Wineinformatics is among the new fields in data science that use wine as domain knowledge. To process large amounts of wine review data in human language format, the computational wine wheel is ...applied. In previous research, the computational wine wheel was created and applied to different datasets of wine reviews developed by Wine Spectator. The goal of this research is to explore the development and application of the computational wine wheel to reviews from a different reviewer, Robert Parker. For comparison, this research collects 513 elite Bordeaux wines that were reviewed by both Robert Parker and Wine Spectator. The full power of the computational wine wheel is utilized, including NORMALIZED, CATEGORY, and SUBCATEGORY attributes. The datasets are then used to predict whether the wine is a classic wine (95 + scores) or not (94 − scores) using the black-box classification algorithm support vector machine. The Wine Spectator’s dataset, with a combination of NORMALIZED, CATEGORY, and SUBCATEGORY attributes, achieves the best accuracy of 76.02%. Robert Parker’s dataset also achieves an accuracy of 75.63% out of all the attribute combinations, which demonstrates the usefulness of the computational wine wheel and that it can be effectively adopted in different wine reviewers’ systems. This paper also attempts to build a classification model using both Robert Parker’s and Wine Spectator’s reviews, resulting in comparable prediction power.
Wineinformatics involves the application of data science techniques to wine-related datasets generated during the grape growing, wine production, and wine evaluation processes. Its aim is to extract ...valuable insights that can benefit wine producers, distributors, and consumers. This study highlights the potential of neural networks as the most effective black-box classification algorithm in wineinformatics for analyzing wine reviews processed by the Computational Wine Wheel (CWW). Additionally, the paper provides a detailed overview of the enhancements made to the CWW and presents a thorough comparison between the latest version and its predecessors. In comparison to the highest accuracy results obtained in the latest research work utilizing an elite Bordeaux dataset, which achieved approximately 75% accuracy for Robert Parker’s reviews and 78% accuracy for the Wine Spectator’s reviews, the combination of neural networks and CWW3.0 consistently yields improved performance. Specifically, this combination achieves an accuracy of 82% for Robert Parker’s reviews and 86% for the Wine Spectator’s reviews on the elite Bordeaux dataset as well as a newly created dataset that contains more than 10,000 wines. The adoption of machine learning algorithms for wine reviews helps researchers understand more about quality wines by analyzing the end product and deconstructing the sensory attributes of the wine; this process is similar to reverse engineering in the context of wine to study and improve the winemaking techniques employed.
The imbalance between neuronal excitation and inhibition (E/I) in neural circuit has been considered to be at the root of numerous brain disorders. We recently reported a novel feedback crosstalk ...between the excitatory neurotransmitter glutamate and inhibitory γ‐aminobutyric acid type A receptor (GABAAR)‐glutamate allosteric potentiation of GABAAR functions through a direct binding of glutamate to the GABAAR itself. Here, we investigated the physiological significance and pathological implications of this cross‐talk by generating the β3E182G knock‐in (KI) mice. We found that β3E182G KI, while had little effect on basal GABAAR‐mediated synaptic transmission, significantly reduced glutamate potentiation of GABAAR‐mediated responses. These KI mice displayed lower thresholds for noxious stimuli, higher susceptibility to seizures and enhanced hippocampus‐related learning and memory. Additionally, the KI mice exhibited impaired social interactions and decreased anxiety‐like behaviors. Importantly, hippocampal overexpression of wild‐type β3‐containing GABAARs was sufficient to rescue the deficits of glutamate potentiation of GABAAR‐mediated responses, hippocampus‐related behavioral abnormalities of increased epileptic susceptibility, and impaired social interactions. Our data indicate that the novel crosstalk among excitatory glutamate and inhibitory GABAAR functions as a homeostatic mechanism in fine‐tuning neuronal E/I balance, thereby playing an essential role in ensuring normal brain functioning.
The β3E182G single mutation is sufficient to eliminate the glutamate potentiation of GABAAR responses, and to cause electrophysiological and behavioral abnormalities, whereas bilateral hippocampal overexpressions of wild type β3‐containing GABAARs rescue these abnormalities. We therefore revealed that glutamate‐GABAAR crosstalk plays a homeostatic role in maintaining a proper balance between neuronal excitation and inhibition under both physiological and pathological conditions.
Alzheimer’s disease (AD) is a leading cause of dementia in the elderly. Mitogen-activated protein kinase phosphatase 1 (MKP-1) plays a neuroprotective role in AD. However, the molecular mechanisms ...underlying the effects of MKP-1 on AD have not been extensively studied. MicroRNAs (miRNAs) regulate gene expression at the post-transcriptional level, thereby repressing mRNA translation. Here, we reported that the microRNA-429-3p (miR-429-3p) was significantly increased in the brain of APP23/PS45 AD model mice and N2AAPP AD model cells. We further found that miR-429-3p could downregulate MKP-1 expression by directly binding to its 3′-untranslated region (3′ UTR). Inhibition of miR-429-3p by its antagomir (A-miR-429) restored the expression of MKP-1 to a control level and consequently reduced the amyloidogenic processing of APP and Aβ accumulation. More importantly, intranasal administration of A-miR-429 successfully ameliorated the deficits of hippocampal CA1 long-term potentiation and spatial learning and memory in AD model mice by suppressing extracellular signal-regulated kinase (ERK1/2)-mediated GluA1 hyperphosphorylation at Ser831 site, thereby increasing the surface expression of GluA1-containing α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptors (AMPARs). Together, these results demonstrate that inhibiting miR-429-3p to upregulate MKP-1 effectively improves cognitive and synaptic functions in AD model mice, suggesting that miR-429/MKP-1 pathway may be a novel therapeutic target for AD treatment.
miR-429-3p inhibits MKP-1 expression by directly binding to its 3′UTR, consequently initiating ERK1/2-mediated hyperphosphorylation of GluA1 at S831, which ultimately leads to synaptic and cognitive dysfunction in AD. Display omitted
Clinical trials have demonstrated the potential neuroprotective effects of uric acid (UA) in Alzheimer’s disease (AD). However, the specific mechanism underlying the neuroprotective effect of UA ...remains unclear. In the present study, we investigated the neuroprotective effect and underlying mechanism of UA in AD mouse models. Various behavioral tests including an elevated plus maze, Barnes maze, and Morris water maze were conducted to evaluate the impact of UA on cognitive function in β-amyloid (Aβ) microinjection and APP23/PS45 double transgenic mice models of AD. Immunohistochemical staining was employed to visualize pathological changes in the brains of AD model mice. Western blotting and immunofluorescence techniques were used to assess levels of autophagy-related proteins and transcription factor EB (TFEB)-related signaling pathways. BV2 cells were used to investigate the association between UA and microglial autophagy. We reported that UA treatment significantly alleviated memory decline in Aβ-induced AD model mice and APP23/PS45 double transgenic AD model mice. Furthermore, UA activated microglia and upregulated the autophagy-related proteins such as LC3II/I ratio, Beclin-1, and LAMP1 in the hippocampus of AD model mice. Similarly, UA protected BV2 cells from Aβ toxicity by upregulating the expressions of Beclin-1, LAMP1, and the LC3II/I ratio, whereas genetic inhibition of TFEB completely abolished these protective effects. Our results indicate that UA may serve as a novel activator of TFEB to induce microglia autophagy and facilitate Aβ degradation, thereby improving cognitive function in AD model mice. Therefore, these findings suggest that UA may be a novel therapeutic agent for AD treatment.
The amyloid-β (Aβ) enhances the number and activity of blood monocyte-derived osteoclasts (OCs). Individuals with osteoporosis (OP) face an increased risk of developing dementia or Alzheimer's ...disease (AD). Despite this association, the contribution of bone-resorbing OCs to the progression of AD pathology remains unclear.
Our objective was to investigate the potential impacts of OCs on the development of AD pathology.
We conducted targeted analysis of publicly available whole blood transcriptomes from patients with AD to characterize the blood molecular signatures and pathways associated with hyperactive OCs. In addition, we used APP23 transgenic (APP23 TG) AD mouse model to assess the effects of OCs pharmacological blockade on AD pathology and behavior.
Patients with AD exhibited increased osteoclastogenesis signature in their blood cells, which appears to be positively correlated with dysfunction of peripheral clearance of Aβ mediated by immune cells. Long-term anti-resorptive intervention with Alendronate inhibited OC activity in APP23 mice, leading to improvements in peripheral monocyte Aβ-degrading enzyme expression, Aβ-deposition, and memory decline.
Our findings suggest that OCs have a disease-promoting role in the development and progression of AD, possibly linked to their modulation of peripheral immunity. These findings guide future research to further elucidate the connection between OP and AD pathogenesis, highlighting the potential benefits of preventing OP in alleviating cognitive burden.
Alzheimer's disease (AD) is a neurodegenerative disease where abnormal amyloidogenic processing of amyloid‐β precursor protein (APP) occurs and has been linked to neuronal dysfunction. Hypometabolism ...of glucose in the brain can lead to synaptic loss and neuronal death, which in turn exacerbates energy deficiency and amyloid‐β peptide (Aβ) accumulation. Lactate produced by anaerobic glycolysis serves as an energy substrate supporting neuronal function and facilitating neuronal repair. Vestigial‐like family member 4 (VGLL4) has been recognized as a key regulator of the hypoxia‐sensing pathway. However, the role of VGLL4 in AD remains unexplored. Here, we reported that the expression of VGLL4 protein was significantly decreased in the brain tissue of AD model mice and AD model cells. We further found that overexpression of VGLL4 reduced APP amyloidogenic processing and ameliorated neuronal synaptic damage. Notably, we identified a compromised hypoxia‐sensitive capability of LDHA regulated by VGLL4 in the context of AD. Upregulation of VGLL4 increased the response of LDHA to hypoxia and enhanced the expression levels of LDHA and lactate by inhibiting the ubiquitination and degradation of LDHA. Furthermore, the inhibition of lactate production by using sodium oxamate, an inhibitor of LDHA, suppressed the neuroprotective function of VGLL4 by increasing APP amyloidogenic processing. Taken together, our findings demonstrate that VGLL4 exerts a neuroprotective effect by upregulating LDHA expression and consequently promoting lactate production. Thus, this study suggests that VGLL4 may be a novel player involved in molecular mechanisms relevant for ameliorating neurodegeneration.
VGLL4 ameliorates neuronal dysfunction in AD models. The expression of VGLL4 is decreased in AD, and the upregulation of VGLL4 can significantly inhibit the process of APP amyloidogenic processing and neuronal synaptic damage by promoting the expression levels of LDHA and lactate.
Wineinformatics, as one of the new fields of Data Science, uses wine as application domain. Wine reviews in human language format are processed by a Natural Language Processing tool called the ...Computational Wine Wheel (CWW). In previous research, the source for wine reviews was Wine Spectator. For this project, two wine sources are collected and used for this research: wine reviews from Robert Parker and wine reviews from Wine Spectator. This project focuses on three main goals: 1. Enhancing the Computational Wine Wheel by analyzing and processing Robert Parker’s review; 2. Evaluating and comparing the consistency of Wine Spectator and Robert Parker’s reviews using the new Computational Wine Wheel 3.0; 3. Proposing new methods to combine different sources of reviews using the new Computational Wine Wheel 3.0 for achieving better results. Five datasets are used to predict whether the wine belongs to Classic Wines (95+ scores) or not (94- scores) by implementing two classification methods: the black-box model Support Vector Machines and the white-box model Naive Bayes. After enhancing the Computational Wine Wheel, 75% datasets have had better performance after applying the new CWW 3.0 than applying the CWW 2.0. The proposed combination method “RPcomWS'' that combines two reviews from Robert Parker and Wine Spectator into one review has achieved accuracy as high as 84.89%, with an F-score of 75.49%, a precision of 84.64%, and a recall of 68.13%. The result shows that the review combination of Robert Parker and Wine Spectator can extract the most wine attributes from reviews to achieve better performance.
•Myocardial infarction induces anxiety-like behavior in adult female rat.•Echocardiographic indices are positive correlation with anxiety-like behavior.•Myocardial infarction promotes cellular ...neuroinflammation and apoptosis in the hippocampus.•Myocardial infarction induces epigenetic signaling alterations in the hippocampus.
Epidemiological and experimental animal studies indicate that there is a high risk for the incidence of neuropsychiatric disorders suffering from cardiovascular diseases such as myocardial infarction (MI). However, the potential mechanism of this association remains largely unknown. This study sought to evaluate whether epigenetic alterations in the hippocampus is associated with MI-induced anxiety-like behavior in rats. MI was induced by occlusion of the left anterior descending artery in adult female rats. Anxiety-like behavior was examined by elevated plus maze, light-dark box, and open field test. Relative gene and protein levels expression in the hippocampus were tested by qRT-PCR and western blotting, respectively. We found that MI rats exhibited anxiety-like behavior compared with those in controls, and there is a positive correlation between MI and anxiety-like behavior. We also found that MI decreased KDM6B while increased SIRT1 expression in the hippocampus of MI rats relative to those in controls. In addition, MI not only increased levels of IL-1β, bax, and cleaved-caspase 3, but also increased Iba-1 and GFAP expression in the hippocampus, as compared to those in controls, suggesting a promotion of neuro-inflammation and apoptosis in hippocampus. Co-immunoprecipitation assay illustrated that H3K27me3 functioned by counteracting with YAP activation in the hippocampus of MI rats relative to those in controls. Together, these results suggest a potential role of hippocampal epigenetic signaling in MI-induced anxiety-like behavior in rats, and pharmacological targeting KDM6B or SIRT1 could be a strategy to ameliorate anxiety-like behavior induced by MI.
Resveratrol, a type of natural polyphenol mainly extracted from the skin of grapes, has been reported to protect against inflammatory responses and exert anxiolytic effect. Yes-associated protein ...(YAP), a major downstream effector of the Hippo signaling pathway, plays a critical role in inflammation. The present study aimed to explore whether YAP pathway was involved in the anxiolytic effect of resveratrol in lipopolysaccharide (LPS)-treated C57BL/6J male mice. LPS treatment induced anxiety-like behavior and decreased sirtuin 1 while increased YAP expression in the hippocampus. Resveratrol attenuated LPS-induced anxiety-like behavior, which was blocked by EX-527 (a sirtuin 1 inhibitor). Mechanistically, the anxiolytic effects of resveratrol were accompanied by a marked decrease in YAP, interleukin-1β and ionized calcium binding adaptor molecule 1 (Iba-1) while a significant increase in autophagic protein expression in the hippocampus. Pharmacological study using XMU-MP-1, a YAP activator, showed that activating YAP could induce anxiety-like behavior and neuro-inflammation as well as decrease hippocampal autophagy. Moreover, activation of YAP by XMU-MP-1 treatment attenuated the ameliorative effects of resveratrol on LPS-induced anxiety-like behavior, while blockade of YAP activation with verteporfin, a YAP inhibitor, attenuated LPS-induced anxiety-like behavior and neuro-inflammation as well as hippocampal autophagy. Finally, rapamycin-mediated promotion of autophagy attenuated LPS-induced anxiety-like behavior and decreased interleukin-1β and Iba-1 expression in the hippocampus. Collectively, these results indicate that amelioration by resveratrol in LPS-induced anxiety-like behavior is through attenuating YAP-mediated neuro-inflammation and promoting hippocampal autophagy, and suggest that inhibition of YAP pathway could be a potential therapeutic target for anxiety-like behavior induced by neuro-inflammation.
•Resveratrol ameliorates LPS-induced anxiety-like behavior by attenuating YAP signaling.•YAP-mediated neuro-inflammation contributes to LPS-induced anxiety-like behavior.•Rapamycin prevents neuro-inflammation and attenuates LPS-induced anxiety-like behavior.•Blocking YAP could be a therapeutic target for LPS-induced anxiety-like behavior.
