Range Of Stimuli Research Articles

Effective doping of single-walled carbon nanotube films with bromine under ultrasound

Carbon nanomaterials such as graphene and carbon nanotubes (CNTs) have attracted considerable interest from the scientific community over the past decades. Due to the extraordinary properties they are envisioned to play a key role in a wide spectrum of applications in the upcoming future. An interesting property of carbon nanostructures is the sensitivity of their electronic properties to a range of chemical stimuli. Consequently, their capabilities for charge propagation may be significantly enhanced upon appropriate combination with a chemical compound, which can affect the Fermi level of the material. In this work, the impact of addition of bromine to single-walled CNT (SWCNT) films on their electrical and thermoelectric properties was investigated. The experimental results revealed that thermoelectric capabilities of the material may be enhanced by two orders of magnitude by sonication-assisted introduction of Br2 into a SWCNT network. Conducted computations unravelled how the dopant affects the electronic properties of the SWCNT host and its charge transport properties.

Fisetin-induced PTEN expression reverses cellular senescence by inhibiting the mTORC2-Akt Ser473 phosphorylation pathway in vascular smooth muscle cells.

Cellular senescence is caused by a wide range of intracellular and extracellular stimuli and influences physiological functions, leading to the progression of age-related diseases. Many studies have shown that cellular senescence is related to phosphatase and tension homolog deleted on chromosome ten (PTEN) loss and mammalian target of rapamycin (mTOR) activation. Although it has been reported that mTOR complex 1 (mTORC1) is major anti-aging target in several cell types, the functions and mechanisms of mTOR complex 2 (mTORC2) during aging have not been elucidated in vascular smooth muscle cells (VSMCs). Therefore, the aim of this study was to reveal the relationship between PTEN and mTORC2 during VSMC senescence. We found adriamycin-induced VSMC senescence was accompanied by reduced PTEN protein expression and upregulation of the mTORC2-Akt (Ser 473) pathway and that fisetin treatment reduced VSMC senescence by increasing PTEN and decreasing mTORC2 protein levels. Furthermore, PTEN played a primary role in the anti-aging effect of fisetin, and fisetin-activated PTEN directly regulated the mTORC2-Akt (Ser 473) signaling pathway, and attenuated senescence phenotypes such as senescence-associated β-galactosidase (SA-β-gal) and the p53-p21 signaling pathway in VSMCs. In mouse aortas, fisetin delayed aging by regulating the PTEN-mTORC2-Akt (Ser473) signaling pathway. These results suggest PTEN and mTORC2 are associated with cellular senescence in VSMCs and that the mTORC2-Akt (Ser 473) signaling pathway be considered a new target for preventing senescence-related diseases.

Split-luciferase complementary assay of NLRP3 PYD-PYD interaction indicates inflammasome formation during inflammation

The NLRP3 inflammasome is a key macromolecular complex of the innate immune system that activates the inflammatory signalling cascade in response to a wide range of stimuli. Structural studies have shown that the intracellular cytosolic receptor NLRP3 oligomerizes upon stimulation and serves as a scaffold to form the ASC filaments necessary for procaspase-1 activation. Despite the abundant structural evidences on NLRP3 inflammasome, the interactions of the NLRP3 Pyrin domain and its functional relevance are poorly understood. In this study, the split luciferase complementation assay is used as an alternative approach to investigate NLRP3PYD-NLRP3PYD interactions during inflammasome formation. Since the homotypic NLRP3 interaction is mainly based on electrostatic interactions, a phosphomimetic residue (S5) at the interface of the NLRP3PYDs interactions has been mutated to show a disruptive effect on luciferase activity. According to the results presented, the designed biosensor was able to monitor the NLRP3PYD-NLRP3PYD interaction in vitro. The current reporter assay not only provides a specific NLRP3PYD-NLRP3PYD assay to study the PYD-PYD interaction in vitro, but also provides a suitable system for screening chemicals and drugs to identify activators and inhibitors of NLRP3.

The calcium signaling enzyme CD38 - a paradigm for membrane topology defining distinct protein functions

CD38 is a single-pass transmembrane enzyme catalyzing the synthesis of two nucleotide second messengers, cyclic ADP-ribose (cADPR) from NAD and nicotinic acid adenine dinucleotide phosphate (NAADP) from NADP. The former mediates the mobilization of the endoplasmic Ca2+-stores in response to a wide range of stimuli, while NAADP targets the endo-lysosomal stores. CD38 not only possesses multiple enzymatic activities, it also exists in two opposite membrane orientations. Type III CD38 has the catalytic domain facing the cytosol and is responsible for producing cellular cADPR. The type II CD38 has an opposite orientation and is serving as a surface receptor mediating extracellular functions such as cell adhesion and lymphocyte activation. Its ecto-NADase activity also contributes to the recycling of external NAD released by apoptosis. Endocytosis can deliver surface type II CD38 to endo-lysosomes, which acidic environment favors the production of NAADP. This article reviews the rationale and evidence that have led to CD38 as a paradigm for membrane topology defining distinct functions of proteins. Also described is the recent discovery of a hitherto unknown cADPR-synthesizing enzyme, SARM1, ushering in a new frontier in cADPR-mediated Ca2+-signaling.

Mesenchymal Stem Cell-Derived Exosomes Attenuate TLR7-Mediated Mast Cell Activation.

Mast cells are immune sentinels in the skin that respond to a wide range of pathological and environmental stimuli; they owe their function to the expression of Toll-like receptors (TLRs). We previously found that tonsil-derived mesenchymal stem cells (T-MSCs) were able to effectively attenuate TLR7-mediated skin inflammation in mice, which was accompanied by an increase in mast cell number. The present study investigated whether T-MSC extracellular vesicles, such as exosomes, are able to regulate mast cell activation in response to TLR7 stimulation. The HMC-1 human mast cell line was treated with a TLR7 agonist in the presence or absence of T-MSC exosomes, and the levels of expressed inflammatory cytokines were assessed. Additionally, mice were repeatedly injected with a TLR7 agonist with or without interval treatments with T-MSC exosomes and assessed dermal distribution of mast cells and related immune cells. We showed that T-MSC exosomes containing microRNAs that target inflammatory cytokines significantly reduced the expression of inflammatory cytokines in TLR7 agonist-treated HMC-1 cells. In addition, T-MSC exosomes inhibited the increase in the number of both dermal mast cells and CD14-positive cells in TLR7 agonist-treated mice. Our data suggest that T-MSC exosomes have regulatory effects on mast cell activation under inflammatory conditions, including TLR7 stimulation.

Hydrodynamic response time of magnetorheological fluid in valve mode: model and experimental verification

The transient behaviour of magnetorheological (MR) actuators affects their performance in progressive semiactive control suspension systems. The two sources of the time delay between the control signal and damping force are (a) dynamics of MR damper hardware and (b) the MR fluid dynamics. The significant part of the MR fluid response time is the so-called hydrodynamic response time which is connected with the transient flow. Due to the above, the main aim of this paper is to experimentally determine the hydrodynamic response time of MR fluid and present systematic means for characterizing it via computational fluid dynamics (CFD) or analytical tools. The unique measurement method using an in-house patented slit flow rheometer is presented. The essence of the method relies on determining the pressure drop variation with the time spent by the fluid in the MR gap. The experimental determined hydrodynamic response time of MR fluid ranges from 0.4 to 1 ms for a selected gap size and a range of magnetic field stimuli. The results show that the higher the magnetic field, the lower the hydrodynamic response time is. Both CFD and analytical models exhibit similar trends as the experimental data. Moreover, the impact of temperature and gap size was determined. Here, the higher the gap size and temperature of MR fluid, the longer the response time is.

Neutrophil NET Formation with Microbial Stimuli Requires Late Stage NADPH Oxidase Activity.

Neutrophils respond to a range of stimuli by releasing extracellular traps (NETs), a mesh consisting of chromatin plus granule and cytoplasmic proteins. We have investigated NET release in response to phorbol myristate acetate (PMA), Pseudomonas aeruginosa (PAO1), Staphylococcus aureus and Candida albicans, and the involvement of NADPH oxidase (NOX2) and myeloperoxidase (MPO) activities. An oxidative mechanism was involved with each stimulus, and the NOX2 inhibitor diphenylene iodonium (DPI) gave almost total inhibition. Notably, DPI added up to 60–90 min after stimulation still gave significant inhibition of subsequent NET formation. As most of the NOX2 activity had already occurred by that time, this indicates a requirement for late-stage low-level oxidant production. Inhibition of histone citrullination did not suppress NET formation, indicating that this was not the essential oxidant-dependent step. With PMA and P. aeruginosa PAO1, MPO activity played an important role in the induction of NETs and MPO inhibitors added up to 30–90 min after stimulation suppressed NET formation. NET formation with S. aureus and C. albicans was insensitive to MPO inhibition. Thus, MPO products are important with some stimuli but not others. Our results extend earlier observations with PMA and show that induction of NETs by microbial stimuli requires late stage oxidant production. Others have shown that NET formation involves NOX2-dependent elastase release from granules. As this is an early event, we conclude from our results that there is more than one oxidant-dependent step.

A comprehensive group-based cognitive behavioural treatment for blood-injection-injury phobia.

A key feature of blood-injection-injury (BII) phobia is activation of disgust responses, in addition to fear. Yet, standard treatments have largely neglected addressing disgust responses. The disorder is further complicated by fainting in 75% of sufferers. Moreover, treatments have been traditionally delivered in an individual format, which may not be as efficient as group treatment. The aim of this study was to develop a group-based programme for BII phobia, with components targeting fear, disgust, and fainting, to determine feasibility and effectiveness of such an intervention. Participants took part in an 8-session, group-based Cognitive Behavioural Therapy (CBT) programme for BII phobia (N = 40). The key outcome measure was the Multidimensional Blood/Injury Phobia Inventory, which assesses a range of phobic stimuli and responses (including fear, disgust, and fainting). There were significant improvements, with large effect sizes, across symptoms over the course of treatment. Participants with higher disgust sensitivity reported higher pre-treatment symptom severity and greater life interference than those with lower disgust scores. Despite this, neither pre-treatment disgust sensitivity nor fainting history impacted on treatment response. For the first time, however, we showed that greater reductions in disgust to BII stimuli were associated with greater overall symptom reductions, highlighting the importance of disgust in the treatment of this disorder, and potentially others. Despite the heterogeneous nature of BII phobia, this group-based, modified CBT intervention was effective in reducing a variety of phobic responses, including fear, disgust, and fainting. Disgust is a key maintaining factor in blood-injection-injury phobia, which clinicians should consider in their assessment and treatment of this disorder. There is little in the existing literature to guide clinicians in this regard. This study examined a novel group treatment for blood-injection-injury phobia which included strategies to target disgust, in addition to traditional CBT strategies to address fear and fainting. The treatment was feasible and acceptable. Symptoms of fear, disgust, and fainting reduced significantly over treatment. Changes in disgust symptoms were associated with overall symptom changes, however a control group is needed to determine the effects of individual treatment components and to make more robust conclusions about the benefits of this enhanced approach.

Agrin-Matrix Metalloproteinase-12 axis confers a mechanically competent microenvironment in skin wound healing

An orchestrated wound healing program drives skin repair via collective epidermal cell proliferation and migration. However, the molecular determinants of the tissue microenvironment supporting wound healing remain poorly understood. Herein we discover that proteoglycan Agrin is enriched within the early wound-microenvironment and is indispensable for efficient healing. Agrin enhances the mechanoperception of keratinocytes by augmenting their stiffness, traction stress and fluidic velocity fields in retaliation to bulk substrate rigidity. Importantly, Agrin overhauls cytoskeletal architecture via enhancing actomyosin cables upon sensing geometric stress and force following an injury. Moreover, we identify Matrix Metalloproteinase-12 (MMP12) as a downstream effector of Agrin’s mechanoperception. We also reveal a promising potential of a recombinant Agrin fragment as a bio-additive material that assimilates optimal mechanobiological and pro-angiogenic parameters by engaging MMP12 in accelerated wound healing. Together, we propose that Agrin-MMP12 pathway integrates a broad range of mechanical stimuli to coordinate a competent skin wound healing niche.

A Computational Model of Phosphene Appearance for Epiretinal Prostheses.

Retinal neuroprostheses are the only FDA-approved treatment option for blinding degenerative diseases. A major outstanding challenge is to develop a computational model that can accurately predict the elicited visual percepts (phosphenes) across a wide range of electrical stimuli. Here we present a phenomenological model that predicts phosphene appearance as a function of stimulus amplitude, frequency, and pulse duration. The model uses a simulated map of nerve fiber bundles in the retina to produce phosphenes with accurate brightness, size, orientation, and elongation. We validate the model on psychophysical data from two independent studies, showing that it generalizes well to new data, even with different stimuli and on different electrodes. Whereas previous models focused on either spatial or temporal aspects of the elicited phosphenes in isolation, we describe a more comprehensive approach that is able to account for many reported visual effects. The model is designed to be flexible and extensible, and can be fit to data from a specific user. Overall this work is an important first step towards predicting visual outcomes in retinal prosthesis users across a wide range of stimuli.

Crossmodal Associations with Olfactory, Auditory, and Tactile Stimuli in Children and Adults.

People associate information with different senses but the mechanism by which this happens is unclear. Such associations are thought to arise from innate structural associations in the brain, statistical associations in the environment, via shared affective content, or through language. A developmental perspective on crossmodal associations can help determine which explanations are more likely for specific associations. Certain associations with pitch (e.g., pitch–height) have been observed early in infancy, but others may only occur late into childhood (e.g., pitch–size). In contrast, tactile–chroma associations have been observed in children, but not adults. One modality that has received little attention developmentally is olfaction. In the present investigation, we explored crossmodal associations from sound, tactile stimuli, and odor to a range of stimuli by testing a broad range of participants. Across the three modalities, we found little evidence for crossmodal associations in young children. This suggests an account based on innate structures is unlikely. Instead, the number and strength of associations increased over the lifespan. This suggests that experience plays a crucial role in crossmodal associations from sound, touch, and smell to other senses.

Heterotrimeric G Proteins in Plants: Canonical and Atypical Gα Subunits.

Heterotrimeric GTP-binding proteins (G proteins), consisting of Gα, Gβ and Gγ subunits, transduce signals from a diverse range of extracellular stimuli, resulting in the regulation of numerous cellular and physiological functions in Eukaryotes. According to the classic G protein paradigm established in animal models, the bound guanine nucleotide on a Gα subunit, either guanosine diphosphate (GDP) or guanosine triphosphate (GTP) determines the inactive or active mode, respectively. In plants, there are two types of Gα subunits: canonical Gα subunits structurally similar to their animal counterparts and unconventional extra-large Gα subunits (XLGs) containing a C-terminal domain homologous to the canonical Gα along with an extended N-terminal domain. Both Gα and XLG subunits interact with Gβγ dimers and regulator of G protein signalling (RGS) protein. Plant G proteins are implicated directly or indirectly in developmental processes, stress responses, and innate immunity. It is established that despite the substantial overall similarity between plant and animal Gα subunits, they convey signalling differently including the mechanism by which they are activated. This review emphasizes the unique characteristics of plant Gα subunits and speculates on their unique signalling mechanisms.

Visual-haptic integration, action and embodiment in virtual reality.

The current generation of virtual reality (VR) technologies has improved substantially from legacy systems, particularly in the resolution and latency of their visual display. The presentation of haptic cues remains challenging, however, because haptic systems do not generalise well over the range of stimuli (both tactile and proprioceptive) normally present when interacting with objects in the world. This study investigated whether veridical tactile and proprioceptive cues lead to more efficient interaction with a virtual environment. Interaction in the world results in spatial and temporal correlation of tactile, proprioceptive and visual cues. When cues in VR are similarly correlated, observers experience a sense of embodiment and agency of their avatars. We investigated whether sensorimotor performance was mediated by embodiment of the avatar hands. Participants performed a Fitts' tapping task in different conditions (VR with no haptics, active haptics, passive haptics, and on a real touchscreen). The active-haptic condition provided abstract tactile cues and the passive haptic condition provided veridical tactile and proprioceptive cues. An additional (hybrid haptics) condition simulated an ideal passive haptic system. Movement efficiency (throughput) and embodiment were higher for the passive than for the active and no-haptics conditions. However, components of embodiment (perceived agency and ownership) did not predict unique variance in throughput. Improved sensorimotor performance and ratings of presence and realism support the use of passive haptics in VR environments where objects are in known and stable locations, regardless of whether performance was mediated by the sense of embodiment.

Quantifying skin sensitivity caused by mechanical insults: A review.

BackgroundSkin sensitivity (SS) is a commonly occurring response to a range of stimuli, including environmental conditions (e.g., sun exposure), chemical irritants (e.g., soaps and cosmetics), and mechanical forces (e.g., while shaving). From both industry and academia, many efforts have been taken to quantify the characteristics of SS in a standardised manner, but the study is hindered by the lack of an objective definition.MethodsA review of the scientific literature regarding different parameters attributed to the loss of skin integrity and linked with exhibition of SS was conducted. Articles included were screened for mechanical stimulation of the skin, with objective quantification of tissue responses using biophysical or imaging techniques. Additionally, studies where cohorts of SS and non‐SS individuals were reported have been critiqued.ResultsThe findings identified that the structure and function of the stratum corneum and its effective barrier properties are closely associated with SS. Thus, an array of skin tissue responses has been selected for characterization of SS due to mechanical stimuli, including: transepidermal water loss, hydration, redness, temperature, and sebum index. Additionally, certain imaging tools allow quantification of the superficial skin layers, providing structural characteristics underlying SS.ConclusionThis review proposes a multimodal approach for identification of SS, providing a means to characterise skin tissue responses objectively. Optical coherence tomography (OCT) has been suggested as a suitable tool for dermatological research with clinical applications. Such an approach would enhance the knowledge underlying the multifactorial nature of SS and aid the development of personalised solutions in medical and consumer devices.

Primary Cilia Are Critical Regulators of White Adipose Tissue Expansion.

The primary cilium is a microtubule-based cellular protrusion found on most mammalian cell types in diverse tissues. It functions as a cellular antenna to sense and transduce a broad range of signals, including odorants, light, mechanical stimuli, and chemical ligands. This diversity in signals requires cilia to display a context and cell type-specific repertoire of receptors. Recently, primary cilia have emerged as critical regulators of metabolism. The importance of primary cilia in metabolic disease is highlighted by the clinical features of human genetic disorders with dysfunctional ciliary signaling, which include obesity and diabetes. This review summarizes the current literature on the role of primary cilia in metabolic disease, focusing on the importance of primary cilia in directing white adipose tissue expansion during obesity.

Psychological and physiological evidence for an initial \u2018Rough Sketch\u2019 calculation of personal space

Personal space has been defined as “the area individuals maintain around themselves into which others cannot intrude without arousing discomfort”. However, the precise relationship between discomfort (or arousal) responses as a function of distance from an observer remains incompletely understood. Also the mechanisms involved in recognizing conspecifics and distinguishing them from other objects within personal space have not been identified. Accordingly, here we measured personal space preferences in response to real humans and human-like avatars (in virtual reality), using well-validated “stop distance” procedures. Based on threshold measurements of personal space, we examined within-subject variations in discomfort-related responses across multiple distances (spanning inside and outside each individual’s personal space boundary), as reflected by psychological (ratings) and physiological (skin conductance) responses to both humans and avatars. We found that the discomfort-by-distance functions for both humans and avatars were closely fit by a power law. These results suggest that the brain computation of visually-defined personal space begins with a ‘rough sketch’ stage, which generates responses to a broad range of human-like stimuli, in addition to humans. Analogous processing mechanisms may underlie other brain functions which respond similarly to both real and simulated human body parts.

Usage of Negative Pressure Wound Therapy in Pseudoepitheliomatous Hyperplasia Secondary to Burn Injury: A Case Series.

Pseudoepitheliomatous hyperplasia (PEH) is a reactive epithelial proliferation secondary to a wide range of stimuli, including traumatic injury, inflammation, infection, and tumors of the skin. PEH secondary to burn injury is rarely reported. We report three cases of PEH patients after burn injury. All three cases were confirmed with the existence of bacterial infection, and all these cases were second- or third-degree burns. All three patients were treated with negative pressure wound therapy after wound debridement or tangential excision. All the wounds healed without split-thickness skin grafting and recurrence.

Sex difference in hospitalized patients with COVID-19 infection

The pandemic of COVID-19 infection is rapidly progressing to one of the most severe threats to human health. The different responses of the immune system in females and males to a range of infectious and inflammatory stimuli were investigated. We aimed to explore the association of sex with the course of infection among the hospitalized COVID-19 patients. This Comparative cross-sectional study was conducted on RT- PCR positive COVID-19 patients. Severe and critical patients who required hospital or ICU admission were included in the study. The total number of patients was 150 (75 males and 75 females) with mean age of 57Y±14.7. There was a statistical significance in age between both groups [mean ± SD: males 60.5 (12.2), females 54 (15.3) (p=0:0.007)]. The prevalence of diabetes mellitus, hypertension, chronic kidney disease and ischemic heart disease was higher among males but without statistical significance. Consolidation was significantly more prevalent in female group (85.3% vs 61.3% in male group). The need of mechanical ventilation was higher in men, but with no statistical significance (44% Vs 32%, p=0.302). Also, mortality rate was higher (48%) in males than in females (37.3%), but with no statistical significance (p=0.262). During the COVID-19 infection, the risk factors of severe disease and progression to the need of mechanical ventilation support in addition to mortality rate are more prevalent among males. However, radiological patterns apart from consolidation, distribution of radiological abnormalities and CT severity score in both groups did not show significant sex difference.

Lightness perception of structured surfaces

AbstractVisual perception of surfaces is of utmost importance in everyday life. Therefore, it comes naturally, that different surface structures evoke different visual impressions in the viewer even if the material underlying these surface structures is the same. This topic is especially virulent for manufacturing processes in which more than one stakeholder is involved, but where the final product needs to meet certain criteria. A common practice to address such slight but perceivable differences in the visual appearance of structured surfaces is that trained evaluators assess the samples and assign a pass or fail. However, this process is both time consuming and cost intensive. Thus, we conducted two studies to analyze the relationship between physical surface structure parameters and participants visual assessment of the samples. With the first experiment, we aimed at uncovering a relationship between physical roughness parameters and visual lightness perception while the second experiment was designed to test participants' discrimination sensitivity across the range of stimuli. Perceived lightness and the measured surface roughness were nonlinearly related to the surface structure. Additionally, we found a linear relationship between the engraving parameter and physical brightness. Surface structure was an ideal predictor for perceived lightness and participants discriminated equally well across the entire range of surface structures.

Kinetx: A Combined Flow Cytometry Assay and Analysis Software Framework to Quantitatively Measure and Categorize Platelet Activation in Real-time.

Platelets react rapidly to vascular injury and undergo activation in response to a range of stimuli to limit blood loss. Many platelet function tests measure endpoint responses after a defined time period and not the rate of platelet activation. However, the rate at which platelets convert extracellular stimuli into a functional response is an essential factor in determining how efficiently they can respond to injury, bind to a forming thrombus, and signal to recruit other platelets. This paper describes a flow cytometry-based platelet function assay that enables simultaneous data acquisition and sample stimulation and utilizes newly developed bespoke open-source software (Kinetx) to enable quantitative kinetic measurements of platelet granule release, fibrinogen binding, and intracellular calcium flux. Kinetix was developed in R so that users can alter parameters such as degree of smoothing, identification of outlying data points, or time scales. To aid users unfamiliar with the R environment, Kinetix analysis of data can be performed by a single command. Together, this allows real-time platelet activation metrics, such as rate, acceleration, time to peak-rate, time to peak-calcium, and qualitative shape changes, to be accurately and reproducibly measured and categorized. Kinetic measurements of platelet activation give a unique insight into platelets' behavior during the first stages of activation and may provide a method of predicting the recruitment of platelets into a forming thrombus.