One of the important challenges in condensed matter science is to understand ultrafast, atomic-scale fluctuations that dictate dynamic processes in equilibrium and non-equilibrium materials. Here, we ...report an important step towards reaching that goal by using a state-of-the-art perfect crystal based split-and-delay system, capable of splitting individual X-ray pulses and introducing femtosecond to nanosecond time delays. We show the results of an ultrafast hard X-ray photon correlation spectroscopy experiment at LCLS where split X-ray pulses were used to measure the dynamics of gold nanoparticles suspended in hexane. We show how reliable speckle contrast values can be extracted even from very low intensity free electron laser (FEL) speckle patterns by applying maximum likelihood fitting, thus demonstrating the potential of a split-and-delay approach for dynamics measurements at FEL sources. This will enable the characterization of equilibrium and, importantly also reversible non-equilibrium processes in atomically disordered materials.
Strongly correlated electron systems often exhibit very strong interactions between structural and electronic degrees of freedom that lead to complex and interesting phase diagrams. For technological ...applications of these materials it is important to learn how to drive transitions from one phase to another. A key question here is the ultimate speed of such phase transitions, and to understand how a phase transition evolves in the time domain. Here we apply time-resolved X-ray diffraction to directly measure the changes in long-range order during ultrafast melting of the charge and orbitally ordered phase in a perovskite manganite. We find that although the actual change in crystal symmetry associated with this transition occurs over different timescales characteristic of the many electronic and vibrational coordinates of the system, the dynamics of the phase transformation can be well described using a single time-dependent 'order parameter' that depends exclusively on the electronic excitation.
Charge density wave (CDW) correlations have been shown to universally exist in cuprate superconductors. However, their nature at high fields inferred from nuclear magnetic resonance is distinct from ...that measured with x-ray scattering at zero and low fields. We combined a pulsed magnet with an x-ray free-electron laser to characterize the CDW in YBa2Cu3O6.67 via x-ray scattering in fields of up to 28 tesla. While the zero-field CDW order, which develops at temperatures below ~150 kelvin, is essentially two dimensional, at lower temperature and beyond 15 tesla, another three-dimensionally ordered CDW emerges. The field-induced CDW appears around the zero-field superconducting transition temperature; in contrast, the incommensurate in-plane ordering vector is field-independent. This implies that the two forms of CDW and high-temperature superconductivity are intimately linked.
Le polyomavirus BK (ou BKPyV) est un virus ubiquitaire infectant de manière asymptomatique 80 % de la population pendant l’enfance. Suite à la primo-infection, il entre en phase de réplication à bas ...bruit dans les epithelia réno-urinaires. Suite à une transplantation, la prise d’un traitement immunosuppresseur diminue les réponses immunitaires et donc le contrôle des infections virales notamment. Dans ce contexte, le BKPyV se comporte en pathogène opportuniste et se réplique activement dans le rein. Cette infection active peut en outre induire le développement d’une néphropathie évolutive, la néphropathie associée aux polyomavirus ou PVAN, caractérisée par une virémie et pouvant conduire au rejet du greffon. La gravité de cette atteinte rénale a été corrélée à l’établissement de cette virémie, dont la cause reste mal connue. Ainsi, le BKPyV est reconnu comme une cause infectieuse majeure de rejet de greffe. Basé sur des propriétés des cellules dendritiques (DC) aujourd’hui bien décrites, telles que la capacité à protéger des virus en surface et à les transmettre à d’autres cellules, et l’observation de DC à proximité immédiate des sites de réactivation du virus dans le rein normal, notre hypothèse est que les DC sont capables de capter le BKPyV et de le transporter avec elles dans l’organisme, favorisant l’établissement de la virémie. Notre groupe a ainsi pu démontrer par cytométrie de flux et par imagerie confocale, que des particules virales infectieuses, mais également des pseudo-particules (VLP), peuvent être capturées spécifiquement par des cellules dendritiques myéloïdes (mDC) in vitro. En outre, nous avons également démontré que la protéine VP1, composant majeur de la capside, était incapable d’activer les mDC. Enfin, nous avons montré que le virus capturé par les mDC peut être transmis à des cellules épithéliales tubulaires rénales très susceptibles à l’infection BKPyV. En conclusion, nous pouvons dire que cette interaction entre des particules infectieuses de BKPyV avec notre modèle de mDC est décrite pour la première fois. Elle doit être confirmée dans d’autres modèles et approfondie. Nous envisageons en collaboration avec les néphrologues nantais d’investiguer le rôle de ces cellules dans les greffons de reins humains après transplantation.
Regulating complement is an important step in the establishment of infection by microbial pathogens.
actively resists complement-mediated killing in non-immune human serum (NHS) by inactivating C3b, ...however the precise molecular basis is unknown. Here, a flow cytometry-based C3b binding assay demonstrated that Type II strains had significantly higher levels of surface-bound C3b than Type I strains. However, both strains efficiently inactivated C3b and were equally resistant to serum killing, suggesting that resistance is not strain-dependent.
activated both the lectin (LP) and alternative (AP) pathways, and the deposition of C3b was both strain and lectin-dependent. A flow cytometry-based lectin binding assay identified strain-specific differences in the level and heterogeneity of surface glycans detected. Specifically, increased lectin-binding by Type II strains correlated with higher levels of the LP recognition receptor mannose binding lectin (MBL). Western blot analyses demonstrated that
recruits both classical pathway (CP) and LP regulator C4b-binding proteins (C4BP) and AP regulator Factor H (FH) to the parasite surface to inactivate bound C3b-iC3b and C3dg and limit formation of the C5b-9 attack complex. Blocking FH and C4BP contributed to increased C5b-9 formation
. However, parasite susceptibility
was only impacted when FH was blocked, indicating that down regulation of the alternative pathway by FH may be more critical for parasite resistance. Infection of C3 deficient mice led to uncontrolled parasite growth, acute mortality, and reduced antibody production, indicating that both the presence of C3, and the ability of the parasite to inactivate C3, was protective. Taken together, our results establish that
regulation of the complement system renders mice resistant to acute infection by limiting parasite proliferation
, but susceptible to chronic infection, with all mice developing transmissible cysts to maintain its life cycle.
Measuring how the magnetic correlations evolve in doped Mott insulators has greatly improved our understanding of the pseudogap, non-Fermi liquids and high-temperature superconductivity. Recently, ...photo-excitation has been used to induce similarly exotic states transiently. However, the lack of available probes of magnetic correlations in the time domain hinders our understanding of these photo-induced states and how they could be controlled. Here, we implement magnetic resonant inelastic X-ray scattering at a free-electron laser to directly determine the magnetic dynamics after photo-doping the Mott insulator Sr2IrO4. We find that the non-equilibrium state, 2 ps after the excitation, exhibits strongly suppressed long-range magnetic order, but hosts photo-carriers that induce strong, non-thermal magnetic correlations. These two-dimensional (2D) in-plane Néel correlations recover within a few picoseconds, whereas the three-dimensional (3D) long-range magnetic order restores on a fluence-dependent timescale of a few hundred picoseconds. The marked difference in these two timescales implies that the dimensionality of magnetic correlations is vital for our understanding of ultrafast magnetic dynamics.
The infection competence of the protozoan pathogen
is critically dependent on the parasite's ability to inactivate the host complement system.
actively resists complement-mediated killing in ...non-immune serum by recruiting host-derived complement regulatory proteins C4BP and Factor H (FH) to the parasite surface to inactivate surface-bound C3 and limit formation of the C5b-9 membrane attack complex (MAC). While decreased complement activation on the parasite surface certainly protects
from immediate lysis, the biological effector functions of C3 split products C3b and C3a are maintained, which includes opsonization of the parasite for phagocytosis and potent immunomodulatory effects that promote pro-inflammatory responses and alters mucosal defenses during infection, respectively. In this review, we discuss how complement regulation by
controls parasite burden systemically but drives exacerbated immune responses locally in the gut of genetically susceptible C57BL/6J mice. In effect,
has evolved to strike a balance with the complement system, by inactivating complement to protect the parasite from immediate serum killing, it generates sufficient C3 catabolites that signal through their cognate receptors to stimulate protective immunity. This regulation ultimately controls tachyzoite proliferation and promotes host survival, parasite persistence, and transmissibility to new hosts.
Heme oxygenases (HOs) catalyze the rate-limiting step in heme degradation, resulting in the formation of iron, carbon monoxide, and biliverdin, the latter of which is subsequently converted to ...bilirubin by biliverdin reductase. Recent attention has focused on the biological effects of product(s) of this enzymatic reaction, which have important antioxidant, anti-inflammatory, and cytoprotective functions. Two major isoforms of the HO enzyme have been described: an inducible isoform, HO-1, and a constitutively expressed isoform, HO-2. A third isoform, HO-3, closely related to HO-2, has also been described. Several stimuli implicated in the pathogenesis of renal injury, such as heme, nitric oxide, growth factors, angiotensin II, cytokines, and nephrotoxins, induce HO-1. Induction of HO-1 occurs as an adaptive and beneficial response to these stimuli, as demonstrated by studies in renal and non-renal disease states. This review will focus on the molecular regulation of the HO-1 gene in renal injury and will highlight the interspecies differences, predominantly between the rodent and human HO-1 genes.
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