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1.
Stem Cell Reports ; 16(9): 2128-2137, 2021 09 14.
Artigo em Inglês | MEDLINE | ID: mdl-34450034

RESUMO

The ε4 allele of APOE-encoding apolipoprotein (ApoE) is one of the strongest genetic risk factors for Alzheimer's disease (AD). One of the overarching questions is whether and how this astrocyte-enriched risk factor initiates AD-associated pathology in neurons such as amyloid-ß (Aß) accumulation. Here, we generate neurons and astrocytes from isogenic human induced pluripotent stem cells (hiPSCs) carrying either APOE ε3 or APOE ε4 allele and investigate the effect of astrocytic ApoE4 on neuronal Aß production. Secretory factors in conditioned media from ApoE4 astrocytes significantly increased amyloid precursor protein (APP) levels and Aß secretion in neurons. We further found that increased cholesterol secretion from ApoE4 astrocytes was necessary and sufficient to induce the formation of lipid rafts that potentially provide a physical platform for APP localization and facilitate its processing. Our study reveals the contribution of ApoE4 astrocytes to amyloidosis in neurons by expanding lipid rafts and facilitating Aß production through an oversupply of cholesterol.


Assuntos
Peptídeos beta-Amiloides/biossíntese , Apolipoproteína E4/genética , Astrócitos/metabolismo , Colesterol/metabolismo , Microdomínios da Membrana/metabolismo , Neurônios/metabolismo , Doença de Alzheimer/etiologia , Doença de Alzheimer/metabolismo , Doença de Alzheimer/patologia , Precursor de Proteína beta-Amiloide/genética , Precursor de Proteína beta-Amiloide/metabolismo , Apolipoproteína E4/metabolismo , Biomarcadores , Comunicação Celular , Meios de Cultivo Condicionados/metabolismo , Meios de Cultivo Condicionados/farmacologia , Espaço Extracelular/metabolismo , Humanos , Células-Tronco Pluripotentes Induzidas/citologia , Células-Tronco Pluripotentes Induzidas/efeitos dos fármacos , Células-Tronco Pluripotentes Induzidas/metabolismo , Neurônios/efeitos dos fármacos
2.
Nanoscale ; 7(15): 6567-73, 2015 Apr 21.
Artigo em Inglês | MEDLINE | ID: mdl-25790123

RESUMO

Recently, carbon materials such as carbon nanotubes and graphene have been proposed as alternatives to indium tin oxide (ITO) for fabricating transparent conducting materials. However, obtaining low sheet resistance and high transmittance of these carbon materials has been challenging due to the intrinsic properties of the materials. In this paper, we introduce highly transparent and flexible conductive films based on a hybrid structure of graphene and an Ag-grid. Electrohydrodynamic (EHD) jet printing was used to produce a micro-scale grid consisting of Ag lines less than 10 µm wide. We were able to directly write the Ag-grid on a large-area graphene/flexible substrate due to the high conductivity of graphene. The hybrid electrode could be fabricated using hot pressing transfer and EHD jet printing in a non-vacuum, maskless, and low-temperature environment. The hybrid electrode offers an effective and simple route for achieving a sheet resistance as low as ∼4 Ω per square with ∼78% optical transmittance. Finally, we demonstrate that transparent flexible heaters based on the hybrid conductive films could be used in a vehicle or a smart window system.

3.
Small ; 10(19): 3918-22, 2014 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-24925213

RESUMO

Highly aligned and patterned silver nanowires (Ag NWs) are investigated by using electrohydrodynamic (EHD) jet printing. Interaction between the flow field and the electric field as well as the mechanical stretching of the fiber jet can successfully align the Ag NWs inside the jet fiber. This technique can be applied in fabricating 1D nanostructures-based printed micro/nanoscale devices.

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