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A hybrid system for producing conducting polymers within a doping hydrogel mesh is presented. These conductive hydrogels demonstrate comparable electroactivity to conventional conducting polymers without requiring the need for mobile doping ions which are typically used in literature. These hybrids have superior mechanical stability and a modulus significantly closer to neural tissue than materials which are commonly used for medical electrodes. Additionally they are shown to support the attachment and differentiation of neural like cells, with improved interaction when compared to homogeneous hydrogels. The system provides flexibility such that biologic incorporation can be tailored for application.  相似文献   
2.
Neuronal extracellular vesicles (EVs) play important roles in intercellular communication and pathogenic protein propagation in neurological disease. However, it remains unclear how cargoes are selectively packaged into neuronal EVs. Here, we show that loss of the endosomal retromer complex leads to accumulation of EV cargoes including amyloid precursor protein (APP), synaptotagmin-4 (Syt4), and neuroglian (Nrg) at Drosophila motor neuron presynaptic terminals, resulting in increased release of these cargoes in EVs. By systematically exploring known retromer-dependent trafficking mechanisms, we show that EV regulation is separable from several previously identified roles of neuronal retromer. Conversely, mutations in rab11 and rab4, regulators of endosome-plasma membrane recycling, cause reduced EV cargo levels, and rab11 suppresses cargo accumulation in retromer mutants. Thus, EV traffic reflects a balance between Rab4/Rab11 recycling and retromer-dependent removal from EV precursor compartments. Our data shed light on previous studies implicating Rab11 and retromer in competing pathways in Alzheimer’s disease, and suggest that misregulated EV traffic may be an underlying defect.  相似文献   
3.
Increasingly, organizations are working to reduce the environmental footprint of their supply chains. The use of environmentally preferable purchasing criteria is one strategy organizations use to address this goal. However, evaluating the environmental performance of these criteria (e.g., recycled content, biodegradable, renewable, and so on) has remained elusive. Life cycle assessment (LCA) can measure the impact reduction potential of sourcing strategies. However, full process‐based LCAs are time‐consuming and costly across multiple criteria of thousands of products and inputs purchased in an organizational setting. A streamlined “hotspot” methodology is presented using a combination of environmentally extended economic input‐output (EEIO) approaches and extant literature to identify hotspots in which to constrain a parameterized process‐based LCA. A case study of breakfast cereal manufacturing is developed to (1) assess the efficiencies associated with the hotspotting approach and (2) demonstrate its applicability in generating comparable decision signals of environmentally preferable sourcing criteria for procurement and supply‐chain managers along the dimensions of global warming potential and water use.  相似文献   
4.
Parkinson''s disease is associated with multiplication of the α-synuclein gene and abnormal accumulation of the protein. In animal models, α-synuclein overexpression broadly impairs synaptic vesicle trafficking. However, the exact steps of the vesicle trafficking pathway affected by excess α-synuclein and the underlying molecular mechanisms remain unknown. Therefore we acutely increased synuclein levels at a vertebrate synapse and performed a detailed ultrastructural analysis of the effects on presynaptic membranes. At stimulated synapses (20 Hz), excess synuclein caused a loss of synaptic vesicles and an expansion of the plasma membrane, indicating an impairment of vesicle recycling. The N-terminal domain (NTD) of synuclein, which folds into an α-helix, was sufficient to reproduce these effects. In contrast, α-synuclein mutants with a disrupted N-terminal α-helix (T6K and A30P) had little effect under identical conditions. Further supporting this model, another α-synuclein mutant (A53T) with a properly folded NTD phenocopied the synaptic vesicle recycling defects observed with wild type. Interestingly, the vesicle recycling defects were not observed when the stimulation frequency was reduced (5 Hz). Thus excess α-synuclein impairs synaptic vesicle recycling evoked during intense stimulation via a mechanism that requires a properly folded N-terminal α-helix.  相似文献   
5.
Purpose

Stakeholders from across supply chains have been prompted to explore ways to reduce the environmental burdens of corn production. To effectively manage these environmental impacts, spatially explicit information accounting for the differences in growing conditions and production practices across the production landscape is essential, allowing for high impact intensity corn to be identified and prioritized for improvement. To support these sustainability efforts, this study examines the spatially explicit life cycle greenhouse gas emissions of US county corn production, providing the most comprehensive assessment to date.

Methods

A streamlined spatial life cycle assessment is conducted, focusing on the three key hotspots of corn production for spatial differentiation at the county scale across the contiguous USA, accounting for almost 60% of total average cradle-to-farm gate impacts. Variations in nitrogen fertilization types and rates, N2O emission rates, and irrigation emission rates are specifically revealed. Spatially distinguished hotspot inputs and related emissions are combined with static national average emission estimates from all other inputs used in corn production to gain a full picture and understand the relative contributions to total cradle-to gate impacts.

Results and discussion

Results show significant variation across corn producing counties, states, and regions. High impact priority locations are highlighted and key contributors of impact for each location are illuminated, providing critical information on the spatially explicit levers to reduce impacts. Results increase the generalizability of emission estimates using expected yields to characterize emission intensity, enabling more practical integration into company supply chain sustainability assessments to align with the time horizons in which decisions are made.

Conclusions

Streamlined life cycle assessment methods are an effective way to characterize spatial heterogeneity around key contributors of impact, helping deliver the necessary information for companies, stakeholders, and policy makers to target their influence to reduce these emissions through various engagement efforts.

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