I18-Microfocus Spectroscopy
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M.
Bourdenx
,
A.
Nioche
,
S.
Dovero
,
M.-l.
Arotcarena
,
S.
Camus
,
G.
Porras
,
M.-l.
Thiolat
,
N. P.
Rougier
,
A.
Prigent
,
P.
Aubert
,
S.
Bohic
,
C.
Sandt
,
F.
Laferrière
,
E.
Doudnikoff
,
N.
Kruse
,
B.
Mollenhauer
,
S.
Novello
,
M.
Morari
,
T.
Leste-lasserre
,
I. Trigo
Damas
,
M.
Goillandeau
,
C.
Perier
,
C.
Estrada
,
N.
Garcia-carrillo
,
A.
Recasens
,
N. N.
Vaikath
,
O. M. A.
El-agnaf
,
M. T.
Herrero
,
P.
Derkinderen
,
M.
Vila
,
J. A.
Obeso
,
B.
Dehay
,
E.
Bezard
Diamond Proposal Number(s):
[13009]
Open Access
Abstract: Dopaminergic neuronal cell death, associated with intracellular α-synuclein (α-syn)–rich protein aggregates [termed “Lewy bodies” (LBs)], is a well-established characteristic of Parkinson’s disease (PD). Much evidence, accumulated from multiple experimental models, has suggested that α-syn plays a role in PD pathogenesis, not only as a trigger of pathology but also as a mediator of disease progression through pathological spreading. Here, we have used a machine learning–based approach to identify unique signatures of neurodegeneration in monkeys induced by distinct α-syn pathogenic structures derived from patients with PD. Unexpectedly, our results show that, in nonhuman primates, a small amount of singular α-syn aggregates is as toxic as larger amyloid fibrils present in the LBs, thus reinforcing the need for preclinical research in this species. Furthermore, our results provide evidence supporting the true multifactorial nature of PD, as multiple causes can induce a similar outcome regarding dopaminergic neurodegeneration.
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May 2020
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I05-ARPES
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Diamond Proposal Number(s):
[15822]
Open Access
Abstract: Van der Waals materials offer unprecedented control of electronic properties via stacking of different types of two-dimensional materials. A fascinating frontier, largely unexplored, is the stacking of strongly correlated phases of matter. We study 4Hb-TaS2, which naturally realizes an alternating stacking of 1T-TaS2 and 1H-TaS2 structures. The former is a well-known Mott insulator, which has recently been proposed to host a gapless spin-liquid ground state. The latter is a superconductor known to also host a competing charge density wave state. This raises the question of how these two components affect each other when stacked together. We find a superconductor with a Tc of 2.7 Kelvin and anomalous properties, of which the most notable one is a signature of time-reversal symmetry breaking, abruptly appearing at the superconducting transition. This observation is consistent with a chiral superconducting state.
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Mar 2020
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I05-ARPES
I09-Surface and Interface Structural Analysis
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Veronika
Sunko
,
F.
Mazzola
,
S.
Kitamura
,
S.
Khim
,
P.
Kushwaha
,
O. J.
Clark
,
M. D.
Watson
,
I.
Markovic
,
D.
Biswas
,
L.
Pourovskii
,
T. K.
Kim
,
T.-l.
Lee
,
P. K.
Thakur
,
H.
Rosner
,
A.
Georges
,
R.
Moessner
,
T.
Oka
,
A. P.
Mackenzie
,
P. D. C.
King
Diamond Proposal Number(s):
[19479, 17699]
Abstract: A nearly free electron metal and a Mott insulating state can be thought of as opposite ends of the spectrum of possibilities for the motion of electrons in a solid. Understanding their interaction lies at the heart of the correlated electron problem. In the magnetic oxide metal PdCrO2, nearly free and Mott-localized electrons exist in alternating layers, forming natural heterostructures. Using angle-resolved photoemission spectroscopy, quantitatively supported by a strong coupling analysis, we show that the coupling between these layers leads to an “intertwined” excitation that is a convolution of the charge spectrum of the metallic layer and the spin susceptibility of the Mott layer. Our findings establish PdCrO2 as a model system in which to probe Kondo lattice physics and also open new routes to use the a priori nonmagnetic probe of photoemission to gain insights into the spin susceptibility of correlated electron materials.
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Feb 2020
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B22-Multimode InfraRed imaging And Microspectroscopy
I08-Scanning X-ray Microscopy beamline (SXM)
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Diamond Proposal Number(s):
[15050, 14953]
Abstract: Precambrian fossils of fungi are sparse, and the knowledge of their early evolution and the role they played in the colonization of land surface are limited. Here, we report the discovery of fungi fossils in a 810 to 715 million year old dolomitic shale from the Mbuji-Mayi Supergroup, Democratic Republic of Congo. Syngenetically preserved in a transitional, subaerially exposed paleoenvironment, these carbonaceous filaments of ~5 μm in width exhibit low-frequency septation (pseudosepta) and high-angle branching that can form dense interconnected mycelium-like structures. Using an array of microscopic (SEM, TEM, and confocal laser scanning fluorescence microscopy) and spectroscopic techniques (Raman, FTIR, and XANES), we demonstrated the presence of vestigial chitin in these fossil filaments and document the eukaryotic nature of their precursor. Based on those combined evidences, these fossil filaments and mycelium-like structures are identified as remnants of fungal networks and represent the oldest, molecularly identified remains of Fungi.
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Jan 2020
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I03-Macromolecular Crystallography
I24-Microfocus Macromolecular Crystallography
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Tao
Ni
,
Fang
Jiao
,
Xiulian
Yu
,
Saša
Aden
,
Lucy
Ginger
,
Sophie I.
Williams
,
Fangfang
Bai
,
Vojtech
Prazak
,
Dimple
Karia
,
Phillip
Stansfeld
,
Peijun
Zhang
,
George
Munson
,
Gregor
Anderluh
,
Simon
Scheuring
,
Robert J. C.
Gilbert
Abstract: Perforin-2 (MPEG1) is thought to enable the killing of invading microbes engulfed by macrophages and other phagocytes, forming pores in their membranes. Loss of perforin-2 renders individual phagocytes and whole organisms significantly more susceptible to bacterial pathogens. Here, we reveal the mechanism of perforin-2 activation and activity using atomic structures of pre-pore and pore assemblies, high-speed atomic force microscopy, and functional assays. Perforin-2 forms a pre-pore assembly in which its pore-forming domain points in the opposite direction to its membrane-targeting domain. Acidification then triggers pore formation, via a 180° conformational change. This novel and unexpected mechanism prevents premature bactericidal attack and may have played a key role in the evolution of all perforin family proteins.
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Jan 2020
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I04-Macromolecular Crystallography
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Diamond Proposal Number(s):
[14843]
Open Access
Abstract: Adenoviruses are clinically important agents. They cause respiratory distress, gastroenteritis, and epidemic keratoconjunctivitis. As non-enveloped, double-stranded DNA viruses, they are easily manipulated, making them popular vectors for therapeutic applications, including vaccines. Species D adenovirus type 26 (HAdV-D26) is both a cause of EKC and other diseases and a promising vaccine vector. HAdV-D26–derived vaccines are under investigation as protective platforms against HIV, Zika, and respiratory syncytial virus infections and are in phase 3 clinical trials for Ebola. We recently demonstrated that HAdV-D26 does not use CD46 or Desmoglein-2 as entry receptors, while the putative interaction with coxsackie and adenovirus receptor is low affinity and unlikely to represent the primary cell receptor. Here, we establish sialic acid as a primary entry receptor used by HAdV-D26. We demonstrate that removal of cell surface sialic acid inhibits HAdV-D26 infection, and provide a high-resolution crystal structure of HAdV-D26 fiber-knob in complex with sialic acid.
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Sep 2019
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Krios II-Titan Krios II at Diamond
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Diamond Proposal Number(s):
[19832]
Open Access
Abstract: Quinol-dependent nitric oxide reductases (qNORs) are membrane-integrated, iron-containing enzymes of the denitrification pathway, which catalyze the reduction of nitric oxide (NO) to the major ozone destroying gas nitrous oxide (N2O). Cryo–electron microscopy structures of active qNOR from Alcaligenes xylosoxidans and an activity-enhancing mutant have been determined to be at local resolutions of 3.7 and 3.2 Å, respectively. They unexpectedly reveal a dimeric conformation (also confirmed for qNOR from Neisseria meningitidis) and define the active-site configuration, with a clear water channel from the cytoplasm. Structure-based mutagenesis has identified key residues involved in proton transport and substrate delivery to the active site of qNORs. The proton supply direction differs from cytochrome c–dependent NOR (cNOR), where water molecules from the cytoplasm serve as a proton source similar to those from cytochrome c oxidase.
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Aug 2019
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I04-1-Macromolecular Crystallography (fixed wavelength)
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Miranda P.
Collier
,
T. Reid
Alderson
,
Carin P.
De Villiers
,
Daisy
Nicholls
,
Heidi Y.
Gastall
,
Timothy
Allison
,
Matteo T.
Degiacomi
,
He
Jiang
,
Georg
Mlynek
,
Dieter O.
Fürst
,
Peter F. M.
Van Der Ven
,
Kristina
Djinovic-carugo
,
Andrew J.
Baldwin
,
Hugh
Watkins
,
Katja
Gehmlich
,
Justin L. P.
Benesch
Diamond Proposal Number(s):
[12346]
Open Access
Abstract: Mechanical force–induced conformational changes in proteins underpin a variety of physiological functions, typified in muscle contractile machinery. Mutations in the actin-binding protein filamin C (FLNC) are linked to musculoskeletal pathologies characterized by altered biomechanical properties and sometimes aggregates. HspB1, an abundant molecular chaperone, is prevalent in striated muscle where it is phosphorylated in response to cues including mechanical stress. We report the interaction and up-regulation of both proteins in three mouse models of biomechanical stress, with HspB1 being phosphorylated and FLNC being localized to load-bearing sites. We show how phosphorylation leads to increased exposure of the residues surrounding the HspB1 phosphosite, facilitating their binding to a compact multidomain region of FLNC proposed to have mechanosensing functions. Steered unfolding of FLNC reveals that its extension trajectory is modulated by the phosphorylated region of HspB1. This may represent a posttranslationally regulated chaperone-client protection mechanism targeting over-extension during mechanical stress.
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May 2019
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I10-Beamline for Advanced Dichroism
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Diamond Proposal Number(s):
[20748]
Open Access
Abstract: The recently discovered topological phase offers new possibilities for spintronics and condensed matter. Even insulating material exhibits conductivity at the edges of certain systems, giving rise to an anomalous quantum Hall effect and other coherent spin transport phenomena, in which heat dissipation is minimized, with potential uses for next-generation energy-efficient electronics. While the metallic surface states of topological insulators (TIs) have been extensively studied, direct comparison of the surface and bulk magnetic properties of TIs has been little explored. We report unambiguous evidence for distinctly enhanced surface magnetism in a prototype magnetic TI, Cr-doped Bi2Se3. Using synchrotron-based x-ray techniques, we demonstrate a “three-step transition” model, with a temperature window of ~15 K, where the TI surface is magnetically ordered while the bulk is not. Understanding the dual magnetization process has strong implications for defining a physical modelof magnetic TIs and lays the foundation for applications to information technology.
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Feb 2019
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I02-Macromolecular Crystallography
I03-Macromolecular Crystallography
I04-1-Macromolecular Crystallography (fixed wavelength)
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Mark
Elliott
,
Christine
Favre-guilmard
,
Sai Man
Liu
,
Jacquie
Maignel
,
Geoffrey
Masuyer
,
Matthew
Beard
,
Christopher
Boone
,
Denis
Carré
,
Mikhail
Kalinichev
,
Stephane
Lezmi
,
Imran
Mir
,
Camille
Nicoleau
,
Shilpa
Palan
,
Cindy
Perier
,
Elsa
Raban
,
Sicai
Zhang
,
Min
Dong
,
Pal
Stenmark
,
Johannes
Krupp
Diamond Proposal Number(s):
[11265, 15806]
Open Access
Abstract: Although botulinum neurotoxin serotype A (BoNT/A) products are common treatments for various disorders, there is only one commercial BoNT/B product, whose low potency, likely stemming from low affinity toward its human receptor synaptotagmin 2 (hSyt2), has limited its therapeutic usefulness. We express and characterize two full-length recombinant BoNT/B1 proteins containing designed mutations E1191M/S1199Y (rBoNT/B1MY) and E1191Q/S1199W (rBoNT/B1QW) that enhance binding to hSyt2. In preclinical models including human-induced pluripotent stem cell neurons and a humanized transgenic mouse, this increased hSyt2 affinity results in high potency, comparable to that of BoNT/A. Last, we solve the cocrystal structure of rBoNT/B1MY in complex with peptides of hSyt2 and its homolog hSyt1. We demonstrate that neuronal surface receptor binding limits the clinical efficacy of unmodified BoNT/B and that modified BoNT/B proteins have promising clinical potential.
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Jan 2019
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