relations spanning multiple generations were likely key to establishing these communities. "It looks like both these cemeteries organized themselves around one or two large groups of biologically related kin, with the vast majority of these individuals being men" said Veeramah. "In addition, these related individuals tended to share the northern/central genetic ancestry associated with rich grave goods." The team concluded that it was unusual to see this genetic ancestry type in Hungary and certainly in Italy in the 6th century. "Though we really need more data, our current results are consistent with the idea of barbarians migrating from north of Danube and east of the Rhine, which would suggest we are observing the invasions previously described by the Romans," said Veeramah. "It is also likely that social organization was based around large high-status male biological kinship groups, and these were key to establishing communities following the migration into Italy." Veeramah, Caramelli, Krause, and Geary stressed that these results represented mere snapshots of the period and that more work in other cemeteries in other regions is vital for truly understanding this period. "It could be that we look at some new cemeteries 50 km away or that are 100 years older or younger and find very different patterns of social organization. People are complicated now, and they almost certainly were during the Migration Period," said Geary. "There are thousands of medieval cemeteries out there for us to look at. This is hopefully just the beginning of our work." The international team of 24 scholars joining Geary, Caramelli, Krause, and Veeramah in producing this paper include Carlos Eduardo G. Amorim and Dean Bobo of Stony Brook University; Stefania Vai, Alessandra Modi, and Martina Lari of Università degli Studi di Firenze; Cosimo Posth of the Max Planck Institute for the Science of Human History and University of Tübingen; István Koncz of Eötvös Loránd University; Susanne Hakenbeck of the University of Cambridge; Maria Cristina La Rocca of Università degli Studi di Padova; Balázs Mende of the Hungarian Academy of Sciences; Tivadar Vida of Eötvös Loránd University and the Hungarian Academy of Sciences; Walter Pohl of Österreichische Akadamie der Wissenschaften; Luisella Pejrani Baricco, Elena Bedini, and Caterina Giostra of Università Cattolica del Sacro Cuore; Paolo Francalacci of Università degli Studi di Sassari; Daniel Winger of Universität Rostock; Uta von Freeden of Deutsches Archäologisches Institut; and Silvia Ghirotto and Guido Barbujani of Università degli Studi di Ferrara. The idea of creating such an interdisciplinary team originated eight years ago in the course of a faculty seminar at the University of California, Los Angeles, supported by a grant from the Andrew W. Mellon Foundation to transform research in the humanities. This work was supported by the National Science Foundation, the Anneliese Maier Research Award of the Alexander von Humboldt Foundation, the Max Planck Society, the German Federal Ministry for Education and Research, the Swedish Riksbankens Jubileumsfond, the Gerard B. Lambert Foundation, and the Italian Ministry for University and Research Department of Excellence Program. Additional funding was provided by the Director's Office of the Institute for Advanced Study.

Neighboring infected and uninfected human macrophages during a Zika virus infection in a lab dish. Zika virus is labeled red; Macrophage nuclei are labeled blue. Macrophages are immune cells that are supposed to protect the body from infection by viruses and bacteria. Yet Zika virus preferentially infects these cells. Researchers at University of California San Diego School of Medicine have now unraveled how the virus shuts down the genes that make macrophages function as immune cells. The study is published September 11 in Proceedings of the National Academy of Sciences. In pregnant women, Zika virus can stunt neonatal brain development, leading to babies born with abnormally small heads, a condition known as microcephaly. Adult brain cells may also be vulnerable to the virus. "We know Zika virus destroys a number of cell types, particularly in the brain, but we don't yet understand how it causes cells to die or malfunction," said first author Aaron Carlin, MD, PhD, associate physician at UC San Diego School of Medicine. "So this loss of general gene transcription and identity we saw in macrophages could also be crucial when a neural stem cell is trying to develop into a new neuron." Carlin led the study with Christopher K. Glass, MD, PhD, professor in the departments of Medicine and Cellular and Molecular Medicine at UC San Diego School of Medicine, and Sujan Shresta, PhD, professor at La Jolla Institute for Allergy and Immunology. Carlin and team first developed a method for tagging the Zika virus inside live cells, and a mechanism for sorting tagged (infected) and untagged (uninfected) human macrophages. Many previous viral studies relied on dishes of cells that had been exposed to the virus, but not necessarily all cells were infected. As a result, the cellular effects measured in a laboratory "infection" are often a mixture of what's going on inside both infected and uninfected cells. "If your goal is to see what a virus is doing to a cell, you need to focus on only infected cells to get true representation," Carlin said. The difference they found with the new technique was startling. "We were surprised at just how different infected and uninfected cells looked, in terms of the genes they had turned on or off, even two cells next to each other," Glass said. "What's amazing is that even though they are exposed to the same environment, their responses are completely different. And now we know those differences are truly due to the virus, not any of the other events going on around the cells during an immune response." This approach provided a more accurate account of Zika's effect on macrophages and revealed that the virus suppressed gene production in the cells by two methods. First, the virus specifically blocks hundreds of macrophage genes that should be stimulated by interferon, a molecule that triggers an immune response. For example, the IFITM1 gene, which inhibits Zika virus, is expressed 73-fold less in Zika-infected cells than in neighboring uninfected cells. Second, Zika infection leads to general suppression of gene production because the virus targets RNA Pol II, a crucial part of the cell's gene transcription machinery. The loss of RNA Pol II is especially notable at genes responsible for macrophage function and identity. Collectively, these approaches allow Zika virus to stop macrophages from making many genes involved in immune cell recruitment and anti-viral defense. Moving forward, Carlin, Glass and team are interested in applying their new sorting technique to cells infected by other viruses. They also hope to examine other cell types infected by Zika virus, such as neural stem cells.

A molecule produced during fasting or calorie restriction has anti-aging effects on the vascular system, which could reduce the occurrence and severity of human diseases related to blood vessels, such as cardiovascular disease, according to a study led by Georgia State University. "As people become older, they are more susceptible to disease, like cancer, cardiovascular disease and Alzheimer's disease," said Dr. Ming-Hui Zou, senior author of the study, director of the Center for Molecular and Translational Medicine at Georgia State and a Georgia Research Alliance Eminent Scholar in Molecular Medicine. "Age is the most important so-called risk factor for human disease. How to actually delay aging is a major pathway to reducing the incident and severity of human disease. "The most important part of aging is vascular aging. When people become older, the vessels that supply different organs are the most sensitive and more subject to aging damage, so studying vascular aging is very important. This study is focused on vascular aging, and in old age, what kind of changes happen and how to prevent vascular aging." In this study, the research team explores the link between calorie restriction (eating less or fasting) and delaying aging, which is unknown and has been poorly studied. The findings are published in the journal Molecular Cell. The researchers identified an important, small molecule that is produced during fasting or calorie restriction conditions. The molecule, ?-Hydroxybutyrate, is one type of a ketone body, or a water-soluble molecule that contains a ketone group and is produced by the liver from fatty acids during periods of low food intake, carbohydrate restrictive diets, starvation and prolonged intense exercise. "We found this compound, ?-Hydroxybutyrate, can delay vascular aging," Zou said. "That's actually providing a chemical link between calorie restriction and fasting and the anti-aging effect. This compound can delay vascular aging through endothelial cells, which line the interior surface of blood vessels and lymphatic vessels. It can prevent one type of cell aging called senescence, or cellular aging." Senescent cells can no longer multiple and divide. The researchers found ?-Hydroxybutyrate can promote cell division and prevent these cells from becoming old. Because this molecule is produced during calorie restriction or fasting, when people overeat or become obese this molecule is possibly suppressed, which would accelerate aging. In addition, the researchers found when ?-Hydroxybutyrate binds to a certain RNA-binding protein, this increases activity of a stem cell factor called Octamer-binding transcriptional factor (Oct4) in vascular smooth muscle and endothelial cells in mice. Oct4 increases a key factor against DNA damage-induced senescence, which can keep blood vessels young. "We think this is a very important discovery, and we are working on finding a new chemical that can mimic the effect of this ketone body's function," Zou said. "We're trying to take the global approach to reducing cardiovascular disease and Alzheimer's disease. It's difficult to convince people not to eat for the next 24 hours to increase the concentration of this compound (?-Hydroxybutyrate), and not everybody can do that, but if we can find something that can mimic this effect and people can still eat, it would make life more enjoyable and help fight disease. "This stem cell factor (Oct4) could be a pharmaceutical or pharmacological target for slowing down or preventing aging. Then, if the vascular system becomes younger, it is less likely to have cardiovascular disease, Alzheimer's disease and cancer because all of these diseases are age-related." In the future, the researchers would like to target senescent cells with the goal of eliminating them and rejuvenating the vascular system to prevent cardiovascular disease.

Multiple sclerosis lesion in the spinal cord. Inflammatory phagocytes appear in red, anti-inflammatory phagocytes in green and intermediate phenotypes in yellow. Mononuclear phagocytes can both promote and inhibit inflammation. A Team from Ludwig-Maximilians-Universitaet (LMU) in Munich has now shown that individual phagocytes in the central nervous system can play both roles, sequentially adopting different phenotypes with distinct functions. Mononuclear phagocytes, which recognize, engulf and digest damaged and infected cells, form an important arm of the innate immune system. However, they also play an important, but paradoxical role in the pathogenesis of inflammatory diseases of the central nervous system, such as multiple sclerosis. On the one hand, they contribute to the initiation of inflammatory reactions that lead to tissue damage. But they are also intimately involved in the subsequent resolution and repair of such lesions. Hence, these cells are capable of exhibiting both pro- and anti-inflammatory phenotypes. In order to explain their apparently contradictory roles at sites of inflammation, it has been postulated that phagocytes can assume functionally different activation states. How and where these phenotypes are specified in the inflamed nervous system, and whether they remain fixed, has so far eluded elucidation. Now a team led by Professor Martin Kerschensteiner, Director of the Institute of Clinical Neuroimmunology at LMU, has characterized the fates of single phagocytes, and shown that their functional properties are not in fact fixed. Instead, individual cells can switch phenotypic states in inflamed tissues. The new findings appear in Nature Neuroscience. The study was carried out in an experimental mouse model of multiple sclerosis. "We used an in vivo imaging approach, which allowed us to distinguish between different phagocyte phenotypes in vivo on the basis of the expression of different fluorescent proteins," says Kerschensteiner. "With the aid of this method, we were able to track individual cells and monitor their phenotypic identity in real time." This approach revealed that pro-inflammatory phagocytes are found, as expected, at the sites of developing lesions, while the differential fluorescence marker expression indicated that the phagocytes associated with resolving lesions have an anti-inflammatory character. By tracking individual phagocytes continuously, the researchers were able to observe that this phenotypic difference was not due to the successive recruitment of two different cell types -- as had been suggested on the basis of results from other model systems. Instead, single phagocytes in the central nervous system can switch from a pro- to an anti-inflammatory state, depending on the nature of the local environment. "In subsequent experiments, we demonstrated that this phenotypic conversion is induced by signals from the central nervous system, in particular by soluble factors secreted by cells known as astrocytes," Kerschensteiner explains. The discovery should enable researchers to obtain a better molecular understanding of the phenotype switch, and allow them to explore the therapeutic potential of targeted manipulation of phagocyte populations in the management of neuroinflammatory conditions.

Researchers at Carnegie Mellon University have devised a way to automatically transform the content of one video into the style of another, making it possible to transfer the facial expressions of one person to the video of another person, or even a cartoon character. Researchers at Carnegie Mellon University have devised a way to automatically transform the content of one video into the style of another, making it possible to transfer the facial expressions of comedian John Oliver to those of a cartoon character, or to make a daffodil bloom in much the same way a hibiscus would. Because the data-driven method does not require human intervention, it can rapidly transform large amounts of video, making it a boon to movie production. It can also be used to convert black-and-white films to color and to create content for virtual reality experiences. "I think there are a lot of stories to be told," said Aayush Bansal, a Ph.D. student in CMU's Robotics Institute. Film production was his primary motivation in helping devise the method, he explained, enabling movies to be produced more quickly and cheaply. "It's a tool for the artist that gives them an initial model that they can then improve," he added. The technology also has the potential to be used for so-called "deep fakes," videos in which a person's image is inserted without permission, making it appear that the person has done or said things that are out of character, Bansal acknowledged. "It was an eye opener to all of us in the field that such fakes would be created and have such an impact," he said. "Finding ways to detect them will be important moving forward." Bansal will present the method today at ECCV 2018, the European Conference on Computer Vision, in Munich. His co-authors include Deva Ramanan, CMU associate professor of robotics. Transferring content from one video to the style of another relies on artificial intelligence. In particular, a class of algorithms called generative adversarial networks (GANs) have made it easier for computers to understand how to apply the style of one image to another, particularly when they have not been carefully matched. In a GAN, two models are created: a discriminator that learns to detect what is consistent with the style of one image or video, and a generator that learns how to create images or videos that match a certain style. When the two work competitively -- the generator trying to trick the discriminator and the discriminator scoring the effectiveness of the generator -- the system eventually learns how content can be transformed into a certain style. A variant, called cycle-GAN, completes the loop, much like translating English speech into Spanish and then the Spanish back into English and then evaluating whether the twice-translated speech still makes sense. Using cycle-GAN to analyze the spatial characteristics of images has proven effective in transforming one image into the style of another. That spatial method still leaves something to be desired for video, with unwanted artifacts and imperfections cropping up in the full cycle of translations. To mitigate the problem, the researchers developed a technique, called Recycle-GAN, that incorporates not only spatial, but temporal information. This additional information, accounting for changes over time, further constrains the process and produces better results. The researchers showed that Recycle-GAN can be used to transform video of Oliver into what appears to be fellow comedian Stephen Colbert and back into Oliver. Or video of John Oliver's face can be transformed a cartoon character. Recycle-GAN allows not only facial expressions to be copied, but also the movements and cadence of the performance. The effects aren't limited to faces, or even bodies. The researchers demonstrated that video of a blooming flower can be used to manipulate the image of other types of flowers. Or clouds that are crossing the sky rapidly on a windy day can be slowed to give the appearance of calmer weather. Such effects might be useful in developing self-driving cars that can navigate at night or in bad weather, Bansal said. Obtaining video of night scenes or stormy weather in which objects can be identified and labeled can be difficult, he explained. Recycle-GAN, on the other hand, can transform easily obtained and labeled daytime scenes into nighttime or stormy scenes, providing images that can be used to train cars to operate in those conditions.

Left: A photograph of the 'rainbow' weevil, with the rainbow-colored spots on its thorax and elytra (wing casings). Right: A microscope image of the rim of a single rainbow spot, showing the different colors of individual scales. Researchers from Yale-NUS College and the University of Fribourg in Switzerland have discovered a novel colour-generation mechanism in nature, which if harnessed, has the potential to create cosmetics and paints with purer and more vivid hues, screen displays that project the same true image when viewed from any angle, and even reduce the signal loss in optical fibres. Yale-NUS College Assistant Professor of Science (Life Science) Vinodkumar Saranathan led the study with Dr Bodo D Wilts from the Adolphe Merkle Institute at the University of Fribourg. Dr Saranathan examined the rainbow-coloured patterns in the elytra (wing casings) of a snout weevil from the Philippines, Pachyrrhynchus congestus pavonius, using high-energy X-rays, while Dr Wilts performed detailed scanning electron microscopy and optical modelling. They discovered that to produce the rainbow palette of colours, the weevil utilised a colour-generation mechanism that is so far found only in squid, cuttlefish, and octopuses, which are renowned for their colour-shifting camouflage. The study was published in the peer-reviewed journal Small. P. c. pavonius, or the "Rainbow" Weevil, is distinctive for its rainbow-coloured spots on its thorax and elytra. These spots are made up of nearly-circular scales arranged in concentric rings of different hues, ranging from blue in the centre to red at the outside, just like a rainbow. While many insects have the ability to produce one or two colours, it is rare that a single insect can produce such a vast spectrum of colours. Researchers are interested to figure out the mechanism behind the natural formation of these colour-generating structures, as current technology is unable to synthesise structures of this size. "The ultimate aim of research in this field is to figure out how the weevil self-assembles these structures, because with our current technology we are unable to do so," Dr Saranathan said. "The ability to produce these structures, which are able to provide a high colour fidelity regardless of the angle you view it from, will have applications in any industry which deals with colour production. We can use these structures in cosmetics and other pigmentations to ensure high-fidelity hues, or in digital displays in your phone or tablet which will allow you to view it from any angle and see the same true image without any colour distortion. We can even use them to make reflective cladding for optical fibres to minimise signal loss during transmission." Dr Saranathan and Dr Wilts examined these scales to determine that the scales were composed of a three-dimensional crystalline structure made from chitin (the main ingredient in insect exoskeletons). They discovered that the vibrant rainbow colours on this weevil's scales are determined by two factors: the size of the crystal structure which makes up each scale, as well as the volume of chitin used to make up the crystal structure. Larger scales have a larger crystalline structure and use a larger volume of chitin to reflect red light; smaller scales have a smaller crystalline structure and use a smaller volume of chitin to reflect blue light. According to Dr Saranathan, who previously examined over 100 species of insects and spiders and catalogued their colour-generation mechanisms, this ability to simultaneously control both size and volume factors to fine-tune the colour produced has never before been shown in insects, and given its complexity, is quite remarkable. "It is different from the usual strategy employed by nature to produce various different hues on the same animal, where the chitin structures are of fixed size and volume, and different colours are generated by orienting the structure at different angles, which reflects different wavelengths of light," Dr Saranathan explained.

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