Warming-induced tree growth may help offset increasing disturbance across the Canadian boreal forest.

Large projected increases in forest disturbance pose a major threat to future wood fiber supply and carbon sequestration in the cold-limited, Canadian boreal forest ecosystem. Given the large sensitivity of tree growth to temperature, warming-induced increases in forest productivity have the potential to reduce these threats, but research efforts to date have yielded contradictory results attributed to limited data availability, methodological biases, and regional variability in forest dynamics. Here, we apply a machine learning algorithm to an unprecedented network of over 1 million tree growth records (1958 to 2018) from 20,089 permanent sample plots distributed across both Canada and the United States, spanning a 16.5 °C climatic gradient. Fitted models were then used to project the near-term (2050 s time period) growth of the six most abundant tree species in the Canadian boreal forest. Our results reveal a large, positive effect of increasing thermal energy on tree growth for most of the target species, leading to 20.5 to 22.7% projected gains in growth with climate change under RCP 4.5 and 8.5. The magnitude of these gains, which peak in the colder and wetter regions of the boreal forest, suggests that warming-induced growth increases should no longer be considered marginal but may in fact significantly offset some of the negative impacts of projected increases in drought and wildfire on wood supply and carbon sequestration and have major implications on ecological forecasts and the global economy.

Tree species growth response to climate warming varies by forest canopy position in boreal and temperate forests.

Reports of forest sensitivity to climate change are based largely on the study of overstory trees, which contribute significantly to forest growth and wood supply. However, juveniles in the understory are also critical to predict future forest dynamics and demographics, but their sensitivity to climate remains less known. In this study, we applied boosted regression tree analysis to compare the sensitivity of understory and overstory trees for the 10 most common tree species in eastern North America using growth information from an unprecedented network of nearly 1.5 million tree records from 20,174 widely distributed, permanent sample plots across Canada and the United States. Fitted models were then used to project the near-term (2041-2070) growth for each canopy and tree species. We observed an overall positive effect of warming on tree growth for both canopies and most species, leading to an average of 7.8%-12.2% projected growth gains with climate change under RCP 4.5 and 8.5. The magnitude of these gains peaked in colder, northern areas for both canopies, while growth declines are projected for overstory trees in warmer, southern regions. Relative to overstory trees, understory tree growth was less positively affected by warming in northern regions, while displaying more positive responses in southern areas, likely driven by the buffering effect of the canopy from warming and climate extremes. Observed differences in climatic sensitivity between canopy positions underscore the importance of accounting for differential growth responses to climate between forest strata in future studies to improve ecological forecasts. Furthermore, latitudinal variation in the differential sensitivity of forest strata to climate reported here may help refine our comprehension of species range shift and changes in suitable habitat under climate change.

Sequential droughts: A silent trigger of boreal forest mortality.

Despite great concern for drought-driven forest mortality, the effects of frequent low-intensity droughts have been largely overlooked in the boreal forest because of their negligible impacts over the short term. In this study, we used data from 6876 permanent plots distributed across most of the Canadian boreal zone to assess the effects of repeated low-intensity droughts on forest mortality. Specifically, we compared the relative impact of sequential years under low-intensity dry conditions with the effects of variables related to the intensity of dry conditions, stand characteristics, and local climate. Then, we searched for thresholds in forest mortality as a function of the number of years between two forest surveys affected by dry conditions of any intensity. Our results showed that, in general, frequent low-intensity dry conditions had stronger effects on forest mortality than the intensity of the driest conditions in the plot. Frequent low-intensity dry conditions acted as an inciting factor of forest mortality exacerbated by stand characteristics and environmental conditions. Overall, the mortality of forests dominated by shade-tolerant conifers was significantly and positively related to frequent low-intensity dry conditions, supporting, in some cases, the existence of thresholds delimiting contrasting responses to drought. In mixtures with broadleaf species, however, sequential dry conditions had a negligible impact. The effects of frequent dry conditions on shade-intolerant forests mainly depended on local climate, inciting or mitigating the mortality of forests located in wet places and dominated by broadleaf species or jack pine, respectively. Our results highlight the importance of assessing not only climate-driven extreme events but also repeated disturbances of low intensity. In the long term, the smooth response of forests to dry conditions might abruptly change leading to disproportional mortality triggered by accumulated stress conditions. Forest and wildlife managers should consider the cumulative effects of climate change on mortality to avoid shortfalls in timber and habitat.

Phosphorylation of Tyrosine 1070 at the GluN2B Subunit Is Regulated by Synaptic Activity and Critical for Surface Expression of N-Methyl-D-aspartate (NMDA) Receptors.

The number and subunit composition of synaptic N-methyl-d-aspartate receptors (NMDARs) play critical roles in synaptic plasticity, learning, and memory and are implicated in neurological disorders. Tyrosine phosphorylation provides a powerful means of regulating NMDAR function, but the underling mechanism remains elusive. In this study we identified a tyrosine site on the GluN2B subunit, Tyr-1070, which was phosphorylated by a proto-oncogene tyrosine-protein (Fyn) kinase and critical for the surface expression of GluN2B-containing NMDARs. The phosphorylation of GluN2B at Tyr-1070 was required for binding of Fyn kinase to GluN2B, which up-regulated the phosphorylation of GluN2B at Tyr-1472. Moreover, our results revealed that the phosphorylation change of GluN2B at Tyr-1070 accompanied the Tyr-1472 phosphorylation and Fyn associated with GluN2B in synaptic plasticity induced by both chemical and contextual fear learning. Taken together, our findings provide a new mechanism for regulating the surface expression of NMDARs with implications for synaptic plasticity.

A facile three-step total synthesis of tanshinone I.

A facile synthetic approach for total synthesis of tanshinone I has been accomplished. The key precursor is a novel compound, epoxy phenanthraquinone. And this synthesis of tanshinone I is achieved in only three simple stages, which include Diels-Alder reaction, Δ(2)-Weitz-Scheffer-type epoxidation, and Feist-Bénary reaction from commercially available styrene.

Adaptor protein APPL1 couples synaptic NMDA receptor with neuronal prosurvival phosphatidylinositol 3-kinase/Akt pathway.

It is well known that NMDA receptors (NMDARs) can both induce neurotoxicity and promote neuronal survival under different circumstances. Recent studies show that such paradoxical responses are related to the receptor location: the former to the extrasynaptic and the latter to the synaptic. The phosphoinositide 3-kinase (PI3K)/Akt kinase cascade is a key pathway responsible for the synaptic NMDAR-dependent neuroprotection. However, it is still unknown how synaptic NMDARs are coupled with the PI3K/Akt pathway. Here, we explored the role of an adaptor protein-adaptor protein containing pH domain, PTB domain, and leucine zipper motif (APPL1)-in this signal coupling using rat cortical neurons. We found that APPL1 existed in postsynaptic densities and associated with the NMDAR complex through binding to PSD95 at its C-terminal PDZ-binding motif. NMDARs, APPL1, and the PI3K/Akt cascade formed a complex in rat cortical neurons. Synaptic NMDAR activity increased the association of this complex, induced activation of the PI3K/Akt pathway, and consequently protected neurons against starvation-induced apoptosis. Perturbing APPL1 interaction with PSD95 by a peptide comprising the APPL1 C-terminal PDZ-binding motif dissociated the PI3K/Akt pathway from NMDARs. Either the peptide or lentiviral knockdown of APPL1 blocked synaptic NMDAR-dependent recruitment and activation of PI3K/Akt pathway, and consequently blocked synaptic NMDAR-dependent neuroprotection. These results suggest that APPL1 contributes to connecting synaptic NMDARs with the intracellular PI3K/Akt cascade and the downstream prosurvival signaling pathway in rat cortical neurons.

Lanthanide ternary complex as a fluorescent probe for highly sensitive and selective detection of copper ions based on selective recognition and photoinduced electron transfer.

Copper ions have a very important role in human health, industrial and agricultural production. Herein, lanthanide ternary complex of 2,6-pyridinedicarboxylic acid (DPA)-Eu3+-polyethyleneimine (PEI) as a fluorescent probe was thus fabricated for highly sensitive and selective detection of copper ions. PEI itself is non-fluorescent, the PEI-Eu3+complex is also non-fluorescent, and PEI has specific recognition to copper ions due to its higher affinity ability to copper ion than other metal ions. It was found that Cu2+ ions cannot quench the characteristic fluorescence of Eu3+ in the DPA-Eu3+ system, while in the DPA-Eu3+-PEI system, Cu2+ ions can greatly quench the characteristic fluorescence of Eu3+ due to photoinduced electron transfer (PET). The luminescent and quenching mechanism was also discussed in detail. The DPA-Eu3+-PEI probe not only has high sensitivity and selectivity, but also has very rapid fluorescence response and the response time is only 1 min. A good linear relationship between the fluorescence ratios of F0/F and the concentrations of Cu2+ was obtained in the range of 0.02 âˆ¼ 10.0 µM (R2 = 0.998), and the limit of detection (LOD) is 8.0 nM. The probe was successfully applied for the detection of Cu2+ ions in the lake and river water samples, wastewater and urine samples. This work may provide a new strategy for fabricating simple and effective fluorescence probe and a promising application for the rapid and on-site detection in environmental monitoring and biological fluids.

Photocurable and elastic polyurethane based on polyether glycol with adjustable hardness for 3D printing customized flatfoot orthosis.

Orthopedic insoles is the most commonly used nonsurgical treatment method for the flatfoot. Polyurethane (PU) plays a crucial role in the manufacturing of orthopedic insoles due to its high wear resistance and elastic recovery. However, preparing orthopedic insoles with adjustable hardness, high-accuracy, and matches the plantar morphology is challenging. Herein, a liquid crystal display (LCD) three-dimensional (3D) printer was used to prepare the customized arch-support insoles based on photo-curable and elastic polyurethane acrylate (PUA) composite resins. Two kinds of photo-curable polyurethanes (DL1000-PUA and DL2000-PUA) were successfully synthesized, and a series of fast-photocuring polyurethane acrylate (PUA) composite resins for photo-polymerization 3D printing were developed. The effects of different acrylate monomers on the Shore hardness, viscosity, and mechanical properties of the PUA composite resins were evaluated. The PUA-3-1 composite resin exhibited low viscosity, optimal hardness, and mechanical properties. A deviation analysis was conducted to assess the accuracy of printed insole. Furthermore, the stress conditions of the PUA composite resin and ethylene vinyl acetate (EVA) under the weight load of healthy adults were compared by finite element analysis (FEA) simulation. The results demonstrated that the stress of the PUA composite resin and EVA were 0.152 MPa and 0.285 MPa, and displacement were 0.051 mm and 3.449 mm, respectively. These results indicate that 3D-printed arch-support insole based on photocurable PUA composite resin are high-accuracy, and can reduce plantar pressure and prevent insoles premature deformation, which show great potential in the physiotherapeutic intervention for foot disorders.

Transmembrane region of N-methyl-D-aspartate receptor (NMDAR) subunit is required for receptor subunit assembly.

N-Methyl-D-aspartate receptors (NMDARs), one of three main classes of ionotropic glutamate receptors, play major roles in synaptic plasticity, synaptogenesis, and excitotoxicity. Unlike non-NMDA receptors, NMDARs are thought to comprise obligatory heterotetrameric complexes mainly composed of GluN1 and GluN2 subunits. When expressed alone in heterogenous cells, such as HEK293 cells, most of the NMDAR subunits can neither leave the endoplasmic reticulum (ER) nor be expressed in the cell membrane because of the ER retention signals. Only when NMDARs are heteromerically assembled can the ER retention signals be masked and NMDARs be expressed in the surface membrane. However, the mechanisms underlying NMDAR assembly remain poorly understood. To identify regions in subunits that mediate this assembly, we made a series of truncated or chimeric cDNA constructs. Using FRET measurement in living cells combined with immunostaining and coimmunoprecipitation analysis, we examined the assembly-determining domains of NMDAR subunits. Our results indicate that the transmembrane region of subunits is necessary for the assembly of NMDAR subunits, both for the homodimer and the heteromer.

Application of Bioprinting in Ophthalmology.

Three-dimensional (3D) bioprinting is an emerging technology that is widely used in regenerative medicine. With the continuous development of the technology, it has attracted great attention and demonstrated promising prospects in ophthalmologic applications. In this paper, we review the three main types of 3D bioprinting technologies: Vat polymerization-based bioprinting, extrusion-based bioprinting, and jetting-based bioprinting. We also present in this review the analysis of the usage of both natural and synthesized hydrogels as well as the types of cells adopted for bioinks. Cornea and retina are the two main types of ocular tissues developed in bioprinting, while other device and implants were also developed for the ocular disease treatment. We also summarize the advantages and limitations as well as the future prospects of the current bioprinting technologies based on systematic reviews.

Estimation of Potential Savings Associated With Switching Medication Formulation.

This cross-sectional study describes the price differences between capsule and tablet or ointment and cream forms of prescription drugs for insured patients.

3D-printed high-density polyethylene scaffolds with bioactive and antibacterial layer-by-layer modification for auricle reconstruction.

High-density polyethylene (HDPE) is a promising material for the development of scaffold implants for auricle reconstruction. However, preparing a personalized HDPE auricle implant with favorable bioactive and antibacterial functions to promote skin tissue ingrowth is challenging. Herein, we present 3D-printed HDPE auricle scaffolds with satisfactory pore size and connectivity. The layer-by-layer (LBL) approach was applied to achieve the improved bioactive and antibacterial properties of these 3D printed scaffolds. The HDPE auricle scaffolds were fabricated using an extrusion 3D printing approach, and the individualized macrostructure and porous microstructure were both adjusted by the 3D printing parameters. The polydopamine (pDA) coating method was used to construct a multilayer ε-polylysine (EPL) and fibrin (FIB) modification on the surface of the 3D HDPE scaffold via the LBL self-assembly approach, which provides the bioactive and antibacterial properties. The results of the in vivo experiments using an animal model showed that LBL-coated HDPE auricular scaffolds were able to significantly enhance skin tissue ingrowth and ameliorate the inflammatory response caused by local stress. The results of this study suggest that the combination of the 3D printing technique and surface modification provides a promising strategy for developing personalized implants with biofunctional coatings, which show great potential as a scaffold implant for auricle reconstruction applications.

Effects of Real-time Prescription Benefit Recommendations on Patient Out-of-Pocket Costs: A Cluster Randomized Clinical Trial.

Importance: Rising drug costs contribute to medication nonadherence and adverse health outcomes. Real-time prescription benefit (RTPB) systems present prescribers with patient-specific out-of-pocket cost estimates and recommend lower-cost, clinically appropriate alternatives at the point of prescribing. Objective: To investigate whether RTPB recommendations lead to reduced patient out-of-pocket costs for medications. Design, Setting, and Participants: In this cluster randomized trial, medical practices in a large, urban academic health system were randomly assigned to RTPB recommendations from January 13 to July 31, 2021. Participants were adult patients receiving outpatient prescriptions during the study period. The analysis was limited to prescriptions for which RTPB could recommend an available alternative. Electronic health record data were used to analyze the intervention's effects on prescribing. Data analyses were performed from August 20, 2021, to June 8, 2022. Interventions: When a prescription was initiated in the electronic health record, the RTPB system recommended available lower-cost, clinically appropriate alternatives for a different medication, length of prescription, and/or choice of pharmacy. The prescriber could select either the initiated order or one of the recommended options. Main Outcomes and Measures: Patient out-of-pocket cost for a prescription. Secondary outcomes were whether a mail-order prescription and a 90-day supply were ordered. Results: Of 867 757 outpatient prescriptions at randomized practices, 36 419 (4.2%) met the inclusion criteria of having an available alternative. Out-of-pocket costs were $39.90 for a 30-day supply in the intervention group and $67.80 for a 30-day supply in the control group. The intervention led to an adjusted 11.2%; (95% CI, -15.7% to -6.4%) reduction in out-of-pocket costs. Mail-order pharmacy use was 9.6% and 7.6% in the intervention and control groups, respectively (adjusted 1.9 percentage point increase; 95% CI, 0.9 to 3.0). Rates of 90-day supply were not different. In high-cost drug classes, the intervention reduced out-of-pocket costs by 38.9%; 95% CI, -47.6% to -28.7%. Conclusions and Relevance: This cluster randomized clinical trial showed that RTPB recommendations led to lower patient out-of-pocket costs, with the largest savings occurring for high-cost medications. However, RTPB recommendations were made for only a small percentage of prescriptions. Trial Registration: ClinicalTrials.gov Identifier: NCT04940988; American Economic Association Registry: AEARCTR-0006909.

Effect of extrusion processing and addition of purple sweet potatoes on the structural properties and in vitro digestibility of extruded rice.

Recently, extruded rice as a functional ingredient has been a hot area of research in food processing. In this study, extruded rice with purple sweet potato (ERPSP) was prepared. Moreover, the effects of extrusion and added purple sweet potato on the structure and in vitro digestibility of extruded rice were studied via numerous detection methods, such as scanning electron microscopy (SEM), water absorption index (WAI), water solubility index (WSI), differential scanning calorimetry (DSC), X-ray diffraction (XRD), and Fourier transform infrared spectroscopy (FT-IR). SEM results showed that there were numerous pits and bubbles in the extruded rice. In particular, compared with raw rice, the WAI and WSI of ERPSP was higher, and the thermal properties also changed noticeably. The results of XRD and FT-IR spectroscopy showed that the semicrystalline structure of extruded rice changed from A-type to A + V-type mixture, and the relative crystallinity of extruded rice changed accordingly. In addition, a significantly lower equilibrium hydrolysis (C∞) and kinetic constant (k) were observed in ERPSP. The novel rice product made from broken rice by extrusion processing and addition of the purple sweet potato exhibited improved structural properties and reduced digestibility, which increased the potential value and application of broken rice in the food industry.

Shape Optimization of Costal Cartilage Framework Fabrication Based on Finite Element Analysis for Reducing Incidence of Auricular Reconstruction Complications.

Skin necrosis is the most common complication in total auricular reconstruction, which is mainly induced by vascular compromise and local stress concentration of the overlying skin. Previous studies generally emphasized the increase in the skin flap blood supply, while few reports considered the mechanical factors. However, skin injury is inevitable due to uneasily altered loads generated by the intraoperative continuous negative suction and uneven cartilage framework structure. Herein, this study aims to attain the stable design protocol of the ear cartilage framework to decrease mechanical damage and the incidence of skin necrosis. Finite element analysis was initially utilized to simulate the reconstructive process while the shape optimization technique was then adopted to optimize the three-pretested shape of the hollows inside the scapha and fossa triangularis under negative suction pressure. Finally, the optimal results would be output automatically to meet clinical requirement. Guided by the results of FE-based shape optimization, the optimum framework with the smallest holes inside the scapha and fossa triangularis was derived. Subsequent finite element analysis results also demonstrated the displacement and stress of the post-optimized model were declined 64.9 and 40.1%, respectively. The following clinical study was performed to reveal that this new design reported lower rates of skin necrosis decrease to 5.08%, as well as the cartilage disclosure decreased sharply from 14.2 to 3.39% compared to the conventional method. Both the biomechanical analysis and the clinical study confirmed that the novel design framework could effectively reduce the rates of skin necrosis, which shows important clinical significance for protecting against skin necrosis.

Acid-treated multi-walled carbon nanotubes as additives for negative active materials to improve high-rate-partial-state-of-charge cycle-life of lead-acid batteries.

In this work, a trace amount of acid-treated multi-walled carbon nanotubes (a-MWCNTs) is introduced into the negative active materials (NAMs) of a lead acid battery (LAB) by simply dispersing a-MWCNTs in the water, which is then added into the dry mixture of lead oxide powder, expanders and carbon black for lead paste preparation. The abundant oxygen-containing groups on the a-MWCNTs show significant influence on the chemical reactions happening during the curing process, leading to the improved properties of NAMs. Specifically, after formation, the NAMs containing 100 ppm a-MWCNTs display a spongy-like structure comprised of interconnected domino-like Pb slices, giving favorable porosity and electroactive surface area of the NAMs. Moreover, the quasi-rod structure of Pb slices provides the channels for fast electron transfer. These two features greatly accelerate the electrochemical reaction between Pb and PbSO4, and hence hinder the accumulation of PbSO4 crystals. As a result, the high-rate partial-state-of-charge (HRPSoC) cycle-life of the simulated cell constructed from the a-MWCNTs-containing negative plate achieves a HRPSoC cycle-life more than 1.5 times longer than the cell constructed when the negative plate contains only carbon black. Since our method is of great convenience and low-cost, it is expected to have a great feasibility in the LAB industry.

The effect of additives combination on rheological properties of dough and quality of bread with Agaricus bisporus powder.

The bread with Agaricus bisporus powder has the defects of poor texture and taste, so it is necessary to optimize the appropriate additives in order to improve its quality. The purpose of this study was to evaluate improvement of the combination of vital wheat gluten, sucrose fatty acid esters and cellulase on the improved Agaricus bisporus powder bread (IABPB), with wheat bread (WB) and bread with Agaricus bisporus powder (ABPB) as control. The results of rheological properties indicated the dough samples improved with three improvers had higher solid-like behaviour than the control sample. The results of nutritional quality analysis showed that the protein and dietary fiber content of IABPB was higher than those of WB and ABPB, but the fat content was relatively low. In addition, the additives combination could effectively improve the baking quality of ABPB. Compared with ABPB without additives, the specific volume increased by 21.22%, the brightness of bread crumb increased by 8.75%, but the crumb hardness decreased by 32.57%. Furthermore, the study on texture property and water migration during the storage showed that the addition of three improvers could delay the aging of bread. Therefore, it was feasible to use additives combination as a special quality improver for ABPB, which could effectively improve its quality.

Adaptor protein APPL1 links neuronal activity to chromatin remodeling in cultured hippocampal neurons.

Local signaling events at synapses or axon terminals are communicated to the nucleus to elicit transcriptional responses, and thereby translate information about the external environment into internal neuronal representations. This retrograde signaling is critical to dendritic growth, synapse development, and neuronal plasticity. Here, we demonstrate that neuronal activity induces retrograde translocation and nuclear accumulation of endosomal adaptor APPL1. Disrupting the interaction of APPL1 with Importin α1 abolishes nuclear accumulation of APPL1, which in turn decreases the levels of histone acetylation. We further demonstrate that retrograde translocation of APPL1 is required for the regulation of gene transcription and then maintenance of hippocampal late-phase long-term potentiation. Thus, these results illustrate an APPL1-mediated pathway that contributes to the modulation of synaptic plasticity via coupling neuronal activity with chromatin remodeling.

Forest structure, not climate, is the primary driver of functional diversity in northeastern North America.

Functional diversity (FD), represented by plant traits, is fundamentally linked to an ecosystem's capacity to respond to environmental change. Yet, little is known about the spatial distribution of FD and its drivers. These knowledge gaps prevent the development of FD-based forest management approaches to increase the trait diversity insurance (i.e., the response diversity) against future environmental fluctuations and disturbances. Our study helps fill these knowledge gaps by (i) mapping the current FD distribution, (ii) and analyzing FD drivers across northeastern North America. Following the stress-dominance hypothesis, we expected a strong environmental filtering effect on FD. Moreover, we expected abundant species to determine the bulk of FD distributions as suggested by the mass-ratio hypothesis. We combined a literature and database review of 44 traits for 43 tree species with terrestrial inventory data of 48,426 plots spanning an environmental gradient from northern boreal to temperate biomes. We evaluated the statistical influence of 25 covariates related to forest structure, climate, topography, soils, and stewardship on FD by employing an ensemble approach consisting of 90 non-parametric models. Temperate forests and the boreal-temperate ecotone east and northeast of the Great Lakes were identified as FD hotspots. Environmental filtering by climate was of secondary importance, with forest structure explaining most of the FD distribution of tree species in northeastern North America. Thus, our study provides only partial support for the stress-dominance hypothesis. Species abundance weightings altered trait diversity distributions and drivers only marginally, supporting the mass-ratio hypothesis. Our results suggest that forest management could increase FD without requiring knowledge of functional ecology by fostering stand structural complexity instead. Further, mixing species from different functional groups identified in this study can enhance the trait diversity insurance of forests to an uncertain future.

α-synuclein aggregates induce c-Abl activation and dopaminergic neuronal loss by a feed-forward redox stress mechanism.

Oxidative stress and α-synuclein aggregation both drive neurodegeneration in Parkinson's disease, and the protein kinase c-Abl provides a potential amplifying link between these pathogenic factors. Suppressing interactions between these factors may thus be a viable therapeutic approach for this disorder. To evaluate this possibility, pre-formed α-synuclein fibrils (PFFs) were used to induce α-synuclein aggregation in neuronal cultures. Exposure to PFFs induced oxidative stress and c-Abl activation in wild-type neurons. By contrast, α-synuclein - deficient neurons, which cannot form α-synuclein aggregates, failed to exhibit either oxidative stress or c-Abl activation. N-acetyl cysteine, a thiol repletion agent that supports neuronal glutathione metabolism, suppressed the PFF - induced redox stress and c-Abl activation in the wild-type neurons, and likewise suppressed α-synuclein aggregation. Parallel findings were observed in mouse brain: PFF-induced α-synuclein aggregation in the substantia nigra was associated with redox stress, c-Abl activation, and dopaminergic neuronal loss, along with microglial activation and motor impairment, all of which were attenuated with oral N-acetyl cysteine. Similar results were obtained using AAV-mediated α-synuclein overexpression as an alternative means of driving α-synuclein aggregation in vivo. These findings show that α-synuclein aggregates induce c-Abl activation by a redox stress mechanism. c-Abl activation in turn promotes α-synuclein aggregation, in a feed-forward interaction. The capacity of N-acetyl cysteine to interrupt this interaction adds mechanistic support its consideration as a therapeutic in Parkinson's disease.