Short-Range Order in VI3.

We present a detailed investigation of the crystal structure of VI3, a two-dimensional van der Waals material of interest for studies of low-dimensional magnetism. As opposed to the average crystal structure that features R3̅ symmetry of the unit cell, our Raman scattering and X-ray atomic pair distribution function analysis supported by density functional theory calculations point to the coexistence of short-range ordered P3̅1c and long-range ordered R3̅ phases. The highest-intensity peak, A1g3, exhibits a moderate asymmetry that might be traced back to the spin-phonon interactions, as in the case of CrI3.

Hybrid Structures for Surface-Enhanced Raman Scattering: DNA Origami/Gold Nanoparticle Dimer/Graphene.

A combination of three innovative materials within one hybrid structure to explore the synergistic interaction of their individual properties is presented. The unique electronic, mechanical, and thermal properties of graphene are combined with the plasmonic properties of gold nanoparticle (AuNP) dimers, which are assembled using DNA origami nanostructures. This novel hybrid structure is characterized by means of correlated atomic force microscopy and surface-enhanced Raman scattering (SERS). It is demonstrated that strong interactions between graphene and AuNPs result in superior SERS performance of the hybrid structure compared to their individual components. This is particularly evident in efficient fluorescence quenching, reduced background, and a decrease of the photobleaching rate up to one order of magnitude. The versatility of DNA origami structures to serve as interface for complex and precise arrangements of nanoparticles and other functional entities provides the basis to further exploit the potential of the here presented DNA origami-AuNP dimer-graphene hybrid structures.

Linking increased airway hydration, ciliary beating, and mucociliary clearance through ENaC inhibition.

Airway dehydration causes mucus stasis and bacterial overgrowth in cystic fibrosis and chronic bronchitis (CB). Rehydration by hypertonic saline is efficacious but suffers from a short duration of action. We tested whether epithelial sodium channel (ENaC) inhibition would rehydrate normal and dehydrated airways to increase mucociliary clearance (MCC) over a significant time frame. For this, we used a tool compound (Compound A), which displays nanomolar ENaC affinity and retention in the airway surface liquid (ASL). Using normal human bronchial epithelial cultures (HBECs) grown at an air-liquid interface, we evaluated in vitro potency and efficacy using short-circuit current (I(sc)) and ASL height measurements where it inhibited I(sc) and increased ASL height by ∼ 50% (0.052 µM at 6 h), respectively. The in vivo efficacy was investigated in a modified guinea pig tracheal potential difference model, where we observed an effective dose (ED50) of 5 µg/kg (i.t.), and by MCC measures in rats and sheep, where we demonstrated max clearance rates at 100 µg/kg (i.t.) and 75 µg/kg (i.t.), respectively. Acute cigarette smoke-induced ASL height depletion in HBECs was used to mimic the situation in patients with CB, and pretreatment prevented both cigarette smoke-induced ASL dehydration and lessened the decrease in ciliary beat frequency. Furthermore, when added after cigarette smoke exposure, Compound A increased the rate of ASL rehydration. In conclusion, Compound A demonstrated significant effects and a link between increased airway hydration, ciliary function, and MCC. These data support the hypothesis that ENaC inhibition may be efficacious in the restoration of mucus hydration and transport in patients with CB.

A texture analysis approach to quantify ventilation changes in hyperpolarised ³He MRI of the rat lung in an asthma model.

In preclinical research, allergic asthma is investigated in rats sensitised with the antigen ovalbumin (OVA), followed by a challenge with aerosolised OVA to induce an inflammatory reaction of the lower airways. This causes diffuse, nonfocal ventilation defects that lead to heterogeneously distributed signal intensities in hyperpolarised (HP) (3)He MR images, which are difficult to assess directly by diagnostic grading or volumetry. Texture analysis can characterise these changes and does not require segmentation of the lung structures prior to the analysis. The aim of this work was to evaluate a texture analysis approach to quantify changes in lung ventilation in HP (3)He MRI of OVA-challenged rats. OVA-challenged animals were treated with two different compound doses to evaluate the sensitivity of the texture analysis. Four groups were investigated using HP (3)He MRI at 4.7 T: controls, vehicle-treated, and low- and high-dose budesonide-treated rats. In addition, broncho-alveolar lavage was performed and the eosinophil cell count was used as a biological reference marker. First-order texture, geometrical features and features based on second-order statistics using run-length and grey-level co-occurrence matrices were calculated. In addition, wavelet transforms were applied to compute first-order statistics on multiple scales. The texture analysis was able to show significant differences between the control and untreated vehicle groups as well as between the vehicle and treatment groups. This is in agreement with the findings of the eosinophil cell counts, which were used as a marker for the severity of inflammation. However, not all features used in the different texture analysis methods could differentiate between the treatment groups. In conclusion, texture analysis can be used to quantify changes in lung ventilation as measured with HP (3)He MRI after therapeutic intervention with budesonide.

Peculiar symmetry-protected electronic dispersions in two-dimensional materials.

Symmetry indicates that low energy spectra of materials could be richer than well-known Dirac, semi-Dirac, or quadratic, hosting some unusual quasiparticles. Performing the systematic study of exact forms of low energy effective Hamiltonians and dispersions in high-symmetry points with fourfold degeneracy of bands, we found new, previously unreported dispersion, which we named poppy flower after its shape. This massless fermion exists in non-magnetic two-dimensional (2D) crystals with spin-orbit coupling, which are invariant under one of the proposed ten noncentrosymmetric layer groups. We suggest real 3D layered materials suitable for exfoliation, having layers that belong to these symmetry groups as candidates for realization of poppy flower fermions. In 2D systems without spin-orbit interaction, fortune teller-like fermions were theoretically predicted, and afterward experimentally verified in the electronic structure of surface layer of silicon. Herein, we show that such fermions can also be hosted in 2D crystals with spin-orbit coupling, invariant under additional two noncentrosymmetric layer groups. This prediction is confirmed by density functional based calculation: layered BiIO4, which has been synthesized already as a 3D crystal, exfoliates to stable monolayer with symmetry pb2_1a, and fortune teller fermion is observed in the band structure. Analytically calculated density of states of the poppy flower shows semimetallic characteristic, in contrast to metallic nature of fortune teller having non-zero density of states at the bands contact energy. We indicate possibilities for symmetry breaking patterns which correspond to the robustness of the proposed dispersions as well as to the transition from Dirac centrosymmetric semimetal to poppy flower.

p38 MAPK signalling regulates cytokine production in IL-33 stimulated Type 2 Innate Lymphoid cells.

Type 2 Innate lymphoid cells (ILC2s) are implicated in helminth infections and asthma where they play a role in the production of Th2-type cytokines. ILC2s express the IL-33 receptor and are a major cell type thought to mediate the effects of this cytokine in vivo. To study the signalling pathways that mediate IL-33 induced cytokine production, a culture system was set up to obtain pure populations of ILC2s from mice. Inhibitors of the p38α/ß and ERK1/2 MAPK pathways reduced the production of IL-5, IL-6, IL-9, IL-13 and GM-CSF by ILC2 in response to IL-33, with inhibition of p38 having the greatest effect. MK2 and 3 are kinases activated by p38α; MK2/3 inhibitors or knockout of MK2/3 in mice reduced the production of IL-6 and IL-13 (two cytokines implicated in asthma) but not IL-5, IL-9 or GM-CSF in response to IL-33. MK2/3 inhibition also suppressed IL-6 and IL-13 production by human ILC2s. MK2/3 were required for maximal S6 phosphorylation, suggesting an input from the p38α-MK2/3 pathway to mTOR1 activation in ILC2s. The mTORC1 inhibitor rapamycin also reduced IL-6 and IL-13 production, which would be consistent with a model in which MK2/3 regulate IL-6 and IL-13 via mTORC1 activation in ILC2s.

Enriched environment attenuates cell genesis in subventricular zone after focal ischemia in mice and decreases migration of newborn cells to the striatum.

BACKGROUND AND PURPOSE: Cells proliferate continuously in the adult mammalian brain, and in rodents, cell genesis is affected by housing conditions and brain injury. Increase in neurogenesis after brain ischemia has been postulated to be linked to functional recovery after stroke. Housing rodents in an enriched environment improves motor function after stroke injury. We have investigated whether changes in cell genesis can explain the beneficial effects of an enriched environment. METHODS: Intact mice and mice subjected to transient occlusion of the middle cerebral artery were exposed to an enriched environment for 1 month. Bromodeoxyuridine was injected daily to label proliferating cells during the first postischemic week. Newborn cells were analyzed immunohistochemically after 4 weeks. RESULTS: The enriched environment increased neurogenesis in the dentate gyrus in both intact and stroke-injured animals. An increased number of newborn cells was found in the subventricular zone of stroke-injured mice, but not in injured mice exposed to an enriched environment. Also, the number of newborn astrocytes (BrdU+/S-100beta+ cells), neuroblasts (dcx+ cells), and reactive astrocytes (vimentin mRNA) in the striatum ipsilateral to the ischemic injury was markedly attenuated and new adult neurons (BrdU+/NeuN+) were not found. The enriched environment did not affect infarct size or mortality. CONCLUSIONS: An enriched environment after experimental stroke increased neurogenesis in the hippocampus, whereas there was a decreased cell genesis and migration of neuroblasts and newborn astrocytes in the striatum.

Structural responses of quasi-two-dimensional colloidal fluids to excitations elicited by nonequilibrium perturbations.

We investigate the response of a dense monodisperse quasi-two-dimensional colloid suspension when a particle is dragged by a constant velocity optical trap. Consistent with microrheological studies of other geometries, the perturbation induces a leading density wave and trailing wake. We also use a hybrid version of Stokesian dynamics simulations to parse direct colloid-colloid and hydrodynamic interactions. We go on to analyze the underlying individual particle-particle collisions in the experimental images. The displacements of particles occur in chains reminiscent of stress propagation in sheared granular materials. From these data, we can reconstruct steady-state dipolar-like flow patterns that were predicted for dilute suspensions and previously observed in granular analogs to our system. The decay of this field differs, however, from point Stokeslet calculations, indicating that the nonzero size of the colloids is important. Moreover, there is a pronounced angular dependence that corresponds to the surrounding colloid structure, which develops in response to the perturbation. Put together, our results show that the response of the complex fluid is highly anisotropic owing to the fact that the effects of the perturbation propagate through the structured medium via chains of colloid-colloid collisions.

Absence of striatal newborn neurons with mature phenotype following defined striatal and cortical excitotoxic brain injuries.

Experimental stroke and excitotoxic brain lesion to the striatum increase the proliferation of cells residing within the ventricular wall and cause subsequent migration of newborn neuroblasts into the lesioned brain parenchyma. In this study, we clarify the different events of neurogenesis following striatal or cortical excitotoxic brain lesions in adult rats. Newborn cells were labeled by intraperitoneal injection of bromo-deoxy-uridine (BrdU), or by green fluorescent protein (GFP)-expressing lentiviral vectors injected into the subventricular zone (SVZ). We show that only neural progenitors born the first 5 days in the SVZ reside and expand within this neurogenic niche over time, and that these early labeled cells are more prone to migrate towards the striatum as neuroblasts. However, these neuroblasts could not mature into NeuN+ neurons in the striatum. Furthermore, we found that cortical lesions, close or distant from the SVZ, could not upregulate SVZ cell proliferation nor promote neurogenesis. Our study demonstrates that both the time window for labeling proliferating cells and the site of lesion are crucial when assessing neurogenesis following brain injury.

A large collapsed-state RNA can exhibit simple exponential single-molecule dynamics.

The process of large RNA folding is believed to proceed from many collapsed structures to a unique functional structure requiring precise organization of nucleotides. The diversity of possible structures and stabilities of large RNAs could result in non-exponential folding kinetics (e.g. stretched exponential) under conditions where the molecules have not achieved their native state. We describe a single-molecule fluorescence resonance energy transfer (FRET) study of the collapsed-state region of the free energy landscape of the catalytic domain of RNase P RNA from Bacillus stearothermophilus (C(thermo)). Ensemble measurements have shown that this 260 residue RNA folds cooperatively to its native state at >or=1 mM Mg(2+), but little is known about the conformational dynamics at lower ionic strength. Our measurements of equilibrium conformational fluctuations reveal simple exponential kinetics that reflect a small number of discrete states instead of the expected inhomogeneous dynamics. The distribution of discrete dwell times, collected from an "ensemble" of 300 single molecules at each of a series of Mg(2+) concentrations, fit well to a double exponential, which indicates that the RNA conformational changes can be described as a four-state system. This finding is somewhat unexpected under [Mg(2+)] conditions in which this RNA does not achieve its native state. Observation of discrete well-defined conformations in this large RNA that are stable on the seconds timescale at low [Mg(2+)] (<0.1 mM) suggests that even at low ionic strength, with a tremendous number of possible (weak) interactions, a few critical interactions may produce deep energy wells that allow for rapid averaging of motions within each well, and yield kinetics that are relatively simple.