I03-Macromolecular Crystallography
I04-Macromolecular Crystallography
I24-Microfocus Macromolecular Crystallography
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Grace Q.
Gong
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Benoit
Bilanges
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Ben
Allsop
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Glenn
Masson
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Victoria
Roberton
,
Trevor
Askwith
,
Sally
Oxenford
,
Ralitsa R.
Madsen
,
Sarah E.
Conduit
,
Dom
Bellini
,
Martina
Fitzek
,
Matt
Collier
,
Osman
Najam
,
Zhenhe
He
,
Ben
Wahab
,
Stephen H.
Mclaughlin
,
A. W. Edith
Chan
,
Isabella
Feierberg
,
Andrew
Madin
,
Daniele
Morelli
,
Amandeep
Bhamra
,
Vanesa
Vinciauskaite
,
Karen E.
Anderson
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Silvia
Surinova
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Nikos
Pinotsis
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Elena
Lopez-Guadamillas
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Matthew
Wilcox
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Alice
Hooper
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Chandni
Patel
,
Maria A.
Whitehead
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Tom D.
Bunney
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Len R.
Stephens
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Phillip T.
Hawkins
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Matilda
Katan
,
Derek M.
Yellon
,
Sean M.
Davidson
,
David M.
Smith
,
James B.
Phillips
,
Richard
Angell
,
Roger L.
Williams
,
Bart
Vanhaesebroeck
Diamond Proposal Number(s):
[28677]
Abstract: Harnessing the potential beneficial effects of kinase signalling through the generation of direct kinase activators remains an underexplored area of drug development1,2,3,4,5. This also applies to the PI3K signalling pathway, which has been extensively targeted by inhibitors for conditions with PI3K overactivation, such as cancer and immune dysregulation. Here we report the discovery of UCL-TRO-1938 (referred to as 1938 hereon), a small-molecule activator of the PI3Kα isoform, a crucial effector of growth factor signalling. 1938 allosterically activates PI3Kα through a distinct mechanism by enhancing multiple steps of the PI3Kα catalytic cycle and causes both local and global conformational changes in the PI3Kα structure. This compound is selective for PI3Kα over other PI3K isoforms and multiple protein and lipid kinases. It transiently activates PI3K signalling in all rodent and human cells tested, resulting in cellular responses such as proliferation and neurite outgrowth. In rodent models, acute treatment with 1938 provides cardioprotection from ischaemia–reperfusion injury and, after local administration, enhances nerve regeneration following nerve crush. This study identifies a chemical tool to directly probe the PI3Kα signalling pathway and a new approach to modulate PI3K activity, widening the therapeutic potential of targeting these enzymes through short-term activation for tissue protection and regeneration. Our findings illustrate the potential of activating kinases for therapeutic benefit, a currently largely untapped area of drug development.
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May 2023
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Krios IV-Titan Krios IV at Diamond
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Abstract: Newly made mRNAs are processed and packaged into mature ribonucleoprotein complexes (mRNPs) and are recognized by the essential transcription–export complex (TREX) for nuclear export1,2. However, the mechanisms of mRNP recognition and three-dimensional mRNP organization are poorly understood3. Here we report cryo-electron microscopy and tomography structures of reconstituted and endogenous human mRNPs bound to the 2-MDa TREX complex. We show that mRNPs are recognized through multivalent interactions between the TREX subunit ALYREF and mRNP-bound exon junction complexes. Exon junction complexes can multimerize through ALYREF, which suggests a mechanism for mRNP organization. Endogenous mRNPs form compact globules that are coated by multiple TREX complexes. These results reveal how TREX may simultaneously recognize, compact and protect mRNAs to promote their packaging for nuclear export. The organization of mRNP globules provides a framework to understand how mRNP architecture facilitates mRNA biogenesis and export.
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Apr 2023
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I06-Nanoscience
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S.
Reimers
,
Y.
Lytvynenko
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Y. R.
Niu
,
E.
Golias
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B.
Sarpi
,
L. S. I.
Veiga
,
T.
Denneulin
,
A.
Kovács
,
R. E.
Dunin-Borkowski
,
J.
Bläßer
,
M.
Klaui
,
M.
Jourdan
Diamond Proposal Number(s):
[30141]
Open Access
Abstract: Current pulse driven Néel vector rotation in metallic antiferromagnets is one of the most promising concepts in antiferromagnetic spintronics. We show microscopically that the Néel vector of epitaxial thin films of the prototypical compound Mn2Au can be reoriented reversibly in the complete area of cross shaped device structures using single current pulses. The resulting domain pattern with aligned staggered magnetization is long term stable enabling memory applications. We achieve this switching with low heating of ≈20 K, which is promising regarding fast and efficient devices without the need for thermal activation. Current polarity dependent reversible domain wall motion demonstrates a Néel spin-orbit torque acting on the domain walls.
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Apr 2023
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Swagatha
Ghosh
,
Doris
Zorić
,
Peter
Dahl
,
Monika
Bjelčić
,
Jonatan
Johannesson
,
Emil
Sandelin
,
Per
Borjesson
,
Alexander
Bjorling
,
Analia
Banacore
,
Petra
Edlund
,
Oskar
Aurelius
,
Mirko
Milas
,
Jie
Nan
,
Anastasya
Shilova
,
Ana
Gonzalez
,
Uwe
Mueller
,
Gisela
Branden
,
Richard
Neutze
Open Access
Abstract: Serial femtosecond crystallography was initially developed for room-temperature X-ray diffraction studies of macromolecules at X-ray free electron lasers. When combined with tools that initiate biological reactions within microcrystals, time-resolved serial crystallography allows the study of structural changes that occur during an enzyme catalytic reaction. Serial synchrotron X-ray crystallography (SSX), which extends serial crystallography methods to synchrotron radiation sources, is expanding the scientific community using serial diffraction methods. This report presents a simple flow cell that can be used to deliver microcrystals across an X-ray beam during SSX studies. This device consists of an X-ray transparent glass capillary mounted on a goniometer-compatible 3D-printed support and is connected to a syringe pump via lightweight tubing. This flow cell is easily mounted and aligned, and it is disposable so can be rapidly replaced when blocked. This system was demonstrated by collecting SSX data at MAX IV Laboratory from microcrystals of the integral membrane protein cytochrome c oxidase from Thermus thermophilus, from which an X-ray structure was determined to 2.12 Å resolution. This simple SSX platform may help to lower entry barriers for non-expert users of SSX.
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Apr 2023
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I05-ARPES
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Seyeong
Cha
,
Giyeok
Lee
,
Sol
Lee
,
Sae Hee
Ryu
,
Yeongsup
Sohn
,
Gijeong
An
,
Changmo
Kang
,
Minsu
Kim
,
Kwanpyo
Kim
,
Aloysius
Soon
,
Keun Su
Kim
Diamond Proposal Number(s):
[19304, 24691]
Open Access
Abstract: A variety of phase transitions have been found in two-dimensional layered materials, but some of their atomic-scale mechanisms are hard to clearly understand. Here, we report the discovery of a phase transition whose mechanism is identified as interlayer sliding in lead iodides, a layered material widely used to synthesize lead halide perovskites. The low-temperature crystal structure of lead iodides is found not 2H polytype as known before, but non-centrosymmetric 4H polytype. This undergoes the order-disorder phase transition characterized by the abrupt spectral broadening of valence bands, taken by angle-resolved photoemission, at the critical temperature of 120 K. It is accompanied by drastic changes in simultaneously taken photocurrent and photoluminescence. The transmission electron microscopy is used to reveal that lead iodide layers stacked in the form of 4H polytype at low temperatures irregularly slide over each other above 120 K, which can be explained by the low energy barrier of only 10.6 meV/atom estimated by first principles calculations. Our findings suggest that interlayer sliding is a key mechanism of the phase transitions in layered materials, which can significantly affect optoelectronic and optical characteristics.
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Apr 2023
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Open Access
Abstract: All-optical control of terahertz pulses is essential for the development of optoelectronic devices for next-generation quantum technologies. Despite substantial research in THz generation methods, polarization control remains difficult. Here, we demonstrate that by exploiting band structure topology, both helicity-dependent and helicity-independent THz emission can be generated from nanowires of the topological Dirac semimetal Cd3As2. We show that narrowband THz pulses can be generated at oblique incidence by driving the system with optical (1.55 eV) pulses with circular polarization. Varying the incident angle also provides control of the peak emission frequency, with peak frequencies spanning 0.21–1.40 THz as the angle is tuned from 15 to 45°. We therefore present Cd3As2 nanowires as a promising novel material platform for controllable terahertz emission.
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Apr 2023
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B21-High Throughput SAXS
I24-Microfocus Macromolecular Crystallography
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Kai
Wu
,
Tanya K.
Ronson
,
Pingru
Su
,
Zhi
Chen
,
Leonard
Goh
,
Andrew W.
Heard
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Xiaopeng
Li
,
Fabian
Klautzsch
,
Christoph A.
Schalley
,
Mladen
Vinković
,
Jonathan R.
Nitschke
Diamond Proposal Number(s):
[31323, 31668]
Abstract: Biological encapsulants, such as viral capsids and ferritin protein cages, use many identical subunits to tile the surface of a polyhedron. Inspired by these natural systems, synthetic chemists have prepared artificial nanocages with well-defined shapes and cavities. Rational control over the self-assembly of discrete, nanometre-scale, hollow coordination cages composed of simple components remains challenging as a result of the entropic costs associated with binding many subunits together, difficulties in the error-correction processes associated with assembly and increasing surface energy as their size grows. Here we demonstrate the construction of nanocages of increasing size derived from a single pentatopic pyrrole-based subcomponent. Reasoned shifts in the preferred coordination number of the metal ions used, along with the denticity and steric hindrance of the ligands, enabled the generation of progressively larger cages. These structural changes of the cages are reminiscent of the differences in the folding of proteins caused by minor variations in their amino acid sequences; understanding how they affect capsule structure and thus cavity size may help to elucidate the construction principles for larger and functional capsules, capable of binding and carrying large biomolecules as cargoes.
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Apr 2023
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I22-Small angle scattering & Diffraction
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Diamond Proposal Number(s):
[27903]
Open Access
Abstract: High strength AA7xxx are attractive for use in the automotive industry, offering significant strength/weight benefits. These alloys are often used in tempers that require long ageing times of several hours. Pre-ageing has been proposed to be effective in suppressing natural ageing, and reducing the total ageing time by integrating the final ageing step into the paint bake cycle. However, the precipitate evolution during the pre-ageing and subsequent paint bake processes remains to be fully understood. In the present work, the pre-ageing process was studied for AA7075 over a wide range of temperatures and times. Small angle X-ray scattering (SAXS) was used as the main technique to investigate the precipitate evolution during the pre-ageing, natural ageing and paint bake, with the support from transmission electron microscopy (TEM) and isothermal calorimetry. For the first time, the results show that 8 h pre-ageing at 80 °C can produce a microstructure consisting of GP zones with an average radius of approximately
0.9 nm, which remains stable up to at least 7 months. After a short paint bake process, 94% of the T6 hardness can be obtained by uniformly distributed precipitates with an average radius of approximately
2.6 nm. The final size and strengthening effect of the precipitates after 20 min baking is found to be insensitive to the heating rate, which has not been reported previously. The present results further suggest this process is robust for industrial application.
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Apr 2023
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I13-2-Diamond Manchester Imaging
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Diamond Proposal Number(s):
[15506]
Open Access
Abstract: Determination of mineral texture and diagenetic features in mudstones is crucial to reveal the history of their pore systems and provides key information to predict their future sealing ability, reactivity and storage capacity for sequestered CO2, hydrogen storage or nuclear waste disposal. To understand the spatial transport and storage of fluids, it is necessary to map the distribution of minerals and fractures in three dimensions (3D). This study proposes a novel, multi-scale three-dimensional (3D) imaging method, i.e., a combination of synchrotron- sourced micro- x-ray tomography and lab- sourced nano-tomography, to investigate the sedimentology and diagenetic features of the Bowland Shale, one of the most volumetrically important mudstone-dominated systems in the UK. Diagenetic minerals have been identified and characterised, including pyrite, calcite, kaolinite, illite, chlorite, dolomite, ankerite and authigenic quartz (micro-sized quartz and quartz overgrowths). Multi-scale 3D images provide detailed information about dolomite-ankerite zonation and carbonate dissolution pores. These features cannot be observed or quantified by conventional 2D methods, and they have not been reported in this subject area before. Using these results, potential reactions during carbon storage and other subsurface storage applications are predicted.
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Apr 2023
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B16-Test Beamline
DIAD-Dual Imaging and Diffraction Beamline
E01-JEM ARM 200CF
E02-JEM ARM 300CF
I08-Scanning X-ray Microscopy beamline (SXM)
I12-JEEP: Joint Engineering, Environmental and Processing
I13-1-Coherence
I13-2-Diamond Manchester Imaging
I14-Hard X-ray Nanoprobe
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Open Access
Abstract: Hard dental tissues possess a complex hierarchical structure that is particularly evident in enamel, the most mineralised substance in the human body. Its complex and interlinked organisation at the Ångstrom (crystal lattice), nano-, micro-, and macro-scales is the result of evolutionary optimisation for mechanical and functional performance: hardness and stiffness, fracture toughness, thermal, and chemical resistance. Understanding the physical–chemical–structural relationships at each scale requires the application of appropriately sensitive and resolving probes. Synchrotron X-ray techniques offer the possibility to progress significantly beyond the capabilities of conventional laboratory instruments, i.e., X-ray diffractometers, and electron and atomic force microscopes. The last few decades have witnessed the accumulation of results obtained from X-ray scattering (diffraction), spectroscopy (including polarisation analysis), and imaging (including ptychography and tomography). The current article presents a multi-disciplinary review of nearly 40 years of discoveries and advancements, primarily pertaining to the study of enamel and its demineralisation (caries), but also linked to the investigations of other mineralised tissues such as dentine, bone, etc. The modelling approaches informed by these observations are also overviewed. The strategic aim of the present review was to identify and evaluate prospective avenues for analysing dental tissues and developing treatments and prophylaxis for improved dental health.
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Apr 2023
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