Gene therapy proved against muscular dystrophy with the ALBA synchrotron

A study by the Sant Joan de Déu Research Institute, ICFO, CIBERER and the ALBA Synchrotron has helped demonstrate that gene therapy can reverse the effects of the mutation that causes the symptoms of congenital muscular dystrophy in patient cells. The mutation, which leads to a disorder in the body’s collagen, has been silenced through a genetic editing technique based on the CRISPR/Cas9 system. Experiments at the MISTRAL beamline in ALBA have revealed previously unknown cell damage. Congenital muscular dystrophy is a rare minority disease that mainly affects children and has no treatment.

Congenital muscular dystrophy is a group of rare neuromuscular diseases. In particular, type VI collagen deficiency-related dystrophy affects less than 1 in 100,000 people, has varying degrees of severity, and has no cure.

Read more on the ALBA website

Image: Three-dimensional reconstruction of whole-cell volumes of control- (“healthy cell”), and patient-derived fibroblasts and CRISPR-treated fibroblasts. The different organelles present in the cells can be seen: nucleus in yellow, mitochondria in light blue, endo/lysosomal-like vesicles in violet, and multivesicular bodies in pink.

Understanding how motor proteins shape our cells

Understanding the busy networks inside our cells can help researchers develop new cancer treatments and prevent dangerous fungal infections.

With the help of the Canadian Light Source (CLS) at the University of Saskatchewan, a research team led by John Allingham from Queen’s University and Hernando Sosa from the Albert Einstein College of Medicine has shed light on a protein that regulates the intricate microscopic networks that give cells their shape and helps ship important molecules to diverse locations.

Using the CMCF beamline at the CLS and the cryo-EM facility at the Simons Electron Microscopy Center (SEMC) at the New York Structural Biology Center, the team found the missing pieces of an important puzzle.

In their published work, they are the first group to clearly describe the mechanism of action of a tiny motor protein called Kinesin-8 that enables it to control the structures of microtubule fiber networks inside the cell.

Read more on the CLS website

Image: Cells, Canadian Light Source.

Targeting a parasite’s DNA could be more effective way to treat malaria

Research from the University of Sheffield using Diamond has explored a new way of killing the Plasmodium parasite that causes malaria. 

According to the World Health Organisation, there were 241 million cases of malaria and 627,000 deaths worldwide in 2020 – making the study and treatment of this disease a high-priority issue for scientists around the world. In a feasibility study, researchers from the University of Sheffield used Diamond to reveal a novel way of fighting the life-threatening disease, malaria. The study discovered molecules that interfered with the parasite’s DNA processing enzyme, but not the equivalent human one. 

A research team from the University of Sheffield’s Department of Infection, Immunity and Cardiovascular Disease examined and targeted an enzyme that maintains the classic double-helical structure of the malaria parasite’s DNA, which contains the blueprint of life, which could be a more effective way to combat malaria.

Read more on the Diamond website

Image: A flap endonuclease cuts DNA (the orange intertwined worms), credit University of Sheffield

X-rays allow us to quickly develop high-strength steels

Knowing how strong a piece of steel is, especially the stainless steel used in everything from cars to buildings, is vitally important for the people who make and use it. This information helps to keep people safe during crashes and to prevent buildings from collapsing.

Accurately predicting the strength of a steel prototype based on its microstructure and composition would be indispensable when designing new types of steel, but it has been nearly impossible to achieve — until now.

“Designing/making the best-strength steel is the hardest task,” said Dr Harishchandra Singh, an adjunct professor at NANOMO and the Centre for Advanced Steels Research at the University of Oulu in Finland.

Estimating the contribution of various factors towards designing high-strength novel steel has traditionally required numerous tests that can take months, according to Singh. Each test also requires a new sample of the prototype. 

Read more on the CLS website

Image: Dr Harishchandra Singh, an adjunct professor at NANOMO and the Centre for Advanced Steels Research at the University of Oulu in Finland. He is standing next to steel components in the spectroscopy lab at NANOMO.

Aleksei Kotlov’s #My1stLight

Aleksei was responsible for setting up the new P66 beamline at PETRA III at DESY

Setting up the P66 beamline was a challenging time. The years of discussions, iterations, doubts, calculations, ordering of parts, and construction end at some point with commissioning of the beamline. Only then could you see the final result of your work and see that all decisions were right. To me personally it was like the birth of a baby. Suddenly you realize, that small beam spot on the sample is a big event for you and whole beamline community and to make it happen you have invested a significant part of your life.

Image: Aleksei on the P66 beamline at PETRA III

Canadian Light Source’s #My1stLight on the Far Infrared Beamline in 2005

The Queen of England helped us get the beamline operating in May of 2005, while she was visiting Saskatchewan and the Canadian Light Source with Prince Philip. The ring had been operating but the IR beamlines needed vacuum bellows installed due to delays in shipment. These would complete the UHV chambers to the window outside the shield wall. There were no beam outages on the schedule long enough to do this for 6 months into the fall, so the IR operation was being badly delayed.

But! the CLS had to shut down for a day before the Royal visit on Friday May 20*, to allow security screening and preparation for the Royals. So with two days of no-beam, the technicians quickly vented the ring magnet cell and installed the bellows and we had nearly 48 hours to pump down and bake the system. Then on Sat May 21 at 12:30 pm there was beam in the ring (thankfully no leaks from the bellows!) and the search for beam began. The M2 mirror was steered until a spot of light was seen glowing near the edge of the UHV window. This glow was adjusted to line up along one side, and a lateral scan was made while recording a video at the window.

At the controls was Dr. Dominique Appadoo, now at the Australian Synchrotron, who was the Far IR beamline scientist at the time. Assisting were Tim May the optics designer/project manager for the IR beamlines, and Craig Hyett a graduate student working on the IR beamlines. Subsequently the first light was steered out of the window port on the Mid IR beamline.

Image: Tim and Dominique searching for first light

* Read more on the CLS website

High pressure synthesis in gallium sulphide chalcogenide

Researchers from Universitat Politècnica de València, Universidad de La Laguna, Universidad de Cantabria and the ALBA Synchrotron have published a new work on high pressure chemistry in gallium (III) sulphide chalcogenide. In this work, relevant fingerprints (vibrational and structural) of a pressure-induced paralectric to ferroelectric phase transition are shown. This is the first time when a tetradymite-like (R3m) phase has been synthesized and observed experimentally in gallium-based sequichalcogenides. High pressure X-ray diffraction measurements were carried out at MSPD beamline of ALBA.

Gallium (III) sulphide (Ga2S3) is a compound of sulphur and gallium, that is a semiconductor that has a wide variety of applications in electronics and photonics: nano optoelectronics, photonic chips, electro-catalysis, energy conversion and storage, solar energy devices, gas sensors, laser-radiation detection, second harmonic generation, phase change memories or photocatalytic water splitting systems.

In this work published in Chemistry of Materials,scientists have shown relevant vibrational and structural fingerprints of a pressure-induced paraelectric to ferroelectric R-3m-to-R3m (β’-to-φ) phase transition under decompression on Ga2S3 chalcogenide.

This transition was theoretically predicted in several III−VI B2X3 compounds at high temperature (where B can be aluminium, gallium or indium and X, sulphur, selenium or tellurium). The novelty of this research stems from the synthesis of both phases: β-(R-3m) and α-In2Se3 (R3m)-like structures on Ga2S3 and tuning them via decreasing pressure. Within the III−VI B2X3 compounds, this R-3m-to-R3m (β’-to-φ-Ga2S3) phase transition had been observed experimentally only in the indium (III) selenide (In2Se3)compound, under varying temperature or pressure, to date.

This finding leads the way for designing cheap, nontoxic, nonrare-earth, and abundant element-based devices for second harmonic generation, photocatalytic splitting, ferroelectric, pyroelectric, and piezoelectric applications based on Ga2S3.

Read more on the ALBA website

Image: Samuel Gallego and Catalin Popescu at the MSPD beamline of ALBA.

A new leap in understanding nickel oxide superconductors

Researchers discover they contain a phase of quantum matter, known as charge density waves, that’s common in other unconventional superconductors. In other ways, though, they’re surprisingly unique.

BY GLENNDA CHUI

A new study shows that nickel oxide superconductors, which conduct electricity with no loss at higher temperatures than conventional superconductors do, contain a type of quantum matter called charge density waves, or CDWs, that can accompany superconductivity.

The presence of CDWs shows that these recently discovered materials, also known as nickelates, are capable of forming correlated states – “electron soups” that can host a variety of quantum phases, including superconductivity, researchers from the Department of Energy’s SLAC National Accelerator Laboratory and Stanford University reported in Nature Physics today.

“Unlike in any other superconductor we know about, CDWs appear even before we dope the material by replacing some atoms with others to change the number of electrons that are free to move around,” said Wei-Sheng Lee, a SLAC lead scientist and  investigator with the Stanford Institute for Materials and Energy Science (SIMES) who led the study.

“This makes the nickelates a very interesting new system – a new playground for studying unconventional superconductors.”

Nickelates and cuprates

In the 35 years since the first unconventional “high-temperature” superconductors were discovered, researchers have been racing to find one that could carry electricity with no loss at close to room temperature. This would be a revolutionary development, allowing things like perfectly efficient power lines, maglev trains and a host of other futuristic, energy-saving technologies.

But while a vigorous global research effort has pinned down many aspects of their nature and behavior, people still don’t know exactly how these materials become superconducting.

So the discovery of nickelate’s superconducting powers by SIMES investigators three years ago was exciting because it gave scientists a fresh perspective on the problem. 

Since then, SIMES researchers have explored the nickelates’ electronic structure – basically the way their electrons behave – and magnetic behavior. These studies turned up important similarities and subtle differences between nickelates and the copper oxides or cuprates – the first high-temperature superconductors ever discovered and still the world record holders for high-temperature operation at everyday pressures.

Since nickel and copper sit right next to each other on the periodic table of the elements, scientists were not surprised to see a kinship there, and in fact had suspected that nickelates might make good superconductors. But it turned out to be extraordinarily difficult to construct materials with just the right characteristics.

“This is still very new,” Lee said. “People are still struggling to synthesize thin films of these materials and understand how different conditions can affect the underlying microscopic mechanisms related to superconductivity.”

Read more on the SLAC website

Image: An illustration shows a type of quantum matter called charge density waves, or CDWs, superimposed on the atomic structure of a nickel oxide superconductor. (Bottom) The nickel oxide material, with nickel atoms in orange and oxygen atoms in red. (Top left) CDWs appear as a pattern of frozen electron ripples, with a higher density of electrons in the peaks of the ripples and a lower density of electrons in the troughs. (Top right) This area depicts another quantum state, superconductivity, which can also emerge in the nickel oxide. The presence of CDWs shows that nickel oxides are capable of forming correlated states – “electron soups” that can host a variety of quantum phases, including superconductivity.

Credit: Greg Stewart/SLAC National Accelerator Laboratory

#SynchroLightAt75 – Operation of the PAL-XFEL in 2020

After the PAL-XFEL was opened to the public in 2017, beamtime for user service has increased every year to provide more opportunities for user experiments. In 2020, 2,819 hours were provided for user beamtime out of the planned 2,910 hours and the beam availability was 96.9%. The provided beamtime of 2,819 hours was a significant increase from 2,409 hours in 2019, as shown in Table 1. To further increase beamtime, the PAL-XFEL has plans for 24-hour operation and simultaneous operation of hard and soft X-ray beamlines in the near future.

YearPlanned BeamtimeProvided BeamtimeAvailability
20182,012 h1,921 h95.5%
20192,503 h2,409 h96.2%
20202,910 h2,819 h96.9%
Table 1. Planned and provided beamtime in 2018, 2019, and 2020

FEL saturation of 0.062 nm (20 keV) was achieved for the first time in PAL-XFEL. The measured FEL energy using the e-loss scan was 408 uJ, the FEL radiation spectrum was 25.3 eV rms (0.127% of the center photon energy), and the FEL pulse duration (FWHM) was 11 fs, which corresponds to 1×1011 photons/pulse. The e-beam energy was 10.4 GeV and the undulator K was 1.4. The undulator gap scan was conducted for 20 undulators to check the FEL saturation as shown in Figure 1. Here, quadratic undulator tapering is applied for the last 6 undulators and the calculated gain length was 3.43 m.

Figure 1. Measurement results of the saturation curve at 20 keV photon energy

Two-color FEL generation with a single electron bunch has been successfully demonstrated for the hard X-ray undulator line, broadening the research capabilities at the PAL-XFEL. Test experiments have been conducted at two photon energies, 9.7 keV and 12.7 keV. A pump pulse is generated with 8 upstream undulators of the self-seeding section and a probe pulse is generated with 12 downstream undulators of the self-seeding section. The photon energies of the pulses can be independently controlled by changing the undulator parameter K and the time delay between two pulses can be controlled from 0 to 120 femtoseconds by using the magnetic chicane installed at the self-seeding section.

Figure 2. Intensity measurement results of two-color FEL generations.

Ultra-bright hard x-ray pulses using the self-seeded FEL were applied to the demonstration of serial femtosecond crystallography (SFX) experiments in 2020. We have consistently improved the spectral purity and peak of the self-seeded FEL using a laser heater and optimized crystal conditions over a hard x-ray range from 3.5 keV to 14.6 keV. The peak brightness for self-seeded hard x-ray pulses was enhanced to almost ten times greater than that of the SASE FEL over hard x-ray ranges. For example, the peak brightness of an x-ray at 9.7 keV is 3.2×1035 photons/(s·mm2·mrad2·0.1%BW), which is the highest peak brightness ever achieved for free-electron laser pulses. Thanks to the ultra-bright x-ray pulse with narrow bandwidth and superior spectral purity, SFX experiment results using the seeded FEL showed better data quality with high resolutions compared with that using the SASE FEL. This work has been published in Nature Photonics (https://doi.org/10.1038/s41566-021-00777-z).

Figure 3. Comparison of measured FEL intensity between SASE and self-seeding FEL.

New insight into how mammal ancestors became warm-blooded

The shapes of the ear canals of mammal ancestors reveal when warm-bloodedness evolved. The study published in Nature demonstrates that mammal ancestors became warm-blooded later than previously thought – nearly 20 million years later-, and that the acquisition of endothermy seems to have occurred very quickly in geological terms, in less than a million years. The international team of scientists, led by London’s Natural History Museum, the University of Lisbon’s Instituto Superior Técnico, the Field Museum in Chicago, and including the University of Witwatersrand, used the ESRF bright X-rays to scan delicate and dense fossils.

Read more on the ESRF website

Image: Comparison of bony labyrinth shape in two examples of warm-blooded (left) and cold-blooded (right) prehistoric mammal ancestors. © Romain David and Ricardo Araújo.

Third-highest oxidation state secures rhodium a place on the podium

Oxidation states of transition metals describe how many electrons of an element are already engaged in bonding, and how many are still available for further reactions. Scientists from Berlin and Freiburg have now discovered the highest oxidation state of rhodium, indicating that rhodium can involve more of its valence electrons in chemical bonding than previously thought. This finding might be relevant for the understanding of catalytic reactions involving highly-oxidized rhodium. The result was recognized as a „very important paper“ in Angewandte Chemie.

Transition metals in high or unusual oxidation states might play an important role as catalysts or reaction intermediates in chemical reactions. Because transition metals are already well characterized in most cases, the discovery of a new oxidation state of rhodium came as a real surprise. The identification of rhodium(VII) was made possible by PhD student Mayara da Silva Santos and co-workers, who were able to isolate the species from any reactant in a low-temperature ion trap, and perform x-ray absorption spectroscopy for its characterization. 

BESSY II was essential for the discovery

These kinds of experiments are highly demanding, and can, at present, only be carried out at BESSY II. „The combination of advanced sample preparation, low-temperature ion trapping, and x-ray spectroscopy is unique. Because these essential tools can even be applied to more complex systems, we anticipate further insight into exotic transition metal oxides“, says Vicente Zamudio-Bayer, head of the ion trap group at beamline UE52-PGM, who develops and operates the ion trap endstation at BESSY II. „What was important for us was that our surprising experimental findings could be substantiated by Sebastian Riedel‘s group at FU Berlin, who performed state-of-the-art calculations on the species in question“, explains Zamudio-Bayer. “Even rhodium in oxidation state +6 is very rare, so we had to be extremely careful about +7. New oxidation states are not discovered every day”, says Mayara da Silva Santos.

Read more on the HZB website

Image: For the first time, a team has detected rhodium in the +7 oxidation state, the third highest oxidation state experimentally among all elements in the periodic table. © https://doi.org/10.1002/anie.202207688

Welcome Jeney Wierman – New MacCHESS Director

Jeney Wierman started as the new MacCHESS Director on July 1st, 2022.  Below is a welcome message to the whole CHESS Community. 

Jeney takes over the MacCHESS directorship from Marian Szebenyi, who will be retiring later this year after 30 years at MacCHESS.

Dear CHESS Community,

It is (hopefully) no secret that I hold a very special place in my heart for CHESS, the people working here, and the community it supports. With that, I am honored and delighted to join CHESS this summer as Director of MacCHESS! First, I must thank Marian Szebenyi for continuing to work with me into the fall startup – I have large shoes to fill and appreciate the overlap support. Second, I would also like to thank all who were a part of the hiring process over the past few months, plus onboarding over the last week. Much appreciated.

It is thrilling to return to the CHESS family! The ingenuity and tenacity of the CHESS spirit (the can-do attitude) speak volumes of its brilliant people.

Read more on the CHESS website

Image: Jeney Wierman has started as the MacCHESS Director on July 1.

Antibody rigidity regulates immune activity

Scientists at the University of Southampton have gained unprecedented new insight into the key properties of an antibody needed to stimulate immune activity to fight off cancer, using the ESRF’s structural biology beamlines, among others.

The interdisciplinary study, published in Science Immunology, revealed how changing the flexibility of the antibody could stimulate a stronger immune response. The findings have enabled the team to design antibodies to activate important receptors on immune cells to “fire them up” and deliver more powerful anti-cancer effects. The researchers believe their findings could pave the way to improve antibody drugs that target cancer, as well as automimmune diseases.

In the study, the team investigated antibody drugs targeting the receptor CD40 for cancer treatment. Clinical development has been hampered by a lack of understanding of how to stimulate the receptors to the right level. The problem being that if antibodies are too active they can become toxic. Previous research by the same team had shown that a specific type of antibody called IgG2 is uniquely suited as a template for pharmaceutical intervention, since it is more active than other antibody types. However, the reason why it is more active had not been determined. What was known, however, is that the structure between the antibody arms, the so called hinges, changes over time.

This latest research harnesses this property of the hinge and explains how it works: the researchers call this process “disulfide-switching”. In their study, the team analysed the effect of modifying the hinge and used a combination of biological activity assays, structural biology, and computational chemistry to study how disulfide switching alters antibody structure and activity.

Read more on the ESRF website

Image: Flexibility of the monoclonal antibody F(ab) arms is conferred by the hinge region disulphide structure

Credit: C. Orr

Ultrafast surface processes observed

SINGLE X-RAY LASER PULSES CAN BE USED TO OBSERVE ULTRAFAST CHANGES ON MATERIAL SURFACES WITH UNPRECEDENTED DEPTH AND TIME RESOLUTION

In a world first, an international team of scientists led by European XFEL and the University of Siegen has demonstrated that the intense pulses produced by an X-ray laser can be used to investigate ultrafast processes occurring on and just below material surfaces with unprecedented depth and time resolution. This allows researchers to capture processes that are more than a billion times faster than what could previously be observed. The results, which the team has just published in Physical Review Research, pave the way for versatile applications that rely on our understanding of ultrafast surface dynamics. Examples are the laser processing of material surfaces to create tailor-made nanoscale structures or the realization of compact laser-based particle or radiation sources.

Using intense laser pulses, nanoscale surface structures can be created with optimized optical, mechanical, and chemical properties. Such tailored structures play a decisive role in many fields with significant societal and economic impact. They can be used to fashion antimicrobial coatings, to improve the bonding of dental implant screws with bone, and to build advanced optical components with high damage thresholds. To be able to better create these structures and comprehend their effects, scientists first need to observe and understand the ultrafast processes that happen when the intense femtosecond laser pulses used in the surface processing hit the material and react with it.

Read more on the European XFEL website

Image: Grazing-incidence small-angle X-ray scattering image obtained from a multilayer sample, measured using single X-ray pulses of the SACLA X-ray laser in Japan. The central black circle is the beamstop used to block the main mirror-like reflection peak, which is much more intense than the scattering pattern. The pattern contains information on the depth-resolved density profile (horizontal axis) and the surface structure (vertical axis).

Ryan Tappero’s #My1stLight

Ryan is the XFM Lead Beamline Scientist at NSLS-II on Long Island, New York. His #My1stLight celebrates the night back in 2017 when the beamline succeeded in taking first light! A smiling team AND results. Definitely worth remembering as part of our 75 Years of Science with Synchrotron Light #My1stLight campaign

Read more about NSLS-II’s XFM beamline here

Giant Rashba semiconductors show unconventional dynamics with potential applications

Germanium telluride is a strong candidate for use in functional spintronic devices due to its giant Rashba-effect. Now, scientists at HZB have discovered another intriguing phenomenon in GeTe by studying the electronic response to thermal excitation of the samples. To their surprise, the subsequent relaxation proceeded fundamentally different to that of conventional semimetals. By delicately controlling the fine details of the underlying electronic structure, new functionalities of this class of materials could be conceived. 

In recent decades, the complexity and functionality of silicon-based technologies has increased exponentially, commensurate with the ever-growing demand for smaller, more capable devices. However, the silicon age is coming to an end.  With increasing miniaturisation, undesirable quantum effects and thermal losses are becoming an ever-greater obstacle. Further progress requires new materials that harness quantum effects rather than avoid them. Spintronic devices, which use spins of electrons rather than their charge, promise more energy efficient devices with significantly enhanced switching times and with entirely new functionalities.

Spintronic devices are coming

Candidates for spintronic devices are semiconductor materials wherein the spins are coupled with the orbital motion of the electrons. This so-called Rashba effect occurs in a number of non-magnetic semiconductors and semi-metallic compounds and allows, among other things, to manipulate the spins in the material by an electric field.

First study in a non equilibrium state

Germanium telluride hosts one of the largest Rashba effects of all semiconducting systems. Until now, however, germanium telluride has only been studied in thermal equilibrium. Now, for the first time, a team led by HZB physicist Jaime-Sanchez-Barriga has specifically accessed a non-equilibrium state in GeTe samples at BESSY II and investigated in detail how equilibrium is restored in the material on ultrafast (<10-12 seconds) timescales. In the process, the physicists encountered a new and unexpected phenomenon.

First, the sample was excited with an infrared pulse and then measured with high time resolution using angle-resolved photoemission spectroscopy (tr-ARPES). “For the first time, we were able to observe and characterise all phases of excitation, thermalisation and relaxation on ultrashort time scales,” says Sánchez-Barriga. The most important result: “The data show that the thermal equilibrium between the system of electrons and the crystal lattice is restored in a highly unconventional and counterintuitive way”, explains one of the lead authors, Oliver Clark.

Read more on the HZB website

Image: Left: Electronic structure of GeTe taken with 11 eV photons at BESSY-II, showing the band dispersions of bulk (BS) and surface Rashba states (SS1, SS2) in equilibrium. Middle: Zoom-in on the region of the Rashba states measured with fs-laser 6 eV photons. Right: Corresponding out-of-equilibrium dispersions following excitation by the pump pulse.