The autoimmune response induced by α-synuclein peptides drives neuronal cell death and glial cell activation.

Parkinson's disease (PD) is a progressive neurodegenerative disorder associated with the loss of dopaminergic neurons and neuroinflammation. Recent studies have identified a role of T cells in the pathogenesis of PD. Additionally, these studies suggested that α-synuclein (α-Syn) is related to abnormal T-cell responses and may act as an epitope and trigger autoimmune T-cell responses. However, it is unclear whether the α-Syn-mediated autoimmune response occurs and whether it is related to neuronal cell death and glial cell activation. In this study, we investigated the autoimmune T-cell response induced by α-Syn peptides and evaluated the neurotoxic effect of the α-Syn peptide-mediated autoimmune response. The immunization of mice with α-Syn peptides resulted in enhanced autoimmune responses, such as the peptide recall response, polarization toward Th1/Th17 cells, and regulatory T cell imbalance. Furthermore, the α-Syn autoimmune response led to the death of primary neurons cocultured with splenocytes. Treatment with conditioned media from α-Syn peptide-immunized splenocytes induced microglia and toxic A1-type astrocyte activation. Taken together, our results provide evidence of the potential role of the α-Syn-initiated autoimmune response and its contribution to neuronal cell death and glial cell activation.

A comparative assessment of reference genes in mouse brown adipocyte differentiation and thermogenesis in vitro.

Adipogenic differentiation and thermogenesis in brown adipose tissue (BAT) undergo dynamic processes, altering phenotypes and gene expressions. Proper reference genes in gene expression analysis are crucial to mitigate experimental variances and ensure PCR efficacy. Unreliable reference genes can lead to erroneous gene expression quantification, resulting in data misinterpretation. This study focused on identifying suitable reference genes for mouse brown adipocyte research, utilizing brown adipocytes from the Ucp1-luciferase ThermoMouse model. Comparative analysis of gene expression data under adipogenesis and thermogenesis conditions was conducted, validating 13 housekeeping genes through various algorithms, including DeltaCq, BestKeeper, geNorm, Normfinder, and RefFinder. Tbp and Rer1 emerged as optimal references for Ucp1 and Pparg expression in brown adipogenesis, while Tbp and Ubc were ideal for the expression analysis of these target genes in thermogenesis. Conversely, certain conventional references, including Actb, Tubb5, and Gapdh, proved unstable as reference genes under both conditions. These findings stress the critical consideration of reference gene selection in gene expression analysis within specific biological systems to ensure accurate conclusions.

Host Subcellular Organelles: Targets of Viral Manipulation.

Viruses have evolved sophisticated mechanisms to manipulate host cell processes and utilize intracellular organelles to facilitate their replication. These complex interactions between viruses and cellular organelles allow them to hijack the cellular machinery and impair homeostasis. Moreover, viral infection alters the cell membrane's structure and composition and induces vesicle formation to facilitate intracellular trafficking of viral components. However, the research focus has predominantly been on the immune response elicited by viruses, often overlooking the significant alterations that viruses induce in cellular organelles. Gaining a deeper understanding of these virus-induced cellular changes is crucial for elucidating the full life cycle of viruses and developing potent antiviral therapies. Exploring virus-induced cellular changes could substantially improve our understanding of viral infection mechanisms.

High spatiotemporal-resolution mapping for a seasonal erosion flooding inundation using time-series Landsat and MODIS images.

Seasonal erosion flooding events present a significant challenge for effective disaster monitoring and land degradation studies. This research addresses this challenge by harnessing the combined capabilities of time-series Landsat and MODIS images to achieve high spatiotemporal-resolution mapping of flooding during such events. The study underscores the critical importance of precise flood monitoring for disaster mitigation and informed land management. To overcome the limitations posed by the trade-off between spatial and temporal resolution in current satellite sensors, we emplyedand theflexible spatiotemporal data fusion (FSDAF) methods to produce synthetic flood images with enhanced spatiotemporal resolutions for mapping by using MODIS and Landsat data from August 29 to September 3, 2016. A comparison was made between flood maps from several post-disaster forecasts based on ground-obtained time-series images of the Tumen River flood in China. According to the FSDAF approach, the input Landsat image of March 25, 2016, and the fused results had a root mean square error (RMSE) of 0.0301, average difference of 0.001, r of 0.941, and structure similarity indexof 0.939, indicating that temporal variation data had been effectively incorporated into a forecast on August 16, 2016. Results also indicated that the FSDAF forecast values are lower than those from the actual Landsat image. The results of the study also showed that the generated images could be effectively used for flood mapping. By using our newly developed simulation model, we were able to produce a comprehensive map of the inundated areas during the event from August 29 to September 3, 2016. This shows that FSDAF holds great potential for flood prediction and study and has the potential to benefit further disaster-related land degradation by combining multi-source images to provide high temporal and spatial resolution remote sensing information.

Manipulating RKIP reverses the metastatic potential of breast cancer cells.

Breast cancer is a common tumor type among women, with a high fatality due to metastasis. Metastasis suppressors encode proteins that inhibit the metastatic cascade independent of the primary tumor growth. Raf kinase inhibitory protein (RKIP) is one of the promising metastasis suppressor candidates. RKIP is reduced or lost in aggressive variants of different types of cancer. A few pre-clinical or clinical studies have capitalized on this protein as a possible therapeutic target. In this article, we employed two breast cancer cells to highlight the role of RKIP as an antimetastatic gene. One is the low metastatic MCF-7 with high RKIP expression, and the other is MDA-MB-231 highly metastatic cell with low RKIP expression. We used high-throughput data to explore how RKIP is lost in human tissues and its effect on cell mobility. Based on our previous work recapitulating the links between RKIP and SNAI, we experimentally manipulated RKIP in the cell models through its novel upstream NME1 and investigated the subsequent genotypic and phenotypic changes. We also demonstrated that RKIP explained the uneven migration abilities of the two cell types. Furthermore, we identified the regulatory circuit that might carry the effect of an existing drug, Epirubicin, on activating gene transcription. In conclusion, we propose and test a potential strategy to reverse the metastatic capability of breast cancer cells by chemically manipulating RKIP expression.

Fermented Soybean Paste Attenuates Biogenic Amine-Induced Liver Damage in Obese Mice.

Biogenic amines are cellular components produced by the decarboxylation of amino acids; however, excessive biogenic amine production causes adverse health problems. The relationship between hepatic damage and biogenic amine levels in nonalcoholic fatty liver disease (NAFLD) remains unclear. In this study, mice were fed a high-fat diet (HFD) for 10 weeks to induce obesity, presenting early-stage of NAFLD. We administered histamine (20 mg/kg) + tyramine (100 mg/kg) via oral gavage for 6 days to mice with HFD-induced early-stage NAFLD. The results showed that combined histamine and tyramine administration increased cleaved PARP-1 and IL-1ß in the liver, as well as MAO-A, total MAO, CRP, and AST/ALT levels. In contrast, the survival rate decreased in HFD-induced NAFLD mice. Treatment with manufactured or traditional fermented soybean paste decreased biogenically elevated hepatic cleaved PARP-1 and IL-1ß expression and blood plasma MAO-A, CRP, and AST/ALT levels in HFD-induced NAFLD mice. Additionally, the biogenic amine-induced reduction in survival rate was alleviated by fermented soybean paste in HFD-induced NAFLD mice. These results show that biogenic amine-induced liver damage can be exacerbated by obesity and may adversely affect life conservation. However, fermented soybean paste can reduce biogenic amine-induced liver damage in NAFLD mice. These results suggest a beneficial effect of fermented soybean paste on biogenic amine-induced liver damage and provide a new research perspective on the relationship between biogenic amines and obesity.

Adaptation strategies for future coastal flooding: Performance evaluation of green and grey infrastructure in South Korea.

Climate change is contributing to an increasing frequency and intensity of floods in Korea. This study predicts areas with a high probability of flooding in coastal areas of South Korea owing to future climate change, which is likely to cause extreme rainfall and sea-level rise, using a spatiotemporal downscaled future climate change scenario with random forest, artificial neural network, and k-nearest neighbor techniques. In addition, the change in coastal flooding risk probability according to the application of different adaptation strategies (green spaces and seawalls) was identified. The results showed a clear difference in the risk probability distribution in the absence and presence of either adaptation strategy. Their effectiveness in moderating future flooding risks is subject to change owing to strategy type, geographic region, and urbanization intensity and the results show that green spaces are slightly more effective than seawalls when forecasting for 2050. This demonstrates the importance of a nature-based strategy. Moreover, this study highlights the need to prepare adaptation measures according to regional characteristics to mitigate the impact of climate change. Korea is surrounded by seas on three sides that have independent geophysical and climate characteristics. The south coast has a higher risk of coastal flooding than the east and west coasts. In addition, a higher urbanization rate is associated with a higher risk probability. This implies that climate change response strategies for coastal cities are necessary as the population and socioeconomic activities of coastal urban areas are likely to increase in the future.

Using buffer analysis to determine urban park cooling intensity: Five estimation methods for Nanjing, China.

Urban parks are part of the blue-green infrastructure of urban ecosystems. Although the cooling effect of urban parks has been widely recognized, the understanding of park cooling intensity (PCI) and its mechanisms remains incomplete. Applicable and accurate quantification could facilitate better design and management of urban parks. We used five methods (equal area method [EAM], equal radius method [ERM], fixed radius method [FRM], turning point method-maximum perspective [TPM-M], and turning point method-accumulation perspective [TPM-A]) to estimate PCI, and established the method selection mechanism, which we evaluated in terms of PCI amplitudes, spatial heterogeneity, and interactions with park landscape features. Using Nanjing as a case study, we employed spatial and statistical analyses to further assess the autocorrelation of PCI and its relationship with park landscape features. The results indicate the following: (1) 62.38 % of Nanjing's urban parks are located above the 90 % confidence level in cold spot areas. (2) Different methods had significant effects on the estimated PCI, were positively correlated, and had similar spatial heterogeneity. (3) All methods revealed that park area (PA), water area proportion (WAP), and the normalized difference vegetation index (NDVI) of the vegetated area (NDVIveg) were the three dominant factors that influenced PCI; WAP and NDVIveg that achieved more effective cooling. (4) The quantification of PCI using the ERM and TPM is recommended over other methods. These findings are essential for landscape planners to understand the formation of PCI and design cooler parks to mitigate the urban heat island (UHI) effect more systematically.

Muscimol Directly Activates the TREK-2 Channel Expressed in GABAergic Neurons through Its N-Terminus.

The two-pore domain K+ (K2P) channel, which is involved in setting the resting membrane potential in neurons, is an essential target for receptor agonists. Activation of the γ-aminobutyric acid (GABA) receptors (GABAAR and GABABR) reduces cellular excitability through Cl- influx and K+ efflux in neurons. Relatively little is known about the link between GABAAR and the K+ channel. The present study was performed to identify the effect of GABAR agonists on K2P channel expression and activity in the neuroblastic B35 cells that maintain glutamic acid decarboxylase (GAD) activity and express GABA. TASK and TREK/TRAAK mRNA were expressed in B35 cells with a high level of TREK-2 and TRAAK. In addition, TREK/TRAAK proteins were detected in the GABAergic neurons obtained from GABA transgenic mice. Furthermore, TREK-2 mRNA and protein expression levels were markedly upregulated in B35 cells by GABAAR and GABABR agonists. In particular, muscimol, a GABAAR agonist, significantly increased TREK-2 expression and activity, but the effect was reduced in the presence of the GABAAR antagonist bicuculine or TREK-2 inhibitor norfluoxetine. In the whole-cell and single-channel patch configurations, muscimol increased TREK-2 activity, but the muscimol effect disappeared in the N-terminal deletion mutant. These results indicate that muscimol directly induces TREK-2 activation through the N-terminus and suggest that muscimol can reduce cellular excitability by activating the TREK-2 channel and by inducing Cl- influx in GABAergic neurons.

Anti-Obesity Effect of Pine Needle Extract on High-Fat Diet-Induced Obese Mice.

BACKGROUND: Obesity due to an excessive intake of nutrient disturbs the hypothalamus-mediated energy metabolism subsequently develops metabolic disorders. In this study, we investigated the effect of pine needle extract (PNE) on the hypothalamic proopiomelanocortin (POMC) neurons involved in the regulation of energy balance via melanocortin system and fat tissue metabolism. METHODS: We performed electrophysiological and immunohistochemical analyses to determine the effect of PNE on POMC neurons. Mice were fed a normal or high-fat diet for 12 weeks, then received PNE for the last 2 weeks to measure the following physiological indices: Body weight, food intake, fat/lean mass, glucose metabolism, and plasma leptin levels. In addition, changes of thermogenic, lipolytic, and lipogenetic markers were evaluated in brown adipose tissue (BAT) and white adipose tissue (WAT) by western blotting, respectively. RESULTS: PNE increased hypothalamic POMC neuronal activity, and the effect was abolished by blockade of melanocortin 3/4 receptors (MC3/4Rs). PNE decreased body weight, fat mass, plasma leptin levels, and improved glucose metabolism after high-fat-induced obesity. However, PNE did not change the expression of thermogenic markers of the BAT in HFD fed groups, but decreased only the lipogenetic markers of WAT. This study suggests that PNE has a potent anti-obesity effect, inhibiting lipogenesis in WAT, even though HFD-induced leptin resistance-mediated disruption of POMC neuronal activity.

Conserving terrestrial linkages that connect natural landscapes of the Korean Peninsula.

Human-induced land degradation fragments natural ecosystems, hinders ecological processes, and threatens biodiversity. Maintaining or restoring ecological flows across landscapes through landscape linkages may provide a solution. Here, we identify a peninsula-wide ecological connectivity network for the Korean Peninsula using two linkage mapping models. We found three major north-south axes of connectivity traversing the Demilitarized Zone (DMZ), which emerged as an important east-west linkage. Only 7% of the highest-ranked connections are currently secured by protected areas. We found 120 linkages in North and South Korea that are intersected by road networks consisting of motorways and trunk roads under both models. These locations should be the focus of immediate attention for conservation planners, as well as 274 and 1130 additional road-impacted linkages under one model or the other. The results can be used for policy support, and potentially as a basis for the two countries to engage in discussions about ecosystem health and climate change adaptation. The approach presented here can also be efficiently used to assess and map natural landscape linkages.

Maximum diameter versus volumetric assessment for the response evaluation of vestibular schwannomas receiving stereotactic radiotherapy.

PURPOSE: To explore the feasibility of maximum diameter as a response assessment method for vestibular schwannomas (VS) after stereotactic radiosurgery or fractionated stereotactic radiotherapy (RT), we analyzed the concordance of RT responses between maximum diameters and volumetric measurements. Materials and. METHODS: Forty-two patients receiving curative stereotactic radiosurgery or fractionated stereotactic RT for VS were analyzed retrospectively. Twelve patients were excluded: 4 did not receive follow-up magnetic resonance imaging (MRI) scans and 8 had initial MRI scans with a slice thickness >3 mm. The maximum diameter, tumor volume (TV), and enhanced tumor volume (ETV) were measured in each MRI study. The percent change after RT was evaluated according to the measurement methods and their concordances were calculated with the Pearson correlation. The response classifications were determined by the assessment modalities, and their agreement was analyzed with Cohen kappa statistics. RESULTS: Median follow-up was 31.0 months (range, 3.5 to 86.5 months), and 90 follow-up MRI studies were analyzed. The percent change of maximum diameter correlated strongly with TV and ETV (r(p) = 0.85, 0.63, p = 0.000, respectively). Concordance of responses between the Response Evaluation Criteria in Solid Tumors (RECIST) using the maximum diameters and either TV or ETV were moderate (kappa = 0.58; 95% confidence interval, 0.32-0.85) or fair (kappa = 0.32; 95% confidence interval, 0.05-0.59), respectively. Conclusions: The percent changes in maximum diameter and the responses in RECIST were significantly concordant with those in the volumetric measurements. Therefore, the maximum diameters can be used for the response evaluation of VS following stereotactic RT.

Assessing shortfalls and complementary conservation areas for national plant biodiversity in South Korea.

Protected areas (PAs) are often considered the most important biodiversity conservation areas in national plans, but PAs often do not represent national-scale biodiversity. We evaluate the current conservation status of plant biodiversity within current existing PAs, and identify potential additional PAs for South Korea. We modeled species ranges for 2,297 plant species using Multivariate Adaptive Regression Splines and compared the level of mean range representation in South Korea's existing PAs, which comprise 5.7% of the country's mainland area, with an equal-area alternative PA strategy selected with the reserve algorithm Marxan. We also used Marxan to model two additional conservation scenarios that add lands to approach the Aichi Biodiversity Target objectives (17% of the country). Existing PAs in South Korea contain an average of 6.3% of each plant species' range, compared to 5.9% in the modeled equal-area alternative. However, existing PAs primarily represent a high percentage of the ranges for high-elevation and small range size species. The additional PAs scenario that adds lands to the existing PAs covers 14,587.55 km2, and would improve overall plant range representation to a mean of 16.8% of every species' range. The other additional PAs scenario, which selects new PAs from all lands and covers 13,197.35 km2, would improve overall plant range representation to a mean of 13.5%. Even though the additional PAs that includes existing PAs represents higher percentages of species' ranges, it is missing many biodiversity hotspots in non-mountainous areas and the additional PAs without locking in the existing PAs represent almost all species' ranges evenly, including low-elevation ones with larger ranges. Some priority conservation areas we identified are expansions of, or near, existing PAs, especially in northeastern and southern South Korea. However, lowland coastal areas and areas surrounding the capital city, Seoul, are also critical for biodiversity conservation in South Korea.

Empathy Bot: Conversational Service for Psychiatric Counseling with Chat Assistant.

There are earlier studies for psychiatric counseling using chat bots. These studies have not considered the user's emotional status and ethical judgment to provide interventions. This paper proposes an intelligent assistant for psychiatric counseling that understands dialogues using high-level features of natural language understanding, and multi-modal emotion recognition. A response generation model using machine leaning provides suitable responses for clinical psychiatric counseling.

Neighborhood Landscape Spatial Patterns and Land Surface Temperature: An Empirical Study on Single-Family Residential Areas in Austin, Texas.

Rapid urbanization has accelerated land use and land cover changes, and generated the urban heat island effect (UHI). Previous studies have reported positive effects of neighborhood landscapes on mitigating urban surface temperatures. However, the influence of neighborhood landscape spatial patterns on enhancing cooling effects has not yet been fully investigated. The main objective of this study was to assess the relationships between neighborhood landscape spatial patterns and land surface temperatures (LST) by using multi-regression models considering spatial autocorrelation issues. To measure the influence of neighborhood landscape spatial patterns on LST, this study analyzed neighborhood environments of 15,862 single-family houses in Austin, Texas, USA. Using aerial photos, geographic information systems (GIS), and remote sensing, FRAGSTATS was employed to calculate values of several landscape indices used to measure neighborhood landscape spatial patterns. After controlling for the spatial autocorrelation effect, results showed that larger and better-connected landscape spatial patterns were positively correlated with lower LST values in neighborhoods, while more fragmented and isolated neighborhood landscape patterns were negatively related to the reduction of LST.

Quantitative analysis of polyhexamethylene guanidine (PHMG) oligomers via matrix-assisted laser desorption/ionization time-of-flight mass spectrometry with an ionic-liquid matrix.

RATIONALE: Quantifying polymers by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOFMS) with a conventional crystalline matrix generally suffers from poor sample-to-sample or shot-to-shot reproducibility. An ionic-liquid matrix has been demonstrated to mitigate these reproducibility issues by providing a homogeneous sample surface, which is useful for quantifying polymers. In the present study, we evaluated the use of an ionic liquid matrix, i.e., 1-methylimidazolium α-cyano-4-hydroxycinnamate (1-MeIm-CHCA), to quantify polyhexamethylene guanidine (PHMG) samples that impose a critical health hazard when inhaled in the form of droplets. METHODS: MALDI-TOF mass spectra were acquired for PHMG oligomers using a variety of ionic-liquid matrices including 1-MeIm-CHCA. Calibration curves were constructed by plotting the sum of the PHMG oligomer peak areas versus PHMG sample concentration with a variety of peptide internal standards. RESULTS: Compared with the conventional crystalline matrix, the 1-MeIm-CHCA ionic-liquid matrix had much better reproducibility (lower standard deviations). Furthermore, by using an internal peptide standard, good linear calibration plots could be obtained over a range of PMHG concentrations of at least 4 orders of magnitude. CONCLUSIONS: This study successfully demonstrated that PHMG samples can be quantitatively characterized by MALDI-TOFMS with an ionic-liquid matrix and an internal standard.

5-Methoxysalicylic acid matrix for ganglioside analysis with matrix-assisted laser desorption/ionization mass spectrometry.

In this note, we report that high quality ganglioside profiles with minimal loss of sialic acid residues can be obtained in the positive ion mode by using a 5-methoxysalicylic acid (MSA) matrix for matrix-assisted laser desorption/ionization (MALDI) mass spectrometry (MS). Our results showed that MSA produced much less sialic acid losses from gangliosides than DHB, although MSA and DHB are differ only by their functional groups at their 5-positions (-OH for DHB and -OCH(3) for MSA). Furthermore, our data also demonstrated that addition of an alkali metal additive was effective for simplifying ganglioside profiles, but not necessary for stabilizing glycosidic bonds of gangliosides if MSA was used as a matrix. This suggests that MALDI MS with MSA has a potential to gain additional benefits from the positive-ion mode analyses without losing performance in ganglioside profiling.

Brain abscess due to odontogenic infection: a case report.

In this report, we describe a case of brain abscess due to odontogenic infection. A 53-year-old female who had been suffering from headache and trismus for two weeks visited the Department of Oral and Maxillofacial Surgery at the Sun Dental Hospital (Daejeon, Korea). Even after several routine tests, we still could not make a diagnosis. However, after the combined multidisciplinary efforts of oral surgeons and neurosurgeons, the patient was treated for odontogenic infection and made an uneventful recovery. Therefore, patients with infections in the head and neck region showing symptoms such as headache, changes in mental state, nausea, vomiting, seizures, hemiplegia, speech disturbance, and visual disturbance, a brain abscess should be included in the list of differential diagnoses.

Early treadmill training promotes motor function after hemorrhagic stroke in rats.

Rehabilitation after a stroke is very important because it has beneficial effects on brain function, including the promotion of plasticity. However, an optimal time window for rehabilitation interventions after hemorrhagic stroke has not been clearly defined. The aim of this study was to determine whether early exercise training initiated 24h after an intracerebral hemorrhage (ICH) might enhance neurologic recovery more than exercise initiated 1 week after ICH without hematoma expansion and edema volume increase. We subjected adult male Sprague-Dawley rats to experimental ICH by the intrastriatal administration of bacterial collagenase. The rats were randomly divided into the following 2 groups: early training group (treadmill exercise started 24h post-ICH; n=18) and late training group (treadmill exercise started 1-week post-ICH; n=18). Two weeks after surgery we performed neurologic tests (rota-rod, modified limb-placing, and adhesive-dot removal tests), and measured hematoma volumes and brain water content. In the late training group, compared with the pre-ICH performance on the rota-rod test (98.3+/-69.4s), the animals had significantly worse performance after the post-ICH rehabilitation (40.5+/-52.6s; p<0.01, paired t-test). In the early training group however, the motor performance after the post-ICH rehabilitation (56.4+/-73.5s) was not significantly different from the baseline pre-ICH performance (79.8+/-33.9s; p=0.24). There were no significant differences between the two groups with respect to the other neurologic tests. Early exercise did not increase hematoma size or brain water content. Early treadmill training could be performed safely, and enhanced motor recovery in a rat model of ICH. Further studies are required to translate the results into clinical significance.