Nanomaterial from the Middle Ages

To gild sculptures in the late Middle Ages, artists often applied ultra-thin gold foil supported by a silver base layer. For the first time, scientists at the Paul Scherrer Institute PSI have managed to produce nanoscale 3D images of this material, known as Zwischgold. The pictures show this was a highly sophisticated mediaeval production technique and demonstrate why restoring such precious gilded artefacts is so difficult.

The samples examined at the Swiss Light Source SLS using one of the most advanced microscopy methods were unusual even for the highly experienced PSI team: minute samples of materials taken from an altar and wooden statues originating from the fifteenth century. The altar is thought to have been made around 1420 in Southern Germany and stood for a long time in a mountain chapel on Alp Leiggern in the Swiss canton of Valais. Today it is on display at the Swiss National Museum (Landesmuseum Zürich). In the middle you can see Mary cradling Baby Jesus. The material sample was taken from a fold in the Virgin Mary’s robe. The tiny samples from the other two mediaeval structures were supplied by Basel Historical Museum.

The material was used to gild the sacred figures. It is not actually gold leaf, but a special double-sided foil of gold and silver where the gold can be ultra-thin because it is supported by the silver base. This material, known as Zwischgold (part-gold) was significantly cheaper than using pure gold leaf. “Although Zwischgold was frequently used in the Middle Ages, very little was known about this material up to now,” says PSI physicist Benjamin Watts: “So we wanted to investigate the samples using 3D technology which can visualise extremely fine details.” Although other microscopy techniques had been used previously to examine Zwischgold, they only provided a 2D cross-section through the material. In other words, it was only possible to view the surface of the cut segment, rather than looking inside the material.  The scientists were also worried that cutting through it may have changed the structure of the sample. The advanced microscopy imaging method used today, ptychographic tomography, provides a 3D image of Zwischgold’s exact composition for the first time.

Read more on the PSI website

Image: The altar examined is thought to have been made around 1420 in Southern Germany and for a long time stood in a mountain chapel on Alp Leiggern in the Swiss canton of Valais. Today it is on display at the Swiss National Museum (Landesmuseum Zürich).

Credit: Swiss National Museum, Landesmuseum Zürich

New fossil sheds light on the evolution of how dinosaurs breathed

An international team of scientists has used high-powered X-rays at the European Synchrotron to show how an extinct South African 200-million-year-old dinosaur, Heterodontosaurus tucki, breathed. The study, published in eLife, demonstrates that not all dinosaurs breathed in the same way.

In 2016, scientists from the Evolutionary Studies Institute at the University of the Witwatersrand in Johannesburg, South Africa, came to the ESRF, the European Synchrotron in Grenoble, France, the brightest synchrotron light source, for an exceptional study: to scan the complete skeleton of a small, 200-million-year-old plant-eating dinosaur. The dinosaur specimen is the most complete fossil ever discovered of a species known as Heterodontosaurus tucki. The fossil was found in 2009 in the Eastern Cape of South Africa by study co-author, Billy de Klerk of the Albany Museum, Makhanda, South Africa. “A farmer friend of mine called my attention to the specimen”, says de Klerk, “and when I saw it I immediately knew we had something special on our hands.”

Fast forward some years: the team of scientists use scans and new algorithms developed by ESRF scientists to virtually reconstruct the skeleton of Heterodontosaurus in unprecedented detail, and thus show how this extinct dinosaur breathed. “This specimen represents a turning point in understanding how dinosaurs evolved” explains Viktor Radermacher, corresponding author, a South African PhD student and now at the University of Minnesota, US.

Read more on the ESRF website

Image: The skull of the Heterodontosaurus tucki dinosaur.

Credit: ESRF

Critical data of insect specimens to be unlocked through 3D imaging

The Natural History Museum is collaborating with Diamond Light Source, the UK’s national synchrotron science facility, on an ambitious project to generate and share immense data from the Museum’s vast insect collections to help further research into their evolution, diversity and extinctions. The Natural History Museum is collaborating with Diamond Light Source, the UK’s national synchrotron science facility, on an ambitious project to generate and share immense data from the Museum’s vast insect collections to help further research into their evolution, diversity and extinctions.

Over 1.6 million of the Museum’s 35 million insects have already been digitised using 2D photography. These specimens have had their images and collections data (information about where in time and space they were collected and what species they are) made available to the public via the Museum’s Data Portal. However, this landmark project is expected to provide valuable new insights and information by providing the beginnings of a high-resolution 3D dataset for all living and fossil insects and their close relatives.

Read more on the Diamond website

Image: Hairy Fungus Beetle – Prepared by Malte Storm

Credit: Diamond Light Source Ltd

How ventilation might impact blood flow in ventilated preterm babies

A large international collaboration led by researchers from the Hudson Institute for Medical Research and Monash University has revealed that the ventilation of preterm babies to prevent lung collapse could create a risk of brain injury.  

A/Prof Flora Wong, a researcher at Hudson Institute and Monash University, and consultant neonatologist at Monash Children’s Hospital, and a team of physiologists used the Imaging and Medical beamline (IMBL) at the Australian Synchrotron to acquire extremely clear and detailed images of blood vessels in large, preterm clinical models, in an investigation to determine if the pressure of lung ventilation affected blood vessels and blood flow.

A/Prof Wong said the group have shown that higher lung pressure causes engorgement and stretching of the brain blood vessels, which could slow down blood flow in the brain. 

 “This may play a role in preterm brain injury,” she said.

Because of the findings, A/Prof Wong alerted hospitals to carefully monitor their ventilation of preterm babies, who now survive after as few as 23 weeks gestation.

IMBL Principal Scientist Dr Daniel Hausermann, a co-author on the paper published in The Journal of Physiology, said that in vivo CT imaging of dynamic physiological processes, such as blood flow, can be captured quickly in real-time video on the IMBL beamline.

Read more on the Australian synchrotron website

Image: Micro-angiography showing micro-vessels

Cell membrane proteins imaged in 3-D

Scientists used lanthanide-binding tags to image proteins at the level of a cell membrane, opening new doors for studies on health and medicine.

A team of scientists including researchers at the National Synchrotron Light Source II (NSLS-II)—a U.S. Department of Energy (DOE) Office of Science User Facility at DOE’s Brookhaven National Laboratory—have demonstrated a new technique for imaging proteins in 3-D with nanoscale resolution. Their work, published in the Journal of the American Chemical Society, enables researchers to identify the precise location of proteins within individual cells, reaching the resolution of the cell membrane and the smallest subcellular organelles.
“In the structural biology world, scientists use techniques like x-ray crystallography and cryo-electron microscopy to learn about the precise structure of proteins and infer their functions, but we don’t learn where they function in a cell,” said corresponding author and NSLS-II scientist Lisa Miller. “If you’re studying a particular disease, you need to know if a protein is functioning in the wrong place or not at all.”
The new technique developed by Miller and her colleagues is similar in style to traditional methods of fluorescence microscopy in biology, in which a molecule called green fluorescent protein (GFP) can be attached to other proteins to reveal their location. When GFP is exposed to UV or visible light, it fluoresces a bright green color, illuminating an otherwise “invisible” protein in the cell.

>Read more on the National Synchrotron Light Source II (NSLS-II) website

Image: Ultrabright x-rays revealed the concentration of erbium (yellow) and zinc (red) in a single E.coli cell expressing a lanthanide-binding tag and incubated with erbium.

Synchrotron X-ray sheds light on some of the world’s oldest dinosaur eggs

An international team of scientists led by the University of the Witwatersrand (South Africa), has been able to reconstruct the skulls of some of the world’s oldest known dinosaur embryos in 3D at the ESRF.

They found that the skulls develop in the same order as those of today’s crocodiles and chickens. The findings are published today in Scientific Reports.
University of the Witwatersrand scientists publish 3D reconstructions of the ~2cm-long skulls of some of the world’s oldest dinosaur embryos in an article in Scientific Reports. The embryos, found in 1976 in Golden Gate Highlands National Park (Free State Province, South Africa) belong to South Africa’s iconic dinosaur Massospondylus carinatus, a 5-meter long herbivore that nested in the Free State region 200 million years ago.

The scientific usefulness of the embryos was previously limited by their extremely fragile nature and tiny size. In 2015, scientists Kimi Chapelle and Jonah Choiniere, from the University of Witwatersrand, brought them to the European Synchrotron (ESRF) in Grenoble, France for scanning. At the ESRF, an 844 metre-ring of electrons travelling at the speed of light emits high-powered X-ray beams that can be used to non-destructively scan matter, including fossils. The embryos were scanned at an unprecedented level of detail – at the resolution of an individual bone cell.

>Read more on the ESRF website

Image: Watercolour painting of the Massospondylus carinatus embryos at 17% through the incubation period, 60% through the incubation period and 100% through the incubation period.
Artwork: Mélanie Saratori.

Imaging how anticancer compounds move inside the cells

Chemotherapeutics are key players in the clinical setting to fight most types of cancer, and novel chemicals hold the promise to facilitate new and unique intracellular interactions that modulate the cell machinery and destroy the tumour cells. Equally necessary are new tools that enable the unequivocal location and quantification of such molecules in the intracellular nano-space, so that their therapeutic action is fully understood.

Researchers from IMDEA Nanociencia, the ALBA Synchrotron, the European Synchrotron Radiation Facility (ESRF) and the National Centre for Biotechnology (CNB) have developed a new family of organo-iridium drug candidates about a hundred times more potent than the clinically used drug cisplatin.
In order to understand the therapeutic potential of the compound, it is mandatory to accurately localize its fate within the cell ultrastructure with minimal perturbation. To this aim researchers have correlated on the same cell, for the first time, two 3D X-ray imaging techniques with a resolution of tenths of nanometers: cryo soft X-ray tomography, at MISTRAL beamline at ALBA Synchrotron, and cryo X-ray fluorescence tomography, at ID16A beamline at ESRF. These techniques help elucidate the 3D architecture of the whole cell and to reveal the intracellular location of different atomic elements, respectively.

>Read more on the ALBA website

X-ray microscopy at BESSY II: Nanoparticles can change cells

Nanoparticles easily enter into cells. New insights about how they are distributed and what they do there are shown for the first time by high-resolution 3D microscopy images from BESSY II.

For example, certain nanoparticles accumulate preferentially in certain organelles of the cell. This can increase the energy costs in the cell. “The cell looks like it has just run a marathon, apparently, the cell requires energy to absorb such nanoparticles” says lead author James McNally.
Today, nanoparticles are not only in cosmetic products, but everywhere, in the air, in water, in the soil and in food. Because they are so tiny, they easily enter into the cells in our body. This is also of interest for medical applications: Nanoparticles coated with active ingredients could be specifically introduced into cells, for example to destroy cancer cells. However, there is still much to be learned about how nanoparticles are distributed in the cells, what they do there, and how these effects depend on their size and coating.

>Read more on the BESSY II at Helmholtz-Zentrum Berlin website

Image: 3D architecture of the cell with different organelles:  mitochondria (green), lysosomes (purple), multivesicular bodies (red), endoplasmic reticulum (cream).
Credit: Burcu Kepsutlu/HZB

Soft X-ray Laminography: 3D imaging with powerful contrast mechanisms

Soft X-ray 3D imaging has already been realized at synchrotron radiation sources using either scanning transmission X-ray microscopy (STXM) schemes or tomography-based concepts. However, the maximum accessible sample volume is severely limited by the reduced penetration depth of the lower-energy soft X-ray radiation. This becomes even more of a drawback in the case of flat and extended specimens, which can be found in various fields of nanoscience.

The generalized geometry of laminography, characterized by a tilted axis of rotation concerning the incident X-ray beam resulting in a constant material thickness during rotation, has proven to be particularly suitable for the investigation of laterally extended and thin objects. The combination of soft X-rays and laminography provides the unique potential of bridging the gap between investigations of elaborate nanostructured thin film samples and taking advantage of the characteristic absorption contrast mechanisms in the soft X-ray range.

>Read more on the Swiss Light Source at PSI website

Image: 3D model constructed from soft X-ray laminography measurements of the front tip of the wing scale from a European peacock butterfly.

Synchrotron light for deciphering Friedreich’s Ataxia

A team from the Germans Trias i Pujol Research Institute (IGTP) in Badalona is performing an experiment at the ALBA Synchrotron to obtain for the first time 3D images of cells with this disease.

Friedreich’s ataxia affects more than 3,000 people in Spain, causing serious mobility problems and other severe illnesses such as heart disease. At present there is no treatment to prevent or cure the disease.

Friedreich’s ataxia is a rare neurodegenerative disease that progressively damages mobility, balance and coordination. It is an inherited disease, caused by a genetic mutation, that can appear when both parents are carriers. A research group from the Germans Trias i Pujol Research Institute (IGTP), at the Can Ruti Campus in Badalona, led by Dr. Antoni Matilla, is looking into the causes and possible treatments for this disease that results in high disability and an important decrease in the patients’ quality of life.

“Today there is no treatment or cure for Friedreich’s ataxia. It is necessary to try to understand how the disease develops in order to propose therapeutic solutions”, says Dr. Ivelisse Sánchez, co-Principal Investigator of this project at the Neurogenetics Unit of the IGTP. Researchers are now analysing donors’ cells in the ALBA Synchrotron to see the changes caused by the disease.

>Read more on the ALBA website

Image: Dr. Ivelisse Sánchez, co-Principal Investigator of the project, and pre-doctoral researcher Eudald Balagué at the MISTRAL beamline.

The future of fighting infections

Scientists analyze 3D model of proteins from disease-causing bacteria at the CLS.

Millions of people are affected by the Streptococcus pneumoniae bacterium, which can cause sinus infections, middle ear infections and more serious life-threatening diseases, like pneumonia, bacteremia, and meningitis. Up to forty percent of the population are carriers of this bacterium.
Researchers from the University of Victoria (UVic) used the Canadian Light Source (CLS) at the University of Saskatchewan to study proteins that the pathogen uses to break down sugar chains (glycans) present in human tissue during infections. These proteins are key tools the bacterium uses to cause disease.

They used the Canadian Macromolecular Crystallography Facility (CMCF) at the CLS to determine the three-dimensional structure of a specific protein, an enzyme, that the bacterium produces to figure out how it interacts with and breaks down glycans.

>Read more on the Canadian Light Source website

Image: The 3D structure of an enzyme from the disease-causing bacterium Streptococcus pneumoniae.

3D X-ray view of an amber fossil

Research team unravels secrets of 50-million-year-old parasite larvae

With the intense X-ray light from DESY’s particle accelerator PETRA III, researchers have investigated an unusual find: a 50-million-year-old insect larva from the era of the Palaeogene. The results offer a unique insight into the development of the extinct insect, as the team reports in the journal Arthropod Systematics & Phylogeny.
When the biologist Hans Pohl from the Friedrich Schiller University in Jena tracked down an insect fossil trapped in amber on eBay, the joy of discovery was great: it was a special specimen, a 50-million-year-old larva of an extinct twisted-wing insect from the order of Strepsiptera. But in order to be able to investigate it in detail, he needed the help of materials researchers from the Helmholtz Centre in Geesthacht, which operates a beamline at DESY’s X-ray source PETRA III.
Strepsiptera are parasites that infest other insects, such as bees and wasps, but also silverfish. “In most of the approximately 600 known species, the females remain in their host throughout their lives,” says Pohl. “Only the males leave it for the wedding flight, but then live only a few hours.” But there are exceptions: In species that infest silverfish, the wingless females also leave their host.

>Read more on the PETRA III at DESY website

Image: The fossil in amber. Its age lies between 42 to 54 million years. This fossil was scientifically examined at the Institute for Zoology and Evolutionary Research at the University of Jena.
Credit: FSU, Hans Pohl 

The interaction between two proteins involved in skin mechanical strength

A research team from the Centro de Investigación del Cáncer of the Universidad de Salamanca has obtained a detailed 3D image of the union between two hemidesmosomal proteins.

The structure of this complex has been unveiled using XALOC beamline techniques, at the ALBA Synchrotron. The results, published in “Structure”, provide insights to understand how these epithelial adhesion structures are formed. Researchers from Centro de Investigación del Cáncer – Instituto de Biología Molecular y Celular del Cáncer of Salamanca, from Centro Universitario de la Defensa in Zaragoza, and from the Netherlands Cancer Institute in Amsterdam have described how two essential proteins interact to each other in order to join epidermis and dermis together. This study reveals at atomic scale how the binding between two hemidesmosomal proteins called integrin α6β4 and BP230 takes place.
Epithelial tissues, such as epidermis, settle on fibrous sheets called basement membrane, formed by extracellular matrix proteins. The junction between epithelia and basement membrane happens through hemidesmosomes, multi-protein complexes located at the membrane of epithelial cells. Integrin α6β4 is an essential protein of the hemidesmosomes, which adheres to proteins of the basement membrane. Inside the cell cytoplasm, plectin and BP230 proteins bind to α6β4 and connect it to the intermediate filaments of the cytoskeleton. Genetic or autoimmune alterations that affect the hemidesmosomal proteins reduce skin resistance and cause diseases such as bullous pemphigoid and various types of epidermolysis bullosa.

>Read more on the ALBA website

Image: Structure of β4(WT)-BP230 complex.

New approach for solving protein structures from tiny crystals

Technique opens door for studies of countless hard-to-crystallize proteins involved in health and disease

Using x-rays to reveal the atomic-scale 3-D structures of proteins has led to countless advances in understanding how these molecules work in bacteria, viruses, plants, and humans—and has guided the development of precision drugs to combat diseases such as cancer and AIDS. But many proteins can’t be grown into crystals large enough for their atomic arrangements to be deciphered. To tackle this challenge, scientists at the U.S. Department of Energy’s (DOE) Brookhaven National Laboratory and colleagues at Columbia University have developed a new approach for solving protein structures from tiny crystals.

The method relies on unique sample-handling, signal-extraction, and data-assembly approaches, and a beamline capable of focusing intense x-rays at Brookhaven’s National Synchrotron Light Source II (NSLS-II)—a DOE Office of Science user facility—to a millionth-of-a-meter spot, about one-fiftieth the width of a human hair.

>Read more on the NSLS-II at Brookhaven Lab website

Image: Wuxian Shi, Martin Fuchs, Sean McSweeney, Babak Andi, and Qun Liu at the FMX beamline at Brookhaven Lab’s National Synchrotron Light Source II, which was used to determine a protein structure from thousands of tiny crystals.

Coelacanth reveals new insights into skull evolution

A team of researchers, in conjunction with the National Museum of Natural History in Paris, presents the first observations of the development of the skull and brain in the living coelacanth Latimeria chalumnae.

The study, published in Nature, uses data from beamline ID19 and provides new insights into the biology of this iconic animal and the evolution of the vertebrate skull.
The coelacanth Latimeria is a marine fish closely related to tetrapods, four-limbed vertebrates including amphibians, mammals and reptiles. Coelacanths were thought to have been extinct for 70 million years, until the accidental capture of a living specimen by a South African fisherman in 1938. Eighty years after its discovery, Latimeria remains of scientific interest for understanding the origin of tetrapods and the evolution of their closest fossil relatives – the lobe-finned fishes.

>Read more on the European Synchrotron website

Image: Overall anterolateral view of the skull of the coelacanth foetus imaged on beamline ID19. The brain is in yellow.
Credit: H. Dutel et al.

Low background noise crucial for single particle imaging experiments

Model experiment brings scientists a step closer to SPI at European XFEL

Taking snapshots of single molecules with X-rays has long been a dream for many scientists. Such experiments have successfully been computationally modelled, but have never been practically demonstrated before.
In a model experiment carried out at the European Synchrotron Radiation Facility (ESRF), European XFEL scientists, together with international collaborators, have now come one step closer to successfully carrying out so-called single particle imaging experiments (SPI) at X-ray laser facilities such as European XFEL. In a paper published today in the journal from the International Union of Crystallography (IUCrJ), scientists demonstrate experimentally that, in principle, a 3D structure can indeed be obtained from many tens of thousands of very weak images, using X-rays with similar properties as produced at X-ray free-electron lasers such as European XFEL.

>Read more on the European XFEL website

Image: Reconstruction of the 3D electron density. (a) Reconstruction from the result derived by EMC. The electron density projected along an axis perpendicular to the drawing plane is shown here. (b) Reconstruction from the reference Fourier volume. Again, the projected electron density is shown. (c) 3D iso-surface rendering of the reconstructed electron density shown in panel (a). The threshold of the iso-surface has been set to 0.2, given a normalized density with values between 0 and 1. (d) Scanning electron micrograph from the original sample.
Image source