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Yu, Lei

Publications and source records attributed to Yu, Lei.

70 records · Page 4
All sourcesNASA NTRSDOE OSTI
DOE OSTI2019

cindr, the Drosophila Homolog of the CD2AP Alzheimer's Disease Risk Gene, Is Required for Synaptic Transmission and Proteostasis

The Alzheimer’s disease (AD) susceptibility gene, CD2-associated protein (CD2AP), encodes an actin binding adaptor protein, but its function in the nervous system is largely unknown. Loss of the Drosophila ortholog cindr enhances neurotoxicity of human Tau, which forms neurofibrillary tangle pathology in AD. We show that Cindr is expressed in neurons and present at synaptic terminals. cindr mutants show impairments in synapse maturation and both synaptic vesicle recycling and release. Cindr associates and genetically interacts with 14-3-3?, regulates the ubiquitin-proteasome system, and affects turnover of Synapsin and the plasma membrane calcium ATPase (PMCA). Loss of cindr elevates PMCA levels and reduces cytosolic calcium. Studies of Cd2ap null mice support a conserved role in synaptic proteostasis, and CD2AP protein levels are inversely related to Synapsin abundance in human postmortem brains. Our results reveal CD2AP neuronal requirements with relevance to AD susceptibility, including for proteostasis, calcium handling, and synaptic structure and function.

Alzheimer's disease, risk gene, cindr, Drosophila,↗
DOE OSTI2019

Cognition may link cortical IGFBP5 levels with motor function in older adults

Alzheimer’s disease and related disorders (ADRD) may manifest cognitive and non-cognitive phenotypes including motor impairment, suggesting a shared underlying biology. We tested the hypothesis that five cortical proteins identified from a gene network that drives AD and cognitive phenotypes are also related to motor function in the same individuals. We examined 1208 brains of older adults with motor and cognitive assessments prior to death. Cortical proteins were quantified with SRM proteomics and we collected indices of AD and other related pathologies. A higher level of IGFBP5 was associated with poorer motor function proximate to death but AK4, HSPB2, ITPK1 and PLXNB1 were unrelated to motor function. The association of IGFBP5 with motor function was unrelated to the presence of indices of brain pathologies. In contrast, the addition of a term for cognition attenuated the association of IGFBP5 with motor function by about 90% and they were no longer related. These data lend support for the idea that unidentified cortical proteins like IGFBP5, which may not manifest a known pathologic footprint, may contribute to motor and cognitive function in older adults.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2019

Microstructural changes in the brain mediate the association of AK4, IGFBP5, HSPB2, and ITPK1 with cognitive decline

The associations of 4 proteins-AK4, ITPK1, HSPB2, and IGFBP5-with cognitive function in older adults were largely unexplained by known brain pathologies. We examined the extent to which individual protein associations with cognitive decline were attributable to microstructural changes in the brain. This study included 521 participants (mean age 90.3, 65.9-108.3) with the postmortem reciprocal of transverse relaxation time (R 2 ) magnetic resonance image. All participants came from one of the 2 ongoing longitudinal cohorts of aging and dementia, the Religious Orders Study and Rush Memory and Aging Project. Higher abundance of AK4, HSPB2, and IGFBP5 was associated with faster cognitive decline and mediated through lower postmortem R 2 in the frontal and temporal white matter regions. In contrast, higher abundance of ITPK1 was associated with slower cognitive decline and mediated through higher postmortem R 2 in the frontal and temporal white matter regions. Lastly, the associations of 4 proteins-AK4, ITPK1, IGFBP5, and HSPB2-with cognition in late life were explained via microstructural changes in the brain.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2019

Association of Cortical ß-Amyloid Protein in the Absence of Insoluble Deposits With Alzheimer Disease.

IMPORTANCE: ß-Amyloid deposits are a pathologic hallmark of Alzheimer disease (AD). However, the extent to which cortical ß-amyloid protein in the absence of insoluble deposits is associated with classic features of AD appear to be unknown. OBJECTIVE: To examine the associations of cortical ß-amyloid protein in the absence of insoluble deposits with cognitive decline, neurofibrillary tangles, other age-associated neuropathologic conditions, and APOE. DESIGN, SETTING, AND PARTICIPANTS: This analysis combines data from 2 community-based clinicopathologic cohort studies of aging. The Religious Orders Study started in 1994, and the Rush Memory and Aging Project started in 1997. Both studies are ongoing. Participants without known dementia were enrolled and agreed to annual clinical evaluations and brain donation after death. Primary analyses focused on individuals without ß-amyloid deposits. Data analyses occurred in mid-September 2018. MAIN OUTCOMES AND MEASURES: ß-Amyloid protein abundance was measured by targeted proteomics using selected reaction monitoring. ß-Amyloid deposits were detected using immunohistochemistry. Other neuropathologic indices were quantified via uniform structured evaluation. Linear mixed models were used to examine the association of ß-amyloid protein with cognitive decline. Regression models examined the protein associations with neuropathologic outcomes and the APOE genotype. RESULTS: By mid-September 2018, 3575 older persons were enrolled, and 1559 had died and undergone brain autopsy. Proteomic data were collected in 1208 individuals, and 5 with missing cognitive scores were excluded. Of the remaining 1203, primary analyses focused on 148 individuals (12.3%) without ß-amyloid deposits. In this group, the mean (SD) age at death was 87.0 (7.0) years, and 84 individuals (56.8%) were women. In the absence of ß-amyloid deposits, we did not observe an association of ß-amyloid protein with decline in episodic memory, but the protein was associated with faster rates of decline in processing speed (mean [SE] change, -0.014 [0.005]; P?=?.008) and visuospatial abilities (mean [SE] change, -0.013 [0.005]; P?=?.006). We did not observe protein association with paired helical filament tau tangle density. The protein was associated with amyloid angiopathy (odds ratio, 1.38 [95% CI, 1.15-1.67]; P?<?.001) but no other brain pathology. The associations with cognitive decline were unchanged after controlling for amyloid angiopathy. Neither APOE e4 nor a polygenic Alzheimer risk score was associated with ß-amyloid protein. CONCLUSIONS AND RELEVANCE: Cortical ß-amyloid protein was associated with faster cognitive decline in the absence of ß-amyloid deposits, which supports the role of cortical soluble ß-amyloid as a neurotoxic agent in aging. The lack of protein association with paired helical filament tau tangles, episodic memory decline, or strong genetic drivers of deposited ß-amyloid suggests an underlying neuropathologic change that may differ from that of AD.

Alzheimer’s disease, Insoluble deposits↗
DOE OSTI2019

Dynamic deformability of individual PbSe nanocrystals during superlattice phase transitions

The behavior of individual nanocrystals during superlattice phase transitions can profoundly affect the structural perfection and electronic properties of the resulting superlattices. However, details of nanocrystal morphological changes during superlattice phase transitions are largely unknown due to the lack of direct observation. Here, we report the dynamic deformability of PbSe semiconductor nanocrystals during superlattice phase transitions that are driven by ligand displacement. Real-time high-resolution imaging with liquid-phase transmission electron microscopy reveals that following ligand removal, the individual PbSe nanocrystals experience drastic directional shape deformation when the spacing between nanocrystals reaches 2 to 4 nm. The deformation can be completely recovered when two nanocrystals move apart or it can be retained when they attach. The large deformation, which is responsible for the structural defects in the epitaxially fused nanocrystal superlattice, may arise from internanocrystal dipole–dipole interactions.

36 MATERIALS SCIENCE↗
DOE OSTI2019

Brain IGFBP-5 modifies the relation of depressive symptoms to decline in cognition in older persons.

BACKGROUND: Brain proteins, including Insulin-like Growth Factor Binding Protein 5 (IGFBP-5), have been associated with cognitive dysfunction in aging. Mechanisms linking depression with cognition are poorly understood. We hypothesize that the association of depressive symptoms with cognition is mediated or modified by brain proteins. METHODS: IGFBP-5, HSPB2, AK4, ITPK1 and PLXNB1 were measured in dorsolateral prefrontal cortex in 1057 deceased participants, who underwent annual assessments of depressive symptoms and cognition for a mean of 8.9 years. The average number of depressive symptoms per year before a dementia diagnosis was calculated for each person. RESULTS: A one standard deviation above the mean IGFBP-5 was associated with a 14% higher odds of having more depressive symptoms (p < 0.031). Higher IGFBP-5 was associated with faster decline in global cognition (p < 0.001) and five cognitive domains (p < 0.008), controlling for depressive symptoms. IGFBP-5 moderated the association of depressive symptoms with decline in global cognition (p?=?0.045). IGFBP-5 mediated ten percent or less of the total effect of depressive symptoms on decline in global cognition and the cognitive domains (p > 0.070). LIMITATIONS: Participants were volunteers and self-selection bias limits the generalizability of our findings. In addition, we used self-reported data on depressive symptoms. However, we also used data on depression medications as sensitivity analyses to confirm findings. CONCLUSIONS: In old age, brain IGFBP-5 is associated with depressive symptoms and cognition. The association of depressive symptoms with cognitive decline is conditional on IGFBP-5

depression, dementia, cognition, IGFBP-5, Protien↗
DOE OSTI2018

Shell-Induced Ostwald Ripening: Simultaneous Structure, Composition, and Morphology Transformations during the Creation of Hollow Iron Oxide Nanocapsules

The creation of nanomaterials requires simultaneous control of not only crystalline structure and composition but also crystal shape and size, or morphology, which can pose a significant synthetic challenge. Approaches to address this challenge include creating nanocrystals whose morphologies echo their underlying crystal structures, such as the growth of platelets of two-dimensional layered crystal structures, or conversely attempting to decouple the morphology from structure by converting a structure or composition after first creating crystals with a desired morphology. A particularly elegant example of this latter approach involves the topotactic conversion of a nanoparticle from one structure and composition to another, since the orientation relationship between the initial and final product allows the crystallinity and orientation to be maintained throughout the process. Here we report a mechanism for creating hollow nanostructures, illustrated via the decomposition of β-FeOOH nanorods to nanocapsules of α-Fe 2 O 3 , γ-Fe 2 O 3 , Fe 3 O 4 , and FeO, depending on the reaction conditions, while retaining single-crystallinity and the outer nanorod morphology. Using in situ TEM, we demonstrate that the nanostructured morphology of the starting material allows kinetic trapping of metastable phases with a topotactic relationship to the final thermodynamically stable phase.

36 MATERIALS SCIENCE↗
DOE OSTI2018

Targeted brain proteomics uncover multiple pathways to Alzheimer's dementia

Objective Previous gene expression analysis identified a network of coexpressed genes that is associated with β‐amyloid neuropathology and cognitive decline in older adults. The current work targeted influential genes in this network with quantitative proteomics to identify potential novel therapeutic targets. Methods Data came from 834 community‐based older persons who were followed annually, died, and underwent brain autopsy. Uniform structured postmortem evaluations assessed the burden of β‐amyloid and other common age‐related neuropathologies. Selected reaction monitoring quantified cortical protein abundance of 12 genes prioritized from a molecular network of aging human brain that is implicated in Alzheimer's dementia. Regression and linear mixed models examined the protein associations with β‐amyloid load and other neuropathological indices as well as cognitive decline over multiple years preceding death. Results Average age at death was 88.6 years. Overall, 349 participants (41.9%) had Alzheimer's dementia at death. A higher level of PLXNB1 abundance was associated with more β‐amyloid load ( p = 1.0 × 10 −7 ) and higher PHFtau tangle density ( p = 2.3 × 10 −7 ), and the association of PLXNB1 with cognitive decline is mediated by these known Alzheimer's disease pathologies. On the other hand, higher IGFBP5, HSPB2, and AK4 and lower ITPK1 levels were associated with faster cognitive decline, and, unlike PLXNB1, these associations were not fully explained by common neuropathological indices, suggesting novel mechanisms leading to cognitive decline. Interpretation Using targeted proteomics, this work identified cortical proteins involved in Alzheimer's dementia and begins to dissect two different molecular pathways: one affecting β‐amyloid deposition and another affecting resilience without a known pathological footprint. Ann Neurol 2018;83:78–88

Yu, Lei↗
DOE OSTI2017

Quantitative Analysis of the Morphology of {101} and {001} Faceted Anatase TiO 2 Nanocrystals and Its Implication on Photocatalytic Activity

The atomistic structure and morphology (shape and size) of nanomaterials have strong influences on their physical and chemical properties. However, many characterization techniques focus exclusively on one length-scale regime or another when developing quantitative morphology/structural models. In this article, we demonstrate that powder X-ray diffraction and neutron pair distribution function (PDF) can be used to obtain accurate average morphology and atomistic structure of {001} and {101} faceted anatase TiO 2 nanocrystals based on differential evolution refinements using Debye scattering equation calculations. It is also demonstrated that the morphology polydispersity of TiO 2 nanocrystals can be effectively obtained from the diffraction data via a numerical refinement routine. The morphology refinement results are in good agreement with those from transmission electron microscopy and the modeling of small angle neutron scattering data. This method is successfully used to quantify the facet-specified photocatalytic hydrogen evolution activity of anatase TiO 2 nanocrystals with different {001} to {101} ratios. It is found that the sample with an intermediate amount of both {001} and {101} facets shows the best photocatalytic hydrogen evolution reaction (HER) activity. It is expected that the simultaneous structure and morphology refinement technique can be generally used to study the relationship between morphology and functionality of nanomaterials.

36 MATERIALS SCIENCE↗
DOE OSTI2016

Simple synthetic route to manganese-containing nanowires with the spinel crystal structure

This report describes a new route to synthesize single-crystalline manganese-containing spinel nanowires (NWs) by a two-step hydrothermal and solid-state synthesis. Interestingly, a nanowire or nanorod morphology is maintained during conversion from MnO{sub 2}/MnOOH to CuMn{sub 2}O{sub 4}/Mg{sub 2}MnO{sub 4}, despite the massive structural rearrangement this must involve. Linear sweep voltammetry (LSV) curves of the products give preliminary demonstration that CuMn{sub 2}O{sub 4} NWs are catalytically active towards the oxygen evolution reaction (OER) in alkaline solution, exhibiting five times the magnitude of current density found with pure carbon black. - Highlights: • Synthesis of single-crystalline manganese-containing spinel nanowires. • Binary oxide nanowire converted to ternary oxide wire through solid state reaction. • Approach to structure conversion with shape retention could be generally applicable. • Copper and Manganese display multiple oxidation states with potential for catalysis. • CuMn{sub 2}O{sub 4} nanowires show promise as catalysts for the oxygen evolution reaction.

37 INORGANIC, ORGANIC, PHYSICAL, AND ANALYTICAL CH↗
DOE OSTI2015

Conformational diversity of flexible ligand in metal-organic frameworks controlled by size-matching mixed ligands

Hydrothermal reactions of N-auxiliary flexible exo-bidentate ligand 1,3-bis(4-pyridyl)propane (bpp) and carboxylates ligands naphthalene-2,6-dicarboxylic acid (2,6-H{sub 2}ndc) or 4,4′-(hydroxymethylene)dibenzoic acid (H{sub 2}hmdb), in the presence of cadmium(II) salts have given rise to two novel metal-organic frameworks based on flexible ligands (FL-MOFs), namely, [Cd{sub 2}(2,6-ndc){sub 2}(bpp)(DMF)]·2DMF (1) and [Cd{sub 3}(hmdb){sub 3}(bpp)]·2DMF·2EtOH (2) (DMF=N,N-Dimethylformamide). Single-crystal X-ray diffraction analyses revealed that compound 1 exhibits a three-dimensional self-penetrating 6-connected framework based on dinuclear cluster second building unit. Compound 2 displays an infinite three-dimensional ‘Lucky Clover’ shape (2,10)-connected network based on the trinuclear cluster and V-shaped organic linkers. The flexible bpp ligand displays different conformations in 1 and 2, which are successfully controlled by size-matching mixed ligands during the self-assembly process. - Graphical abstract: Compound 1 exhibits a 3D self-penetrating 6-connected framework based on dinuclear cluster, and 2 displays an infinite 3D ‘Lucky Clover’ shape (2,10)-connected network based on the trinuclear cluster. The flexible 1,3-bis(4-pyridyl)propane ligand displays different conformations in 1 and 2, which successfully controlled by size-matching mixed ligands during the self-assembly process.

37 INORGANIC, ORGANIC, PHYSICAL, AND ANALYTICAL CH↗
DOE OSTI2015

Nanoporous Delafossite CuAlO 2 from Inorganic/Polymer Double Gels: A Desirable High-Surface-Area p-Type Transparent Electrode Material

Nanoporous structures of a p-type semiconductor, delafossite CuAlO2, with a high crystallinity have been fabricated through an inorganic/polymer double-gel process and characterized for the first time via Mott–Schottky measurements. The effect of the precursor concentration, calcination temperature, and atmosphere were examined to achieve high crystallinity and photoelectrochemical properties while maximizing the porosity. The optical properties of the nanoporous CuAlO2 are in good agreement with the literature with an optical band gap of 3.9 eV, and the observed high electrical conductivity and hole concentrations conform to highly crystalline and well-sintered nanoparticles observed in the product. The Mott–Schottky plot from the electrochemical impedance spectroscopy studies indicates a flat-band potential of 0.49 V versus Ag/AgCl. It is concluded that CuAlO2 exhibits band energies very close to those of NiO but with electrical properties very desirable in the fabrication of photoelectrochemical devices including dye-sensitized solar cells.

36 MATERIALS SCIENCE↗
DOE OSTI2015

Effect of reducing system on capacitive behavior of reduced graphene oxide film: Application for supercapacitor

To determine the best chemical reduction of graphene oxide film with hydriodic acid that gives maximum energy and power density, we studied the effect of two reducing systems, hydriodic acid/water and hydriodic acid/acetic acid, on the morphology and electrochemical features of reduced graphene oxide film. Using acetic acid as solvent results in high electrical conductivity (5195 S m{sup −1}), excellent specific capacitance (384 F g{sup −1}) and good cyclic stability (about 98% of its initial response after 4000 cycles). Using water as a solvent, results in an ideal capacitive behavior and excellent cyclic stability (about 6% increase of its initial response after 2100 cycles). - Graphical abstract: The choice of reducing system determines the morphology and structure of the chemically reduced graphene film and, as a result, affects largely the capacitive behavior. - Highlights: • The structure of the graphene film has a pronounced effect on capacitive behavior. • The use of water/HI as reducing system results in an ideal capacitive behavior. • The use of acetic acid/HI as reducing system results in a high specific capacitance.

37 INORGANIC, ORGANIC, PHYSICAL, AND ANALYTICAL CH↗
DOE OSTI2014

A simple template-based transfer method to fabricate Bradbury–Nielsen gates with uniform tension for ion mobility spectrometry

A Bradbury–Nielsen gate (BNG) consists of two interleaved and electrically isolated sets of wires. It is usually used to gate or modulate ion beams. Uniformly tense wires can remain parallel, equidistant, and coplanar over a wide working temperature range, which is critical to reliable BNG performance. Hence, this study analyzes the non-uniform tension of wires wound using traditional sequential winding methods in which the elastic modulus of the metal wire is much larger than that of the insulation substrate. To address this problem, a simple and reliable template-based transfer method is developed. First, a template with large elastic modulus is used to fabricate a wire mesh with uniform tension. The mesh is then transferred to the substrate. Theoretically, this method reduces the non-uniformity of the tension in wires to less than 2%; therefore, it is used to construct a BNG with stainless steel wire, a stainless steel template, and a printed circuit board substrate. The BNG was installed in our homebuilt ion mobility spectrometer. To confirm that the performance of the BNG meets the requirements of portable ion mobility spectrometry, signal intensity and resolution (approximately 30) were experimentally determined.

46 INSTRUMENTATION RELATED TO NUCLEAR SCIENCE AND ↗