Striatal neuroinflammation promotes parkinsonism in rats

The specific role of neuroinflammation in the pathogenesis of Parkinson's disease remains to be fully elucidated. By infusing lipopolysaccharide (LPS) into the striatum, we investigated the effect of neuroinflammation on the dopamine nigrostriatal pathway. Here, we report that LPS-induced neuroinflammation in the striatum causes progressive degeneration of the dopamine nigrostriatal system, which is accompanied by motor impairments resembling parkinsonism. Our results indicate that neurodegeneration is associated with defects in the mitochondrial respiratory chain related to extensive S-nitrosylation/nitration of mitochondrial proteins. Mitochondrial injury was prevented by treatment of L-N^6^-(l-iminoethyl)-lysine, an inducible nitric oxide synthase (iNOS) inhibitor, suggesting that iNOS-derived NO is responsible for mitochondrial dysfunction. Furthermore, the nigral dopamine neurons exhibited intracytoplasmic [alpha]-synuclein and ubiquitin accumulation. These results demonstrate that degeneration of nigral dopamine neurons by neuroinflammation is associated with mitochondrial malfunction induced by NO-mediated S-nitrosylation/nitration of mitochondrial proteins

How Korean K-12 Educators Adapted to Online Teaching and Promoted Digital Equity During COVID-19: A Mixed-Method Study on Practices and Perceptions

The abrupt transitions to online teaching during COVID-19 have exacerbated educational discrepancies worldwide. South Korean schools faced similar challenges primarily due to the insufficient infrastructure and pedagogical guidelines for online teaching. This mixed-method case study investigated how Korean K-12 teachers and administrators converted to online teaching and addressed related digital equity issues during their first semester of online teaching in response to the pandemic. Interviews, as well as survey responses at the beginning and end of the semester, were analyzed through Activity Theory (AT) and Technological Pedagogical Content Knowledge (TPACK) frameworks. The study's key insights were that the digital equity issue is related to quality teaching issues beyond infrastructural problems and that teachers took various strategies to maximize the effectiveness of their blended teaching. We aim to shed light on supporting equitable online learning and sustaining positive changes in the post-COVID era

Estimating remineralized phosphate and its remineralization rate in the northern East China Sea during Summer 1997 : a snapshot study before Three-Gorges Dam construction

© The Author(s), 2016. This article is distributed under the terms of the Creative Commons Attribution License. The definitive version was published in Terrestrial, Atmospheric and Oceanic Sciences 27 (2016): 955-963, doi:10.3319/TAO.2016.01.24.01(Oc).The northern East China Sea (a.k.a., “The South Sea”) is a dynamic zone that exerts a variety of effects on the marine ecosystem due to Three-Gorges Dam construction. As the northern East China Sea region is vulnerable to climate forcing and anthropogenic impacts, it is important to investigate how the remineralization rate in the northern East China Sea has changed in response to such external forcing. We used an historical hydrographic dataset from August 1997 to obtain a baseline for future comparison. We estimate the amount of remineralized phosphate by decomposing the physical mixing and biogeochemical process effect using water column measurements (temperature, salinity, and phosphate). The estimated remineralized phosphate column inventory ranged from 0.8 to 42.4 mmol P m-2 (mean value of 15.2 ± 12.0 mmol P m-2). Our results suggest that the Tsushima Warm Current was a strong contributor to primary production during the summer of 1997 in the study area. The estimated summer (June - August) remineralization rate in the region before Three-Gorges Dam construction was 18 ± 14 mmol C m-2 d-1.T. Lee was supported by 2-Year Research Grant of Pusan National University. H.-C. Kim was partly supported by KOPRI project (PG15010). I.-N. Kim was partly supported by the National Research Foundation of Korea (NRF) grant funded by the Korea government (MSIP) (No. 2015R1C1A1A01052051). K.-T. Park was partly supported by KOPRI project (PE17010). J.-H. Kim was partly supported by the program of “Management of Marine Organisms Causing Ecological Disturbance and Harmful Effects” funded by KIMST/MOF. A.M. Macdonald’s contribution was supported by NOAA grant: #NA110AR4310063 and NSF grant: #OCE-1059881

Endogenous dynorphin protects against neurotoxin-elicited nigrostriatal dopaminergic neuron damage and motor deficits in mice

BACKGROUND: The striato-nigral projecting pathway contains the highest concentrations of dynorphin in the brain. The functional role of this opioid peptide in the regulation of mesencephalic dopaminergic (DAergic) neurons is not clear. We reported previously that exogenous dynorphin exerts potent neuroprotective effects against inflammation-induced dopaminergic neurodegeneration in vitro. The present study was performed to investigate whether endogenous dynorphin has neuroprotective roles in vivo. METHODS: 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) and methamphetamine (MA), two commonly used neurotoxins in rodent models of Parkinson\u27s disease, were administered to wild-type (Dyn⁺/⁺) and prodynorphin-deficient mice (Dyn⁻/⁻). We examined dopaminergic neurotoxicity by using an automated video tracking system, HPLC, immunocytochemistry, and reverse transcription and polymerase chain reaction (RT-PCR). RESULTS: Treatment with MPTP resulted in behavioral impairments in both strains. However, these impairments were more pronounced in Dyn-l- than in Dyn⁺/⁺. Dyn⁻/⁻ showed more severe MPTP-induced dopaminergic neuronal loss in the substantia nigra and striatum than Dyn⁺/⁺. Similarly, the levels of dopamine and its metabolites in the striatum were depleted to a greater extent in Dyn⁻/⁻ than in Dyn⁺/⁺. Additional mechanistic studies revealed that MPTP treatment caused a higher degree of microglial activation and M1 phenotype differentiation in Dyn⁻/⁻ than in Dyn⁺/⁺. Consistent with these observations, prodynorphin deficiency also exacerbated neurotoxic effects induced by MA, although this effect was less pronounced than that of MPTP. CONCLUSIONS: The in vivo results presented here extend our previous in vitro findings and further indicate that endogenous dynorphin plays a critical role in protecting dopaminergic neurons through its anti-inflammatory effects

Tolerability and Outcomes of First-Line Pemetrexed-Cisplatin Followed by Gefitinib Maintenance Therapy Versus Gefitinib Monotherapy in Korean Patients with Advanced Nonsquamous Non-small Cell Lung Cancer: A Post Hoc Descriptive Subgroup Analysis of a Randomized, Phase 3 Trial

Purpose We recently reported on a randomized, open-label, phase 3 trial comparing pemetrexedcisplatin chemotherapy followed by gefitinib maintenance therapy (PC/G) with gefitinib monotherapy in patients with non-small cell lung cancer (NSCLC). Here, we report on a post hoc subgroup analysis of that study assessing the demographics and disposition of the Korean patient subgroup, and comparing the tolerability of PC/G and gefitinib monotherapy and the tumor response with respect to epidermal growth factor receptor (EGFR) status. Materials and Methods Patients, who were 18 years, chemonalve, Korean, light ex-smokers/never-smokers with advanced NSCLC, were randomly assigned (1:1) to PC/G or gefitinib monotherapy. Treatment-emergent adverse events (TEAEs) were graded, and tumor response was measured as change in lesion sum from baseline at best response. The study was registered with ClinicalTrials.gov, NCT01017874. Results Overall, 111 Korean patients were treated (PC/G, 51; gefitinib, 60). Between-arm characteristics were balanced and similar to those of the overall population. Treatment discontinuations due to adverse events were low (PC/G: 1, 2.0%; gefitinib: 7, 11.7%). Overall, 92 patients (82.9%) reported >= 1 TEAE (PC/G, 44; gefitinib, 48); few patients (PC/G, 16; gefitinib, 7) reported severe TEAEs; the most frequent was neutropenia (PC/G arm) and elevated alanine aminotransferase (gefitinib arm). The lesion sum was decreased by PC/G treatment in most patients, regardless of EGFR mutation status, while gefitinib monotherapy reduced the lesion sum in EGFR-positive patients but had no effect in EGFR-negative patients. Conclusion Our results confirm that both PC/G and gefitinib were well tolerated in Korean patients, regardless of EGFR status; however, patients with EGFR wild-type NSCLC may not benefit from gefitinib monotherapy.

Depression and suicide risk prediction models using blood-derived multi-omics data

More than 300 million people worldwide experience depression; annually, ~800,000 people die by suicide. Unfortunately, conventional interview-based diagnosis is insufficient to accurately predict a psychiatric status. We developed machine learning models to predict depression and suicide risk using blood methylome and transcriptome data from 56 suicide attempters (SAs), 39 patients with major depressive disorder (MDD), and 87 healthy controls. Our random forest classifiers showed accuracies of 92.6% in distinguishing SAs from MDD patients, 87.3% in distinguishing MDD patients from controls, and 86.7% in distinguishing SAs from controls. We also developed regression models for predicting psychiatric scales with R2 values of 0.961 and 0.943 for Hamilton Rating Scale for Depression???17 and Scale for Suicide Ideation, respectively. Multi-omics data were used to construct psychiatric status prediction models for improved mental health treatment

Spatial and temporal variabilities of spring Asian dust events and their impacts on chlorophyll-a concentrations in the western North Pacific Ocean

Author Posting. © American Geophysical Union, 2017. This article is posted here by permission of American Geophysical Union for personal use, not for redistribution. The definitive version was published in Geophysical Research Letters 44 (2017): 1474–1482, doi:10.1002/2016GL072124.As the western North Pacific Ocean is located downwind of the source regions for spring Asian dust, it is an ideal location for determining the response of open waters to these events. Spatial analysis of spring Asian dust events from source regions to the western North Pacific, using long-term daily aerosol index data, revealed three different transport pathways supported by the westerly wind system: one passing across the northern East/Japan Sea (40°N–50°N), a second moving over the entire East/Japan Sea (35°N–55°N), and a third flowing predominantly over the Siberian continent (>50°N). Our results indicate that strong spring Asian dust events can increase ocean primary productivity by more than 70% (>2-fold increase in chlorophyll-a concentrations) compared to weak/nondust conditions. Therefore, attention should be paid to the recent downturn in the number of spring Asian dust events and to the response of primary production in the western North Pacific to this change.Korean government (MSIP) Grant Numbers: 2015R1C1A1A01052051, NRF-C1ABA001-2011-0021064; Korea Polar Research Institute (KOPRI) Grant Number: PE17030; NOAA Grant Number: NA11OAR4310063; WHOI2017-08-1