Related Cues Research Articles

Contribution of hypothalamic orexin (hypocretin) circuits to pathologies of motivation.

The orexin (also known as hypocretin) system, consisting of neuropeptides orexin-A and orexin-B, was discovered over 25 years ago and was immediately identified as a central regulator of sleep and wakefulness. These peptides interact with two G-protein coupled receptors, orexin 1 (OX1) and orexin 2 (OX2) receptors which are capable of coupling to all heterotrimeric G-protein subfamilies, but primarily transduce increases in calcium signalling. Orexin neurons are regulated by a variety of transmitter systems and environmental stimuli that signal reward availability, including food and drug related cues. Orexin neurons are also activated by anticipation, stress, cues predicting motivationally relevant information, including those predicting drugs of abuse, and engage neuromodulatory systems, including dopamine neurons of the ventral tegmental area (VTA) to respond to these signals. As such, orexin neurons have been characterized as motivational activators that coordinate a range of functions, including feeding and arousal, that allow the individual to respond to motivationally relevant information, critical for survival. This review focuses on the role of orexins in appetitive motivation and highlights a role for these neuropeptides in pathologies characterized by inappropriately high levels of motivated arousal (overeating, anxiety and substance use disorders) versus those in which motivation is impaired (depression).

Rats rely on airflow cues for self-motion perception

Self-motion perception is a vital skill for all species. It is an inherently multisensory process that combines inertial (body-based) and relative (with respect to the environment) motion cues. Although extensively studied in human and non-human primates, there is currently no paradigm to test self-motion perception in rodents using both inertial and relative self-motion cues. We developed a novel rodent motion simulator using two synchronized robotic arms to generate inertial, relative, or combined (inertial and relative) cues of self-motion. Eight rats were trained to perform a task of heading discrimination, similar to the popular primate paradigm. Strikingly, the rats relied heavily on airflow for relative self-motion perception, with little contribution from the (limited) optic flow cues provided-performance in the dark was almost as good. Relative self-motion (airflow) was perceived with greater reliability vs. inertial. Disrupting airflow, using a fan or windshield, damaged relative, but not inertial, self-motion perception. However, whiskers were not needed for this function. Lastly, the rats integrated relative and inertial self-motion cues in a reliability-based (Bayesian-like) manner. These results implicate airflow as an important cue for self-motion perception in rats and provide a new domain to investigate the neural bases of self-motion perception and multisensory processing in awake behaving rodents.

The influence of absolute and relative spatial cues on change detection performance

ABSTRACT Two experiments investigate how absolute and relative spatial cues influence perceptual comparisons between visual short-term memory (VSTM) and current vision. The core question concerned the role of task demands in this process. Two tasks were given across two experiments, differing in the extent they required object-level comparisons. Experiment 1, a feature comparison task, required reporting if any new colour was present in the second of two interleaved displays of four colours inside a surround; Experiment 2, an object comparison task, required report of any changes in colour-shape pairings in the second of two interleaved displays of four coloured shapes in a surround. Absolute and relative spatial organization was manipulated in both experiments by presenting compared displays on the same or contralateral sides, and by having the second display items in the same locations within the surround, in new locations, or repositioned into previous locations of other items. In sensitivity, both tasks showed an advantage for absolute spatial cues, but only the object task showed an advantage for relative spatial cues. In bias, both tasks were similarly influenced by both absolute and relative cues. Results suggest relative spatial cues are always available but only used when making object-level comparisons.

Moving object detection based on bioinspired background subtraction

Flying insects rely mainly upon visual motion to detect and track objects. There has been a lot of research on fly inspired algorithms for object detection, but few have been developed based on visual motion alone. One of the daunting difficulties is that the neural and circuit mechanisms underlying the foreground-background segmentation are still unclear. Our previous modeling study proposed that the lobula held parallel pathways with distinct directional selectivity, each of which could retinotopically discriminate figures moving in its own preferred direction based on relative motion cues. The previous model, however, did not address how the multiple parallel pathways gave the only detection output at their common downstream. Since the preferred directions of the pathways along either horizontal or vertical axis were opposite to each other, the background moving in the opposite direction to an object also activated the corresponding lobula pathway. Indiscriminate or ungated projection from all the pathways to their downstream would mix objects with the moving background, making the previous model fail with non-stationary background. Here, we extend the previous model by proposing that the background motion-dependent gating of individual lobula projections is the key to object detection. Large-field lobula plate tangential cells are hypothesized to perform the gating to realize bioinspired background subtraction. The model is shown to be capable of implementing a robust detection of moving objects in video sequences with either a moving camera that induces translational optic flow or a static camera. The model sheds light on the potential of the concise fly algorithm in real-world applications.

Frontal alpha asymmetries and behavioral immune system: moderating role of behavioral inhibition system

Background and purpose: Behavioral immune system is a cluster of psychological mechanisms enabling detection and avoidance of pathogens in one’s immediate environment. Its presumed activation has been implicated in myriads of psychological phenomena, stemming from pathogen related disgust to more complex behaviors, such as mate choice and xenophobic cognitions. However, little is known about its biological underpinnings. The aim of this preliminary study was twofold: 1) to explore the role of another neuropsychological system governing avoidant motivations, the behavioral inhibition system, in pathogen-induced disgust and 2) to determine if frontal hemispheric asymmetries (a neural correlate of avoidant motivations) might serve as indicators of behavioral immune system activation. Materials and methods: 62 participants completed the Behavioral inhibition scale. Based on their z-scores, two extreme groups were formed: high (n=9) and low behavioral inhibition (n=9) group. After the baseline EEG recordings, participants were exposed to a set of neutral stimuli, followed by a set of pathogen disgust inducing stimuli. The frontal asymmetry (FAA) indexes (lnR-LnL) were calculated within both low (8-10 Hz) and high (11-13 Hz) alpha frequency bands on analogue pairs of frontal electrodes. Results: There were no baseline FAA differences between groups. However, compared to low behavioral inhibition group, high behavioral inhibition group showed larger shifts in FAA on frontopolar locations while watching the pathogen related disgust-inducing stimuli, as compared to neutral photographs. Conclusions: This pattern of FAA shifts suggests that high behavioral inhibition individuals attend to pathogen threat related cues more readily, i.e., have a more reactive behavioral immune system. With this preliminary study we are proposing a new line of research in order to determine if there is evidence of a calibrated response in terms of interplay between one’s immune status and pathogen treat related neural reactivity.

Relational Cues are Affectively Differentiated

Relational Cues are Affectively Differentiated

Effects of sensory cues on consumers’ wine taste perceptions and behavior: evidence from a wine-tasting experiment

PurposeThis study aims to investigate how sensory cue order, wine knowledge and visual–olfactory (V–O) congruence affect consumer’s taste perceptions of wine and their subsequent behavior.Design/methodology/approachAn experiment was performed to identify the effects of sensory cue congruence and sensory cue order on wine consumers’ perceptions of wine, affective evaluations, cognitive evaluations and purchase intentions.FindingsWine experts exhibited positive emotional responses to congruent sensory cues in the V–O order. Experts’ enjoyment of wine’s aroma, their emotional responses, their cognitive evaluations and their purchase intentions were lower in the incongruent condition. Consumers’ negative emotions elicited by the V–O sequence were also less intense than those triggered by the olfactory–visual (O–V) sequence. Wine experts demonstrated more positive emotional responses in the V–O sensory congruent condition.Research limitations/implicationsThis study highlights how visual and olfactory sensory cue order, wine knowledge and sensory cue congruence interact to clarify wine-related behavioral intention. Findings reveal the roles of these factors in shaping sensory perceptions, cognitive evaluations, affective evaluations and behavior related to wine consumption.Practical implicationsThis study holds implications for various stakeholders, including winemakers, wine businesses, restaurants and the broader hospitality industry. Wine businesses can enhance advertising effectiveness by tailoring their marketing efforts to customers’ knowledge levels and emphasizing the inherent attributes that align with individuals’ preferences. Winemakers can improve consumers’ sensory experiences by enhancing the natural color of wines. Restaurants can strive to ignite diners’ positive emotions and experiences by providing congruent information. Furthermore, sensory-driven strategies can be used in the hospitality sector to elevate customers’ positive emotions.Originality/valueThis study fills gaps in wine research by delineating how wine knowledge and related sensory cues can influence consumers’ sensory perceptions, cognitive evaluations, affective evaluations and behavior. These aspects have been largely overlooked in previous work.

Cortisol Levels Chorelated with Exposure to Alcohol Related Visual Stimuli in Patients with Alcohol Use Disorder

IntroductionThe mechanism of craving is not yet fully understood. It implies numerous factors contributing to the decisions an individual has to ponder when faced with a stimulus that has resemblance with the previous experiences related to it. Neural pathways implying the reward mechanism play a significant role in the interpretation of visual, auditory, olfactive stimuli, polarizing the perception towards positive or negative experiences with that substance of abuse.Objectives In this study we focus on the cravings related to alcohol use, in a sample of patients admitted in hospital due to alcohol use disorder pathologies, providing the fact that Romania has the 2nd highest prevalence of heavy episodic drinking at least once a month (35% of adults, in a statistic published by Eurostat in 2019).Methods We included 30 patients with alcohol use disorder. The PACS (Penn Alcohol Craving Scale) was used to assess the severity of craving in the week prior to the hospital admission.Before visualising any alcohol related cues using VRET, patients will have a half hour of group therapy to lower levels of anxiety. Cortisol and blood sugar will be measured after this half hour to set a baseline . Afterwards, using VRET, subjects will be asked to watch a number of visual stimuli that will include cues to alcohol consumption and different types of beverages. Half hour after visualising cues of alcohol, the craving will be assessed by measuring blood sugar and salivary cortisol levels once again. Completing these measurement, patients will be asked to complete the PACS scale one more time to corelate the patients craving with the biological findings. Blood sugar levels will be measured with a blood glucose meter with test strips. Cortisol levels will be measured using salivary levels of cortisol. We choose measuring the salivary levels of cortisol, due to the fact that using this method, the biological active, free cortisol. Measurements of the serum cortisol indicate the total quantity, but not the biologically effective cortisol.ResultsVisual stimuli of alcohol, with the help of VRET modifies the autonomous glucocorticoid secretion, and provide objective information complimentary to the each individual’s craving assessmentConclusionsThere are a great number of strong ties between alcoholic craving in patients and endogenous shifts in cortisol secretion. We aimed towards a better understanding on craving in patients hospitalised for AUD. Other directions for future research are to find out if it possible to consider craving a form of stress or if we could limit craving, by limiting stress.Disclosure of InterestNone Declared

Predicting the memorability of scene pictures: Improved accuracy through one's own experience.

There are conflicting findings regarding the accuracy of metamemory for scene pictures. Judgements of stimulus memorability in general (memorability judgements [MJs]) have been reported to be unpredictive of actual image memorability. However, other studies have found that judgements of learning (JOLs)-predictions of one's own later memory performance for recently studied items-are moderately predictive of people's own actual recognition memory for pictures. The current study directly compared the relative accuracy and cue basis of JOLs and MJs for scene pictures. In Experiments 1 and 2, participants completed an MJ task and a JOL task in counterbalanced order. In the MJ task, they judged the general memorability of each picture. In the JOL task, they studied pictures and made JOLs during a learning phase, followed by a recognition memory test. Results showed that MJs were predictive of general scene memorability and relied on the same cues as JOLs, but MJ accuracy considerably improved after the JOL task. Experiment 3 demonstrated that prior learning experiences drove this increase in MJ accuracy. This work demonstrates that people can predict not only their own future memory performance for scene pictures with moderate accuracy but also the general memorability of scene pictures. In addition, experiences with one's own learning and memory support the ability to assess scene memorability in general. This research contributes to our understanding of the basis and accuracy of different metamemory judgements.

Relative cue precision and prior knowledge contribute to the preference of proximal and distal landmarks in human orientation

A prevailing argument posits that distal landmarks dominate over proximal landmarks as orientation cues. However, no studies have tested this argument or examined the underlying mechanisms. This project aimed to close this gap by examining the roles of relative cue precision and prior knowledge in cue preference. Participants learned object locations with proximal and distal landmarks in an immersive virtual environment. After walking a path without seeing objects or landmarks, participants disoriented themselves by spinning in place and pointed to the objects with the reappearance of a proximal landmark being rotated −50°, a distal landmark being rotated 50°, or both (Conflict). Heading errors were examined. Experiment 1 manipulated the relative cue precision. Results showed that in Conflict condition, the observed weight on the distal cue (exceeding 0.5) changed with but remained higher than the weight predicted by the relative cue precision. This indicates that besides the relative cue precision, prior knowledge of distal cue dominance also influences orientation cue usage. In Experiments 2 and 3, participants walked a path stopping at one object location. Participants were informed of it explicitly in Experiment 2 but not in Experiment 3. Results showed that distal cue dominance still occurred in Experiment 3. However, in Experiment 2, proximal cue dominance appeared, and it was not predicted by the relative cue precision. These results suggest that prior knowledge of proximal cue dominance might have been invoked by the instruction of locations. Consistent with the Bayesian inference model, human cue usage in orientation is determined by relative cue precision and prior knowledge. The choice of prior knowledge can be influenced by instructions.

Occluded pedestrian re-identification based on Multiple Fusion and Semantic feature Mining

The field of person re-identification (re-ID) encounters challenges such as inter-person similarity and occlusion. In this paper, we introduce an occluded pedestrian re-ID method based on Multiple Fusion and Semantic feature Mining (MFSM) to mitigate the adverse effects of occlusion on feature representation. Specifically, we devise a Multi-branch Strategic Enhancement Module (SEM) to bolster the robustness of data augmentation in addressing the issues posed by data memorization more consistently. This module emulates various real-world disturbances by implementing distinct and independent augmentation strategies. Furthermore, we propose the Triplet Cross Unit (TCU) to comprehensively exploit and consolidate both regional and relational visual cues, as well as multi-level features. The TCU facilitates transformers in acquiring an early understanding of translation invariance in images by transferring local patterns such as edges, textures, and colors from the lower CNN layers to the shallower transformer layers. Simultaneously, deeper transformer features offer more abstracted semantic visual representations that complement CNN's high-level semantic features. Lastly, we introduce the Global Squeeze-Excitation Fusion (GSEF) module to address the challenge of global feature segregation across different models in final outputs. The GSEF selectively merges features based on attention mechanisms, prioritizing the comprehensive utilization of valid global features. Extensive experiments demonstrate the state-of-the-art performance of our model in handling pedestrian occlusion, thus validating the efficacy of our method.

The acute effects of cannabis, with and without cannabidiol, on attentional bias to cannabis related cues: a randomised, double-blind, placebo-controlled, cross-over study

RationaleAttentional bias to drug-related stimuli is hypothesised to contribute towards addiction. However, the acute effects of Δ9-tetrahydrocannabinol (THC) on attentional bias to cannabis cues, the differential response in adults and adolescents, and the moderating effect of cannabidiol (CBD) are unknown.ObjectivesOur study investigated (1) the acute effects of vaporised cannabis on attentional bias to cannabis-related images in adults and adolescents and (2) the moderating influences of age and CBD.MethodsWe conducted a randomised, double-blind, placebo-controlled, cross-over study where three weight-adjusted vaporised cannabis preparations: ‘THC’ (8 mg THC for a 75-kg person), ‘THC + CBD’ (8 mg THC and 24 mg CBD for a 75-kg person) and PLA (matched placebo). Cannabis was administered on 3 separate days to 48 participants, who used cannabis 0.5–3 days/week: 24 adolescents (12 females, aged 16–17) and 24 adults (12 females, aged 26–29). Participants completed a visual probe task with cannabis cues. Our primary outcome was attentional bias to cannabis stimuli, measured using the differential reaction time to a cannabis vs. neutral probe, on 200-ms trials.ResultsIn contrast to hypotheses, attention was directed away from cannabis cues on placebo, and there was a main effect of the drug (F(2,92) = 3.865, p = 0.024, η2p = 0.077), indicating THC administration eliminated this bias. There was no significant impact of CBD nor an age-by-drug interaction.ConclusionsAcute THC intoxication eliminated attentional bias away from cannabis cues. There was no evidence of differential response in adolescents compared to adults and no evidence that a moderate vaporised dose of CBD altered the impact of cannabis on attentional bias.Trial registrationThis study was listed with the US National Library of Medicine and registered on ClinicalTrials.gov, URL: Do Adolescents and Adults Differ in Their Acute Response to Cannabis?—Full Text View—ClinicalTrials.gov, registration number: NCT04851392.

Striving for Relationality: Teacher Responsiveness to Relational Cues When Eliciting Students’ Science Ideas

Analyses highlighting the epistemic dimension of students’ participation in science have dominated science education literature for the past several years. While most of this literature has focused on how students learn together, the relational nature of these knowledge-building interactions has been under-examined. In response, this paper empirically examines how these epistemic interactions are also relational. Building upon Noddings’ ethic of care and Maheux and Roth’s argument that “being-in-the-know” in mathematics is always “being-in-the-know-with” others, I develop the construct of relationality as a moral and ethical orientation to teaching that is also visible in moment-to-moment interaction. I present a micro-interactional analysis of what enacting relationality can look like in the context of science teaching through two excerpts in which 8th grade students made unexpected bids to shift their participation. I illustrate how these relationally- and epistemically-entangled bids, and the teachers’ attention and responses to them, precipitated role negotiations: explorations and expansions of what it could mean to “be-in-the-know-with” while building science knowledge. This analysis suggests that learning to notice students’ bids for new roles and learning to interpret those bids as simultaneously relational and epistemic moves is an essential aspect of responsive teaching that cultivates trusting relationships as participation in sophisticated disciplinary practices. I conclude with a discussion of how micro-level relational dynamics function as a mechanism by which meso-level classroom cultures and macro-level social narratives are constituted and contested, and the implications of these constitutions and contestations for science, teachers, and science teacher education.

Single-cell RNA sequencing of aging neural progenitors reveals loss of excitatory neuron potential and a population with transcriptional immune response.

In the adult murine brain, neural stem cells (NSCs) can be found in two main niches: the dentate gyrus (DG) and the subventricular zone (SVZ). In the DG, NSCs produce intermediate progenitors (IPs) that differentiate into excitatory neurons, while progenitors in the SVZ migrate to the olfactory bulb (OB), where they mainly differentiate into inhibitory interneurons. Neurogenesis, the process of generating new neurons, persists throughout life but decreases dramatically with aging, concomitantly with increased inflammation. Although many cell types, including microglia, undergo significant transcriptional changes, few such changes have been detected in neural progenitors. Furthermore, transcriptional profiles in progenitors from different neurogenic regions have not been compared on a single-cell level, and little is known about how they are affected by aging-related inflammation. We have generated a single cell RNA sequencing dataset enriched for IPs, which revealed that most aged neural progenitors only acquire minor transcriptional changes. However, progenitors set to become excitatory neurons decrease faster than others. In addition, a population in the aged SVZ, not detected in the OB, acquired major transcriptional activation related to immune responses. This suggests that differences in age related neurogenic decline between regions is not due to tissue differences but rather cell type specific intrinsic transcriptional programs, and that subset of neuroblasts in the SVZ react strongly to age related inflammatory cues.

An explorative single-arm clinical study to assess craving in patients with alcohol use disorder using Virtual Reality exposure (CRAVE)—study protocol

BackgroundAlcohol use disorder (AUD) belongs to the most burdensome clinical disorders worldwide. Current treatment approaches yield unsatisfactory long-term effects with relapse rates up to 85%. Craving for alcohol is a major predictor for relapse and can be intentionally induced via cue exposure in real life as well as in Virtual Reality (VR). The induction and habituation of craving via conditioned cues as well as extinction learning is used in Cue Exposure Therapy (CET), a long-known but rarely used strategy in Cognitive Behavioral Therapy (CBT) of AUD. VR scenarios with alcohol related cues offer several advantages over real life scenarios and are within the focus of current efforts to develop new treatment options. As a first step, we aim to analyze if the VR scenarios elicit a transient change in craving levels and if this is measurable via subjective and psychophysiological parameters.MethodsA single-arm clinical study will be conducted including n = 60 patients with AUD. Data on severity of AUD and craving, comorbidities, demographics, side effects and the feeling of presence in VR will be assessed. Patients will use a head-mounted display (HMD) to immerse themselves into three different scenarios (neutral vs. two target situations: a living room and a bar) while heart rate, heart rate variability, pupillometry and electrodermal activity will be measured continuously. Subjective craving levels will be assessed before, during and after the VR session.DiscussionResults of this study will yield insight into the induction of alcohol craving in VR cue exposure paradigms and its measurement via subjective and psychophysiological parameters. This might be an important step in the development of innovative therapeutic approaches in the treatment of patients with AUD.Trial registrationThis study was approved by the Charité—Universitätsmedizin Berlin Institutional Review Board (EA1/190/22, 23.05.2023). It was registered on ClinicalTrials.gov (NCT05861843).

Identifying Which Relational Cues Users Find Helpful to Allow Tailoring of e-Coach Dialogues

Relational cues are extracts from actual verbal dialogues that help build the therapist–patient working alliance and stronger bond through the depiction of empathy, respect and openness. ECAs (Embodied conversational agents) are human-like virtual agents that exhibit verbal and non-verbal behaviours. In the digital health space, ECAs act as health coaches or experts. ECA dialogues have previously been designed to include relational cues to motivate patients to change their current behaviours and encourage adherence to a treatment plan. However, there is little understanding of who finds specific relational cues delivered by an ECA helpful or not. Drawing the literature together, we have categorised relational cues into empowering, working alliance, affirmative and social dialogue. In this study, we have embedded the dialogue of Alex, an ECA, to encourage healthy behaviours with all the relational cues (empathic Alex) or with none of the relational cues (neutral Alex). A total of 206 participants were randomly assigned to interact with either empathic or neutral Alex and were also asked to rate the helpfulness of selected relational cues. We explore if the perceived helpfulness of the relational cues is a good predictor of users’ intention to change the recommended health behaviours and/or development of a working alliance. Our models also investigate the impact of individual factors, including gender, age, culture and personality traits of the users. The idea is to establish whether a certain group of individuals having similarities in terms of individual factors found a particular cue or group of cues helpful. This will establish future versions of Alex and allow Alex to tailor its dialogue to specific groups, as well as help in building ECAs with multiple personalities and roles.

Simultaneous relative cue reliance in speech-on-speech masking.

Modern hearing research has identified the ability of listeners to segregate simultaneous speech streams with a reliance on three major voice cues, fundamental frequency, level, and location. Few of these studies evaluated reliance for these cues presented simultaneously as occurs in nature, and fewer still considered the listeners' relative reliance on these cues owing to the cues' different units of measure. In the present study trial-by-trial analyses were used to isolate the listener's simultaneous reliance on the three voice cues, with the behavior of an ideal observer [Green and Swets (1966). (Wiley, New York), pp.151-178] serving as a comparison standard for evaluating relative reliance. Listeners heard on each trial a pair of randomly selected, simultaneous recordings of naturally spoken sentences. One of the recordings was always from the same talker, a distracter, and the other, with equal probability, was from one of two target talkers differing in the three voice cues. The listener's task was to identify the target talker. Among 33 clinically normal-hearing adults only one relied predominantly on voice level, the remaining were split between voice fundamental frequency and/or location. The results are discussed regarding their implications for the common practice in studies of using target-distracter level as a dependent measure of speech-on-speech masking.

An Ideal-observer standard for evaluating relative cue reliance on multi-talker speech segregation

Modern hearing research identifies the ability of listeners to segregate simultaneous speech streams with a reliance on three major voice cues, fundamental frequency, level, and location. Few of these studies, however, present cues simultaneously as in natural listening, and fewer still consider the relative reliance listeners placed on these cues owing to the cues’ different units of measure. In the present study, trial-by-trial analyses were used to isolate listener reliance on the three voice cues presented simultaneously, with the behavior of an ideal observer (Green and Swets, 1966, pp. 151–178) serving as standard for determining their relative reliance. Listeners heard on each trial a pair of randomly selected, simultaneously recordings of naturally spoken sentences. One of the recordings was always from the same talker, a distracter, the other, with equal probability, was from one of two target talkers differing in the three voice cues. The listener’s task was to identify the target talker. Among 33 clinically normal-hearing adults only one relied predominantly on voice level, the remaining were split between voice fundamental frequency and location. The results are discussed regarding their implications for the common practice of using target-distracter level as a dependent measure of multi-talker speech segregation.

Pursuing Safety in Social Connection: A Flexibly Fluid Perspective on Risk Regulation in Relationships.

People are fundamentally motivated to be included in social connections that feel safe, connections where they are consistently cared for and protected, not hurt or exploited. Romantic relationships have long played a crucial role in satisfying this fundamental need. This article reconceptualizes the risk-regulation model to argue that people draw on experiences from inside and outside their romantic relationships to satisfy their fundamental need to feel safe depending on others. We first review the direct relational cues (i.e., a partner's affectionate touch, responsive versus unresponsive behavior, and relative power) and indirect cues (i.e., bodily sensations, collective value in the eyes of others, and living conditions) that signal the current safety of social connection and motivate people to connect to others or protect themselves against them. We then review how people's chronic capacity to trust in others controls their sensitivity and reactivity to the safety cues. The article concludes with future research directions.

MtrA modulates Mycobacterium tuberculosis cell division in host microenvironments to mediate intrinsic resistance and drug tolerance

The success of Mycobacterium tuberculosis (Mtb) is largely attributed to its ability to physiologically adapt and withstand diverse localized stresses within host microenvironments. Here, we present a data-driven model (EGRIN 2.0) that captures the dynamic interplay of environmental cues and genome-encoded regulatory programs in Mtb. Analysis of EGRIN 2.0 shows how modulation of the MtrAB two-component signaling system tunes Mtb growth in response to related host microenvironmental cues. Disruption of MtrAB by tunable CRISPR interference confirms that the signaling system regulates multiple peptidoglycan hydrolases, among other targets, that are important for cell division. Further, MtrA decreases the effectiveness of antibiotics by mechanisms of both intrinsic resistance and drug tolerance. Together, the model-enabled dissection of complex MtrA regulation highlights its importance as a drug target and illustrates how EGRIN 2.0 facilitates discovery and mechanistic characterization of Mtb adaptation to specific host microenvironments within the host.