The African fly of death might also save lives

For the first time, an international team of scientists recreated in the lab the molecule that allows the tsetse fly to feed on blood. It’s a powerful yet small anticoagulant with a unique and strong binding to thrombin, the key enzyme of the coagulation pathway. X-ray diffraction measurements at two synchrotron facilities ––ALBA and ESRF–– were instrumental to understand the structure and the mechanism of action of this molecule, which suggests it is also a promising platform for designing improved anticoagulant drugs.

 In the waiting rooms of health care facilities around the world, millions of patients take anticoagulants every day. These are life-saving drugs for the treatment of cardiovascular diseases, which now are also being explored for their benefits to patients with advanced symptoms of COVID-19.

And, as incredible as it may seem, the tsetse fly, responsible for the sleeping sickness disease in humans, is now on the spotlight in the efforts to develop more powerful and safer anticoagulants. 

In a study co-authored by Bárbara Calisto, researcher at the ALBA Synchrotron, an international team of scientists has become the first to recreate in the lab the molecule that the tsetse fly uses to prevent coagulation when it bites to feed. These bites are also the entry channel for the parasite that causes sleeping sickness, a life-threatening disorder, if untreated. And the reason why the tsetse fly has been dubbed as the fly of death in Africa.

Read more on the ALBA website

Image:  Bárbara Calisto at the XALOC beamline of the ALBA Synchrotron

Credit: ALBA

ESRF and UCL scientists awarded Chan Zuckerberg Initiative grant for human organ imaging project

The project, named “Anatomical to cellular synchrotron imaging of the whole human body”, promises to develop a transformational X-ray tomography technology that will enable the scanning of a whole human body with resolution of 25 microns, thinner than a human hair – tens of times the resolution of a CT scanner. Further, it can then zoom into local areas with cellular-level imaging, or one micron – over 100x better resolution than a CT scanner. This imaging project is based on the recent Extremely Brilliant Source (EBS) upgrade to the ESRF that has created the world’s first high-energy fourth-generation synchrotron, which is currently the brightest X-ray source in the world. Feasibility studies have already demonstrated it can resolve unprecedented detail revealing the damage caused by COVID-19 on human lungs, linking from the major airways all the way down to the finest micro-vasculature in an intact lung.

The project is led by an international multidisciplinary team of synchrotron imaging scientists (at UCL and ESRF), mathematicians and computer scientists (at UCL) and medics (at Hannover-biobank, Mainz and Heidelberg), brought together to image deep-tissue in COVID-19-injured organs.

Read more on the ESRF website

Image: Paul Tafforeau, ESRF scientist imaging the complete brain and lung of a COVID-19 victim using HiP-CT at the ESRF-EBS, the world’s brightest X-ray source. By resolving cellular features (ca. one-micron resolution) in local areas we hope to help determine if COVID-19 affects the vasculature in the organs.
Credit: ESRF

Uncovering the secrets of a fish with a super strong jaw

Black drum is a fish from the United States with one of the strongest bite force in the fish world. It can easily crunch through shells, its main source of food. Weight for weight, it has a bite that is as strong as the bite of a crocodile.

The jaw of this fish has scientists fascinated: it is not made of cortical bone, like most jaws, and it has a 3D arrangement of beams. “This is something never seen before in any other animal. It looks like a sponge… how can such a structure, which seems weak, carry all this load?” queries project leader Ron Shahar, veterinarian and engineer at The Hebrew University of Jerusalem in Israel. 

In the quest to find how this structure is built and how it operates, Shahar is joined by Paul Zaslansky, a dentist at the Charité Hospital in Berlin (Germany), as well as physicists Alexander Rack and Marta Majkut at the ESRF.

Read more on the ESRF website

Image: A detailed view of the set-up with the jaw and all the teeth

Credit: A. Rack

Red and black ink from Egyptian papyri unveil ancient writing practices

Scientists led by the ESRF and the University of Copenhagen have discovered the composition of red and black inks in ancient Egyptian papyri from circa 100-200 AD, leading to different hypotheses about writing practices. The analysis shows that lead was probably used as a dryer rather than as a pigment, similar to its usage in 15th century Europe during the development of oil paintings. They publish their results today in PNAS.

The earliest examples of preserving human thought by applying ink on a flexible and durable material, papyrus, are found in ancient Egypt at the dawn of recorded history (c. 3200 BCE). Egyptians used black ink for writing the main body of text, while red ink was often used to highlight headings, instructions or keywords. During the last decade, many scientific studies have been conducted to elucidate the invention and history of ink in ancient Egypt and in the Mediterranean cultures, for instance ancient Greece and Rome.

Read more on The European Synchrotron website

Image: Detail of a medical treatise (inv. P. Carlsberg 930) from the Tebtunis temple library with headings marked in red ink. Credit: The Papyrus Carlsberg Collection and the ESRF.

Opening of ESRF-Extremely Brilliant Source (EBS), a new generation of synchrotron

25 August 2020 – A brilliant new light shines in Grenoble, France, with the opening of the ESRF-Extremely Brilliant Source (ESRF-EBS), the first-of-a-kind fourth-generation high-energy synchrotron. After a 20-month shutdown, scientific users are back at the ESRF to carry out experiments with the new EBS source.

The ring-shaped machine, 844 metres in circumference, generates X-ray beams 100 times brighter than its predecessor’s, and 10 trillion times brighter than medical X-rays. This intense X-ray beam hails a new era for science to understand the complexity of materials and living matter at the nanometric level. ESRF-EBS will contribute to tackling global challenges in key areas such as health, environment, energy and new industrial materials, and to unveiling hidden secrets of our natural and cultural heritage through the non-destructive investigation of precious artefacts and palaeontological treasures. A shining example of international cooperation, EBS has been funded by 22 countries joining forces to construct this innovative and world-unique research infrastructure with an investment of 150 million euros over 2015-2022, lighting the way for more than a dozen projects worldwide, including in the United States and Japan.

“The opening of the first high-energy fourth-generation synchrotron to users is a landmark for the whole X-ray science community. We are all thrilled to envisage the revolutionary science to be carried out and  the new applications that will start to emerge. All ESRF staff should be commended for such an achievement, attained on time and on budget in spite of the current circumstances,” says Miguel Ángel García Aranda, chair of the ESRF council.

Read more on the ESRF website

Image: Panoramic view of the ESRF. Credit: S. Candé.

New nanoimaging method traces metal presence in Parkinson’s brain

Many neurodegenerative diseases like Parkinson’s and Alzheimer’s often exhibit an excess of iron in the brain. Scientists have developed a method to trace the presence of metals in brain at the sub-cellular level, particularly in organelles of neurons vulnerable to these diseases. The results are published in Communications Biology.

The level and distribution of iron in the brain normally contributes to essential cellular functions, including mitochondrial respiration, via its capability to transfer electrons. In vulnerable populations of neurons however, iron dysregulation can have detrimental effects. Genetic defects affecting iron metabolism cause brain diseases, including Parkinson’s and Alzheimer’s, both associated with iron overload. “It is important to be able to explore metal distribution in neurons and glia (non-neuronal cells), with the aim to identify potential causal mechanisms in neurodegeneration”, explains Bernard Schneider, scientist at EPFL and co-author of the study.

Until now, there was no method that could trace the elements with sensitivity and nanometre resolution. A team of scientists from LGL-TPE (Laboratoire de Géologie de Lyon : Terre, Planètes et Environnement), Institut des Sciences de la terre (ISTerre) de Grenoble, the ESRF and the EPFL (École Polytechnique Fédérale de Lausanne) have now combined the techniques of transmission electron microscopy and synchrotron X-ray fluorescence at the ESRF in order to evaluate the element unbalance in Parkinson’s disease.

Read more on the ESRF website

Image : Composition of P/Fe/S in a section of a neuron of the substantia nigra. The neuron and its nucleus are highlighted by dashed lines. Cytoplasmic granules rich in Fe and S are pointed out by arrows. 

Credit: Lemelle, L, et al, Communications Biology, DOI : 10.1038/s42003-020-1084-0.

Researchers find the key to preserving The Scream

Moisture is the main environmental factor that triggers the degradation of the masterpiece The Scream (1910?) by Edvard Munch, according to the finding of an international team of scientists led by the CNR (Italy), using a combination of in situ non-invasive spectroscopic methods and synchrotron Xray techniques. After exploiting the capability of the European mobile platform MOLAB in situ and non-invasively at the Munch Museum in Oslo, the researchers came to the ESRF, the European Synchrotron (Grenoble, France), the world’s brightest X-ray source, to carry out non-destructive
experiments on micro-flakes originating from one of the most well-known versions of The Scream. The findings could help better preserve this masterpiece, which is seldom exhibited due to its degradation. The study is published in Science Advances.


The Scream is among the most famous paintings of the modern era. The now familiar image is interpreted as the ultimate representation of anxiety and mental anguish. There are a number of versions of The Scream, namely two paintings, two pastels, several lithographic prints and a few drawings and sketches. The two most well-known versions are the paintings that Edvard Munch created in 1893 and 1910. Each version of The Scream is unique. Munch clearly experimented to find the exact colours to represent his personal experience, mixing diverse binding media (tempera, oil and pastel) with brilliant and bold synthetic pigments to make ‘screaming colours’. Unfortunately, the extensive use of these new coloured materials poses a challenge for the long-term preservation of Munch’s artworks.

Read more on the ESRF website

Image: ESRF scientist Marine Cotte during the synchrotron experiment at ID21 beamline, at the ESRF, the European Synchrotron, Grenoble, France.

Credit: ESRF/Stef Candé

Out of the blue: X-rays shed light on on ultramarine blue in masterpieces

According to a survey led by Nature in 2016, 70% of scientists admitted they could not reproduce another scientist’s experiments and more than half could not reproduce their own. In order to improve sharing and, in turn, enhancing innovation, the European Union is working on implementing the European Open Science Cloud (EOSC), a kind of “library” of all experimental raw data and methods, available to everyone.

The ESRF is doing its bit by leading the PaNOSC (Photon and Neutron Open Science Cloud) project: “We are in the process of implementing the ESRF Data Policy to organise the data from experiments in an archive, which ultimately everyone will be able to access. The scientific teams will have three years to keep their data closed to the public, and after that any other scientist can try to repeat or do new data analysis of the very same experiment if he or she wishes to”, explains Andy Götz, coordinator of the project. The final goal of PaNOSC and the EOSC is to make data from publicly funded research in Europe Findable, Accessible, Interoperable and Reusable (FAIR).

>Read more on the ESRF website

Image: Alessa Gambardella at a stereomicroscope looking at ultramarine blue in Hendrick per Brugghen’s The Adoration of the Kings (1619)

Credit: Courtesy of Department of Conservation & Science, Rijksmuseum.

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.

Lucy had an ape-like brain, but prolonged brain growth like humans

A study led by the Max Planck Institute for Evolutionary Anthropology reveals that Lucy’s species, Australopithecus afarensis, had an ape-like brain.

However, the protracted brain growth suggests that infants may have had a long dependence on caregivers, as in humans. The study, in collaboration with the ESRF, is published in Science Advances.

The species Australopithecus afarensis, well-known as Lucy’s species, inhabited East Africa more than three million years ago, and occupies a key position in the hominin family tree.. “Lucy and her kind provide important evidence about early hominin behavior. They walked upright, had brains that were around 20 percent larger than those of chimpanzees and may have used sharp stone tools,” explains senior author Zeresenay Alemseged from the University of Chicago, who directs the Dikika field project in Ethiopia, where the skeleton of an Australopithecus afarensis child, known as Dikika child and nicknamed Selam, was found in the year 2000. “Our new results show how their brains developed, and how they were organized,” adds Alemseged.

>Read more on the European Synchrotron website

Image: Brain imprints in fossil skulls of the speciesAustralopithecus afarensis(famous for “Lucy” and the “Dikika child” from Ethiopia pictured here) shed new lighton the evolution of brain growth and organization. The exceptionally preservedendocranial imprint of the Dikika child reveals an ape-likebrain organization, and nofeatures derived towards humans.
Credit: Philipp Gunz, MPI EVA Leipzig.

X-rays shine again in the Experimental Hall

It’s a great achievement for the EBS project. Beamlines saw first EBS beam one month ahead of schedule.

30 January 2020, after reaching in the last two days stable operation conditions of the EBS storage ring at 100 mA injection current, 65% injection efficiency and stable and rapid vacuum conditioning, 26 out of 27 Insertion Device beamlines opened their front-end with 5 mA stored electron beam current. 

The EBS X-ray beam – on all these beamlines, at distances from the source varying from 45 to 160 m, depending on the specific beamline – was found within fractions of millimetres from its position as measured in December 2018 before the start of the shutdown.

>Read more on the ESRF website

First stored beam

6 December, 12.30 pm. Today, the electrons have been stored for the first time, in the new Extremely Brilliant Source (EBS) storage ring.

Today, 6 December 12:30 pm was a great and intense moment for all the ESRF teams: the electrons have been stored for the first time in the new EBS storage ring, only five days after the start of the EBS storage ring commissioning. This is a new key milestone on the way to opening to the international scientific community the first high-energy fourth-generation synchrotron light source, known as EBS – Extremely Brilliant Source.

” Seeing the first beam stored only five days after the start of the commissioning is a huge achievement and an intense moment for all involved. EBS is becoming a reality.” said Pantaleo Raimondi, ESRF accelerator and source director and EBS storage ring concept inventor and project leader.

>Read more on the European Synchrotron website

First electrons turn in the ESRF’s Extremely Brilliant Source Storage Ring

This is an important milestone on the way to opening to the international scientific community the first high-energy fourth-generation synchrotron light source, known as EBS – Extremely Brilliant Source.

It marks the successful completion of the engineering and installation of a worldwide-unique accelerator within the existing ESRF infrastructure, and the start of the commissioning phase of a brand-new generation of high-energy synchrotron.
Expectation was high in the ESRF’s control room on 2 December as teams carefully monitored the first turns of the electrons around the new EBS storage ring. “Seeing the first electrons circulating is a huge achievement and proof of the hard work and expertise of the teams who have been working on this since 2015,” said Pantaleo Raimondi, ESRF accelerator and source director and EBS storage ring concept inventor and project leader. “It’s a great moment for all involved.”

>Read more on the ESRF website

Image: The first three turns of electrons in the new EBS storage ring.

The mechanism of the most commonly used antimalarial drugs unveiled

For centuries, quinoline has been an effective compound in antimalarial drugs, although no one knew its mode of action in vivo.

Today, a team led by the Weizmann Institute has discovered its mechanism in infected red blood cells in near-native conditions, by using the ESRF, Alba Synchrotron and BESSY. They publish their results in PNAS.

Malaria remains one of the biggest killers in low-income countries. Estimates of the number of deaths each year range from 450,000 to 720,000, with the majority of deaths happening in Africa. In the last two decades, the malaria parasite has evolved into drug-resistant strains. “Recently, the increasing geographical spread of the species, as well as resistant strains has concerned the scientific community, and in order to improve antimalarial drugs we need to know how they work precisely”, explains Sergey Kapishnikov, from the University of Copenhagen, in Denmark, and the Weizmann Institute, in Israel, and leader of the study.

Plasmodium parasite, when infecting a human, invades a red blood cell, where it ingests hemoglobin to grow and multiply. Hemoglobin releases then iron-containing heme molecules, which are toxic to the parasite. However, these molecules crystallise into hemozoin, a disposal product formed from the digestion of blood by the parasite that makes the molecules inert. For the parasite to survive, the rate at which the heme molecules are liberated must be slower or the same as the rate of hemozoin crystallization. Otherwise there would be an accumulation of the toxic heme within the parasite.

>Read more on the ESRF website

Image (taken from BESSY II article): The image shows details such as the vacuole of the parasites (colored in blue and green) inside an infected blood cell.
Credit:
S. Kapishnikov

Two other institutes, BESSY II at HZB and ALBA Synchrotron, have participated in this research. Please find here their published articles:

> X-ray microscopy at BESSY II reveal how antimalaria-drugs might work

> The mechanism of the most commonly used antimlalarial drugs in near- native conditions unveiled

Direct evidence of small airway closure in acute respiratory distress syndrome

Airway closure is thought to play an important role in acute respiratory distress syndrome (ARDS).

Airway closure has been imaged for the first time in an ARDS model by synchrotron phase contrast imaging providing direct evidence of this phenomenon.

ARDS is an acute inflammatory lung condition associated with high permeability oedema, surfactant dysfunction and widespread collapse of pulmonary alveoli, called atelectasis, which leads to decreased lung compliance and volume [1]. Clinicians have long suspected that the collapsibility of small airways is increased in this clinical syndrome, causing atelectasis [2,3]. While patients invariably require mechanical ventilation to survive, this life support measure can worsen lung injury due to exaggerated stress and strain applied to the tissue, which is magnified by mechanical inhomogeneity of lung tissue and atelectasis. Efforts to develop ventilation strategies that protect the lung, critically depend on our understanding of the mechanical behaviour of lung tissue and airways at the microscale. However, traditional computed tomography studies have not been able to clearly identify airway closure as a cause of atelectasis, due to their limited spatial resolution. To better identify the mechanisms involved in airway closure, it is necessary to use approaches that allow the study of individual airways. Here, the same individual small airways in intact lungs of anesthetised and mechanically ventilated rabbits with ARDS was studied using high resolution synchrotron phase-contrast computed tomography at beamline ID17.

>Read more on the European Synchrotron (ESRF) website

Ultra-white beetle scales may be the key to more sustainable paint

An international team of researchers has managed to mimic the colour of the Cyphochilus beetle scales – one of the brightest whites in nature, thanks to the ESRF’s imaging capabilities. This could help the development of ultra-white, sustainable paints.

Cyphochilus beetle scales are one of the brightest whites in nature. Until now, researchers did not known how their ultra-white appearance is created. X-ray nanotomography experiments at the ESRF have shown that the nanostructure in their tiny scales creates the colour, not the use of pigment or dyes.
Andrew Parnell, from the University of Sheffield and corresponding author of the study said: “In the natural world, whiteness is usually created by a foamy Swiss cheese-like structure made of a solid interconnected network and air. Until now, how these structures form and develop and how they have evolved light-scattering properties has remained a mystery.”
The findings show that the foamy structure of the beetles’ scales has the right proportion of empty spaces, in a highly interconnected nano-network, which optimise the scattering of light – creating the ultra-white colouring.

>Read more on the European Synchrotron website

Image: Andrew Denison and Stephanie Burg in the experimental hutch of beamline ID16B.