Nonspecific Stimuli Research Articles

Influence of Unspecific Visual-Perceptual-Cognitive Task Constraints on Jump Ability and Reactive Strength in Federated Soccer Players.

Soccer players must react quickly and execute complex mental processes to adapt to competitive scenarios while maintaining peak physical performance. Perceptual-cognitive training methods integrate reaction tasks using nonspecific visual stimuli with game-like motor actions, but the impact on explosive strength responses is unclear. This study investigates the effect of nonspecific visual stimuli with varying perceptual-cognitive constraints on jump performance, including countermovement jump height, reactive strength index modified, action time, and reaction time. A total of 299 soccer players were randomly assigned to four groups to assess the impact of different perceptual-cognitive tasks on countermovement jump performance. The results showed a significant reduction in jump height in all groups, with the most pronounced effect in the divided/attention simple reaction time task group (Δ height = -4.74 cm; p < 0.001). Action time was significantly shorter in all experimental jumps compared with controls (p < 0.001), and the reactive strength index modified increased across perceptual-cognitive tasks (p < 0.001) except in the divided/attention simple reaction time (p = 0.593). Reaction time increased in all groups, with the highest in the complex elective reaction time task (487.32 ± 153.75 ms; p < 0.001). These findings suggest that nonspecific visual stimuli negatively affect countermovement jump performance, highlighting the importance of analyzing sport-specific perceptual-cognitive demands in the development of efficient training programs.

Language-Specific Sound-Shape Matching at 12-Months of Age

ABSTRACT By 12 months of age, infants exhibit behavioral sensitivity to sound symbolism (e.g. sound-shape correspondences) when they hear universally sound symbolic pseudowords (e.g. “bouba,” “kiki”). Here, we investigated whether infant’s sensitivity to sound-shape correspondences is affected when they hear language-specific sound symbolic words. Using the spontaneous preference-looking paradigm, we tested 12-month-old monolingual Spanish (n = 13) and Basque (n = 16) infants matching Spanish-like pseudowords (i.e. “bubano,” “raceto”) with rounded and spiky shapes. These pseudowords were created by Spanish-Basque bilingual adults, who then rated pseudowords as more Spanish or Basque-like, and more rounded or spikey-like. Infants were presented with eight congruent (e.g. “bubano” presented with a rounded shape) and incongruent (e.g. “bubano” presented with a spiky shape) trials. Both Spanish and Basque-learning infants displayed similar increased sensitivity to incongruent than to congruent trials. We found weak evidence that language background modulates sound-shape correspondence. These results suggest that at 12 months of age, specific language experience (e.g. Spanish vs. Basque) most likely does not alter sound-shape bias when hearing Spanish-like sound combinations. This study was the first to utilize language-specific instead of language nonspecific stimuli. Nonetheless, similar to previous investigations, the sound-shape bias effect was exhibited at 12 months of age in both language groups.

Universal Signal Switch Based on a Mesostructured Silica Xerogel-Confined ECL Polymer for Epigenetic Quantification.

The development of a highly accurate electrochemiluminescence (ECL) signal switch to avoid nonspecific stimulus responses is currently a significant and challenging task. Here, we constructed a universal signal switch utilizing a luminophore-quencher pair of mesostructured silica xerogel-confined polymer and gold nanoparticles (Au NPs) that can accurately detect low-abundance epigenetic markers in complex sample systems. Notably, the ECL polymer encapsulated in mesostructured silica xerogel acts as a luminophore, which demonstrated a highly specific dependence on the Au NPs-mediated energy transfer quenching. To demonstrate the feasibility, we specifically labeled the 5-hydroxymethylcytosine (5hmC) site on the random sequence using a double-stranded (dsDNA) tag that was skillfully designed with the CRISPR/Cas12a activator and recombinant polymerase amplification (RPA) template. After amplification by RPA, a large amount of dsDNA tag was generated as the activator to initiate the trans-cleavage activity of CRISPR/Cas12a and subsequently activate the signal switch, allowing for precise quantification of 5hmC. The ECL signal switch improves the stability of the luminophore and prevents nonspecific stimulus responses, providing a new paradigm for constructing high-precision biosensors.

Мониторинг загрузки управляющих функций в решении инсайтных задач с использованием парадигмы сингл-тон

Abandoning the strategy of consciously searching for a solution can be an insight mechanism. A number of studies have shown that control is important for both insightful and non-insightful tasks. From this it follows that the control has different functions. Insight occurs in several stages, at which the role of control is different. In the beginning, the task is solved as noninsightful and control is needed for intelligence. This continues until an impasse in the solution is reached. Next, intuitive processes come to the first role, and the role of control is decreasing. To study the dynamics of control, the subject performs a dual task, solving the main task (insightful or non-insightful, visual or verbal) and simultaneously reacting to sound stimuli (two levels of complexity of reactions). To study the role of control, we propose to use modally non-specific stimuli (sound signals) presented in the single tone paradigm. Twenty-five people took part in the study. No significant differences in dynamics were obtained. The probe-task was performed much more slowly from the middle stage of solving a non-insightful task to the end of the solution. The execution of the probe-task when solving the insightful task was uniform. A non-insightful task forces you to operate with voluminous intermediate data; this requires more resources of the central executor block.

Toll-like receptors: their roles in pathomechanisms of atopic dermatitis.

The skin functions as a physical barrier and represents the first line of the innate immune system. There is increasing evidence that toll-like receptors (TLRs) are involved in the pathomechanisms of not only infectious diseases, but also non-infectious inflammatory diseases. Interestingly, it has been demonstrated that TLRs recognize both exogenous threats, e.g. bacteria and viruses, and endogenous danger signals related to inflammation, cell necrosis, or tissue damage. Atopic dermatitis (AD) is a chronic relapsing inflammatory skin disease, which is associated with impaired skin barrier function, increased skin irritability to non-specific stimuli, and percutaneous sensitization. The impairment of skin barrier function in AD allows various stimuli, such as potential allergens and pathogens, to penetrate the skin and activate the innate immune system, including TLR signaling, which can lead to the development of adaptive immune reactions. In this review, I summarize the current understanding of the roles of TLR signaling in the pathogenesis of AD, with special emphasis on skin barrier function and inflammation.

Lower female survival from an opportunistic infection reveals progesterone-driven sex bias in trained immunity

Immune responses differ between females and males, although such sex-based variance is incompletely understood. Observing that bacteremia of the opportunistic pathogen Burkholderia gladioli caused many more deaths of female than male mice bearing genetic deficiencies in adaptive immunity, we determined that this was associated with sex bias in the innate immune memory response called trained immunity. Female attenuation of trained immunity varies with estrous cycle stage and correlates with serum progesterone, a hormone that decreases glycolytic capacity and recall cytokine secretion induced by antigen non-specific stimuli. Progesterone receptor antagonism rescues female trained immune responses and survival from controlled B.gladioli infection to magnitudes similar to those of males. These data demonstrate progesterone-dependent sex bias in trained immunity where attenuation of female responses is associated with survival outcomes from opportunistic infection.

A pull to be close: The differentiating effects of oxytocin and grief stimulus type on approach behavior in complicated grief

Theoretical models of complicated grief (CG) suggest that maladaptive motivational tendencies (e.g., perseverative proximity-seeking of the deceased; excessive avoidance of reminders) interfere with a person's ability to recover from their loved one's death. Due in part to conflicting evidence, little mechanistic understanding of how these behaviors develop in grief exists. We sought to (1) identify behavioral differences between CG and non-CG groups based on approach/avoidance bias for grief-, deceased-, and social-related stimuli, and (2) test the role of the neuropeptide oxytocin in shaping approach/avoidance bias. Widowed older adults with (n = 17) and without (n = 22) CG completed an approach/avoidance task measuring implicit bias for both personalized and non-specific grief-related stimuli (among other stimuli). In a double-blinded, randomized, counterbalanced design, each participant attended both an intranasal oxytocin session and a placebo session. Aims were to (1) identify differential effects of CG and stimulus type on implicit approach/avoidance bias [placebo session], and (2) investigate interactive effects of CG, stimulus type, and oxytocin vs. placebo on approach/avoidance bias [both sessions]. In the placebo session, participants in the non-CG group demonstrated an approach bias across all stimuli. Intranasal oxytocin had an overall slowing effect on the CG group's response times. Further, oxytocin decreased avoidance bias in response to photos of the deceased spouse in the CG group only. Findings support the hypothesis that oxytocin has a differential effect on motivational tendency in CG compared to non-CG, strengthening evidence for its role in CG. Findings also emphasize the need to consider differences in personalized vs. generic stimuli when designing grief-relevant tasks.

New models of Parkinson's like neuroinflammation in human microglia clone 3: Activation profiles induced by INF-γ plus high glucose and mitochondrial inhibitors.

Microglia activation and neuroinflammation have been extensively studied in murine models of neurodegenerative diseases; however, to overcome the genetic differences between species, a human cell model of microglia able to recapitulate the activation profiles described in patients is needed. Here we developed human models of Parkinson's like neuroinflammation by using the human microglia clone 3 (HMC3) cells, whose activation profile in response to classic inflammatory stimuli has been controversial and reported only at mRNA levels so far. In fact, we showed the increased expression of the pro-inflammatory markers iNOS, Caspase 1, IL-1β, in response to IFN-γ plus high glucose, a non-specific disease stimulus that emphasized the dynamic polarization and heterogenicity of the microglial population. More specifically, we demonstrated the polarization of HMC3 cells through the upregulation of iNOS expression and nitrite production in response to the Parkinson's like stimuli, 6-hydroxidopamine (6-OHDA) and 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), the latter depending on the NF-κB pathway. Furthermore, we identified inflammatory mediators that promote the pro-inflammatory activation of human microglia as function of different pathways that can simulate the phenotypic transition according to the stage of the pathology. In conclusion, we established and characterized different systems of HMC3 cells activation as in vitro models of Parkinson's like neuroinflammation.

Exploring acute and non-specific effects of mobile app-based response inhibition training on food evaluation and intake

Previous studies have demonstrated that response inhibition training can modify the appeal of palatable and energy-dense foods, thus serving as a potential intervention for weight management, via changes in food selection and intake. However, empirical findings of efficacy have been inconsistent across studies due to heterogenous approaches to measuring salient appetitive outcomes, training implementation strategies, and sample recruitment. Systematic assessment of both affective and motivational components of food reward may help characterise to what extent devaluation can be generalised to nutritionally similar foods post-training. In this mixed factorial experiment, a non-clinical, adult sample completed time-matched single sessions with mobile app-based response inhibition training and control tasks of short (12 min; n = 27) or long (20 min; n = 25) duration. Participants were assessed on two discrete facets of food reward pre- and post-training: pleasure (i.e., explicit liking) and desire (i.e., implicit wanting) for non-specific (i.e., novel) food stimuli differing in energy-density. Consumption of snacks categorised by energy density was also assessed in a laboratory ad libitum taste test post-training. No significant differences were found between intervention and control sessions on explicit liking or implicit wanting for non-specific energy-dense foods. Moreover, participants ate a similar volume of snack foods during both sessions. Training duration did not significantly moderate differences between intervention and control sessions in primary outcomes. Variance between intervention and control sessions in chocolate intake and frequency of choice for energy-dense foods, but not explicit liking, was associated with a higher BMI. Methodological and theoretical implications for appropriate intervention implementation and underlying mechanisms, respectively, are discussed.

Application of a Cold Dry Air Provocation Test in Pediatric Patients with Asthma.

Asthma is a chronic inflammatory airway disease characterized by reversible airway obstruction and airway hyperreactivity. We proposed a cold dry air (CDA) provocation test and investigated its application in pediatric patients with asthma. We enrolled 72 children and adolescents older than 5 years who presented to our hospital with chronic cough, shortness of breath, and wheezing. We analyzed the results of allergy, pulmonary function, methacholine provocation, and CDA provocation tests. The FEV1 change 5 min after the provocation was recorded as CDA5 dFEV1; that after 15 min was recorded as CDA15 dFEV1. PT10 was the provocation time causing a 10% decrease in FEV1; a decrease of >10% in dFEV1 was considered a positive CDA test. Among the 72 subjects, 51 were diagnosed with asthma. A positive CDA test in patients with asthma correlated with non-eosinophilic asthma. In patients with asthma, sputum eosinophils and eosinophil cationic protein (ECP) levels of the patients with a positive CDA test were significantly lower than those of patients with a negative test. CDA5 dFEV1 correlated with PC20 and total immunoglobulin E. CDA15 dFEV1 correlated with PC20, sputum eosinophils, and ECP. PT10 became shorter as the peripheral blood eosinophil, FVC, FEV1, FEV1/FVC, and FEF25-75 decreased. The CDA provocation test showed airway hyperreactivity to non-specific stimuli, a high correlation with non-eosinophilic asthma, and the possibility of assessing asthma severity via PT10.

Palatine tonsils functional reserve in children by immunological indicators evaluation

Today, indications for tonsillectomy are based mainly on clinical criteria rather than on the functional state of palatine tonsils (PT). Determination of secretory immunoglobulin A (sIgA) levels in the oropharyngeal secretion before and after antigen load on PT is one of the methods for determining their functional capacity. However, this method has certain disadvantages, in particular not only PT were in the area of influence of both specific and non-specific stimuli, but also other lymphoid structures of the pharynx. The aim of the study is to improve the assessment of the immunofunctional state of PT. Materials and methods. The authors investigated by enzyme-linked immunosorbent assay (ELISA) sIgA and IFN-α content in oropharyngeal secretions in children with CT before and after antigen challenge vaccine OM-85 and the physical impact of ultrasound frequency of 880 kHz on the palatine tonsils. All the results were statistically processed using U-test (Mann–Whitney–Wilcoxon test) and Fisher's z-transformation. Results and Conclusion. The proposed method has significant advantages over the existing one, namely it is more selective, and therefore more accurate in determining the functional state of PT. Increased levels of sIgA and IFN-α in children’s oropharyngeal secretions suggest maintaining the functional reserve of the tonsils; the absence of positive dynamics or negative dynamics of this indicator shows a functional failure of PT and can serve as an indication for surgical treatment of children with CT. The research was carried out in accordance with the principles of the Declaration of Helsinki. The research protocol was approved by the Local Ethics Committee of all the institutions mentioned in the work. Informed consent of the children’s parents was obtained for the research. No conflict of interests was declared by the authors. Key words: chronic tonsillitis, saliva, tonsillectomy indications, functional reserve.

Robust engraftment of fetal nonhuman primate CD34-positive cells in immune-deficient mice.

Nonhuman primates (NHPs) represent one of the most important models for preclinical studies of novel biomedical interventions. In contrast with small animal models, however, widespread utilization of NHPs is restricted by cost, logistics, and availability. Therefore, we sought to develop a translational primatized mouse model, akin to a humanized mouse, to allow for high-throughput in vivo experimentation leveraged to inform large animal immunology-based studies. We found that adult rhesus macaque mobilized blood (AMb) CD34+-enriched hematopoietic stem and progenitor cells (HSPCs) engrafted at low but persistent levels in immune-deficient mice harboring transgenes for human (NHP cross-reactive) GM-CSF and IL3, but did not in mice with wild-type murine cytokines lacking NHP cross-reactivity. To enhance engraftment, fetal liver-derived HSPCs were selected as the infusion product based on an increased CD34hi fraction compared with AMb and bone marrow. Coupled with cotransplantation of rhesus fetal thymic fragments beneath the mouse kidney capsule, fetal liver-derived HSPC infusion in cytokine-transgenic mice yielded robust multilineage lymphohematopoietic engraftment. The emergent immune system recapitulated that of the fetal monkey, with similar relative frequencies of lymphocyte, granulocyte, and monocyte subsets within the thymic, secondary lymphoid, and peripheral compartments. Importantly, while exhibiting a predominantly naïve phenotype, in vitro functional assays demonstrated robust cellular activation in response to nonspecific and allogenic stimuli. This primatized mouse represents a viable and translatable model for the study of hematopoietic stem cell physiology, immune development, and functional immunology in NHPs. Summary Sentence: Engraftment of rhesus macaque hematopoietic tissues in immune-deficient mice yields a robust BLT/NeoThy-type primatized mouse model for studying nonhuman primate hematopoiesis and immune function in vivo.

Ketamine inhibits TNF-\u03b1-induced cecal damage by enhancing RIP1 ubiquitination to attenuate lethal SIRS

Systemic inflammatory response syndrome (SIRS) is a sepsis-associated inflammatory state and a self-defense mechanism against specific and nonspecific stimuli. Ketamine influences many key processes that are altered during sepsis. However, the underlying mechanisms remain incompletely understood. In this study, TNF-α-treated mice, as well as HT-29 and L929 cell models, were applied to characterize TNF-α-induced systemic and local cecal tissue inflammatory responses. Behavioral, biochemical, histological, and molecular biological approaches were applied to illustrate the related processes. Mice with TNF-α-induced SIRS showed systemic and local cecal tissue inflammatory responses, as indicated by increased levels of high mobility group box 1 protein (HMGB1), chemokines (C-X-C motif) ligand 10 (CXCL10), interleukin-6 (IL-6), and IL-10, as well as high mortality. Ketamine pretreatment alleviated death rates, symptoms, and the production of inflammatory cytokines induced by TNF-α in mice. Moreover, ketamine also protected the mice from TNF-α-induced cecal damage by suppressing the phosphorylation of receptor-interacting serine/threonine-protein kinase 3 (RIP3) and mixed lineage kinase domain-like protein (MLKL). In addition, our results showed that ketamine efficiently inhibited TNF-α-induced necroptosis in HT-29 and L929 cells. Furthermore, we explored the mechanism using different L929 cell lines. The results displayed that ketamine inhibited TNF-α-induced necroptosis by enhancing RIP1 ubiquitination and reducing the RIP1-RIP3 and RIP3-MLKL interactions, as well as the formation of necrosomes. Thus, our study may provide a new theoretical and experimental basis for treating diseases characterized by SIRS-associated inflammatory factor storms. Moreover, our exploration may provide potential molecular mechanisms and targets for therapeutic intervention and clinical application of ketamine.

Mast cell activation syndrome-anesthetic challenges in two different clinical scenarios.

Mast cell activation syndrome (MCAS) includes a group of disorders that result in the inappropriate release of inflammatory mediators from mast cells. These mediators can affect multiple organ systems and lead to significant morbidity, and possible fatality. Although reactions, typically in response to various nonspecific stimuli, are usually mild, they may put those with MCAS at increased risk of anaphylaxis. In this case report, we present two clinical scenarios of MCAS, and identify possible factors triggering mast cell mediator release. We also define a preoperative preventive pathway, outline anesthetic considerations, and discuss the management of immediate hypersensitivity reactions in patients with MCAS. Meticulous preoperative preparation, avoidance of triggers, and development of a plan to treat possible adverse organ responses are paramount of good outcomes.

Ozone-Induced Models of Airway Hyperreactivity and Epithelial Injury.

Ozone (O3), a criterion air pollutant produced as a product of internal combustion, generates increased inflammation, lung permeability, and airway hyperreactivity when exposed to rodents in laboratory settings. Airway hyperreactivity is defined as an exaggerated acute obstructive response of the airways to one or more nonspecific stimuli. Lung permeability is a measure of barrier functions that separate internal and external environments to limit access of pathogens and other noxious material. By modeling in vivo O3 exposure in rodents, this allows investigators to explore pulmonary and nonpulmonary O3 effects as a means of understanding its impact on human health and lung function. Furthermore, direct effects of O3 on epithelial permeability can be defined using in vitro exposures to airway epithelial cells. This chapter will focus on methods of generating O3 and then exposing rodents and cultured epithelial cells in laboratory settings.

DIFFERENCES BETWEEN BEGINNING AND ADVANCED STUDENTS USING SPECIFIC ANALOGICAL STIMULI DURING DESIGN-BY-ANALOGY

AbstractStudies reported the effects of different types and different levels of abstraction of analogical stimuli on designers. However, specific, single visual analogical stimuli on the effects of designers have not been reported. We define this type of stimuli as specific analogical stimuli. We used the extended linkography method to analyze the facilitating and limiting effects of specific analogical stimuli and free association analogical stimuli (nonspecific analogical stimuli) on the students' creativity at different design levels. The results showed that: (1) Advanced students focused on exploring the depth of the design problem while beginning students tended to explore the breadth of the design problem. (2) Nonspecific analogical stimuli enhanced the creativity of beginning students. However, its impact on advanced students is less pronounced. (3) The specific analogical stimuli attract the students into design fixation. Furthermore, it has a more pronounced effect on advanced students. These results illustrate the differences in the effects of specific analogy stimuli on the students at different design levels. It clarifies the use of analogical stimuli in design and the teaching of analogical design methods in design education.

Neural processing of emotional facial stimuli in specific phobia: An fMRI study.

Patients with specific phobia (SP) show altered brain activation when confronted with phobia-specific stimuli. It is unclear whether this pathogenic activation pattern generalizes to other emotional stimuli. This study addresses this question by employing a well-powered sample while implementing an established paradigm using nonspecific aversive facial stimuli. N = 111 patients with SP, spider subtype, and N = 111 healthy controls (HCs) performed a supraliminal emotional face-matching paradigm contrasting aversive faces versus shapes in a 3-Tmagnetic resonance imaging scanner. We performed region of interest (ROI) analyses for the amygdala, the insula, and the anterior cingulate cortex using univariate as well as machine-learning-based multivariate statistics based on this data. Additionally, we investigated functional connectivity by means of psychophysiological interaction (PPI). Althoughthe presentation of emotional faces showed significant activation in all three ROIs across both groups, no group differences emerged in all ROIs. Across both groups and in the HC > SP contrast, PPI analyses showed significant task-related connectivity of brain areas typically linked to higher-order emotion processing with the amygdala. The machine learning approach based on whole-brain activity patterns could significantly differentiate the groups with 73% balanced accuracy. Patients suffering from SP are characterized by differences in the connectivity of the amygdala and areas typically linked to emotional processing in response to aversive facial stimuli (inferior parietal cortex, fusiform gyrus, middle cingulate, postcentral cortex, and insula). This might implicate a subtle difference in the processing of nonspecific emotional stimuli and warrants more research furthering our understanding of neurofunctional alteration in patients with SP.

Detection of the potentiality before the actuality: Measurement of T-cell proliferation before cell division occurs.

Detection of the potentiality before the actuality: Measurement of T-cell proliferation before cell division occurs.

Therapies Targeting Trained Immune Cells in Inflammatory and Autoimmune Diseases.

The concept of trained immunity has recently emerged as a mechanism contributing to several immune mediated inflammatory conditions. Trained immunity is defined by the immunological memory developed in innate immune cells after a primary non-specific stimulus that, in turn, promotes a heightened inflammatory response upon a secondary challenge. The most characteristic changes associated to this process involve the rewiring of cell metabolism and epigenetic reprogramming. Under physiological conditions, the role of trained immune cells ensures a prompt response. This action is limited by effective resolution of inflammation and tissue repair in order to restore homeostasis. However, unrestrained activation of innate immune cells contributes to the development of chronic inflammation and tissue destruction through the secretion of inflammatory cytokines, proteases and growth factors. Therefore, interventions aimed at reversing the changes induced by trained immunity provide potential therapeutic approaches to treat inflammatory and autoimmune diseases like rheumatoid arthritis (RA). We review cellular approaches that target metabolism and the epigenetic reprogramming of dendritic cells, macrophages, natural killer cells, and other trained cells in the context of autoimmune inflammatory diseases.

Airway hyperresponsiveness development and the toxicity of PM2.5.

Airway hyperresponsiveness (AHR) is characterized by excessive bronchoconstriction in response to nonspecific stimuli, thereby leading to airway stenosis and increased airway resistance. AHR is recognized as a key characteristic of asthma and is associated with significant morbidity. At present, many studies on the molecular mechanisms of AHR have mainly focused on the imbalance in Th1/Th2 cell function and the abnormal contraction of airway smooth muscle cells. However, the specific mechanisms of AHR remain unclear and need to be systematically elaborated. In addition, the effect of air pollution on the respiratory system has become a worldwide concern. To date, numerous studies have indicated that certain concentrations of fine particulate matter (PM2.5) can increase airway responsiveness and induce acute exacerbation of asthma. Of note, the concentration of PM2.5 does correlate with the degree of AHR. Numerous studies exploring the toxicity of PM2.5 have mainly focused on the inflammatory response, oxidative stress, genotoxicity, apoptosis, autophagy, and so on. However, there have been few reviews systematically elaborating the molecular mechanisms by which PM2.5 induces AHR. The present review separately sheds light on the underlying molecular mechanisms of AHR and PM2.5-induced AHR.