Merging Top-Down and Bottom-Up Approaches to Fabricate Artificial Photonic Nanomaterials with a Deterministic Electric and Magnetic Response

Artificial photonic nanomaterials made from densely packed scatterers are frequently realized either by top-down or bottom-up techniques. While top-down techniques offer unprecedented control over achievable geometries for the scatterers, by trend they suffer from being limited to planar and periodic structures. In contrast, materials fabricated with bottom-up techniques do not suffer from such disadvantages but, unfortunately, they offer only little control on achievable geometries for the scatterers. To overcome these limitations, a nanofabrication strategy is introduced that merges both approaches. A large number of scatterers are fabricated with a tailored optical response by fast character projection electron-beam lithography and are embedded into a membrane. By peeling-off this membrane from the substrate, scrambling, and densifying it, a bulk material comprising densely packed and randomly arranged scatterers is obtained. The fabrication of an isotropic material from these scatterers with a strong electric and magnetic response is demonstrated. The approach of this study unlocks novel opportunities to fabricate nanomaterials with a complex optical response in the bulk but also on top of arbitrarily shaped surfaces. © 2019 The Authors. Published by WILEY-VCH Verlag GmbH & Co. KGaA, Weinhei

Boron and Lithium in Calcium Sulfate Veins: Tracking Precipitation of Diagenetic Materials in Vera Rubin Ridge, Gale Crater

The NASA Curiosity rover’s ChemCam instrument suite has detected boron in calcium‐sulfate‐filled fractures throughout the sedimentary strata of Gale crater including Vera Rubin ridge (VRR). The presence of elevated B concentration provides insights into Martian subsurface aqueous processes. In this study we extend the dataset of B in Ca‐sulfate veins across Gale crater, comparing the detection frequency and relative abundances with Li. We report 33 new detections of B within veins analyzed between sols 1548 and 2311 where detections increase in Pettegrove Point and Jura members, which form VRR. The presence of B and Li in the Ca‐sulfate veins is possibly due to dissolution of pre‐existing B in clays of the bedrock by acids or neutral water and redistribution of the elements into the veins. Elevated frequency of B detection in veins of Gale crater correlate with presence of dehydration features such as desiccation cracks, altered clay minerals and detections of evaporites such as Mg‐sulfates, chloride salts in the host rocks. The increased observations of B also coincide with decreased Li concentration in the veins (average Li concentration of veins drops by ~15 ppm). Boron and Li have varying solubilities and Li does not form salts as readily upon dehydration as B, causing it to remain in the solution. So, the weak negative correlation between B and Li may reflect the crystallization sequence during dehydration on Vera Rubin ridge

The Comprehensive Native Interactome of a Fully Functional Tagged Prion Protein

The enumeration of the interaction partners of the cellular prion protein, PrPC, may help clarifying its elusive molecular function. Here we added a carboxy proximal myc epitope tag to PrPC. When expressed in transgenic mice, PrPmyc carried a GPI anchor, was targeted to lipid rafts, and was glycosylated similarly to PrPC. PrPmyc antagonized the toxicity of truncated PrP, restored prion infectibility of PrPC-deficient mice, and was physically incorporated into PrPSc aggregates, indicating that it possessed all functional characteristics of genuine PrPC. We then immunopurified myc epitope-containing protein complexes from PrPmyc transgenic mouse brains. Gentle differential elution with epitope-mimetic decapeptides, or a scrambled version thereof, yielded 96 specifically released proteins. Quantitative mass spectrometry with isotope-coded tags identified seven proteins which co-eluted equimolarly with PrPC and may represent component of a multiprotein complex. Selected PrPC interactors were validated using independent methods. Several of these proteins appear to exert functions in axomyelinic maintenance

No relationship between 2',3'-cyclic nucleotide 3'-phosphodiesterase and schizophrenia in the Chinese Han population: an expression study and meta-analysis

<p>Abstract</p> <p>Background</p> <p>2',3'-Cyclic nucleotide 3'-phosphodiesterase (<it>CNP</it>), one of the promising candidate genes for schizophrenia, plays a key part in the oligodendrocyte function and in myelination. The present study aims to investigate the relationship between <it>CNP </it>and schizophrenia in the Chinese population and the effect of different factors on the expression level of <it>CNP </it>in schizophrenia.</p> <p>Methods</p> <p>Five <it>CNP </it>single nucleotide polymorphisms (SNPs) were investigated in a Chinese Han schizophrenia case-control sample set (n = 180) using direct sequencing. The results were included in the following meta-analysis. Quantitative real-time polymerase chain reaction (PCR) was conducted to examine <it>CNP </it>expression levels in peripheral blood lymphocytes.</p> <p>Results</p> <p>Factors including gender, genotype, sub-diagnosis and antipsychotics-treatment were found not to contribute to the expression regulation of the <it>CNP </it>gene in schizophrenia. Our meta-analysis produced similar negative results.</p> <p>Conclusion</p> <p>The results suggest that the <it>CNP </it>gene may not be involved in the etiology and pathology of schizophrenia in the Chinese population.</p

Early B-cell Factor gene association with multiple sclerosis in the Spanish population

BACKGROUND: The etiology of multiple sclerosis (MS) is at present not fully elucidated, although it is considered to result from the interaction of environmental and genetic susceptibility factors. In this work we aimed at testing the Early B-cell Factor (EBF1) gene as a functional and positional candidate risk factor for this neurological disease. Axonal damage is a hallmark for multiple sclerosis clinical disability and EBF plays an evolutionarily conserved role in the expression of proteins essential for axonal pathfinding. Failure of B-cell differentiation was found in EBF-deficient mice and involvement of B-lymphocytes in MS has been suggested from their presence in cerebrospinal fluid and lesions of patients. METHODS: The role of the EBF1 gene in multiple sclerosis susceptibility was analyzed by performing a case-control study with 356 multiple sclerosis patients and 540 ethnically matched controls comparing the EBF1 polymorphism rs1368297 and the microsatellite D5S2038. RESULTS: Significant association of an EBF1-intronic polymorphism (rs1368297, A vs. T: p = 0.02; OR = 1.26 and AA vs. [TA+TT]: p = 0.02; OR = 1.39) was discovered. This association was even stronger after stratification for the well-established risk factor of multiple sclerosis in the Major Histocompatibility Complex, DRB1*1501 (AA vs. [TA+TT]: p = 0.005; OR = 1.78). A trend for association in the case-control study of another EBF1 marker, the allele 5 of the very informative microsatellite D5S2038, was corroborated by Transmission Disequilibrium Test of 53 trios (p = 0.03). CONCLUSION: Our data support EBF1 gene association with MS pathogenesis in the Spanish white population. Two genetic markers within the EBF1 gene have been found associated with this neurological disease, indicative either of their causative role or that of some other polymorphism in linkage disequilibrium with them

Systemic proteasome inhibition triggers neurodegeneration in a transgenic mouse model expressing human α-synuclein under oligodendrocyte promoter: implications for multiple system atrophy

Multiple system atrophy (MSA) is a progressive late onset neurodegenerative α-synucleinopathy with unclear pathogenesis. Recent genetic and pathological studies support a central role of α-synuclein (αSYN) in MSA pathogenesis. Oligodendroglial cytoplasmic inclusions of fibrillar αSYN and dysfunction of the ubiquitin–proteasome system are suggestive of proteolytic stress in this disorder. To address the possible pathogenic role of oligodendroglial αSYN accumulation and proteolytic failure in MSA we applied systemic proteasome inhibition (PSI) in transgenic mice with oligodendroglial human αSYN expression and determined the presence of MSA-like neurodegeneration in this model as compared to wild-type mice. PSI induced open field motor disability in transgenic αSYN mice but not in wild-type mice. The motor phenotype corresponded to progressive and selective neuronal loss in the striatonigral and olivopontocerebellar systems of PSI-treated transgenic αSYN mice. In contrast no neurodegeneration was detected in PSI-treated wild-type controls. PSI treatment of transgenic αSYN mice was associated with significant ultrastructural alterations including accumulation of fibrillar human αSYN in the cytoplasm of oligodendroglia, which resulted in myelin disruption and demyelination characterized by increased g-ratio. The oligodendroglial and myelin pathology was accompanied by axonal degeneration evidenced by signs of mitochondrial stress and dysfunctional axonal transport in the affected neurites. In summary, we provide new evidence supporting a primary role of proteolytic failure and suggesting a neurodegenerative pathomechanism related to disturbed oligodendroglial/myelin trophic support in the pathogenesis of MSA

Targeted Ablation of Oligodendrocytes Triggers Axonal Damage

Glial dysfunction has been implicated in a number of neurodegenerative diseases. In this study we investigated the consequences of glial and oligodendrocyte ablation on neuronal integrity and survival in Drosophila and adult mice, respectively. Targeted genetic ablation of glia was achieved in the adult Drosophila nervous system using the GAL80-GAL4 system. In mice, oligodendrocytes were depleted by the injection of diphtheria toxin in MOGi-Cre/iDTR double transgenic animals. Acute depletion of oligodendrocytes induced axonal injury, but did not cause neuronal cell death in mice. Ablation of glia in adult flies triggered neuronal apoptosis and resulted in a marked reduction in motor performance and lifespan. Our study shows that the targeted depletion of glia triggers secondary neurotoxicity and underscores the central contribution of glia to neuronal homeostasis. The models used in this study provide valuable systems for the investigation of therapeutic strategies to prevent axonal or neuronal damage