Magnetite pollution nanoparticles in the human brain Maher, Barbara A.; Ahmed, Imad A. M.; Karloukovski, Vassil ...
Proceedings of the National Academy of Sciences - PNAS,
09/2016, Letnik:
113, Številka:
39
Journal Article
Recenzirano
Odprti dostop
Biologically formed nanoparticles of the strongly magnetic mineral, magnetite, were first detected in the human brain over 20 y ago Kirschvink JL, Kobayashi-Kirschvink A, Woodford BJ (1992) Proc Natl ...Acad Sci USA 89(16):7683–7687. Magnetite can have potentially large impacts on the brain due to its unique combination of redox activity, surface charge, and strongly magnetic behavior. We used magnetic analyses and electron microscopy to identify the abundant presence in the brain of magnetite nanoparticles that are consistent with high-temperature formation, suggesting, therefore, an external, not internal, source. Comprising a separate nanoparticle population from the euhedral particles ascribed to endogenous sources, these brain magnetites are often found with other transition metal nanoparticles, and they display rounded crystal morphologies and fused surface textures, reflecting crystallization upon cooling from an initially heated, iron-bearing source material. Such high-temperature magnetite nanospheres are ubiquitous and abundant in airborne particulate matter pollution. They arise as combustion-derived, iron-rich particles, often associated with other transition metal particles, which condense and/or oxidize upon airborne release. Those magnetite pollutant particles which are <∼200 nm in diameter can enter the brain directly via the olfactory bulb. Their presence proves that externally sourced iron-bearing nanoparticles, rather than their soluble compounds, can be transported directly into the brain, where they may pose hazard to human health.
A
bstract
One of the most striking successes of the lightcone bootstrap has been the perturbative computation of the anomalous dimensions and OPE coefficients of double-twist operators with large ...spin. It is expected that similar results for multiple-twist families can be obtained by extending the lightcone bootstrap to multipoint correlators. However, very little was known about multipoint lightcone blocks until now, in particular for OPE channels of comb topology. Here, we develop a systematic theory of lightcone blocks for arbitrary OPE channels based on the analysis of Casimir and vertex differential equations. Most of the novel technology is developed in the context of five- and six-point functions. Equipped with new expressions for lightcone blocks, we analyze crossing symmetry equations and compute OPE coefficients involving two double-twist operators that were not known before. In particular, for the first time, we are able to resolve a discrete dependence on tensor structures at large spin. The computation of anomalous dimensions for triple-twist families from six-point crossing equations will be addressed in a sequel to this work.
We classified the reddest (r − J > 2.2) stars observed by the NASA Kepler mission into main-sequence dwarf or evolved giant stars and determined the properties of 4216 M dwarfs based on a comparison ...of available photometry with that of nearby calibrator stars, as well as available proper motions and spectra. We revised the properties of candidate transiting planets using the stellar parameters, high-resolution imaging to identify companion stars, and, in the case of binaries, fitting light curves to identify the likely planet host. In 49 of 54 systems, we validated the primary as the host star. We inferred the intrinsic distribution of M dwarf planets using the method of iterative Monte Carlo simulation. We compared several models of planet orbital geometry and clustering and found that one where planets are exponentially distributed and almost precisely coplanar best describes the distribution of multiplanet systems. We determined that Kepler M dwarfs host an average of 2.2 ± 0.3 planets with radii of 1–4 R⊕ and orbital periods of 1.5–180 d. The radius distribution peaks at ∼1.2 R⊕ and is essentially zero at 4 R⊕, although we identify three giant planet candidates other than the previously confirmed Kepler-45b. There is suggestive but not significant evidence that the radius distribution varies with orbital period. The distribution with logarithmic orbital period is flat except for a decline for orbits less than a few days. 12 candidate planets, including two Jupiter-size objects, experience an irradiance below the threshold level for a runaway greenhouse on an Earth-like planet and are thus in a ‘habitable zone’.
Background:
Over the past decade, total ankle arthroplasty (TAA) has become a mainstay in the treatment of end-stage ankle arthritis. Currently in its fourth generation, the Scandanavian Total Ankle ...Replacement (STAR) is the only 3-piece mobile bearing ankle prosthesis available in the United States. Our current study reports implant survivorship at 15 years and patient outcomes for a subset of these survivors available for study.
Methods:
Eighty-four TAAs were performed between 1998 and 2000. Metal component survivorship at 15 years was calculated with a Kaplan-Meier curve. Twenty-four (29%) of 84 patients were available for participation with a minimum 15-year follow-up. Any radiographic changes were documented. All additional procedures and complications were recorded. Clinical findings, self-reported performance and pain evaluations, and AOFAS ankle/hindfoot scores were noted.
Results:
Metal implant survival was 73% at 15 years. Of the 24 patients available for clinical evaluation, 18 of 24 patients (70.7%) had no change in prosthetic alignment from the immediate postoperative radiograph. Only 1 subtalar fusion was required for symptomatic adjacent joint arthritis. Three patients sustained a broken polyethylene component. AOFAS scores improved from an average of 39.6 points preoperatively, to an average of 71.6. More than half (52.4%) of patients with retained implants required an additional surgical procedure; 3 required 2 additional procedures. The average time to subsequent procedure was 10.2 years.
Conclusion:
Our small cohort demonstrated STAR ankles with retention at 9 years were highly likely to survive to 15 years, and patients continued to have significant improvement in pain relief and minimal decrease in function. At 15 years from TAA, metal survivorship was 73%. As with all ankle replacements, supplementary procedures were common.
Level of Evidence:
Level IV, case series.
Liver biopsy is currently the most reliable way of evaluating liver fibrosis in patients with non-alcoholic fatty liver disease (NAFLD). Its inherent risks limit its widespread use. Differential ...liver DNA methylation of peroxisome proliferator-activated receptor gamma (PPARγ) gene promoter has recently been shown to stratify patients in terms of fibrosis severity but requires access to liver tissue. The aim of this study was to assess whether DNA methylation of circulating DNA could be detected in human plasma and potentially used to stratify liver fibrosis severity in patients with NAFLD.
Patients with biopsy-proven NAFLD and age-matched controls were recruited from the liver and gastroenterology clinics at the Newcastle upon Tyne Hospitals NHS Foundation Trust. Plasma cell-free circulating DNA methylation of PPARγ was quantitatively assessed by pyrosequencing. Liver DNA methylation was quantitatively assessed by pyrosequencing NAFLD explant tissue, subjected to laser capture microdissection (LCM). Patients with alcoholic liver disease (ALD) were also subjected to plasma DNA and LCM pyrosequencing.
26 patients with biopsy-proven NAFLD were included. Quantitative plasma DNA methylation of PPARγ stratified patients into mild (Kleiner 1-2) and severe (Kleiner 3-4) fibrosis (CpG1: 63% vs 86%, p<0.05; CpG2: 51% vs 65% p>0.05). Hypermethylation at the PPARγ promoter of plasma DNA correlated with changes in hepatocellular rather than myofibroblast DNA methylation. Similar results were demonstrated in patients with ALD cirrhosis.
Differential DNA methylation at the PPARγ promoter can be detected within the pool of cell-free DNA of human plasma. With further validation, plasma DNA methylation of PPARγ could potentially be used to non-invasively stratify liver fibrosis severity in patients with NAFLD. Plasma DNA methylation signatures reflect the molecular pathology associated with fibrotic liver disease.
The Wnt system is highly complex and is comprised of canonical and non-canonical pathways leading to the activation of gene expression. Our aim was to examine changes in the expression of Wnt ligands ...and regulators during hepatic stellate cell (HSC) transdifferentiation and assess the relative contributions of the canonical and non-canonical Wnt pathways in fibrogenic activated HSC. The expression profile of Wnt ligands and regulators in HSC was not supportive for a major role for β-catenin-dependent canonical Wnt signalling, this verified by inability to induce Topflash reporter activity in HSC even when expressing a constitutive active β-catenin. We detected expression of Wnt5a in activated HSC which can signal via non-canonical mechanisms and showed evidence for non-canonical signalling in these cells involving phosphorylation of Dvl2 and pJNK. Stimulation of HSC or Kupffer cells with Wnt5a regulated HSC apoptosis and expression of TGF-β1 and MCP1 respectively. We were unable to confirm a role for β-catenin-dependent canonical Wnt in HSC and instead propose autocrine and paracrine functions for Wnts expressed by activated HSC via non-canonical pathways. The data warrant detailed investigation of Wnt5a in liver fibrosis.
Intracellular filamentous tau pathology is the defining feature of tauopathies, which form a subset of neurodegenerative diseases. We have analyzed pathological tau in Alzheimer’s disease, and in ...frontotemporal lobar degeneration associated with tauopathy to include cases with Pick bodies, corticobasal degeneration, progressive supranuclear palsy, and ones due to intronic mutations in
MAPT
. We found that the C-terminal band pattern of the pathological tau species is distinct for each disease. Immunoblot analysis of trypsin-resistant tau indicated that the different band patterns of the 7–18 kDa fragments in these diseases likely reflect different conformations of tau molecular species. Protein sequence and mass spectrometric analyses revealed the carboxyl-terminal region (residues 243–406) of tau comprises the protease-resistant core units of the tau aggregates, and the sequence lengths and precise regions involved are different among the diseases. These unique assembled tau cores may be used to classify and diagnose disease strains. Based on these results, we propose a new clinicopathological classification of tauopathies based on the biochemical properties of tau.
Metasurfaces have been enabling the miniaturization and integration of complex optical functionalities within an ultrathin platform by engineering the scattering features of localized modes. However, ...these efforts have mostly been limited to the manipulation of externally produced coherent light, e.g., from a laser. In parallel, the past two decades have seen the development of structured surfaces that emit partially coherent radiation via thermally populated, spatially extended (nonlocal) modes. However, the control over thermally emitted light is severely limited compared to optical metasurfaces, and even basic functionalities such as unidirectional emission to an arbitrary angle and polarization remain elusive. Here, we derive the necessary conditions to achieve full control over thermally emitted light, pointing to the need for simultaneously tailoring local and nonlocal scattering features across the structure. Based on these findings, we introduce a platform for thermal metasurfaces based on quasibound states in the continuum that satisfies these requirements and completes the program of compactification of optical systems by enabling a full degree of control of partially coherent light emission from structured thin films, including unidirectional emission of circularly polarized light, focusing, and control of spatial and temporal coherence, as well as wave-front control with designer spin and angular orbital momenta.
Topological photonic insulators have attracted significant attention for their robust transport of light, impervious to scattering and disorder. This feature is ideally suited for slow light ...applications, which are typically limited by disorder-induced attenuation. However, no practical approach to broadband topologically protected slow light has been demonstrated yet. In this work, we achieve slow light in topologically unidirectional waveguides based on periodically loading an edge termination with suitably tailored resonances. The resulting edge state dispersion can wind around the Brillouin zone multiple times sustaining broadband, topologically robust slow light, opening exciting opportunities in various photonic scenarios.Topological photonic insulators have attracted significant attention for their robust transport of light, impervious to scattering and disorder. This feature is ideally suited for slow light applications, which are typically limited by disorder-induced attenuation. However, no practical approach to broadband topologically protected slow light has been demonstrated yet. In this work, we achieve slow light in topologically unidirectional waveguides based on periodically loading an edge termination with suitably tailored resonances. The resulting edge state dispersion can wind around the Brillouin zone multiple times sustaining broadband, topologically robust slow light, opening exciting opportunities in various photonic scenarios.
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