Effects Of Stimuli Research Articles

Understanding responses of people with ASD in diverse reasoning tasks: A formal study.

Recent studies have shown that in some reasoning tasks people with Autism Spectrum Disorder perform better than typically developing people. This paper compares four such tasks, namely a syllogistic task, two decision-making tasks, and a task from the heuristics and biases literature, the aim being to identify common structure as well as differences. In the terminology of David Marr's three levels of cognitive systems, the tasks show commonalities on the computational level in terms of the effect of contextual stimuli, though an in-depth analysis of such contexts provides certain distinguishing features in the algorithmic level. We also make some general remarks on our approach, so as to set the stage for further studies in the area which could provide a better understanding of the reasoning process of ASD individuals.

Enhanced multisensory gain in older adults may be a by-product of inverse effectiveness: Evidence from a speeded response-time task.

Older adults experience a greater benefit from multisensory integration than their younger counterparts, but it is unclear why. One hypothesis is that age-related sensory decline weakens unisensory stimulus effectiveness, causing a boost in multisensory gain through inverse effectiveness. Many previous studies present stimuli at the same intensity for both younger and older adults (i.e., stimulus-matched), as opposed to accounting for each participant's unique perceptual ability (i.e., perception-matched). This makes it difficult to discern the source of age-related differences in multisensory gain. As such, we used two experiments to examine whether sensory decline is contributing to age-related differences in multisensory gain. In the first, we presented auditory (pure tones in noise), visual (Gabor patches in noise), and audiovisual stimuli and recorded response times from 31 younger (18-25) and 30 older (55-80) adults. Importantly, all participants were given identical stimuli, with the expectation that older adults would show worse unisensory performance, inducing inverse effectiveness. The second task was identical (younger N = 31, older N = 34), except stimuli were presented at each participant's 50% detection threshold, identified with an adaptive psychophysical staircase, controlling for any influence of inverse effectiveness. Older adults were found to exhibit greater multisensory gain (as measured by race model violations) on stimulus- but not perception-matched tasks, thus aligning with the principle of inverse effectiveness. That is, when accounting for potential age-related differences in perceptual abilities, older adults no longer experienced greater benefit from multisensory integration. These two experiments together suggest that the age-related increases in multisensory integration previously reported may be in part due to age-related declines in vision and audition. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Concentrated Growth Factor (CGF): A Potential New Player in Periodontal Regeneration

Regenerative procedures have become a key focus in contemporary rehabilitation therapies. In dentistry, research on growth factors for bone regeneration has identified autologous growth factors as the most effective stimuli for tissue regeneration and healing. These bioactive proteins play a crucial role in wound healing. Concentrated growth factor (CGF) is a recent advancement in 2 nd generation platelet concentrates. The use of different centrifugation speeds helps to obtain a significantly dense fibrin. Also, it contains more amount of growth factors than the other platelet concentrates available.

Preclinical evaluation of abuse potential of the peripherally-restricted kappa opioid receptor agonist HSK21542

HSK21542 is a peripherally-restricted kappa opioid receptor (KOR) agonist developed for pain treatment. Because of the CNS pharmacological concern of opioid receptor activation, such as physical dependence and addiction potential, an assessment of abuse potential of HSK21542 was required prior to marketing approval. The preclinical abuse potential assessments for HSK21542 included the following studies: 1) intravenous self-administration study to explore the relative reinforcing efficacy in rats self-administering remifentanil; 2) rat drug discrimination study to examine the pharmacological similarity of the interoceptive or subjective effects of HSK21542 in rats discriminating pentazocine; 3) rat conditioned place preference (CPP) paradigm to test the rewarding effects; 4) rat natural physical dependence-spontaneous withdrawal study in rats chronically treated with HSK21542; 5) naloxone-precipitated withdrawal assay following chronic HSK21542 exposure to evaluate its physical dependence potential. The results showed that HSK21542 was devoid of behavioral evidence of positive reinforcing effect and did not share similar discriminative stimulus effects with pentazocine. HSK21542 also did not produce CPP in rats. In addition, HSK21542 did not produce spontaneous withdrawal or naloxone-precipitated withdrawal in rats with chronic treatments. Collectively, these preclinical findings suggest that HSK21542 has no abuse potential in animals, which demonstrate low abuse potential in humans.

Relationship between Sensory Processing Sensitivity and Personality Traits

Reactions to stimuli vary from person to person. The same stimulus has different effects depending on the perception of different people and the physical and mental states they are in. Considering this difference, situations can be seen in which a person perceives a specific stimulus or group of stimuli as negative and disturbing for themselves. In particular, people with high levels of sensory processing sensitivity feel the negative effects of stimuli more intensely both in terms of their internal processes (hunger, pain, sadness, stress, etc.) and the situation of the physical environment (loud noise, bright light, pungent odor, etc.) which they are in. On the other hand, the existence of situations where sensory processing sensitivity has a positive effect is also noticeable. In this context, the relationship between sensory processing sensitivity and personality traits is examined. The concept of personality is explained in different ways by many different theorists in the international literature. In order to avoid confusion that may arise in the definition and understanding of personality traits, in this review study, personality traits are examined on the basis of the Five Factor Personality Theory. Within the framework of the personality definition of the Five Factor Personality Theory, The relationship between five basic personality traits and sensory processing sensitivity is examined by also considering the subdimensions of each five personality traits.

A Comparison of Ocular Vestibular Evoked Myogenic Potentials via Audiometric and Nonaudiometric Bone Vibrators.

There is limited evidence demonstrating the ability of audiometric bone vibrators to elicit ocular vestibular evoked myogenic potentials (oVEMPs). The RadioEar B71 bone vibrator has insufficient power output to reliably evoke oVEMPs, which has previously left nonaudiometric and nonmedically approved devices such as the Brüel & Kjær Mini-shaker 4810 as the only feasible alternative. The newer RadioEar B81 model has a higher power output than its predecessor, but evidence for its suitability for eliciting oVEMPs has so far been mixed. This variability may be due to factors other than simply the power output, such as whether sufficient static force is applied to hold the transducer in place and transfer vibratory energy into the bone. This study aimed to test the hypothesis that bone-conducted oVEMPs can be obtained with the B81 that are equivalent to those from the Mini-shaker, the de facto gold-standard transducer for this response, when the outputs of the two transducers are matched and they are coupled with sufficient static force. oVEMPs elicited by both transducers were recorded in a counterbalanced within-groups design. Sixteen healthy adults (12 female; 22-47 years) with no history of hearing, balance, or neurological disorders were included in the study. One-cycle alternating tone-burst stimuli at 500 Hz were delivered to the mastoid from each transducer. The vibratory force levels were matched at 127 dB peak-to-peak equivalent force levels, and both were held in place with a static force around 10 N. oVEMP waveforms were gathered from the contralateral eye using the belly-tendon montage and were assessed for statistical equivalence. There was an absence of any statistically significant difference in N10 and N10-P15 amplitudes in oVEMPs from each transducer. Our results indicate that B81 can elicit oVEMPs with no meaningful differences to those from the Mini-shaker, provided effective stimulus levels are matched and static force is sufficient. Although further work is necessary to investigate equivalence at other stimulus frequencies and stimulation sites, the results support the use of the B81 to elicit 500Hz oVEMPs at the mastoid in a clinical setting.

Combined Effects of Cyclic Hypoxic and Mechanical Stimuli on Human Bone Marrow Mesenchymal Stem Cell Differentiation: A New Approach to the Treatment of Bone Loss.

Background: The prevention and treatment of bone loss and osteoporotic fractures is a public health challenge. Combined with normobaric hypoxia, whole-body vibration has a high clinic potential in bone health and body composition. The effect of this therapy may be mediated by its action on bone marrow mesenchymal stem cells (MSCs). Objectives: Evaluate the effects of cyclic low-vibration stimuli and/or hypoxia on bone marrow-derived human MSC differentiation. Methods: MSCs were exposed four days per week, two hours/day, to hypoxia (3% O2) and/or vibration before they were induced to differentiate or during differentiation into osteoblasts or adipocytes. Gene and protein expression of osteoblastic, adipogenic, and cytoskeletal markers were studied, as well as extracellular matrix mineralization and lipid accumulation. Results: early osteoblastic markers increased in undifferentiated MSCs, pretreated in hypoxia and vibration. This pretreatment also increased mRNA levels of osteoblastic genes and beta-catenin protein in the early stages of differentiation into osteoblasts without increasing mineralization. When MSCs were exposed to vibration under hypoxia or normoxia during osteoblastic differentiation, mineralization increased with respect to cultures without vibrational stimuli. In MSCs differentiated into adipocytes, both in those pretreated as well as exposed to different conditions during differentiation, lipid formation decreased. Changes in adipogenic gene expression and increased beta-catenin protein were observed in cultures treated during differentiation. Conclusions: Exposure to cyclic hypoxia in combination with low-intensity vibratory stimuli had positive effects on osteoblastic differentiation and negative ones on adipogenesis of bone marrow-derived MSCs. These results suggest that in elderly or frail people with difficulty performing physical activity, exposure to normobaric cyclic hypoxia and low-density vibratory stimuli could improve bone metabolism and health.

Static magnetic field contributes to osteogenic differentiation of hPDLSCs through the H19/Wnt/β-catenin axis

BackgroundStatic magnetic field (SMF) as an effective physical stimulus is capable of osteogenic differentiation for multiple mesenchymal stem cells, including human periodontal ligament stem cells (hPDLSCs). However, the exact molecular mechanism is still unknown. Therefore, this study intends to excavate molecular mechanisms related to SMF in hPDLSCs using functional experiments. MethodshPDLSCs were treated with different intensities of SMF, H19 lentivirus, and Wnt/β-catenin pathway inhibitor (XAV939). Changes in osteogenic markers (Runx2, Col Ⅰ, and BMP2), Wnt/β-catenin markers (β-catenin and GSK-3β), and calcified nodules were examined using RT-qPCR, western blotting, and alizarin red staining in hPDLSCs. ResultsSMF upregulated the expression of H19, and SMF and overexpressing H19 facilitated the expression of osteogenic markers (Runx2, Col Ⅰ, and BMP2), activation of the Wnt/β-catenin pathway, and mineralized sediment in hPDLSCs. Knockdown of H19 alleviated SMF function, and treatment with XAV939 limited SMF- and H19-mediated osteogenic differentiation of hPDLSCs. Notably, the expression of hsa-miR-532-3p, hsa-miR-370-3p, hsa-miR-18a-5p, and hsa-miR-483-3p in hPDLSCs was regulated by SMF, and may form an endogenous competitive RNA mechanism with H19 and β-catenin. ConclusionSMF contributes to the osteogenic differentiation of hPDLSCs by mediating the H19/Wnt/β-catenin pathway, and hsa-miR-532-3p, hsa-miR-370-3p, hsa-miR-18a-5p, and hsa-miR-483-3p may be the key factors in it.

Government size and the effectiveness of fiscal policy: the bigger the better?

Abstract This study investigates the effect of government size, as measured by the tax revenue to gross domestic product (tax-GDP) ratio, on output responses to increases in government purchases. First, we show that in a standard static neoclassical model, the stimulus effect of fiscal expansion on output increases with the tax-GDP ratio. This finding is quantitatively confirmed using a dynamic neoclassical model with standard functional forms and parameter values. To empirically test the theoretical findings, we analyze the responses of macroeconomic variables to an unanticipated increase in government purchases for 12 Organisation for Economic Cooperation and Development (OECD) countries during 1985–2019 using a state-dependent local projection method. The estimation results reveal that while output responses to an unanticipated fiscal expansion are significantly positive when the tax-GDP ratio is high, they are statistically indistinguishable from zero when the ratio is low. Overall, our findings suggest that fiscal expansion can stimulate output more effectively at high tax rates, unlike the well-known predictions of the traditional Keynesian model.

Cell‐preserving scheme for mechanobiological research on dedifferentiation of chondrocytes

AbstractIn the present work, we introduce a scheme for efficient mechanobiological research on the dedifferentiation of chondrocytes (CHs) using a deep neural network (DNN) model that does not require sacrificing the cells and thus, saving resources. Cells are a part of active biological systems subjected to physical stimuli such as mechanical loading. Such loading affects cellular processes including proliferation, differentiation, and the interplay with the surrounding environment. CHs are mechanosensitive cells that produce and maintain the cartilaginous matrix that allows cartilage to bear and distribute mechanical loads in joints; their role in cartilage regeneration and treatment of osteoarthritis (OA) has been the focus of research projects. Nevertheless, it remains an open challenge to fully understand the effect of mechanical stimuli on CHs. One of the unresolved mechanobiological behaviors of CHs is dedifferentiation. Dedifferentiation of CHs is the phenomenon where isolated CHs alter their phenotype when cultured in a 2D in vitro environment over passages. While intact, cobblestone‐shaped CHs mainly produce collagen II, dedifferentiated CHs with elongated shapes produce fibroblastic collagen I. This limits the scalability of a promising treatment for OA, called ‘autologous chondrocyte implantation (ACI)’. To overcome this limit, research is being carried out to understand the dedifferentiation mechanism in detail. This proposed scheme is composed of three parts: (i) the cell‐seeded specimens are loaded in a bioreactor system, (ii) an optical microscope is used to obtain the phase‐contrast images of living cells, and (iii) the images are analyzed using a DNN. This scheme provides an efficient tool to analyze the ratio of intact to dedifferentiated CHs while preserving cells on our way to elucidate the effects of mechanical loading on the dedifferentiation of CHs.

DCE attribute development investigating public policy for the provision of medicinal cannabis

Background Defining attributes and attribute levels for a discrete choice experiment (DCE) poses a significant challenge for practitioners exploring preferences for new or unfamiliar products due to the dearth of available information and limits in stakeholder knowledge. This study outlines a comprehensive process for identifying attributes and levels in a DCE aimed at gauging public preferences for health policies related to medicinal cannabis (MC). Methods A rigorous four-stage attribute development process was utilized and included i) the formulation of a preliminary attribute list from a scoping review and document analysis, ii) reduction of attributes via focus groups, iii) removal of inappropriate attributes using Delphi studies and research team knowledge, and iv) refinement of attribute language based on the feedback from think-aloud interviews. Results A base attribute list formed from the scoping review and document analysis served as effective discussion stimuli in focus groups, especially for participants with limited subject knowledge. Structured focus group activities proved more effective than open-ended discussions in engaging naive participants. Delphi studies were found to be overcomplex for expert-led attribute prioritization. Think-aloud interviews during a pilot DCE were essential for assessing attribute language and clarity and understanding participants’ decision-making processes. Conclusion The development of DCE attributes measuring preferences for an unfamiliar health product requires a multi-method approach. Evaluating the outcomes from various methods of attribute development yielded a refined list of attributes that were significant to stakeholders, allowed for meaningful trade-offs, and were presented in language accessible to the target population.

Some properties of habituation of siphon withdrawal in the slimy clam (Ruditapes decussatus)

A first approximation to the study of learning processes in bivalves is presented. A habituation procedure was developed using the slimy clam Ruditapes decussatus. The percentage of siphon withdrawal when they were exposed to a white light was measured. In Experiment 1, a habituation-discrimination procedure was used to study the stimulus intensity effect (350-lm vs 806 lm). Clams exposed to 350-lm showed a faster habituation than those exposed to 806-lm. Experiment 2 studied the effect of stimulus and intertrial interval (ITI) duration using a 2×2 design. Trials lasted 20 or 180 seconds, and the ITI lasted 5 or 10 minutes. A combined effect of these two parameters was obtained. Habituation was faster in clams exposed to 180-sec trials with a 5-min ITI. Finally, in Experiment 3 clams were trained with five blocks of five trials with a 5-min ITI. Groups differed on trial duration (20 or 180 s). The results showed a general spontaneous recovery effect that was more pronounced for the 180 s group. Also, it was found in this experimental condition a reduced response 24 hours after finishing training (long-term habituation). Altogether, this series of experiments constitutes a first systematic demonstration of habituation in bivalves.

Differential Anti-Inflammatory Effects of Electrostimulation in a Standardized Setting.

The therapeutic usage of physical stimuli is framed in a highly heterogeneous research area, with variable levels of maturity and of translatability into clinical application. In particular, electrostimulation is deeply studied for its application on the autonomous nervous system, but less is known about the anti- inflammatory effects of such stimuli beyond the inflammatory reflex. Further, reproducibility and meta-analyses are extremely challenging, owing to the limited rationale on dosage and experimental standardization. It is specifically to address the fundamental question on the anti-inflammatory effects of electricity on biological systems, that we propose a series of controlled experiments on the effects of direct and alternate current delivered on a standardized 3D bioconstruct constituted by fibroblasts and keratinocytes in a collagen matrix, in the presence or absence of TNF-α as conventional inflammation inducer. This selected but systematic exploration, with transcriptomics backed by metabolomics at specific time points allows to obtain the first systemic overview of the biological functions at stake, highlighting the differential anti-inflammatory potential of such approaches, with promising results for 5 V direct current stimuli, correlating with the wound healing process. With our results, we wish to set the base for a rigorous systematic approach to the problem, fundamental towards future elucidations of the detailed mechanisms at stake, highlighting both the healing and damaging potential of such approaches.

Exploration on the spiking response of a single compartment neuron with multiple active properties under electrical stimuli

The study of modulating the neuronal signals by electrical stimuli is important to intervene the abnormal neuronal firing and bring them to a normal state. Spike trains, which are the highest quality of brain signals, have been deficiently explored and analyzed owing to the challenges of obtaining them in reality. In this regard, this paper aims to investigate and analyze the effect of electrical stimuli on the spiking response of neurons, and the following work is to be carried out. The relationships between the spiking response and three parameters (namely, the amplitude of the electrode current (EC), the angular velocity of the electric field current (EFC), and the signal-noise ratio (SNR)) are examined on a neuronal model with spatial length and multiple active properties. When specific currents with different SNRs are imposed on the neurons, their influence on the spiking response is further explored. With regard to the spiking response, the main focus is on three characteristics, i.e., the spiking pattern, the spike count (SC), and the spiking arrangement. An algorithm, called the return map distance (RMD) algorithm, is proposed in this paper, and gives the classification of spiking patterns a quantitative criterion. Based on it, the spiking patterns are classified in this paper as busting spike train, regular spike train (RST), and meager spike train (MST). Simulation results indicate that both the amplitude of the EC and the angular velocity of the EFC change the neuronal spiking patterns. As the amplitude (angular velocity) of the EC (EFC) increases, the spiking pattern of the Soldado-Magraner model (SMM) eventually tends to RST (MST). In addition, the SC increases with the amplitude of the EC, while it does not hold for the SC with respect to the angular velocity of the EFC. Furthermore, the spiking arrangement and the SC are severely destroyed for the EC with low SNRs, while three spiking features of the SMM under EFC are all robust to the different SNRs, which implies that compared with the EC, the spiking responses of the SMM under EFC are more stable. The findings in this paper may provide some theoretical guidance to the fields related to neuronal firing, such as brain-computer interfaces and electrotherapy. The RMD algorithm proposed here can be applied to more individual neurons, and the spiking arrangement discussed here could be regarded as an effective encoding way for spike trains.

Synergistic effects of biological stimuli and flexion induce microcavities promote hypertrophy and inhibit chondrogenesis during in vitro culture of human mesenchymal stem cell aggregates.

Interzone/cavitation are key steps in early stage joint formation that have not been successfully developed in vitro. Further, current models of endochondral ossification, an important step in early bone formation, lack key morphology morphological structures such as microcavities found during development in vivo. This is possibly due to the lack of appropriate strategies for incorporating chemical and mechanical stimuli that are thought to be involved in joint development. We designed a bioreactor system and investigated the synergic effect of chemical stimuli (chondrogenesis-inducing [CIM] and hypertrophy-inducing medium [HIM]) and mechanical stimuli (flexion) on the growth of human mesenchymal stem cells (hMSCs) based linear aggregates under different conditions over 4 weeks of perfusion culture. Computational studies were used to evaluate tissue stress qualitatively. After harvesting, both Safranin-O and hematoxylin & eosin (H&E) staining histology demonstrated microcavity structures and void structures in the region of higher stresses for tissue aggregates cultured only in HIM under flexion. In comparison to either HIM treatment or flexion only, increased glycosaminoglycan (GAG) content in the extracellular matrix (ECM) at this region indicates the morphological change resembles the early stage of joint cavitation; while decreased type II collagen (Col II), and increased type X collagen (Col X) and vascular endothelial growth factor (VEGF) with a clear boundary in the staining section indicates it resembles the early stage of ossification. Further, cell alignment analysis indicated that cells were mostly oriented toward the direction of flexion in high-stress region only in HIM under flexion, resembling cell morphology in both joint cavitation and hypertrophic cartilage in growth plate. Collectively, our results suggest that flexion and HIM inhibit chondrogenesis and promote hypertrophy and development of microcavities that resemble the early stage of joint cavitation and endochondral ossification. We believe the tissue model described in this work can be used to develop in vitro models of joint tissue for applications such as pathophysiology and drug discovery.

An Opinion on the Interpretation of Bone Turnover Markers Following Acute Exercise or Nutrition Intervention and Considerations for Applied Research.

It is important for athlete and public health that we continue to develop our understanding of the effects of exercise and nutrition on bone health. Bone turnover markers (BTMs) offer an opportunity to accelerate the progression of bone research by revealing a bone response to exercise and nutrition stimuli far more rapidly than current bone imaging techniques. However, the association between short-term change in the concentration of BTMs and long-term bone health remains ambiguous. Several other limitations also complicate the translation of acute BTM data to applied practice. Importantly, several incongruencies exist between the effects of exercise and nutrition stimuli on short-term change in BTM concentration compared with long-term bone structural outcomes to similar stimuli. There are many potential explanations for these inconsistencies, including that short-term study designs fail to encompass a full remodeling cycle. The current article presents the opinion that data from relatively acute studies measuring BTMs may not be able to reliably inform applied practice aiming to optimize bone health. There are important factors to consider when interpreting or translating BTM data and these are discussed.

A Pro-Inflammatory Stimulus versus Extensive Passaging of DITNC1 Astrocyte Cultures as Models to Study Astrogliosis.

Astrogliosis is a process by which astrocytes, when exposed to inflammation, exhibit hypertrophy, motility, and elevated expression of reactivity markers such as Glial Fibrillar Acidic Protein, Vimentin, and Connexin43. Since 1999, our laboratory in Chile has been studying molecular signaling pathways associated with "gliosis" and has reported that reactive astrocytes upregulate Syndecan 4 and αVβ3 Integrin, which are receptors for the neuronal glycoprotein Thy-1. Thy-1 engagement stimulates adhesion and migration of reactive astrocytes and induces neurons to retract neurites, thus hindering neuronal network repair. Reportedly, we have used DITNC1 astrocytes and neuron-like CAD cells to study signaling mechanisms activated by the Syndecan 4-αVβ3 Integrin/Thy-1 interaction. Importantly, the sole overexpression of β3 Integrin in non-reactive astrocytes turns them into reactive cells. In vitro, extensive passaging is a simile for "aging", and aged fibroblasts have shown β3 Integrin upregulation. However, it is not known if astrocytes upregulate β3 Integrin after successive cell passages. Here, we hypothesized that astrocytes undergoing long-term passaging increase β3 Integrin expression levels and behave as reactive astrocytes without needing pro-inflammatory stimuli. We used DITNC1 cells with different passage numbers to study reactivity markers using immunoblots, immunofluorescence, and astrocyte adhesion/migration assays. We also evaluated β3 Integrin levels by immunoblot and flow cytometry, as well as the neurotoxic effects of reactive astrocytes. Serial cell passaging mimicked the effects of inflammatory stimuli, inducing astrocyte reactivity. Indeed, in response to Thy-1, β3 Integrin levels, as well as cell adhesion and migration, gradually increased with multiple passages. Importantly, these long-lived astrocytes expressed and secreted factors that inhibited neurite outgrowth and caused neuronal death, just like reactive astrocytes in culture. Therefore, we describe two DITNC1 cell types: a non-reactive type that can be activated with Tumor Necrosis Factor (TNF) and another one that exhibits reactive astrocyte features even in the absence of TNF treatment. Our results emphasize the importance of passage numbers in cell behavior. Likewise, we compare the pro-inflammatory stimulus versus long-term in-plate passaging of cell cultures and introduce them as astrocyte models to study the reactivity process.

The path to the G protein-coupled receptor structural landscape: Major milestones and future directions.

G protein-coupled receptors (GPCRs) play a crucial role in cell function by transducing signals from the extracellular environment to the inside of the cell. They mediate the effects of various stimuli, including hormones, neurotransmitters, ions, photons, food tastants and odorants, and are renowned drug targets. Advancements in structural biology techniques, including X-ray crystallography and cryo-electron microscopy (cryo-EM), have driven the elucidation of an increasing number of GPCR structures. These structures reveal novel features that shed light on receptor activation, dimerization and oligomerization, dichotomy between orthosteric and allosteric modulation, and the intricate interactions underlying signal transduction, providing insights into diverse ligand-binding modes and signalling pathways. However, a substantial portion of the GPCR repertoire and their activation states remain structurally unexplored. Future efforts should prioritize capturing the full structural diversity of GPCRs across multiple dimensions. To do so, the integration of structural biology with biophysical and computational techniques will be essential. We describe in this review the progress of nuclear magnetic resonance (NMR) to examine GPCR plasticity and conformational dynamics, of atomic force microscopy (AFM) to explore the spatial-temporal dynamics and kinetic aspects of GPCRs, and the recent breakthroughs in artificial intelligence for protein structure prediction to characterize the structures of the entire GPCRome. In summary, the journey through GPCR structural biology provided in this review illustrates how far we have come in decoding these essential proteins architecture and function. Looking ahead, integrating cutting-edge biophysics and computational tools offers a path to navigating the GPCR structural landscape, ultimately advancing GPCR-based applications.

Stimulus effects of extremely low-frequency electric field exposure on calcium oscillations in a human cortical spheroid.

High-intensity, low-frequency (1 Hz to 100 kHz) electric and magnetic fields (EF and MF) cause electrical excitation of the nervous system via an induced EF (iEF) in living tissue. However, the biological properties and thresholds of stimulus effects on synchronized activity in a three-dimensional (3D) neuronal network remain uncertain. In this study, we evaluated changes in neuronal network activity during extremely low-frequency EF (ELF-EF) exposure by measuring intracellular calcium ([Ca2+]i) oscillations, which reflect neuronal network activity. For ELF-EF exposure experiments, we used a human cortical spheroid (hCS), a 3D-cultured neuronal network generated from human induced pluripotent stem cell (hiPSC)-derived cortical neurons. A 50 Hz sinusoidal ELF-EF exposure modulated [Ca2+]i oscillations with dependencies on exposure intensity and duration. Based on the experimental setup and results, the iEF distribution inside the hCS was estimated using high-resolution numerical dosimetry. The numerical estimation revealed threshold values ranging between 255-510 V/m (peak) and 131-261 V/m (average). This indicates that thresholds of neuronal excitation in the hCS were equivalent to those of a thin nerve fiber.

Comparison of Studies Conducted in the Field of Neuromarketing and Artificial Intelligence Using Bibliometric Method

Abstract Neuromarketing research focuses on consumer purchase intention, decision-making processes, purchase behavior, brand awareness, brand loyalty, and repeat purchase behavior. In these studies, consumer behavior has been analyzed using neuroscientific methods and tools. The most commonly used tools include Functional Magnetic Resonance Imaging (fMRI), Eye Tracking, Electroencephalogram (EEG), Positron Emission Tomography (PET), Transcranial Magnetic Stimulation (TMS), Magnetoencephalogram (MEG), Steady State Topography (SST), Implicit Association Test (IAT), Facial Electromyography (fEMG), Automatic Face Coding (AFC), Skin Conductance Response (SCR), and other methods for measuring physiological responses. However, the use of these neuroscientific tools is not always possible due to economic constraints and lack of experimental design. Neuroscientific imaging and measurement methods are not preferred in every study due to their high costs and expertise requirements. However, when neuromarketing studies are examined, it is seen that methods such as Eye Tracking, EEG and fMRI are used more widely. These tools contribute to a deeper understanding of consumer behavior. In order to better analyze consumer behavior, it is of great importance to convey marketing stimuli and messages correctly. In the field of marketing, the effect of stimuli conveyed to consumers using the five senses is one of the focal points of neuromarketing. More than one neuroscientific method should be used together to understand consumer intentions, thoughts and purchasing behaviors. In this way, the obtained data can be analyzed more comprehensively and clearer insights can be provided about neuromarketing. The aim of this study is to present a comprehensive assessment of the use of neuroscientific tools by examining the publications in the field of neuromarketing in the Web of Science database between 2010-2024 with bibliometric analysis. The study will address the limitations of not using more than one neuroscientific tool together in neuromarketing research and the inadequacy of analyses supported by artificial intelligence. A more holistic approach will be proposed to address these shortcomings and a guiding resource for future research will be created.