Autonomous Responses Research Articles

Autonomous nervous system responses to environmental-level exposure to 5G's first deployed band (3.5GHz) in healthy human volunteers.

Following the global progressive deployment of 5G networks, considerable attention has focused on assessing their potential impact on human health. This study aims to investigate autonomous nervous system changes by exploring skin temperature and electrodermal activity (EDA) among 44 healthy young individuals of both sexes during and after exposure to 3.5GHz antenna-emitted signals, with an electrical field intensity ranging from 1 to 2V/m. The study employed a randomized, cross-over design with triple-blinding, encompassing both 'real' and 'sham' exposure sessions, separated by a maximum interval of 1week. Each session comprised baseline, exposure and postexposure phases, resulting in the acquisition of seven runs. Each run initiated with a 150s segment of EDA recordings stimulated by 10 repeated beeps. Subsequently, the collected data underwent continuous decomposition analysis, generating specific indicators assessed alongside standard metrics such as trough-to-peak measurements, global skin conductance and maximum positive peak deflection. Additionally, non-invasive, real-time skin temperature measurements were conducted to evaluate specific anatomical points (hand, head and neck). The study suggests that exposure to 3.5GHz signals may potentially affect head and neck temperature, indicating a slight increase in this parameter. Furthermore, there was a minimal modulation of certain electrodermal metrics after the exposure, suggesting a potentially faster physiological response to auditory stimulation. However, while the results are significant, they remain within the normal physiological range and could be a consequence of an uncontrolled variable. Given the preliminary nature of this pilot study, further research is needed to confirm the effects of 5G exposure.

Autonomous Responses to the Russia–Ukraine Conflict? Evidence from the Feminist Foreign Policy in Latin America

AbstractGiven the conflict between Russia and Ukraine and the Feminist Foreign Policy (FFP) institutionalisation by Mexico (2020) and Chile (2023), this study analyses their differentiated responses to empirically assess FFP's promised potential to achieve autonomy in foreign policymaking. Through a thematic analysis, we examined the official stances towards the war, diplomatic interactions, and specific cooperation policies proposed or supported by the two countries. The results are twofold: (1) theoretically, FFP challenges conventional theories on international relations and foreign policymaking by fostering a nuanced understanding of the war thus creating conditions for developing autonomous discourses and policies, and (2) empirically, FFP has practical limitations evidenced in Mexico and Chile's heterogeneous – and sometimes unexpected – responses.

Addressing non-economic loss and damage: learning from autonomous responses in Bangladesh

People in the Majority World disproportionately experience Loss and Damage (L&D) related to climate change. Policymakers and researchers are exploring ways to address L&D. However, significant knowledge gaps remain, including how to address what has been termed Non-Economic Loss and Damage (NELD). We contribute to filling this knowledge gap by analysing the NELD people are experiencing and by exploring autonomous responses to these impacts. This study took place in two regions of Bangladesh: the southwestern Shyamnagar Upazila and the northcentral Durgapur Upazila. We find that people autonomously formulate responses to various NELD from different climate-related hazards (e.g., droughts, floods, and heatwaves). In doing so, people rely on various factors, such as financial assets and social relationships, to respond to NELD. However, because marginalised groups and individuals have little capacity to respond, they are forced to adopt certain responses that further erode their well-being. Moving forward, interventions responding to NELD can identify, build on, support and complement some of these existing responses. We argue that strengthening the capacity of affected people will better enable people to formulate non-erosive responses to NELD.

Modeling Autonomous Vehicle Responses to Novel Observations Using Hierarchical Cognitive Representations Inspired Active Inference

Equipping autonomous agents for dynamic interaction and navigation is a significant challenge in intelligent transportation systems. This study aims to address this by implementing a brain-inspired model for decision making in autonomous vehicles. We employ active inference, a Bayesian approach that models decision-making processes similar to the human brain, focusing on the agent’s preferences and the principle of free energy. This approach is combined with imitation learning to enhance the vehicle’s ability to adapt to new observations and make human-like decisions. The research involved developing a multi-modal self-awareness architecture for autonomous driving systems and testing this model in driving scenarios, including abnormal observations. The results demonstrated the model’s effectiveness in enabling the vehicle to make safe decisions, particularly in unobserved or dynamic environments. The study concludes that the integration of active inference with imitation learning significantly improves the performance of autonomous vehicles, offering a promising direction for future developments in intelligent transportation systems.

UCP1-dependent brown adipose activation accelerates cardiac metabolic remodeling and reduces initial hypertrophic and fibrotic responses to pathological stress.

Brown adipose tissue (BAT) is correlated to cardiovascular health in rodents and humans, but the physiological role of BAT in the initial cardiac remodeling at the onset of stress is unknown. Activation of BAT via 48 h cold (16°C) in mice following transverse aortic constriction (TAC) reduced cardiac gene expression for LCFA uptake and oxidation in male mice and accelerated the onset of cardiac metabolic remodeling, with an early isoform shift of carnitine palmitoyltransferase 1 (CPT1) toward increased CPT1a, reduced entry of long chain fatty acid (LCFA) into oxidative metabolism (0.59 ± 0.02 vs. 0.72 ± 0.02 in RT TAC hearts, p < .05) and increased carbohydrate oxidation with altered glucose transporter content. BAT activation with TAC reduced early hypertrophic expression of β-MHC by 61% versus RT-TAC and reduced pro-fibrotic TGF-β1 and COL3α1 expression. While cardiac natriuretic peptide expression was yet to increase at only 3 days TAC, Nppa and Nppb expression were elevated in Cold TAC versus RT TAC hearts 2.7- and 2.4-fold, respectively. Eliminating BAT thermogenic activation with UCP1 KO mice eliminated differences between Cold TAC and RT TAC hearts, confirming effects of BAT activation rather than autonomous cardiac responses to cold. Female responses to BAT activation were blunted, with limited UCP1 changes with cold, partly due to already activated BAT in females at RT compared to thermoneutrality. These data reveal a previously unknown physiological mechanism of UCP1-dependent BAT activation in attenuating early cardiac hypertrophic and profibrotic signaling and accelerating remodeled metabolic activity in the heart at the onset of cardiac stress.

DROWSINESS DETECTION USING

This review paper delves into the critical realm of drowsiness detection systems designed to mitigate the perilous consequences of driver fatigue. As instances of accidents caused by drowsy driving continue to pose significant risks on roadways, the proposed work adopts a comprehensive approach. Leveraging advanced technologies such as machine learning, computer vision, and sensor integration, the system focuses on early detection of drowsiness indicators. The algorithm, refined through iterative development, analyses facial expressions, eye movements, and physiological data for enhanced accuracy. Customizable alert mechanisms and autonomous responses, including auto-driver modes and forced parking, aim to provide timely interventions. Prospects involve multi-sensor fusion, adaptive machine learning, and integration with autonomous vehicles. As technology evolves, the goal is to create a user friendly, adaptive system that not only detects drowsiness effectively but also actively prevents potential accidents, contributing to a safer driving environment. Keywords: Drowsiness Detection, Adaptive Machine Learning, Forced Parking, Human- Machine Collaboration, Digital Object Identifier (DOI), Real- time Processing, - Friendly Design.

The Aversive Musical Experience Scale (AMES): Measuring individual differences in the intensity of music-evoked aversion

Strongly disliked music has the capacity to evoke strong negative emotions and physical sensations—at least in some listeners. Although previous (qualitative) studies on disliked music have provided valuable descriptions of listeners’ experiences, more generalizable approaches are needed for understanding individual differences in the intensity of music-evoked aversive experiences. This study set out to explore these individual differences by developing a standardized questionnaire to measure the intensity of aversive musical experiences, the Aversive Musical Experience Scale (AMES). Furthermore, we explored the hypothesized predictors and potential underlying mechanisms (such as emotional contagion and a general sensitivity to sounds) by measuring trait emotional contagion, misophonia, tendency to experience autonomous sensory meridian responses (ASMR) and frissons, and personality. Based on the results of exploratory and confirmatory factor analyses, a final 18-item version of AMES was constructed, comprising three subscales: Sensations, Social, and Features. Misophonia and emotional contagion emerged as the strongest predictors of global AMES and its subscales. Furthermore, the personality traits of neuroticism, agreeableness, and openness to experience, as well as age and musical expertise emerged as significant predictors of at least one of the scales. The implications and limitations of the findings are discussed with respect to sound-sensitivity, music-induced emotions, and personality theory.

The experience of a tele-operated avatar being touched increases operator's sense of discomfort.

Recent advancements in tele-operated avatars, both on-screen and robotic, have expanded opportunities for human interaction that exceed spatial and physical limitations. While numerous studies have enhanced operator control and improved the impression left on remote users, one area remains underexplored: the experience of operators during touch interactions between an avatar and a remote interlocutor. Touch interactions have become commonplace with avatars, especially those displayed on or integrated with touchscreen interfaces. Although the need for avatars to exhibit human-like touch responses has been recognized as beneficial for maintaining positive impressions on remote users, the sensations and experiences of the operators behind these avatars during such interactions remain largely uninvestigated. This study examines the sensations felt by an operator when their tele-operated avatar is touched remotely. Our findings reveal that operators can perceive a sensation of discomfort when their on-screen avatar is touched. This feeling is intensified when the touch is visualized and the avatar reacts to it. Although these autonomous responses may enhance the human-like perceptions of remote users, they might also lead to operator discomfort. This situation underscores the importance of designing avatars that address the experiences of both remote users and operators. We address this issue by proposing a tele-operated avatar system that minimizes unwarranted touch interactions from unfamiliar interlocutors based on social intimacy.

Previous Experience Matters: An in-Person Investigation of Expectations in Human–Robot Interaction

The human–robot interaction (HRI) field goes beyond the mere technical aspects of developing robots, often investigating how humans perceive robots. Human perceptions and behavior are determined, in part, by expectations. Given the impact of expectations on behavior, it is important to understand what expectations individuals bring into HRI settings and how those expectations may affect their interactions with the robot over time. For many people, social robots are not a common part of their experiences, thus any expectations they have of social robots are likely shaped by other sources. As a result, individual expectations coming into HRI settings may be highly variable. Although there has been some recent interest in expectations within the field, there is an overall lack of empirical investigation into its impacts on HRI, especially in-person robot interactions. To this end, a within-subject in-person study (N=31\\documentclass[12pt]{minimal} \\usepackage{amsmath} \\usepackage{wasysym} \\usepackage{amsfonts} \\usepackage{amssymb} \\usepackage{amsbsy} \\usepackage{mathrsfs} \\usepackage{upgreek} \\setlength{\\oddsidemargin}{-69pt} \\begin{document}$$N=31$$\\end{document}) was performed where participants were instructed to engage in open conversation with the social robot Pepper during two 2.5 min sessions. The robot was equipped with a custom dialogue system based on the GPT-3 large language model, allowing autonomous responses to verbal input. Participants’ affective changes towards the robot were assessed using three questionnaires, NARS, RAS, commonly used in HRI studies, and Closeness, based on the IOS scale. In addition to the three standard questionnaires, a custom question was administered to capture participants’ views on robot capabilities. All measures were collected three times, before the interaction with the robot, after the first interaction with the robot, and after the second interaction with the robot. Results revealed that participants to large degrees stayed with the expectations they had coming into the study, and in contrast to our hypothesis, none of the measured scales moved towards a common mean. Moreover, previous experience with robots was revealed to be a major factor of how participants experienced the robot in the study. These results could be interpreted as implying that expectations of robots are to large degrees decided before interactions with the robot, and that these expectations do not necessarily change as a result of the interaction. Results reveal a strong connection to how expectations are studied in social psychology and human-human interaction, underpinning its relevance for HRI research.

Exploring the technological dimension of Autonomous sensory meridian response-induced physiological responses.

In recent years, the scientific community has been captivated by the intriguing Autonomous sensory meridian response (ASMR), a unique phenomenon characterized by tingling sensations originating from the scalp and propagating down the spine. While anecdotal evidence suggests the therapeutic potential of ASMR, the field has witnessed a surge of scientific interest, particularly through the use of neuroimaging techniques including functional magnetic resonance imaging (fMRI) as well as electroencephalography (EEG) and physiological measures such as eye tracking (Pupil Diameter), heart rate (HR), heartbeat-evoked potential (HEP), blood pressure (BP), pulse rates (PR), finger photoplethysmography (PPG), and skin conductance (SC). This article is intended to provide a comprehensive overview of technology's contributions to the scientific elucidation of ASMR mechanisms. A meticulous literature review was undertaken to identify studies that have examined ASMR using EEG and physiological measurements. The comprehensive search was conducted across databases such as PUBMED, SCOPUS, and IEEE, using a range of relevant keywords such as 'ASMR', 'Autonomous sensory meridian response', 'EEG', 'fMRI', 'electroencephalography', 'physiological measures', 'heart rate', 'skin conductance', and 'eye tracking'. This rigorous process yielded a substantial number of 63 PUBMED and 166 SCOPUS-related articles, ensuring the inclusion of a wide range of high-quality research in this review. The review uncovered a body of research utilizing EEG and physiological measures to explore ASMR's effects. EEG studies have revealed distinct patterns of brain activity associated with ASMR experiences, particularly in regions implicated in emotional processing and sensory integration. In physiological measurements, a decrease in HR and an increase in SC and pupil diameter indicate relaxation and increased attention during ASMR-triggered stimuli. The findings of this review underscore the significance of EEG and physiological measures in unraveling the psychological and physiological effects of ASMR. ASMR experiences have been associated with unique neural signatures, while physiological measures provide valuable insights into the autonomic responses elicited by ASMR stimuli. This review not only highlights the interdisciplinary nature of ASMR research but also emphasizes the need for further investigation to elucidate the mechanisms underlying ASMR and explore its potential therapeutic applications, thereby paving the way for the development of novel therapeutic interventions.

Embedded software of the KM3NeT central logic board

The KM3NeT Collaboration is building and operating two deep sea neutrino telescopes at the bottom of the Mediterranean Sea. The telescopes consist of latices of photomultiplier tubes housed in pressure-resistant glass spheres, called digital optical modules and arranged in vertical detection units. The two main scientific goals are the determination of the neutrino mass ordering and the discovery and observation of high-energy neutrino sources in the Universe. Neutrinos are detected via the Cherenkov light, which is induced by charged particles originated in neutrino interactions. The photomultiplier tubes convert the Cherenkov light into electrical signals that are acquired and timestamped by the acquisition electronics. Each optical module houses the acquisition electronics for collecting and timestamping the photomultiplier signals with one nanosecond accuracy. Once finished, the two telescopes will have installed more than six thousand optical acquisition nodes, completing one of the more complex networks in the world in terms of operation and synchronization. The embedded software running in the acquisition nodes has been designed to provide a framework that will operate with different hardware versions and functionalities. The hardware will not be accessible once in operation, which complicates the embedded software architecture. The embedded software provides a set of tools to facilitate remote manageability of the deployed hardware, including safe reconfiguration of the firmware. This paper presents the architecture and the techniques, methods and implementation of the embedded software running in the acquisition nodes of the KM3NeT neutrino telescopes. Program summaryProgram title: Embedded software for the KM3NeT CLBCPC Library link to program files:https://doi.org/10.17632/s847hpsns4.1Licensing provisions: GNU General Public License 3Programming language: CNature of problem: The challenge for the embedded software in the KM3NeT neutrino telescope lies in orchestrating the Digital Optical Modules (DOMs) to achieve the synchronized data acquisition of the incoming optical signals. The DOMs are the crucial component responsible for capturing neutrino interactions deep underwater. The embedded software must configure and precisely time the operation of each DOM. Any deviation or timing mismatch could compromise data integrity, undermining the scientific value of the experiment. Therefore, the embedded software plays a critical role in coordinating, synchronizing, and operating these modules, ensuring they work in unison to capture and process neutrino signals accurately, ultimately advancing our understanding of fundamental particles in the Universe.Solution method: The embedded software on the DOMs provides a solution based on a C-based bare-metal application, operating without a real-time embedded OS. It is loaded into the RAM during FPGA configuration, consuming less than 256 kB of RAM. The software architecture comprises two layers: system software and application. The former offers OS-like features, including a multitasking scheduler, firmware updates, peripheral drivers, a UDP-based network stack, and error handling utilities. The application layer contains a state machine ensuring consistent program states. It is navigated via slow control events, including external inputs and autonomous responses. Subsystems within the application code control specific acquisition electronics components via the associated driver abstractions.Additional comments including restrictions and unusual features: Due to the operation conditions of the neutrino telescope, where access is restricted, the embedded software implements a fail-safe procedure to reconfigure the firmware where the embedded software runs.

Alternative splicing induced by bacterial pore-forming toxins sharpens CIRBP-mediated cell response to Listeria infection.

Cell autonomous responses to intracellular bacteria largely depend on reorganization of gene expression. To gain isoform-level resolution of these modes of regulation, we combined long- and short-read transcriptomic analyses of the response of intestinal epithelial cells to infection by the foodborne pathogen Listeria monocytogenes. Among the most striking isoform-based types of regulation, expression of the cellular stress response regulator CIRBP (cold-inducible RNA-binding protein) and of several SRSFs (serine/arginine-rich splicing factors) switched from canonical transcripts to nonsense-mediated decay-sensitive isoforms by inclusion of 'poison exons'. We showed that damage to host cell membranes caused by bacterial pore-forming toxins (listeriolysin O, perfringolysin, streptolysin or aerolysin) led to the dephosphorylation of SRSFs via the inhibition of the kinase activity of CLK1, thereby driving CIRBP alternative splicing. CIRBP isoform usage was found to have consequences on infection, since selective repression of canonical CIRBP reduced intracellular bacterial load while that of the poison exon-containing isoform exacerbated it. Consistently, CIRBP-bound mRNAs were shifted towards stress-relevant transcripts in infected cells, with increased mRNA levels or reduced translation efficiency for some targets. Our results thus generalize the alternative splicing of CIRBP and SRSFs as a common response to biotic or abiotic stresses by extending its relevance to the context of bacterial infection.

Zoom-in to molecular mechanisms underlying root growth and function under heterogeneous soil environment and abiotic stresses.

The review describes tissue-specific and non-cell autonomous molecular responses regulating the root system architecture and function in plants. Phenotypic plasticity of roots relies on specific molecular and tissue specific responses towards local and microscale heterogeneity in edaphic factors. Unlike gravitropism, hydrotropism in Arabidopsis is regulated by MIZU KUSSIE1 (MIZ1)-dependent asymmetric distribution of cytokinin and activation of Arabidopsis response regulators, ARR16 and ARR17 on the lower water potential side of the root leading to higher cell division and root bending. The cortex specific role of Abscisic acid (ABA)-activated SNF1-related protein kinase 2.2 (SnRK2.2) and MIZ1 in elongation zone is emerging for hydrotropic curvature. Halotropism involves clathrin-mediated internalization of PIN FORMED 2 (PIN2) proteins at the side facing higher salt concentration in the root tip, and ABA-activated SnRK2.6 mediated phosphorylation of cortical microtubule-associated protein Spiral2-like (SP2L) in the root transition zone, which results in anisotropic cell expansion and root bending away from higher salt. In hydropatterning, Indole-3-acetic acid 3 (IAA3) interacts with SUMOylated-ARF7 (Auxin response factor 7) and prevents expression of Lateral organ boundaries-domain 16 (LBD16) in air-side of the root, while on wet side of the root, IAA3 cannot repress the non-SUMOylated-ARF7 thereby leading to LBD16 expression and lateral root development. In root vasculature, ABA induces expression of microRNA165/microRNA166 in endodermis, which moves into the stele to target class III Homeodomain leucine zipper protein (HD-ZIP III) mRNA in non-cell autonomous manner. The bidirectional gradient of microRNA165/6 and HD-ZIP III mRNA regulates xylem patterning under stress. Understanding the tissue specific molecular mechanisms regulating the root responses under heterogeneous and stress environments will help in designing climate-resilient crops.

Thermal-sensing actuator based on conductive polymer ionogel for autonomous human-machine interaction

Empowering soft robots with the ability to perceive will greatly improve human-machine interaction, enabling autonomous robotic systems. However, integrating additional sensing components into soft actuators poses significant challenges, particularly in terms of adhesion and stiffness matching. Here, we present a novel dual-functional thermal-sensing actuator (TSA) with conductive polymer ionogel electrodes. This TSA leverages ion diffusion for thermal sensing and electrochemical actuation, all within a single device. One remarkable feature of this TSA is its ability to not only sense temperature through heat conduction upon contact, but also remotely sense thermal radiation, especially from the human body. We further designed a sensing-actuation smart control system and demonstrated robotic hands, bionic butterflies and flytraps that exhibit autonomous and programmable responses when approached by a human hand. This work represents a pioneering effort in integrating thermal sensing and actuation functions within a single device. It not only facilitates proprioceptive actuation but also offers fresh insights for the development of autonomous robots.

Effects of Non-Invasive Neuromodulation of the Vagus Nerve for the Management of Cluster Headache: A Systematic Review.

Cluster headache (CH) is a type of headache that has a global prevalence of 0.5-3/1000 people, provokes severe, strictly unilateral pain through the first branch of the trigeminal nerve, and is associated with observable autonomous responses. CH provokes intense pain and decreases quality of life. In this study, we aimed to carry out a systematic review of the effectiveness of non-invasive neuromodulation of the vagus nerve in patients with cluster headaches, which was registered on PROSPERO No. CRD42021265126. Six databases were used from their date of inception to February 2023 to obtain studies with the group intervention of non-invasive neuromodulation of the vagus nerve for cluster headache, with outcomes based on pain attacks, duration, and disabilities. Data on the subjects, group intervention, main outcomes, and results were collected by two authors. The search provided 1003 articles, with three clinical trials being eligible for inclusion in the review. The methodological quality scores ranged from 6 to 8 points (mean: 7.3, SD: 0.8) out of a maximum of 10 points. The post-treatment results showed some positive effects using n-VNS as a treatment for cluster headache, more specifically regarding cervical neuromodulation of the vagus nerve. The systematic review found moderate-to-high-quality evidence supporting that n-VNS and cervical n-VNS may have some positive effects at the end of the treatment being effective to relieve the frequency and intensity of cluster headaches. The poor quantity of studies available and the lack of homogeneity in the study protocols did not allow the pooling of data for a meta-analysis.

Two Ascending Thermosensory Pathways from the Lateral Parabrachial Nucleus That Mediate Behavioral and Autonomous Thermoregulation.

Thermoregulatory behavior in homeothermic animals is an innate behavior to defend body core temperature from environmental thermal challenges in coordination with autonomous thermoregulatory responses. In contrast to the progress in understanding the central mechanisms of autonomous thermoregulation, those of behavioral thermoregulation remain poorly understood. We have previously shown that the lateral parabrachial nucleus (LPB) mediates cutaneous thermosensory afferent signaling for thermoregulation. To understand the thermosensory neural network for behavioral thermoregulation, in the present study, we investigated the roles of ascending thermosensory pathways from the LPB in avoidance behavior from innocuous heat and cold in male rats. Neuronal tracing revealed two segregated groups of LPB neurons projecting to the median preoptic nucleus (MnPO), a thermoregulatory center (LPB→MnPO neurons), and those projecting to the central amygdaloid nucleus (CeA), a limbic emotion center (LPB→CeA neurons). While LPB→MnPO neurons include separate subgroups activated by heat or cold exposure of rats, LPB→CeA neurons were only activated by cold exposure. By selectively inhibiting LPB→MnPO or LPB→CeA neurons using tetanus toxin light chain or chemogenetic or optogenetic techniques, we found that LPB→MnPO transmission mediates heat avoidance, whereas LPB→CeA transmission contributes to cold avoidance. In vivo electrophysiological experiments showed that skin cooling-evoked thermogenesis in brown adipose tissue requires not only LPB→MnPO neurons but also LPB→CeA neurons, providing a novel insight into the central mechanism of autonomous thermoregulation. Our findings reveal an important framework of central thermosensory afferent pathways to coordinate behavioral and autonomous thermoregulation and to generate the emotions of thermal comfort and discomfort that drive thermoregulatory behavior.SIGNIFICANCE STATEMENT Coordination of behavioral and autonomous thermoregulation is important for maintaining thermal homeostasis in homeothermic animals. However, the central mechanism of thermoregulatory behaviors remains poorly understood. We have previously shown that the lateral parabrachial nucleus (LPB) mediates ascending thermosensory signaling that drives thermoregulatory behavior. In this study, we found that one pathway from the LPB to the median preoptic nucleus mediates heat avoidance, whereas the other pathway from the LPB to the central amygdaloid nucleus is required for cold avoidance. Surprisingly, both pathways are required for skin cooling-evoked thermogenesis in brown adipose tissue, an autonomous thermoregulatory response. This study provides a central thermosensory network that coordinates behavioral and autonomous thermoregulation and generates thermal comfort and discomfort that drive thermoregulatory behavior.

Lipocalin-2 regulates the expression of interferon-stimulated genes and the susceptibility of prostate cancer cells to oncolytic virus infection

Lipocalin-2 (LCN2) performs pleiotropic and tumor context-dependent functions in cancers of diverse etiologies. In prostate cancer (PCa) cells, LCN2 regulates distinct phenotypic features, including cytoskeleton organization and expression of inflammation mediators. Oncolytic virotherapy uses oncolytic viruses (OVs) to kill cancer cells and induce anti-tumor immunity. A main source of specificity of OVs towards tumor cells stems from cancer-induced defects in interferon (IFN)-based cell autonomous immune responses. However, the molecular underpinnings of such defects in PCa cells are only partially understood. Moreover, LCN2 effects on IFN responses of PCa cells and their susceptibility to OVs are unknown. To examine these issues, we queried gene expression databases for genes coexpressed with LCN2, revealing co-expression of IFN-stimulated genes (ISGs) and LCN2. Analysis of human PCa cells revealed correlated expression of LCN2 and subsets of IFNs and ISGs. CRISPR/Cas9-mediated stable knockout of LCN2 in PC3 cells or transient overexpression of LCN2 in LNCaP cells revealed LCN2-mediated regulation of IFNE (and IFNL1) expression, activation of JAK/STAT pathway, and expression of selected ISGs. Accordingly, and dependent on a functional JAK/STAT pathway, LCN2 reduced the susceptibility of PCa cells to infection with the IFN-sensitive OV, EHDV-TAU. In PC3 cells, LCN2 knockout increased phosphorylation of eukaryotic initiation factor 2α (p-eIF2α). Inhibition of PKR-like ER kinase (PERK) in PC3-LCN2-KO cells reduced p-eIF2α while increasing constitutive IFNE expression, phosphorylation of STAT1, and ISG expression; and decreasing EHDV-TAU infection. Together, these data propose that LCN2 regulates PCa susceptibility to OVs through attenuation of PERK activity and increased IFN and ISG expression.

The phenomenology of auditory verbal hallucinations among clients with schizophrenia: The association with acceptance and autonomous action responses

BackgroundLiving with the experience of hearing voices without trying to ignore or suppress them is referred to as accepting auditory verbal hallucinations (AVH). It varies depending on the phenomenology of AVH itself; some clients may find it challenging to acquire new coping mechanisms with the voices. AimExamine the association between the phenomenology of AVH and acceptance or autonomous action among clients with schizophrenia. DesignA descriptive correlational study was conducted on 200 clients with schizophrenia using the following instruments; Sociodemographic and clinical data tools, Psychotic Symptom Rating Scales (PSYRATS-AH), and Voices Acceptance and Action Scale (VAAS). ResultsMost patients have moderate to severe levels of AVH (95.5 %), with a mean score of 25.34. The emotional characteristics reflected the high mean score (11.24). A highly statistically negative correlation was found between the total Voices Acceptance and Action Scale and severity of AVH (P = −0.448, sig = 0.000). A predictable significant effect of user acceptance and autonomous actions response coping with decreasing the severity of AVH was found (adjusted r square = 0.196, sig = 0.000) and model equation = Severity of Verbal auditory hallucinations = 31.990–0.257 X Total of Voice Acceptance and Autonomous Action Scale (VAAS). ConclusionThe severity of all phenomenological characteristics of AVH can be successfully reduced by using voice acceptance and autonomous action responses rather than resistance or engagement responses. Subsequently, it must be improved and learned by psychiatric nurses the patients with schizophrenia in the hospitals by applying Acceptance and Commitment Therapy as a crucial intervention.

Comparative study of GBP recruitment on two cytosol-dwelling pathogens, Francisella novicida and Shigella flexneri highlights differences in GBP repertoire and in GBP1 motif requirements.

Guanylate-Binding Proteins are interferon-inducible GTPases that play a key role in cell autonomous responses against intracellular pathogens. Despite sharing high sequence similarity, subtle differences among GBPs translate into functional divergences that are still largely not understood. A key GBP feature is the formation of supramolecular GBP complexes on the bacterial surface. Such complexes are observed when GBP1 binds lipopolysaccharide (LPS) from Shigella and Salmonella and further recruits GBP2-4. Here, we compared GBP recruitment on two cytosol-dwelling pathogens, Francisella novicida and S. flexneri. Francisella novicida was coated by GBP1 and GBP2 and to a lower extent by GBP4 in human macrophages. Contrary to S. flexneri, F. novicida was not targeted by GBP3, a feature independent of T6SS effectors. Multiple GBP1 features were required to promote targeting to F. novicida while GBP1 targeting to S. flexneri was much more permissive to GBP1 mutagenesis suggesting that GBP1 has multiple domains that cooperate to recognize F. novicida atypical LPS. Altogether our results indicate that the repertoire of GBPs recruited onto specific bacteria is dictated by GBP-specific features and by specific bacterial factors that remain to be identified.

Heart rate variability responses to cognitive stress in fibromyalgia are characterised by inadequate autonomous system stress responses: a clinical trial

Fibromyalgia (FM) is associated with sympathetically dominant dysautonomia, but the connection between dysautonomia and FM symptoms is unclear. Dysautonomia can be analysed with heart rate variability (HRV) and it has been proposed that FM patients comprise subgroups with differing profiles of symptom severity. In our study, 51 female FM patients aged 18 to 65 years and 31 age-matched healthy female controls followed a 20-min protocol of alternating relaxation and cognitive stress (mental arithmetic). Heart rates and electrocardiograms were registered. The HRV measures of heart rate (HR), mean interval between heart beats (RRmean), root mean squared interval differences of successive beats (RMSSD), and the standard deviation of intervals between normal heart beats (SDNN) were analysed with generalized linear modelling. Features in HRV reactivity which differed between FM patients and controls were used to cluster the FM patients and cluster characteristics were analysed. FM patients had higher baseline HR (72.3 [SD 12.7] vs 64.5 [7.80], p < 0.001) and lower RRmean (0.844 [0.134] vs 0.934 [0.118], p = 0.002), compared with controls. They also reacted to repeated cognitive stress with an attenuated rise in HR (− 4.41 [95% CI − 7.88 to − 0.93], p = 0.013) and attenuated decrease of RRmean (0.06 [95 CI 0.03 to 0.09], p < 0.001), compared with controls. Clustering of FM patients by HRV reactivity resulted in three clusters characterised by (1) normal levels of HRV and HRV reactivity with low levels of depressive mood and anxiety, (2) reduced levels of HRV and impaired HRV reactivity with increased levels of depressive mood and high levels of anxiety, and (3) lowest HRV and most impaired HRV reactivity with the highest scores for depressive mood and anxiety. Our results show that FM patients have lower HRV than healthy controls and their autonomous reactions to cognitive stress are attenuated. Dysautonomia in FM associates with mood disturbance.Trial registration ClinicalTrials.gov (NCT03300635). Registered October 3 2017—Retrospectively registered, https://clinicaltrials.gov/ct2/show/NCT03300635.