Search Results (26)

The plague, caused by Yersinia pestis, has resulted in significant mortality over the past century. Despite advances in antimicrobial therapy, plague remains a re-emerging infectious disease with ongoing outbreaks and increasing concerns regarding antimicrobial resistance. Today, plague cases are still being reported, and the loss of effectiveness of treatment methods remains a major challenge. Therefore, effective treatment strategies are needed. In this study, we aimed to develop aptamers specific to Yersinia outer protein M (YopM), a key immunosuppressive protein that is essential for virulence. Our goal was to develop an aptamer that binds to YopM and inhibits its interaction with the human DEAD-box helicase 3 (DDX3) protein. YopM-DDX3 protein interaction was targeted because of its key role in nucleocytoplasmic shuttling of YopM. To achieve this, we developed the YopM16 aptamer using magnetic bead-based (Systematic Evolution of Ligands by Exponential Enrichment) (SELEX). The selected YopM16 aptamer exhibited a half-maximal inhibitory concentration(IC₅₀) value of 103.3 ± 2 nM and effectively inhibited the interaction between YopM and DDX3. The inhibitory effect of the aptamer on protein interaction was confirmed using a pull-down assay and colorimetric test. Given that protein–protein interaction surfaces are considered undruggable, YopM16 is a promising inhibitor with the potential to serve as a molecular tool to investigate the virulence mechanism of YopM, as well as a novel antibacterial agent upon validation of its inhibition in cellular models. Full article

Growing mobility demand and declining vehicle utilization motivate dual-use vehicles that can alternately transport passengers and freight. This work presents an early-stage utility value analysis to select a baseline concept and integrates it into model-based systems-engineering architecture development of an autonomous dual-use shuttle. Existing dual-use-capable shuttle concepts were screened and comparatively assessed using a utility value analysis with exclusion criteria and weighted evaluation criteria, including operational versatility, module exchange flexibility, infrastructure effort, battery positioning, and technology readiness. Criterion weights were derived by pairwise preference analysis, emphasizing the versatility of use scenarios. The highest-ranking concept, 101 Modular Mobility, was selected as the reference architecture. Subsequently, a SysML system model was developed in a MagicGrid-structured model-based systems-engineering (MBSE) process, covering stakeholder needs, key use cases such as transport service usage, module exchange, and automated charging, and the resulting system context and interfaces. The system model is augmented by a tailored Grey Box structural viewpoint within the MagicGrid workflow to make module boundaries and inter-module interfaces explicit for the modular dual-use shuttle architecture. The resulting model provides a traceable early architectural baseline for further refinement and subsequent verification activities. Full article

Silver iodide (AgI) and potassium iodide (KI), which are used in cloud seeding, were administered to bees in a variety of pretreatments (low or high dosing) and analyzed through a series of experiments to determine the effect on bees’ ability to learn. Cloud seeding is the process of dispersing chemicals into an already-formed cloud to attract water molecules that fall to Earth as rain or snow. These chemicals then enter the ecosystem through water and soil. Honey bees were used because they represent a robust and ecologically appropriate model organism to study the behavioral impacts of cloud seeding. The first experiment utilized a shuttle box to test whether honey bees could avoid shock in a punishment experiment. Results revealed that the majority of the pretreatments did inhibit bees’ ability to learn to avoid shock. Experiment 2 consists of two proboscis extension reflex experiments (PER) where bees are trained to associate an odor with a sucrose feeding. Using the PER paradigm, we investigated simple conditioning and odor discrimination. Results revealed that in both the simple conditioning and discrimination experiments, learning was inhibited by the pretreatment of chemicals regardless of dosing amount. The final experiment explored reward discrimination in a free-flying flower patch paradigm. Results revealed that learning ability was not affected; however, return times were greatly impacted. Overall, results showed that AgI and KI throughout each experiment (i.e., shuttle box, PER, and free-flying discrimination) had some degree of negative effect on honey bee behavior. Full article

Background/Objectives: The bidirectional selection of the Roman low- (RLA) and Roman high-avoidance (RHA) rat strains for extremely slow vs. very rapid acquisition of the two-way (shuttle-box) avoidance response has generated two divergent phenotypic profiles: RHA rats exhibit a behavioural pattern and gene expression profile in the frontal cortex and hippocampus (HPC) that are relevant to social and attentional/cognitive schizophrenia-linked symptoms; on the other hand, RLA rats display phenotypic traits linked to increased anxiety and sensitivity to stress-induced depression-like behaviours. The present studies aimed to evaluate the enduring and potentially positive effects of neonatal handling-stimulation (NH) on the traits differentiating these two strains of rats. Methods: We evaluated the effects of NH on anxious behaviour, prepulse inhibition of startle (PPI), spatial working memory, and hormone responses to stress in adult rats of both strains. Furthermore, given the proposed involvement of neuronal/synaptic plasticity and neurotrophic factors in the development of anxiety, stress, depression, and schizophrenia-related symptoms, using Western blot (WB) we assessed the effects of NH on the content of brain-derived neurotrophic factor (BDNF), its trkB receptor and Polysialilated-Neural Cell Adhesion Molecule (PSA-NCAM), in the prefrontal cortex (PFC), anterior cingulate cortex (ACg), ventral (vHPC), and dorsal (dHPC) hippocampus of adult rats from both strains. Results: NH increased novelty-induced exploration and reduced anxiety, particularly in RLA rats, attenuated the stress-induced increment in corticosterone and prolactin plasma levels, and improved PPI and spatial working memory in RHA rats. These effects correlated to long-lasting increases of BDNF and PSA-NCAM content in PFC, ACg, and vHPC. Conclusions: Collectively, these findings show enduring and distinct NH effects on neuroendocrine and behavioural and cognitive processes in both rat strains, which may be linked to neuroplastic and synaptic changes in the frontal cortex and/or hippocampus. Full article

Recently, compounds of plant origin have been the focus of increased scientific interest. Micromeria frivaldszkyana is a rare species endemic to Bulgaria, whose biological activity remains unknown. This article aims to evaluate the subchronic toxicity of Micromeria frivaldszkyana methanolic extract and its effect on cognition in rats. Following 90 days of oral administration, a histopathological evaluation of brain, kidney, and liver tissues was conducted. Additionally, serum levels of total bilirubin (TB), conjugated bilirubin (CB), alanine aminotransferase (ALT), aspartate aminotransferase (AST), creatinine (CR), uric acid (UA), and urea (U) were measured. Cognitive function was studied after 7 d of treatment using activity cage test, along with tests for active memory, passive memory, anxiety, spatial and working memory, and explorative activity. The experiments showed no toxic effects of the extract in subchronic application. No adverse effects on brain function were observed after 14 days of treatment. While the extract increased the motor activity of the animals, it did not significantly improve the learning and memory processes. In conclusion, the methanolic extract of Micromeria frivaldszkyana in doses 250 and 500 mg/kg bw did not induce toxicity after 90-day treatment in rats. These doses did not significantly affect central nervous system (CNS) functions, although increased motor activity was observed after 14 days of treatment with the extract. Full article

Mooring systems are incorporated from mooring (thin) lines that are constituted of fiber ropes, steel wires, and chains. Mooring systems are used for the stationary keeping of floating units during the drilling process of oil and gas from offshore deep water, and the unloading of productions to the shuttle storage tanker. However, it is crucial to monitor mooring systems for early-stage failure detection in mooring lines during offshore mooring operations to avoid any unexpected losses, including human injuries, and catastrophic failure. This paper addresses the challenges of mooring line detection, and proposes a deep learning-based approach for the detection of mooring lines from marine images using the bounding box. A convolutional neural network, Inception v3, is used for the detection and classification of thin-line objects from marine images, and it is a pre-trained model with 1000 classes. Furthermore, various testing samples have been evaluated for assessing the performance of the pre-trained proposed model. According to the results, it has been observed that the proposed model obtained the highest accuracy (87.33%) in classifying the mooring line objects from images, but failed to accurately detect mooring lines. Furthermore, in a few highlighted cases, the performance of the model decreased in terms of accuracy due to the misclassification and wrong detection of mooring line objects. Despite this, the proposed study furnishes a potential solution for the detection of failure in mooring lines from marine images. Full article

Selegiline and rasagiline are two selective monoamine oxidase B (MAO-B) inhibitors used in the treatment of Parkinson’s disease. In their clinical application, however, differences in L-dopa-sparing potencies have been observed. The aim of this study was to find neurochemical and behavioral explanations for the antiparkinsonian effects of these drugs. We found that selegiline possesses a dopaminergic enhancer effect: it stimulated the electrically induced [³H]dopamine release without influencing the resting [³H]dopamine release from rat striatal slices in 10⁻¹⁰–10⁻⁹ mol/L concentrations. Rasagiline added in 10⁻¹³ to 10⁻⁵ mol/L concentrations did not alter the resting or electrically stimulated [³H]dopamine release. Rasagiline (10⁻⁹ mol/L), however, suspended the stimulatory effect of selegiline on the electrically induced [³H]dopamine release. The trace amine-associated receptor 1 (TAAR1) antagonist EPPTB (10⁻⁸–10⁻⁷ mol/L) also inhibited the stimulatory effect of selegiline on [³H]dopamine release. The effect of selegiline in its enhancer dose (5.33 nmol/kg) against tetrabenazine-induced learning deficit measured in a shuttle box apparatus was abolished by a 5.84 nmol/kg dose of rasagiline. The selegiline metabolite (−)methamphetamine (10⁻⁹ mol/L) also exhibited enhancer activity on [³H]dopamine release. We have concluded that selegiline acts as an MAO-B inhibitor and a dopaminergic enhancer drug, and the latter relates to an agonist effect on TAAR1. In contrast, rasagiline is devoid of enhancer activity but may act as an antagonist on TAAR1. Full article

A lack of transparency in machine learning models can limit their application. We show that analysis of variance (ANOVA) methods extract interpretable predictive models from them. This is possible because ANOVA decompositions represent multivariate functions as sums of functions of fewer variables. Retaining the terms in the ANOVA summation involving functions of only one or two variables provides an efficient method to open black box classifiers. The proposed method builds generalised additive models (GAMs) by application of L1 regularised logistic regression to the component terms retained from the ANOVA decomposition of the logit function. The resulting GAMs are derived using two alternative measures, Dirac and Lebesgue. Both measures produce functions that are smooth and consistent. The term partial responses in structured models (PRiSM) describes the family of models that are derived from black box classifiers by application of ANOVA decompositions. We demonstrate their interpretability and performance for the multilayer perceptron, support vector machines and gradient-boosting machines applied to synthetic data and several real-world data sets, namely Pima Diabetes, German Credit Card, and Statlog Shuttle from the UCI repository. The GAMs are shown to be compliant with the basic principles of a formal framework for interpretability. Full article

New treatment targets are needed for colorectal cancer (CRC). We define expression of High Mobility Group Box 1 (HMGB1) protein throughout colorectal neoplastic progression and examine the biological consequences of aberrant expression. HMGB1 is a ubiquitously expressed nuclear protein that shuttles to the cytoplasm under cellular stress. HMGB1 impacts cellular responses, acting as a cytokine when secreted. A total of 846 human tissue samples were retrieved; 6242 immunohistochemically stained sections were reviewed. Subcellular epithelial HMGB1 expression was assessed in a CRC Tissue Microarray (n = 650), normal colonic epithelium (n = 75), adenomatous polyps (n = 52), and CRC polyps (CaP, n = 69). Stromal lymphocyte phenotype was assessed in the CRC microarray and a subgroup of CaP. Normal colonic epithelium has strong nuclear and absent cytoplasmic HMGB1. With progression to CRC, there is an emergence of strong cytoplasmic HMGB1 (p < 0.001), pronounced at the leading cancer edge within CaP (p < 0.001), and reduction in nuclear HMGB1 (p < 0.001). In CRC, absent nuclear HMGB1 is associated with mismatch repair proteins (p = 0.001). Stronger cytoplasmic HMGB1 is associated with lymph node positivity (p < 0.001) and male sex (p = 0.009). Stronger nuclear (p = 0.011) and cytoplasmic (p = 0.002) HMGB1 is associated with greater CD4⁺ T-cell density, stronger nuclear HMGB1 is associated with greater FOXP3⁺ (p < 0.001) and ICOS⁺ (p = 0.018) lymphocyte density, and stronger nuclear HMGB1 is associated with reduced CD8⁺ T-cell density (p = 0.022). HMGB1 does not directly impact survival but is associated with an ‘immune cold’ tumour microenvironment which is associated with poor survival (p < 0.001). HMGB1 may represent a new treatment target for CRC. Full article

This study attempts to investigate the relationship between the accuracy of different Digital Elevation Model (DEM) and fractal dimension D and to solve the problem of determining the optimal catchment area threshold in plain watersheds. In this study, the fractal dimensions of the Shuttle Radar Topographic Survey Digital Elevation Model (SRTM) V4.1 DEM, Hydrology 1K (HYDRO1K) DEM, and Advanced Spaceborne Thermal Emission and Reflection Radiometer Global Digital Elevation Model (ASTER GDEM) with 90 m horizontal resolution and 30 m ASTER GDEM were calculated using the box dimension method, and the relationship between the horizontal resolution and accuracy of three data sources and fractal dimension D was studied. The optimal catchment area threshold in the study area was determined. The response of river network similarity and topographic features to DEM accuracy was explored, and the optimal catchment area threshold for the study area was verified. The result shows that, with the increase in the catchment area threshold, the fractal dimension D shows three stages of rapid decline, gentle fluctuation, and tend to 1. Compared with the horizontal resolution of DEM, the vertical accuracy has more influence on the fractal dimension D. The fractal dimension D accuracy increases with the increase in the vertical accuracy of DEM. The main order of influence of the three data sources is SRTM V4.1 DEM > ASTER GDEM > HYDRO1K DEM. The fractal dimension of the digital river network extracted by SRTM V4.1 DEM is 1.0245, the same as the fractal dimension of the actual river network. The optimal catchment area threshold of the study area is 4.05 km², which has the highest coincidence with the actual river network. In summary, using the SRTM V4.1 DEM as the DEM data source is feasible to determine the optimal catchment area threshold in plain watersheds. Full article

(1) Background: Exercise exerts many neuroprotective effects in diabetes-induced brain disorders. In this study, we investigated the effect of high-intensity interval training (HIIT) on brain molecular changes and cognitive and anxiety-like behaviors in rats with type 2 diabetes. (2) Methods: Twenty-eight adult male rats were divided into four groups (n = 7): control (C), exercise + control (C+EX), diabetes (DM), and diabetes + exercise (DM+EX). Diabetes was induced using a two-month high-fat diet and a single dose of streptozotocin (35 mg/kg) in the DM and DM+EX groups. After, the C+EX and DM+EX groups performed HIIT for eight weeks (five sessions per week, running at 80–100% of V_Max, 4–10 intervals) on a motorized treadmill. Then, the elevated plus maze (EPM) and open field test (OFT) were performed to evaluate anxiety-like behaviors. The Morris water maze (MWM) and shuttle box were used to assess cognitive function. The hippocampal levels of beta-amyloid and tau protein were also assessed using Western blot. (3) Results: The hippocampal levels of beta-amyloid and tau protein were increased in the DM group, but HIIT restored these changes. While diabetes led to a significant decrease in open arm time percentage (%OAT) and open arm enters percentage (%OAE) in the EPM, indicating anxiety-like behavior, HIIT restored them. In the OFT, grooming was decreased in diabetic rats, which was restored by HIIT. No significant difference between groups was seen in the latency time in the shuttle box or for learning and memory in the MWM. (4) Conclusions: HIIT-induced hippocampal molecular changes were associated with anxiety-like behavior improvement but not cognitive function in rats with type 2 diabetes. Full article

Stress induces neuroinflammation and disrupts sleep, which together can promote a number of stress-related disorders. Fear memories associated with stress can resurface and reproduce symptoms. Our previous studies have demonstrated sleep outcomes can be modified by stressor controllability following stress and fear memory recall. However, it is unknown how stressor controllability alters neuroinflammatory signaling and its association with sleep following fear memory recall. Mice were implanted with telemetry transmitters and experienced escapable or inescapable footshock and then were re-exposed to the shuttlebox context one week later. Gene expression was assessed with Nanostring^® panels using RNA extracted from the basolateral amygdala and hippocampus. Freezing and temperature were examined as behavioral measures of fear. Increased sleep after escapable stress was associated with a down-regulation in neuro-inflammatory and neuro-degenerative related genes, while decreased sleep after inescapable stress was associated with an up-regulation in these genes. Behavioral measures of fear were virtually identical. Sleep and neuroimmune responses appear to be integrated during fear conditioning and reproduced by fear memory recall. The established roles of disrupted sleep and neuroinflammation in stress-related disorders indicate that these differences may serve as informative indices of how fear memory can lead to psychopathology. Full article

We evaluated the determinants of cognitive performance in children and adolescents. This is a longitudinal study, secondary analysis of the Physical Activity and Nutrition in Children (PANIC) study. We assessed 502 children (51.6% girls) at middle childhood (range: 6.6 to 9.0 years), at late childhood, 437 children (51.0% girls, range: 8.8 to 11.2 years), and in 277 adolescents (54.5% girls, range: 15.0 to 17.4 years). Raven’s progressive matrices tests estimated the participants’ cognitive performance (outcome variable) at all time points. In total, we evaluated 29 factors from various dimensions (prenatal, neonatal, child fitness, lifestyle and anthropometrics). None of the neonatal and anthropometric parameters were associated with cognitive performance. Preeclampsia (prenatal) and listening to music, writing, arts and craft and watching TV (lifestyle) were negatively associated with cognitive performance. Shuttle run and box and block tests (fitness), and playing music, reading and time at the computer (lifestyle) were positive determinants of cognitive performance in children and adolescents. Fitness and lifestyle factors during childhood and adolescence diminished the importance of prenatal factors on cognitive performance and lifestyle factors were especially relevant in regard to cognitive performance. Reading was positively associated with cognitive performance, regardless of age and time dedicated, and should be promoted. Full article

The transition to terrestrial plants was accompanied by a progressive loss of microtubule minus-end-directed dynein motors. Instead, the minus-end-directed class-XIV kinesins expanded considerably, likely related to novel functions. One of these motors, OsDLK (Dual Localisation Kinesin from rice), decorates cortical microtubules but moves into the nucleus in response to cold stress. This analysis of loss-of-function mutants in rice indicates that OsDLK participates in cell elongation during development. Since OsDLK harbours both a nuclear localisation signal and a putative leucin zipper, we asked whether the cold-induced import of OsDLK into the nucleus might correlate with specific DNA binding. Conducting a DPI-ELISA screen with recombinant OsDLKT (lacking the motor domain), we identified the Opaque2 motif as the most promising candidate. This motif is present in the promoter of NtAvr9/Cf9, the tobacco homologue of Cold-Box Factor 4, a transcription factor involved in cold adaptation. A comparative study revealed that the cold-induced accumulation of NtAvr9/Cfp9 was specifically quelled in transgenic BY−2 cells overexpressing OsDLK-GFP. These findings are discussed as a working model, where, in response to cold stress, OsDLK partitions from cortical microtubules at the plasma membrane into the nucleus and specifically modulates the expression of genes involved in cold adaptation. Full article

Objective: To explore the effect and mechanism of peppermint essential oil on learning and memory ability of APP/PS1 transgenic mice. Methods: Morris water maze test and shuttle box test were used to explore the changes in learning and memory ability of APP/PS1 transgenic mice after sniffing essential oil. The cellular status of neurons in the hippocampal CA1 region of the right hemisphere, Aβ deposition, oxidative stress level, and serum metabonomics were detected to explore its mechanism. Results: Sniffing peppermint essential oil can improve the learning and memory ability of APP/PS1 transgenic mice. Compared with the model group, the state of neurons in the hippocampal CA1 region of the peppermint essential oil group returned to normal, and the deposition of Aβ decreased. The MDA of brain tissue decreased significantly, and the activity of SOD and GSH-PX increased significantly to the normal level. According to the results of metabonomics, it is speculated that peppermint essential oil may improve cognitive function in AD by regulating arginine and proline metabolism, inositol phosphate metabolism, and cysteine and methionine metabolism. Full article