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Objectives: Anti‐reflux mucosectomy (ARMS) and anti‐reflux mucosal ablation (ARMA) were developed as interventions for proton pump inhibitor (PPI)‐refractory/‐dependent gastroesophageal reflux disease (GERD). Although ARMS and ARMA are established treatments for PPI‐refractory GERD, reliance on natural healing for ulcer scar formation introduces uncertainty and bleeding risk. To address these issues, we introduced a novel approach called anti‐reflux mucoplasty (ARM‐P), which involves immediate closure of mucosal defects following mucosectomy. This pilot study aims to evaluate the safety, feasibility, and efficacy of ARM‐P. Methods: A retrospective single‐center study was conducted using prospectively collected data from October 2022 to July 2023. Patients with PPI‐refractory/‐dependent GERD who underwent ARM‐P were included. The study evaluated technical success of ARM‐P, before and after ARM‐P GERD‐Health Related Quality of Life Questionnaire, GerdQ, and Frequency Scale for the Symptoms of GERD scores, along with PPI discontinuation and endoscopic esophagogastric junction morphology. Results: A total of 20 patients with a median age of 61.5 years underwent the ARM‐P procedure. The procedure achieved 100% technical success without adverse events. After ARM‐P, 55.0% discontinued PPI usage and 15.0% reduced PPI dose by half. Median GERD‐Health Related Quality of Life Questionnaire score improved from 21 to 6 (P = 0.0026), median GerdQ score improved from 9 to 7 (P = 0.0022), and median Frequency Scale for the Symptoms of GERD score decreased from 16 to 7 (P = 0.0003). Median Hill's Classification significantly improved from grade III to grade I (P = 0.0001). Conclusions: This study presents the first pilot report of ARM‐P, demonstrating its procedural safety, technical feasibility, and short‐term efficacy. [ABSTRACT FROM AUTHOR]

Rationale: Prepulse inhibition (PPI) impairment reflects sensorimotor gating problems, i.e. in schizophrenia. This study aims to enlighten the role of orexinergic regulation on PPI in a psychosis-like model. Objectives: In order to understand the impact of orexinergic innervation on PPI and how it is modulated by age and baseline PPI (bPPI), chronic orexin A (OXA) injections was carried on non-sleep-deprived and sleep-deprived rats that are grouped by their bPPI. Methods: bPPI measurements were carried on male Wistar rats on P45 or P90 followed by grouping into low-PPI and high-PPI rats. The rats were injected with OXA twice per day for four consecutive days starting on P49 or P94, while the control groups received saline injections. 72 h REMSD was carried on via modified multiple platform technique on P94 and either OXA or saline was injected during REMSD. PPI tests were carried out 30 min. after the last injection. Results: Our previous study with acute OXA injection after REMSD without bPPI grouping revealed that low OXA doses might improve REMSD-induced PPI impairment. Our current results present three important conclusions: (1) The effect of OXA on PPI is bPPI-dependent and age-dependent. (2) The effect of REMSD is bPPI-dependent. (3) The effect of OXA on PPI after REMSD also depends on bPPI. Conclusion: Orexinergic regulation of PPI response with and without REMSD can be predicted by bPPI levels. Our findings provide potential insights into the regulation of sensorimotor gating by sleep/wakefulness systems and present potential therapeutic targets for the disorders, where PPI is disturbed. [ABSTRACT FROM AUTHOR]

Background: Sexual behaviour is an intricate process, controlled by the endocrine constitution of an animal and influenced by the social environment, sensory capability and sexual stimuli. Variations in temperature associated with global warming are startling for fertility of animals. The objective of the present study was to assess the seasonal variation in sexual behaviour of Deoni (Bos indicus) breeding bulls. Methods: A total of six mature Deoni bulls, maintained for artificial insemination at Livestock Research Center, Southern Regional Station of ICAR-NDRI, Bengaluru, were monitored for sexual behavior during the semen collection at weekly intervals throughout the year using standard techniques. The period of study was divided into three seasons i.e., winter (November to February), summer (March to June) and rainy (July to October). Result: The season had a non-significant (P>0.05) effect on sexual behavior except dismounting time in Deoni bulls. The libido score (0-10), reaction time (seconds) and the total time taken in mounting (seconds) were non-significantly (P>0.05) higher during winter (7.50±0.23, 42.00±4.8, 44.00±4.8, respectively) as compared to the other seasons. The protrusion score (0-4) and the intensity of thrust (0-4) were non-significantly (P>0.05) higher during summer (2.60±0.14 and 2.50±0.13) as compared to the other seasons. The dismounting time (seconds) was significantly (P<0.05) higher during summer (2.90±0.16) as compared to the other seasons. It can be concluded that Deoni bulls had good sexual behavior throughout the year, however, bulls showed better sexual behavior except for dismounting time during winter as compared to the other seasons. [ABSTRACT FROM AUTHOR]

This article discusses a study on the temporal dynamics of positive emotion regulation using facial electromyography (EMG). The study found distinct patterns in emotion regulation, showing the possibility of one-dimensional positive affect change with a neutralize goal and sequential two-dimensional change with a transform goal. The research provides insights into the time course of emotional change brought about by different regulatory goals. The study also examined the effects of different emotion regulation goals on emotional reactivity, finding that the neutralize goal led to a neutral emotional state, while the transform goal resulted in a transition from positive to negative emotion. Overall, the findings highlight the complex and dynamic nature of emotion regulation. [Extracted from the article]

The COVID-19 epidemic is a novel collective traumatic event. Different types of traumatic events lead to different symptomatic structures of posttraumatic stress disorder (PTSD). To understand the symptom structure of PTSD in the context of this particular traumatic event and its possible development, we explored the interrelationships among PTSD symptoms and the interrelationships between PTSD symptoms and anxiety, depression, suicidal ideation, and quality of life. Participants were recruited from the psychological assistance hotline platform based at Central China Normal University. 308 participants who met the provisional diagnosis of PTSD were included in the analysis. This study estimated the interrelationships among PTSD symptoms, with the symptom in addition to four covariates of anxiety, depression, suicidal ideation, and quality of life by network analysis to construct Gaussian graphical models and directed acyclic graphs. The core of the PTSD symptom network was nightmares. Five pairs of symptoms showed the strongest connections: Hypervigilance and exaggerated startle response, avoidance of thoughts and avoidance of reminders, negative beliefs and negative trauma-related emotions, nightmares and flashbacks, and flashbacks and emotional cue reactivity. The network did not change significantly with the inclusion of anxiety, depression, suicidal ideation, and quality of life. Nightmares may be the core of the development of PTSD resulting from the COVID-19 epidemic. In this particular context, interventions for PTSD focus on nightmares may contribute to the relief of other symptoms and improve the efficiency and effectiveness of the intervention. [ABSTRACT FROM AUTHOR]

The interaction of Plasmodium falciparum—infected red blood cells (iRBCs) with the vascular endothelium plays a crucial role in malaria pathology and disease. KAHRP is an exported P. falciparum protein involved in iRBC remodelling, which is essential for the formation of protrusions or "knobs" on the iRBC surface. These knobs and the proteins that are concentrated within them allow the parasites to escape the immune response and host spleen clearance by mediating cytoadherence of the iRBC to the endothelial wall, but this also slows down blood circulation, leading in some cases to severe cerebral and placental complications. In this work, we have applied genetic and biochemical tools to identify proteins that interact with P. falciparum KAHRP using enhanced ascorbate peroxidase 2 (APEX2) proximity-dependent biotinylation and label-free shotgun proteomics. A total of 30 potential KAHRP-interacting candidates were identified, based on the assigned fragmented biotinylated ions. Several identified proteins have been previously reported to be part of the Maurer's clefts and knobs, where KAHRP resides. This study may contribute to a broader understanding of P. falciparum protein trafficking and knob architecture and shows for the first time the feasibility of using APEX2-proximity labelling in iRBCs. [ABSTRACT FROM AUTHOR]

Proton pump inhibitors (PPIs) are widely used in the long-term treatment of gastroesophageal reflux disease (GERD) and other upper gastrointestinal disorders, such as the healing of peptic ulcers and/or prophylactic treatment of peptic ulcers. PPIs are also widely used as symptomatic treatment in patients with functional dyspepsia. One of the adverse effects of the long-term use of PPI is rebound acid hypersecretion (RAHS), which can occur after the withdrawal of PPI therapy due to a compensatory increase in gastric acid production. Mechanisms of the RAHS have been well established. Studies have shown that pentagastrin-stimulated acid secretion after the discontinuation of PPIs increased significantly compared to that before treatment. In healthy volunteers treated with PPIs, the latter induced gastrointestinal symptoms in 40–50% of subjects after the discontinuation of PPI therapy but after stopping the placebo. It is important for practicing physicians to be aware and understand the underlying mechanisms and inform patients about potential RAHS before discontinuing PPIs in order to avoid continuing unnecessary PPI therapy. This is important because RAHS may lead patients to reuptake PPIs as symptoms are incorrectly thought to originate from the recurrence of underlying conditions, such as GERD. Mechanisms of RAHS have been well established; however, clinical implications and the risk factors for RAHS are not fully understood. Further research is needed to facilitate appropriate management of RAHS in the future. [ABSTRACT FROM AUTHOR]

The sensorimotor gating is a nervous system function that modulates the acoustic startle response (ASR). Prepulse inhibition (PPI) phenomenon is an operational measure of sensorimotor gating, defined as the reduction of ASR when a high intensity sound (pulse) is preceded in milliseconds by a weaker stimulus (prepulse). Brainstem nuclei are associated with the mediation of ASR and PPI, whereas cortical and subcortical regions are associated with their modulation. However, it is still unclear how the modulatory units can influence PPI. In the present work, we developed a computational model of a neural circuit involved in the mediation (brainstem units) and modulation (cortical and subcortical units) of ASR and PPI. The activities of all units were modeled by the leaky-integrator formalism for neural population. The model reproduces basic features of PPI observed in experiments, such as the effects of changes in interstimulus interval, prepulse intensity, and habituation of ASR. The simulation of GABAergic and dopaminergic drugs impaired PPI by their effects over subcortical units activity. The results show that subcortical units constitute a central hub for PPI modulation. The presented computational model offers a valuable tool to investigate the neurobiology associated with disorder-related impairments in PPI. [ABSTRACT FROM AUTHOR]

Hepatitis C virus (HCV) is a major medical health burden and the leading cause of chronic liver disease and cancer worldwide. More than 58 million people are chronically infected with HCV, with 1.5 million new infections occurring each year. An effective HCV vaccine is a major public health and medical need as recognized by the World Health Organization. However, due to the high variability of the virus and its ability to escape the immune response, HCV rapidly accumulates mutations, making vaccine development a formidable challenge. An effective vaccine must elicit broadly neutralizing antibodies (bnAbs) in a consistent fashion. After decades of studies from basic research through clinical development, the antigen of choice is considered the E1E2 envelope glycoprotein due to conserved, broadly neutralizing antigenic domains located in the constituent subunits of E1, E2, and the E1E2 heterodimeric complex itself. The challenge has been elicitation of robust humoral and cellular responses leading to broad virus neutralization due to the relatively low immunogenicity of this antigen. In view of this challenge, structure-based vaccine design approaches to stabilize key antigenic domains have been hampered due to the lack of E1E2 atomic-level resolution structures to guide them. Another challenge has been the development of a delivery platform in which a multivalent form of the antigen can be presented in order to elicit a more robust anti-HCV immune response. Recent nanoparticle vaccines are gaining prominence in the field due to their ability to facilitate a controlled multivalent presentation and trafficking to lymph nodes, where they can interact with both the cellular and humoral components of the immune system. This review focuses on recent advances in understanding the E1E2 heterodimeric structure to facilitate a rational design approach and the potential for development of a multivalent nanoparticle-based HCV E1E2 vaccine. Both aspects are considered important in the development of an effective HCV vaccine that can effectively address viral diversity and escape. [ABSTRACT FROM AUTHOR]

Background: Rats with a loss-of-function mutation in the contactin-associated protein-like 2 (Cntnap2) gene have been validated as an animal model of autism spectrum disorder (ASD). Similar to many autistic individuals, Cntnap2 knock-out rats (Cntnap2-/-) are hyperreactive to sound as measured through the acoustic startle response. The brainstem region that mediates the acoustic startle response is the caudal pontine reticular nucleus (PnC), specifically giant neurons in the PnC. We previously reported a sex-dependent genotypic effect in the sound-evoked neuronal activity recorded from the PnC, whereby female Cntnap2-/- rats had a dramatic increase in soundevoked responses compared with wildtype counterparts, but male Cntnap2-/- rats showed only a modest increase in PnC activity that cannot fully explain the largely increased startle in male Cntnap2-/- rats. The present study therefore investigates activation and histological properties of PnC giant neurons in Cntnap2-/- rats and wildtype littermates. Methods: The acoustic startle response was elicited by presenting rats with 95 dB startle pulses before rats were euthanized. PnC brain sections were stained and analyzed for the total number of PnC giant neurons and the percentage of giant neurons that expressed phosphorylated cAMP response element binding protein (pCREB) in response to startle stimuli. Additionally, in vitro electrophysiology was conducted to assess the resting state activity and intrinsic properties of PnC giant neurons. Results: Wildtype and Cntnap2-/- rats had similar total numbers of PnC giant neurons and similar levels of baseline pCREB expression, as well as similar numbers of giant neurons that were firing at rest. Increased startle magnitudes in Cntnap2-/- rats were associated with increased percentages of pCREB-expressing PnC giant neurons in response to startle stimuli. Male rats had increased pCREB-expressing PnC giant neurons compared with female rats, and the recruited giant neurons in males were also larger in soma size. Conclusions: Recruitment and size of PnC giant neurons are important factors for regulating the magnitude of the acoustic startle response in Cntnap2-/- rats, particularly in males. These findings allow for a better understanding of increased reactivity to sound in Cntnap2-/- rats and in CNTNAP2-associated disorders such as ASD. [ABSTRACT FROM AUTHOR]

Medial olivocochlear (MOC) efferents modulate outer hair cell motility through specialized nicotinic acetylcholine receptors to support encoding of signals in noise. Transgenic mice lacking the alpha9 subunits of these receptors (α9KOs) have normal hearing in quiet and noise, but lack classic cochlear suppression effects and show abnormal temporal, spectral, and spatial processing. Mice deficient for both the alpha9 and alpha10 receptor subunits (α9α10KOs) may exhibit more severe MOC-related phenotypes. Like α9KOs, α9α10KOs have normal auditory brainstem response (ABR) thresholds and weak MOC reflexes. Here, we further characterized auditory function in α9α10KO mice. Wild-type (WT) and α9α10KO mice had similar ABR thresholds and acoustic startle response amplitudes in quiet and noise, and similar frequency and intensity difference sensitivity. α9α10KO mice had larger ABR Wave I amplitudes than WTs in quiet and noise. Other ABR metrics of hearing-in-noise function yielded conflicting findings regarding α9α10KO susceptibility to masking effects. α9α10KO mice also had larger startle amplitudes in tone backgrounds than WTs. Overall, α9α10KO mice had grossly normal auditory function in quiet and noise, although their larger ABR amplitudes and hyperreactive startles suggest some auditory processing abnormalities. These findings contribute to the growing literature showing mixed effects of MOC dysfunction on hearing. [ABSTRACT FROM AUTHOR]

Simple Summary: Hatchery-reared Rainbow trout are released into freshwater systems, often to support recreational fishing, but the best age to release fish to maximise their chances of survival is unknown. Using laboratory tests of fish behaviour at six ages, we report age-related changes in emergence, exploration, food neophobia, habitat choice and predator avoidance. We suggest that an understanding of age-related changes in behaviour should be applied to support management decisions around the best age to release Rainbow trout. Millions of hatchery-reared Rainbow trout are currently released in Australian waters to support recreational fisheries objectives, yet many of these fish die soon after release. In addition, little is known whether these fish harbour parasites that can potentially threaten freshwater ecosystems and human health. Here, we tested the behaviour of hatchery-reared trout using six tank-based tests at six different ages to evaluate their chances of survival and then dissected fish to investigate parasite prevalence. At 7 weeks of age fish readily emerged from a hide and showed the greatest number of startle responses to predators. Behaviour around 25–29 weeks of age was relatively "shy", staying in shelter and avoiding open water. At around 37–41 weeks of age though, behaviour changed, with fish emerging from a hide more readily and exploring the environment. Interestingly, at 58 weeks of age fish were slower to initiate exploration, possibly indicating a return to "shyer" behaviour. All fish underwent thorough parasite examination, revealing no infections. We conclude that knowledge of the behaviour of hatchery-reared fish at different ages is useful for decisions around the timing of release that balance the needs of recreational fishers whilst managing the impact on freshwater ecosystem. [ABSTRACT FROM AUTHOR]

Background: Deficiencies in the thyroid hormone transporter monocarboxylate 8 (MCT8) due to pathogenic variants in the SLC16A2 gene (OMIM 300095) result in a complex phenotype with main endocrine and neurologic symptoms. This rare disorder, named Allan–Herndon–Dudley syndrome (AHDS) (OMIM 300523), is inherited in an X‐linked trait. One of the prominent features of AHDS is the presence of movement disorders (MD), which are complex and carry a significant burden of the disease. Cases: Patient 1: male with hypotonia since birth, developmental delay, dystonic posturing at 4 months and at 15 months, and startle reaction developed with sensory stimuli. Patient 2: male, at 2 months, shows hypotonia and developmental delay, paroxysmal episodes triggered by a stimulus with sudden blush, tonic asymmetric posture, and no epileptiform activity. At 10 months, generalized dystonic posturing. Patient 3: typical neurodevelopmental milestones until 6 months; at 24 months, dystonia, startle reaction, and upper motoneuron signs. Conclusions: We aim to describe our patients diagnosed with AHDS, focusing on MD phenomenology and strengthening the phenotype–genotype correlations for this rare condition. [ABSTRACT FROM AUTHOR]

Rationale: Previous work identified an attenuating effect of the matrix metalloproteinase (MMP) inhibitor doxycycline on fear memory consolidation. This may present a new mechanistic approach for the prevention of trauma-related disorders. However, so far, this has only been unambiguously demonstrated in a cued delay fear conditioning paradigm, in which a simple geometric cue predicted a temporally overlapping aversive outcome. This form of learning is mainly amygdala dependent. Psychological trauma often involves the encoding of contextual cues, which putatively necessitates partly different neural circuits including the hippocampus. The role of MMP signalling in the underlying neural pathways in humans is unknown. Methods: Here, we investigated the effect of doxycycline on configural fear conditioning in a double-blind placebo-controlled randomised trial with 100 (50 females) healthy human participants. Results: Our results show that participants successfully learned and retained, after 1 week, the context-shock association in both groups. We find no group difference in fear memory retention in either of our pre-registered outcome measures, startle eye-blink responses and pupil dilation. Contrary to expectations, we identified elevated fear-potentiated startle in the doxycycline group early in the recall test, compared to the placebo group. Conclusion: Our results suggest that doxycycline does not substantially attenuate contextual fear memory. This might limit its potential for clinical application. [ABSTRACT FROM AUTHOR]

Introduction: Chronic adolescent stress profoundly affects prefrontal cortical networks regulating top‐down behavior control. However, the neurobiological pathways contributing to stress‐induced alterations in the brain and behavior remain largely unknown. Chronic stress influences brain growth factors and immune responses, which may, in turn, disrupt the maturation and function of prefrontal cortical networks. The tumor necrosis factor alpha‐converting enzyme/a disintegrin and metalloproteinase 17 (TACE/ADAM17) is a sheddase with essential functions in brain maturation, behavior, and inflammatory responses. This study aimed to determine the impact of stress on the prefrontal cortex and whether TACE/ADAM17 plays a role in these responses. Methods: We used a Lewis rat model that incorporates critical elements of chronic psychosocial stress, such as uncontrollability, unpredictability, lack of social support, and re‐experiencing of trauma. Results: Chronic stress during adolescence reduced the acoustic startle reflex and social interactions while increasing extracellular free water content and TACE/ADAM17 mRNA levels in the medial prefrontal cortex. Chronic stress altered various ethological behavioral domains in the observation home cages (decreased ingestive behaviors and increased walking, grooming, and rearing behaviors). A group of rats was injected intracerebrally either with a novel Accell™ SMARTpool TACE/ADAM17 siRNA or a corresponding siRNA vehicle (control). The RNAscope Multiplex Fluorescent v2 Assay was used to visualize mRNA expression. Automated puncta quantification and analyses demonstrated that TACE/ADAM17 siRNA administration reduced TACE/ADAM17 mRNA levels in the medial prefrontal cortex (59% reduction relative to control). We found that the rats that received prefrontal cortical TACE/ADAM17 siRNA administration exhibited altered eating patterns (e.g., increased food intake and time in the feeding zone during the light cycle). Conclusion: This study supports that the prefrontal cortex is sensitive to adolescent chronic stress and suggests that TACE/ADAM17 may be involved in the brain responses to stress. [ABSTRACT FROM AUTHOR]

This study aimed to investigate the efficiency of epoxy and para rubber glue for attaching artificial satellite tags to juvenile green sea turtles (Chelonia mydas). Two groups of 10 juvenile C. mydas each were monitored for two months before and after tag attachment. Measurements and analyses of straight carapace length (SCL), straight carapace width (SCW), weight, and behaviors were conducted. The results showed that there were no significant differences in the final SCL, SCW, and weight of the turtles between the two adhesive treatments. However, the average daily gains in SCL and SCW were significantly different before and after the attachment of epoxy. The most frequently observed behavior in both adhesive groups was buoyancy, which decreased in frequency after tag attachment in both treatments. Other behaviors, such as scratching, startle responses and underwater movement also exhibited changes after attachment, varying with the type of adhesive used. The study demonstrated that natural adhesive materials serve as an alternative method for attaching satellite tags to rapidly growing juvenile sea turtles, minimizing injury and maintaining flexibility to prevent changes in carapace shape. Overall, the findings suggest the potential for using natural adhesive materials in future satellite tagging efforts to minimize negative impacts on sea turtles. [ABSTRACT FROM AUTHOR]

Simple Summary: Infectious hematopoietic necrosis virus (IHNV) is listed in the World Organization for Animal Health (WOAH) for its serious infection in salmonid fish. MicroRNAs (miRNA) were important regulators in the immune responses during viral infections. However, the roles of miRNAs during IHNV infection are rarely known. Our previous work found that IHNV infection upregulated the expression of miRNA146a-3p. The present study is intended to detail the molecular mechanism underlying the role of miRNA146a-3p in IHNV infection. This will provide new insight into IHNV pathopoiesis and might benefit the development of antiviral strategies against IHNV. Infectious hematopoietic necrosis virus (IHNV) is a serious pathogen that causes great economic loss to the salmon and trout industry. Previous studies showed that IHNV alters the expression patterns of splenic microRNAs (miRNAs) in rainbow trout. Among the differentially expressed miRNAs, miRNA146a-3p was upregulated by IHNV. However, it is unclear how IHNV utilizes miRNA146a-3p to escape the immune response or promote viral replication. The present study suggested that one multiplicity of infection (MOI) of IHNV induced the most significant miR-146a-3p expression at 1 day post infection (dpi). The upregulation of miR-146a-3p by IHNV was due to viral N, P, M, and G proteins and relied on the interferon (IFN) signaling pathway. Further investigation revealed that Wingless-type MMTV integration site family 3a (WNT3a) and G1/S-specific cyclin-D1-like (CCND1) are the target genes of miRNA-146a-3p. The regulation of IHNV infection by miRNA-146a-3p is dependent on WNT3a and CCND1. MiRNA-146a-3p was required for the downregulation of WNT3a and CCND1 by IHNV. Moreover, we also found that WNT3a and CCND1 are novel proteins that induce the type-I IFN response in RTG-2 cells, and both of them could inhibit the replication of IHNV. Therefore, IHNV-induced upregulation of miRNA-146a-3p promotes early viral replication by suppressing the type-I IFN response by targeting WNT3a and CCND1. This work not only reveals the molecular mechanism of miRNA-146a-3p during IHNV infection but also provides new antiviral targets for IHNV. [ABSTRACT FROM AUTHOR]

Featured Application: The outcome of this study has the potential to open a new direction to optimise the success of asset management and of financial markets in general. The new focus is not algorithms, but the non-conscious mind in humans. In the world of finance, considerable attention is given to improving machine learning techniques to predict the future of stock markets. However, for obvious reasons, this turns out to be an unsolvable mission, most likely because the real world is not driven by algorithms but by human beings. In response to this, the present study has its focus on raw affective responses in actual asset managers during their decision making regarding controlled financial scenarios. Nineteen asset managers were invited and asked to make sell/buy decisions related to visual presentations of three different price developments of different assets. The three scenarios were "crash", "stable" and "gain". Parallel to their decision making, startle reflex modulation (SRM) was used to measure non-conscious affective responses without demanding any respective explicit responses (no conscious language processing involved). Interestingly, two further factors were introduced. First, all participants had to make their decisions once while being informed that 0% prior investments (low exposure) have been made into the presented assets, and once being informed that a large investment consisting of 25% of ones' overall portfolio has been made prior to making the decision (high exposure). Second, the factor experience was included dividing all participants into two groups, one with low experience and the other with high experience. First, across both these extra factors, it was found that "crash" scenarios resulted in the most negative affective responses. The most positive affective responses were found for "gain" scenarios, while the "stable" condition was in between. Interestingly, the factor of prior investment (i.e., exposure) had an effect. Non-conscious affective responses during decision making related to the "stable" condition varied as a function of "exposure". In the low exposure condition, affective responses to decision making during the "stable" scenario were most negative, even more negative than in "crash" scenarios. The factor experience also had an effect, but due to the small sample size, no significant interaction occurred. However, t-tests revealed the same significant effects in the experienced group as found in the 0% prior investment condition. To our knowledge, this is the first empirical investigation measuring non-conscious affective responses during decision making in the context of asset management. Thus, this study might form an interesting basis for new strategies to explore non-conscious human brain functions instead of inventing new algorithms to make asset management more successful. [ABSTRACT FROM AUTHOR]

Pulse tube refrigerators are a critical enabling technology for many disciplines that require low temperatures. These refrigerators dominate the total power consumption of most modern cryostats, including those that reach millikelvin temperatures using additional cooling stages. In state-of-the-art commercial pulse tube refrigerators, the acoustic coupling between the driving compressor and the refrigerator is fixed and optimized for operation at base temperature. We show that this optimization is incorrect during the cooldown process, which results in wasted power consumption by the compressor and slow cooldown speed. After developing analytic expressions that demonstrate the need for acoustic tuning as a function of temperature, we dynamically optimize the acoustics of a commercial pulse tube refrigerator and show that the cooldown speed can be increased to 1.7 to 3.5 times the original value. Acoustic power measurements show that loss mechanism(s)—and not the capacity of the compressor—limit the maximum cooling available at high temperatures, suggesting that even faster cooldown speeds can be achieved in the future. This work has implications for the accessibility of cryogenic temperatures and the cadence of research in many disciplines such as quantum computing. Pulse tube refrigerators are a critical enabling technology for many disciplines that require low temperatures, including quantum computing. Here, the authors show that dynamically optimizing the acoustic parameters of the refrigerator can improve conventional cooldown speeds up to 3.5 times. [ABSTRACT FROM AUTHOR]

Background: Alzheimer's disease (AD) and amyotrophic lateral sclerosis/frontotemporal dementia (ALS/FTD) are debilitating neurodegenerative diseases for which there are currently no cures. Familial cases with known genetic causes make up less than 10% of these diseases, and little is known about the underlying mechanisms that contribute to sporadic disease. Accordingly, it is important to expand investigations into possible pathways that may contribute to disease pathophysiology. Glycerophosphodiester phosphodiesterase 2 (GDE2 or GDPD5) is a membrane-bound enzyme that acts at the cell surface to cleave the glycosylphosphatidylinositol (GPI)-anchor that tethers distinct proteins to the membrane. GDE2 abnormally accumulates in intracellular compartments in the brain of patients with AD, ALS, and ALS/FTD, indicative of GDE2 dysfunction. Mice lacking GDE2 (Gde2KO) show neurodegenerative changes such as neuronal loss, reduced synaptic proteins and synapse loss, and increased Aβ deposition, raising the possibility that GDE2 disruption in disease might contribute to disease pathophysiology. However, the effect of GDE2 loss on behavioral function and learning/memory has not been characterized. Results: Here, we show that GDE2 is expressed throughout the adult mouse brain in areas including the cortex, hippocampus, habenula, thalamus, and amygdala. Gde2KO and WT mice were tested in a set of behavioral tasks between 7 and 16 months of age. Compared to WT, Gde2KO mice display moderate hyperactivity that becomes more pronounced with age across a variety of behavioral tests assessing novelty-induced exploratory activity. Additionally, Gde2KO mice show reduced startle response, with females showing additional defects in prepulse inhibition. No changes in anxiety-associated behaviors were found, but Gde2KOs show reduced sociability. Notably, aged Gde2KO mice demonstrate impaired short/long-term spatial memory and cued fear memory/secondary contextual fear acquisition. Conclusions: Taken together, these observations suggest that loss of GDE2 leads to behavioral deficits, some of which are seen in neurodegenerative disease models, implying that loss of GDE2 may be an important contributor to phenotypes associated with neurodegeneration. [ABSTRACT FROM AUTHOR]

The perceived intensity of an intense stimulus as well as the startle reflex it elicits can both be reduced when preceded by a weak stimulus (prepulse). Both phenomena are used to characterise the processes of sensory gating in clinical and non-clinical populations. The latter phenomenon, startle prepulse inhibition (PPI), is conceptualised as a measure of pre-attentive sensorimotor gating due to its observation at short latencies. In contrast, the former, prepulse inhibition of perceived stimulus intensity (PPIPSI), is believed to involve higher-order cognitive processes (e.g., attention), which require longer latencies. Although conceptually distinct, PPIPSI is often studied using parameters that elicit maximal PPI, likely limiting what we can learn about sensory gating's influence on conscious perception. Here, we tested an array of stimulus onset asynchronies (SOAs; 0–602 ms) and prepulse intensities (0–3× perceptual threshold) to determine the time course and sensitivity to the intensity of electrotactile PPIPSI. Participants were required to compare an 'unpleasant but not painful' electric pulse to their left wrist that was presented alone with the same stimulus preceded by an electric prepulse, and report which pulse stimulus felt more intense. Using a 2× perceptual threshold prepulse, PPIPSI emerged as significant at SOAs from 162 to 602 ms. We conclude that evidence of electrotactile PPIPSI at SOAs of 162 ms or longer is consistent with gating of perception requiring higher-level processes, not measured by startle PPI. The possible role of attentional processes, stimuli intensity, modality-specific differences, and methods of investigating PPIPSI further are discussed. [ABSTRACT FROM AUTHOR]

Introduced species can represent quasi-experimental, anthropogenic case studies of both ecological and evolutionary principles. When these species are firmly established, competitive interactions between native and introduced species, including foraging, spacing, and breeding competition, may be among the ecological costs incurred from such species invasions. In turn, genetic and/or plasticity-driven changes in behavior and morphology could also take place in the invading species with increasing introduction lag (time since the onset of introduction). Critically, however, introduction lag is difficult to study in any single non-native population without long-term observations, and, instead, it requires geographically repeated measures of the focal response variables across invasive populations that were introduced at different times. Here we tested a priori predictors of predator-avoidance behaviors through the flight initiation distance (FID) assay of a widely distributed invasive bird species, the common myna Acridotheres tristis. The species was extensively and consistently sampled throughout most of its independently introduced ranges across all hemispheres. Critically, FID increased with greater introduction lag. We also detected additional functional patterns in that FID increased towards the rural range within a continuous metric of urban-rural gradient and also at shorter distances from the Equator. Any robust study of FID must also include proximate predictors as well and, accordingly, we found that FID increased with greater starting distance, with lower immediate human density, with flighted over walking escape responses, and at lower heights of a bird's perch above ground but was unrelated to myna group size. Respectively, these factors are informative about the sensory cues triggering anti-predator behaviors in invasive mynas and imply an adaptive set of patterns of anti-predator responses in the introduced ranges of this species. Control measures of invasive common myna populations should take into account their extensive behavioral and cognitive flexibilities and adjust the planned management methods accordingly. [ABSTRACT FROM AUTHOR]

Background: Sleep deprivation (SD) impairs pre-stimulus inhibition, but the effect of quetiapine (QET) remains largely unknown. Objective: This study aimed to investigate the behavioral and cognitive effects of QET in both naïve and sleep-deprived rats. Materials and methods: Seven groups (n = 49) of male Wistar Albino rats were used in this study. SD was performed using the modified multiple platform technique in a water tank for 72 h. Our study consists of two experiments investigating the effect of QET on pre-pulse inhibition (PPI) of the acoustic startle reflex. The first experiment tested the effect of short- and long-term administration of QET on PPI response in non-sleeping (NSD) rats. The second experiment used 72 h REM sleep deprivation as a model for SD-induced impairment of the PPI response. Here, we tested the effect of QET on the % PPI of SD rats by short- and long-term intraperitoneal injection at the last 90 min of sleep SD and immediately subsequently tested for PPI. Results: 72 h SD impaired PPI, reduced startle amplitude, and attenuated the PPI% at + 4 dB, + 8 dB, and + 16 dB prepulse intensities. 10 mg/kg short and long-term QET administration completely improved sensorimotor gating deficit, increased startle amplitude, and restored the impaired PPI% at + 4 dB, + 8 dB, and + 16 dB after 72 h SD in rats. Conclusion: Our results showed short- and long-term administration of QET improved sensorimotor gating deficit in 72 h SD. Further research is required for the etiology of insomnia and the dose-related behavioral effects of QET. [ABSTRACT FROM AUTHOR]

On the example of an underwater sound channel typical of the Philippine Sea [1–3], it was established by numerical simulation using mode theory that during experimental studies of the propagation of explosive signals by R.A. Vadov [1–3], manifestation of a weakly divergent beam in the spatiotemporal structure of the acoustic field was observed for the first time: at certain locations of the corresponding points in the oceanic waveguide, in addition to classical quadruples of pulses, additional acoustic signals with small time delays with respect to them. [ABSTRACT FROM AUTHOR]

Rationale: Preclinical research suggests that pharmacologically elevating cannabinoid levels may attenuate fear memory expression and enhance fear extinction. Objectives: We studied the effects of cannabidiol (CBD) on fear memory expression and fear re-extinction in 69 patients with panic disorder with agoraphobia or with social anxiety disorder. Moderation by sex, diagnosis, and serotonergic antidepressant (AD) use was explored. Methods: A cued fear conditioning paradigm was applied before the first treatment session with 300 mg CBD/placebo augmented exposure therapy. Study medication was administered orally preceding 8 weekly sessions. Fear acquisition and suboptimal extinction took place prior to the first medication ingestion (T0). After the first medication ingestion (T1), we investigated effects on fear memory expression at retention and fear re-extinction. Subjective fear, shock expectancy, skin conductance, and startle responses to conditioned (CS+) and safety stimulus (CS−) were measured. Results: Across the sample, CBD reduced shock expectancy at retention under low and ambiguous threat of shock, but fear re-extinction at T1 was unaffected by CBD. However, in AD users, re-extinction of subjective fear was impaired in the CBD condition compared to placebo. In female AD users, CBD interfered with safety learning measured with fear-potentiated startle. Conclusions: The current findings provide no evidence for enhanced fear re-extinction by CBD. However, CBD acutely decreased threat expectation at retention, without affecting other indices of fear. More studies are needed to elucidate possible interactions with AD use and sex, as well as potential effects of CBD on threat expectancies. [ABSTRACT FROM AUTHOR]

Introduction: The concept of affordance refers to the opportunities for action provided by the environment, often conveyed through visual information. It has been applied to explain visuomotor processing and movement planning. As emotion modulates both visual perception and the motor system, it is reasonable to ask whether emotion can influence affordance judgments. If present, this relationship can have important ontological implications for affordances. Thus, we investigated whether the emotional value of manipulable objects affected the judgment of the appropriate grasping that could be used to interact with them (i.e., their affordance). Methods: Volunteers were instructed to use a numerical scale to report their judgment on how an observed object should be grasped. We compared these judgments across emotional categories of objects (pleasant, unpleasant and neutral), while also considering the expected effect of object size. Results: We found that unpleasant objects were rated as more appropriately graspable by a precision grip than pleasant and neutral objects. Simultaneously, smaller object size also favored this judgment. This effect was seen in all emotional categories examined in equal magnitude. Discussion: Our findings suggest that the emotional value of objects modulates affordance judgments in a way that favors careful manipulation and minimal physical contact with aversive stimuli. Finally, we discuss how this affective aspect of our experience of objects overlaps with what affordances are conceptualized to be, calling for further reexamination of the relationship between affordances and emotions. [ABSTRACT FROM AUTHOR]

Thymic stromal lymphopoietin is a key cytokine involved in the pathogenesis of asthma and other allergic diseases. Targeting TSLP and its signaling pathways is increasingly recognized as an effective strategy for asthma treatment. This study focused on enhancing the affinity of the T6 antibody, which specifically targets TSLP, by integrating computational and experimental methods. The initial affinity of the T6 antibody for TSLP was lower than the benchmark antibody AMG157. To improve this, we utilized alanine scanning, molecular docking, and computational tools including mCSM-PPI2 and GEO-PPI to identify critical amino acid residues for site-directed mutagenesis. Subsequent mutations and experimental validations resulted in an antibody with significantly enhanced blocking capacity against TSLP. Our findings demonstrate the potential of computer-assisted techniques in expediting antibody affinity maturation, thereby reducing both the time and cost of experiments. The integration of computational methods with experimental approaches holds great promise for the development of targeted therapeutic antibodies for TSLP-related diseases. Author summary: Computer-assisted affinity maturation significantly reduces experimental time and lowers research costs. Targeting thymic stromal lymphopoietin and its signaling pathways with specific antibody drugs is widely recognized as an effective strategy for treating asthma. In our study, we successfully identified a TSLP-targeting antibody from the fully synthetic human phage antibody libraries. We integrated computer-assisted methods to enhance the antibody's affinity. These techniques enabled efficient prediction of critical amino acid residues, guiding targeted mutagenesis experiments. By combining computer-assisted approaches with experimental methods, we have successfully developed a mature method for enhancing antibody affinity. Through this research, we have obtained an antibody with high affinity for TSLP, providing a new avenue for treating asthma and other TSLP-related diseases. The computer-assisted affinity maturation strategy brings hope for speeding up the drug development process. [ABSTRACT FROM AUTHOR]

Behavioral thresholds define the lowest stimulus intensities sufficient to elicit a behavioral response. Establishment of baseline behavioral thresholds during development is critical for proper responses throughout the animal's life. Despite the relevance of such innate thresholds, the molecular mechanisms critical to establishing behavioral thresholds during development are not well understood. The acoustic startle response is a conserved behavior whose threshold is established during development yet is subsequently acutely regulated. We have previously identified a zebrafish mutant line (escapist) that displays a decreased baseline or innate acoustic startle threshold. Here, we identify a single base pair substitution on Chromosome 25 located within the coding sequence of the synaptotagmin 7a (syt7a) gene that is tightly linked to the escapist acoustic hypersensitivity phenotype. By generating animals in which we deleted the syt7a open reading frame, and subsequent complementation testing with the escapist line, we demonstrate that loss of syt7a function is not the cause of the escapist behavioral phenotype. Nonetheless, escapist mutants provide a powerful tool to decipher the overlap between acute and developmental regulation of behavioral thresholds. Extensive behavioral analyses reveal that in escapist mutants the establishment of the innate acoustic startle threshold is impaired, while regulation of its acute threshold remains intact. Moreover, our behavioral analyses reveal a deficit in baseline responses to visual stimuli, but not in the acute regulation of responses to visual stimuli. Together, this work eliminates loss of syt7a as causative for the escapist phenotype and suggests that mechanisms that regulate the establishment of behavioral thresholds in escapist larvae can operate independently from those regulating acute threshold regulation. [ABSTRACT FROM AUTHOR]

Background: Swimmer's itch, an allergic contact dermatitis caused by avian and mammalian blood flukes, is a parasitic infection affecting people worldwide. In particular, avian blood flukes of the genus Trichobilharzia are infamous for their role in swimmer's itch cases. These parasites infect waterfowl as a final host, but incidental infections by cercariae in humans are frequently reported. Upon accidental infections of humans, parasite larvae will be recognized by the immune system and destroyed, leading to painful itchy skin lesions. However, one species, Trichobilharzia regenti, can escape this response in experimental animals and reach the spinal cord, causing neuroinflammation. In the last few decades, there has been an increase in case reports across Europe, making it an emerging zoonosis. Methods: Following a reported case of swimmer's itch in Kampenhout in 2022 (Belgium), the transmission site consisting of a private pond and an adjacent creek was investigated through a malacological and parasitological survey. Results: Six snail species were collected, including the widespread Ampullaceana balthica, a well-known intermediate host for Trichobilharzia parasites. Shedding experiments followed by DNA barcoding revealed a single snail specimen to be infected with T. regenti, a new species record for Belgium and by extension the Benelux. Moreover, it is the most compelling case to date of the link between this neurotropic parasite and cercarial dermatitis. Additionally, an Echinostomatidae sp. and Notocotylus sp. were isolated from two other specimens of A. balthica. However, the lack of reference DNA sequences for these groups in the online repositories prevented genus- and species-level identification, respectively. Conclusions: The presence of T. regenti in Belgium might have severe clinical implications and its finding highlights the need for increased vigilance and diagnostic awareness among medical professionals. The lack of species-level identification of the other two parasite species showcases the barcoding void for trematodes. Overall, these findings demonstrate the need for a Belgian framework to rapidly detect and monitor zoonotic outbreaks of trematode parasites within the One Health context. [ABSTRACT FROM AUTHOR]

Disease-associated variants of TUBA4A (alpha-tubulin 4A) have recently been identified in familial ALS. Interestingly, a downregulation of TUBA4A protein expression was observed in familial as well as sporadic ALS brain tissue. To investigate whether a decreased TUBA4A expression could be a driving factor in ALS pathogenesis, we assessed whether TUBA4A knockdown in zebrafish could recapitulate an ALS-like phenotype. For this, we injected an antisense oligonucleotide morpholino in zebrafish embryos targeting the zebrafish TUBA4A orthologue. An antibody against synaptic vesicle 2 was used to visualize motor axons in the spinal cord, allowing the analysis of embryonic ventral root projections. Motor behavior was assessed using the touch-evoked escape response. In post-mortem ALS motor cortex, we observed reduced TUBA4A levels. The knockdown of the zebrafish TUBA4A orthologue induced a motor axonopathy and a significantly disturbed motor behavior. Both phenotypes were dose-dependent and could be rescued by the addition of human wild-type TUBA4A mRNA. Thus, TUBA4A downregulation as observed in ALS post-mortem motor cortex could be modeled in zebrafish and induced a motor axonopathy and motor behavior defects reflecting a motor neuron disease phenotype, as previously described in embryonic zebrafish models of ALS. The rescue with human wild-type TUBA4A mRNA suggests functional conservation and strengthens the causal relation between TUBA4A protein levels and phenotype severity. Furthermore, the loss of TUBA4A induces significant changes in post-translational modifications of tubulin, such as acetylation, detyrosination and polyglutamylation. Our data unveil an important role for TUBA4A in ALS pathogenesis, and extend the relevance of TUBA4A to the majority of ALS patients, in addition to cases bearing TUBA4A mutations. [ABSTRACT FROM AUTHOR]

Innate defensive responses, though primarily instinctive, must also be highly adaptive to changes in risk assessment. However, adaptive changes can become maladaptive, following severe stress, as seen in posttraumatic stress disorder (PTSD). In a series of experiments, we observed long-term changes in innate escape behavior of male mice towards a previously non-threatening stimulus following an adverse shock experience manifested as a shift in the threshold of threat response. By recording neural activity in the superior colliculus (SC) while phototagging specific responses to afferents, we established the crucial influence of input arriving at the SC from the medial prefrontal cortex (mPFC), both directly and indirectly, on escape-related activity after adverse shock experience. Inactivating these specific projections during the shock effectively abolished the observed changes. Conversely, optogenetically activating them during encounters controlled escape responses. This establishes the necessity and sufficiency of those specific mPFC inputs into the SC for adverse experience related changes in innate escape behavior. Significant aversive experience can cause lasting behavioral changes due to shifts in arousal thresholds and filter mechanisms. Here, in male mice, the authors identify a change in a neural circuit, underlying adversity driven enhanced threat response. [ABSTRACT FROM AUTHOR]

According to the bio-informational theory of emotion by Lang, mental imagery of fearful stimuli activates physiological and behavioural response systems, even in the absence of sensory input. We investigated whether instructed mental imagery of pain-associated (not painful) interoceptive sensations entails a threat value and elicits increased startle response, skin conductance level (SCL), and heart rate (HR) indicative of defensive mobilization in adolescents with chronic pain. Additionally, self-reported measures (fear, fear of pain, desire to avoid) were assessed. Adolescents (11-18 years) with chronic headache (CH, n = 46) or chronic abdominal pain (CAP, n = 29) and a control group (n = 28) were asked to imagine individualized pain-associated, neutral and standardized fear scripts. During pain-associated compared with neutral imagery, both pain groups showed higher mean HR, with CH also showing higher HR reactivity, while HR acceleration was not observed within control group. In contrast, during pain-associated compared with neutral imagery, startle response magnitude and SCL remained unchanged in all groups. Additionally, overall levels in self-reports were higher during pain-associated compared with neutral imagery, but significantly more pronounced in the pain groups compared with the control group. Results suggest that the mere imagination of pain-associated sensations elicits specific autonomic fear responses accompanied by increased self-reported fear in adolescents with chronic pain. The specific modulation of heart rate shed new light on our understanding of multimodal fear responses in adolescents with chronic pain and may help to refine paradigms to decrease fear of interoceptive sensations in chronic pain. [ABSTRACT FROM AUTHOR]

For whole-body sway patterns, a compound motor response following an external stimulus may comprise reflexes, postural adjustments (anticipatory or compensatory), and voluntary muscular activity. Responses to equilibrium destabilization may depend on both motor set and a subject's expectation of the disturbing stimulus. To disentangle these influences on lower limb responses, we studied a model in which subjects (n = 14) were suspended in the air, without foot support, and performed a fast unilateral wrist extension (WE) in response to a passive knee flexion (KF) delivered by a robot. To characterize the responses, electromyographic activity of rectus femoris and reactive leg torque was obtained bilaterally in a series of trials, with or without the requirement of WE (motor set), and/or beforehand information about the upcoming velocity of KF (subject's expectation). Some fast-velocity trials resulted in StartReact responses, which were used to subclassify leg responses. When subjects were uninformed about the upcoming KF, large rectus femoris responses concurred with a postural reaction in conditions without motor task, and with both postural reaction and postural adjustment when WE was required. WE in response to a low-volume acoustic signal elicited no postural adjustments. When subjects were informed about KF velocity and had to perform WE, large rectus femoris responses corresponded to anticipatory postural adjustment rather than postural reaction. In conclusion, when subjects are suspended in the air and have to respond with WE, the prepared motor set includes anticipatory postural adjustments if KF velocity is known, and additional postural reactions if KF velocity is unknown. [ABSTRACT FROM AUTHOR]

Coastal habitats are increasingly threatened by multiple anthropogenic-related activities, which include ocean warming and loss of structural habitat complexity. These two pressures have the potential to severely affect the structure and function of marine biodiversity. Early life stages of many fish species recruit to coastal habitats at the end of their pelagic phase, benefiting from access to food, shelter and protection. However, changes in temperature have been shown to influence ecologically relevant behaviours in post-settlement stage fish, and the loss of structural habitat complexity has been related to low recruitment and deleterious behaviours of fish in coastal habitats. Here, we evaluated the individual and interactive effects of prolonged exposure to increasing temperature and changed structural habitat complexity on routine swimming speed and escape response of post-settlement white seabream, Diplodus sargus (Linnaeus, 1758). Fish were reared under different temperatures (control 19 °C; high 22 °C) and structural habitat complexity (low and high) scenarios, in a cross-experimental design, and the routine swimming and escape responses were analyzed after 6 weeks of exposure. Change in temperature did not induce alterations at the behavioural level, but loss of structural habitat complexity increased speed and distance travelled during routine swimming, and responsiveness to a stimulus during the escape response behaviour. The interaction of the two factors did not influence performance. Determining how species are affected by changes in their environment, and the mechanisms that underlie these changes, will be critical to understanding the fish recruitment and populations' fitness and survival. [ABSTRACT FROM AUTHOR]

Disruption of the immune system during embryonic brain development by environmental chemicals was proposed as a possible cause of neurodevelopmental disorders. We previously found adverse effects of di-n-octyltin dichloride (DOTC) on maternal and developing immune systems of rats in an extended one-generation reproductive toxicity study according to the OECD 443 test guideline. We hypothesize that the DOTC-induced changes in the immune system can affect neurodevelopment. Therefore, we used in-vivo MRI and PET imaging and genomics, in addition to behavioral testing and neuropathology as proposed in OECD test guideline 443, to investigate the effect of DOTC on structural and functional brain development. Male rats were exposed to DOTC (0, 3, 10, or 30 mg/kg of diet) from 2 weeks prior to mating of the F0-generation until sacrifice of F1-animals. The brains of rats, exposed to DOTC showed a transiently enlarged volume of specific brain regions (MRI), altered specific gravity, and transient hyper-metabolism ([18F]FDG PET). The alterations in brain development concurred with hyper-responsiveness in auditory startle response and slight hyperactivity in young adult animals. Genomics identified altered transcription of key regulators involved in neurodevelopment and neural function (e.g. Nrgrn, Shank3, Igf1r, Cck, Apba2, Foxp2); and regulators involved in cell size, cell proliferation, and organ development, especially immune system development and functioning (e.g. LOC679869, Itga11, Arhgap5, Cd47, Dlg1, Gas6, Cml5, Mef2c). The results suggest the involvement of immunotoxicity in the impairment of the nervous system by DOTC and support the hypothesis of a close connection between the immune and nervous systems in brain development. [ABSTRACT FROM AUTHOR]

Context: The interface of Hsp70-Bim protein–protein interaction (PPI) has been identified as a specific target for Chronic Myeloid Leukemia (CML) therapy and the specific inhibitors were developed to exhibit in vivo anti-leukemia activities. Herein, we explored the binding mechanism of a Hsp70-Bim inhibitor, 6-(cyclohexylthio)-3-((2-morpholinoethyl) amino)-1-oxo-1H-phenalene-2-carbonitrile (S1g-6), to Hsp70 at the atomic level by MD simulation. TYR-149, THR-222, ALA-223, and GLY-224 on Hsp70 were identified as four key residues that contribute to Hsp70/S1g-6 complex. Moreover, the site mutation validation demonstrated the TYR-149 of Hsp70 is a "hot-spot" in the Hsp70-Bim PPI interface. These results could benefit the design of further inhibitors to occupy the Bim binding site on the Hsp70 surface. Methods: The binding mechanism of S1g-6 and Hsp70 was predicted through the molecular dynamics (MD) method by Gromacs-2021.3. The MD simulation was performed with 100-ps NVT and 100-ps NPT ensemble, and the force field was chosen as the Charmm36 force field. The temperature was set as 300 K, the time step was 2 fs and the total MD simulation time was 500 ns. [ABSTRACT FROM AUTHOR]

Unconditioned responding (UCR) to a naturally aversive stimulus is associated with defensive responding to a conditioned threat cue (CS+) and a conditioned safety cue (CS−) in trauma‐exposed individuals during fear acquisition. However, the relationships of UCR with defensive responses during extinction training, posttraumatic stress disorder (PTSD) symptom severity, and fearful traits in trauma‐exposed individuals are not known. In a sample of 100 trauma‐exposed adults with a continuum of PTSD severity, we recorded startle responses and skin conductance responses (SCR) during fear acquisition and extinction training using a 140 psi, 250‐ms air blast to the larynx as the unconditioned stimulus. We explored dimensional associations of two different measures of UCR (unconditioned startle and unconditioned SCR) with conditioned defensive responding to CS+ and CS−, conditioned fear (CS+ minus CS−), PTSD symptom severity, and a measure of fearful traits (composite of fear survey schedule, anxiety sensitivity index, and Connor‐Davidson resilience scale). Unconditioned startle was positively associated with startle potentiation to the threat cue and the safety cue across both learning phases (CS+ Acquisition, CS− Acquisition, CS+ Extinction Training, CS− Extinction Training) and with fearful traits. Unconditioned SCR was positively associated with SCR to the CS+ and CS− and SCR difference score during Acquisition. Neither type of UCR was associated with PTSD symptom severity. Our findings suggest that UCR, particularly unconditioned startle to a naturally aversive stimulus, may inform research on biomarkers and treatment targets for symptoms of pervasive and persistent fear in trauma‐exposed individuals. Our study adds evidence that unconditioned aversive responding is associated with persistent defensive responding to conditioned threat and safety cues and with trait‐level fear in daily life, in trauma‐exposed adults. We complement previous evidence that unconditioned responding (UCR) is associated with defensive responding during fear acquisition and provide empirical support for the theory that UCR may inform research on biomarkers and treatment targets for symptoms of pervasive and persistent fear in trauma‐exposed individuals. [ABSTRACT FROM AUTHOR]

Objective of our study is to identify characteristics of Traditional Chinese Medicine(TCM) symptom of spastic CP, thereby establishing correlations between the TCM symptom and the disease, providing a more scientific theoretical foundation for TCM treatments on spastic CP, enabling a deeper comprehension of clinical interventions, ultimately, improving rehabilitation outcomes in TCM treatment for spastic CP. Methods: We conducted a data mining study on TCM symptom of spastic CP children aged 4– 14 years old treated at Xi'an Encephalopathy Hospital Affiliated to Shaanxi University of Chinese Medicine, from October 2021 to March 2023. The medical records of all eligible and complete spastic CP patients were extracted, processed for data cleansing, transformed, and subsequently analyzed to discern distinctive TCM symptom. K-Means Clustering Analysis and Association Rule Analysis were used for data mining. Results: Core symptoms identified for spastic CP encompassed "Motor Dysfunction", "Impaired Speech", "Delayed Development", "Limb Stiffness", "Rigidity in the limbs", "Intellectual Impairment", "Timidity and susceptibility to startle responses", "Muscle Wasting", and "Pale or Dull Complexion". Among the top-ranking associations of symptom, patterns emerge wherein "Motor dysfunction" intertwine with "Impaired speech", "Motor dysfunction" coexist with "Delayed development", and "Impaired speech" are accompanied by "Delayed development". Conclusion: This study identified the core symptom of spastic CP and tentatively suggests that the clinical manifestations of spastic CP are essentially consistent with the TCM pattern "liver exuberance and spleen weakness". This finding has facilitated the preliminary establishment of correlations between TCM pattern differentiation and the disease in medicine. It is anticipated that this correlation will bring tangible benefits to a larger number of children with spastic CP. [ABSTRACT FROM AUTHOR]

Background: Psoriasis, a chronic skin condition characterized by systemic inflammation and altered gut microbiota, has been a target of Traditional Chinese Medicine (TCM) for centuries. Shenling Baizhu Powder (SLBZP), a TCM formulation, holds promise for treating inflammatory diseases, but its specific role in psoriasis and impact on gut microbiota is not fully understood. Objective: This study aims to elucidate the mechanism of SLBZP in treating psoriasis, integrating component analysis, network pharmacology, and experimental validation in mice models. Methods: We commenced with a detailed component analysis of SLBZP using liquid chromatograph and mass spectrometer (LC-MS). Network pharmacology analysis was used to predict the potential action targets and pathways of SLBZP in psoriasis. An in vivo experiment was conducted with psoriasis mice models, treated with SLBZP. Therapeutic effects were assessed via symptomatology, histopathology, and immunohistochemical analysis. Gut microbiota composition was analyzed using 16S rRNA gene sequencing. Results: A total of 42 main components and quality markers were identified, primarily from licorice and ginseng, including flavonoids, saponins and other markers. PPI topology analysis showed that TNF, IL-6, IL-1ß, TP53 and JUN were the core DEPs. 168 signaling pathways including lipid and atherosclerosis, AGERAGE signaling pathway, IL-17 signaling pathway and Th17 cell differentiation were enriched by KEGG. SLBZP demonstrated significant therapeutic effects on psoriasis in mice, with alterations in skin pathology and biomarkers. Additionally, notable changes in gut microbiota composition were observed post-treatment, indicating a possible gut-skin axis involvement. Conclusion: This research has pinpointed lipid metabolism as a key pathway in the treatment of psoriasis with SLBZP. It explores how SLBZP's modulation of gut microbiota and lipid metabolism can alleviate psoriasis, suggesting that balancing gut microbiota may reduce inflammation mediators and offer therapeutic benefits. This underscores lipid metabolism modulation as a potential new strategy in psoriasis treatment. [ABSTRACT FROM AUTHOR]

Background: Turner syndrome (TS) is a rare disorder associated either with complete or partial loss of one X chromosome in women. The information on the genotype–phenotype relationship in TS is inadequate. Comparing the healthy and Turner syndrome patients may help elucidate the mechanisms involved in TS pathophysiology. Gene expression differences between healthy and individuals with Turner syndrome were characterized using the systems-biology approach of weighted gene coexpression network analysis (WGCNA) on 182 microarray peripheral mononuclear blood samples (PBMC). Results: The coexpression networks of healthy and TS had scale-free topology that ensures network robustness. In the process, five modules were preserved between healthy and TS, which carry several genes common in each module. Two of them, SMCHD1 and PGK1, have already been reported to be involved in TS. Previously reported genes of TS, specifically, PTPN22, RPS4X, CSF2RA, and TIMP1, were missing in their respective modules. Dysfunction, differential expression, or absence of these genes could lead to a progressive disruption of molecular pathways leading to the pathophysiology of TS. Indeed, we observed a significant difference in the functions of these modules when compared within and across the healthy and TS samples. We identified four clusters in the PPI network constructed from the top 15 KME enriched in significant functions. Conclusion: Overall, our work highlights the potential molecular functions, pathways, and molecular targets of TS that can be exploited therapeutically in the human healthcare system. [ABSTRACT FROM AUTHOR]

In humans and animals, surprise is a physiological reaction to an unexpected event, but how surprise can be linked to plausible models of neuronal activity is an open problem. We propose a self-supervised spiking neural network model where a surprise signal is extracted from an increase in neural activity after an imbalance of excitation and inhibition. The surprise signal modulates synaptic plasticity via a three-factor learning rule which increases plasticity at moments of surprise. The surprise signal remains small when transitions between sensory events follow a previously learned rule but increases immediately after rule switching. In a spiking network with several modules, previously learned rules are protected against overwriting, as long as the number of modules is larger than the total number of rules—making a step towards solving the stability-plasticity dilemma in neuroscience. Our model relates the subjective notion of surprise to specific predictions on the circuit level. Author summary: Everybody knows the subjective feeling of surprise and behavioral reactions to surprising events such as startle response and pupil dilation are widely studied—but how can surprise arise from neural activity? And why is surprise useful? To answer these questions we use a modeling approach. We design a self-supervised spiking neural network capable of extracting surprising information from its own activity. Surprise is measured by a mismatch between the representation of the current stimulus inside the model and the expectations of the model given previous stimuli. We propose a specific network architecture which allows the network—in combination with a three-factor NeoHebbian learning rule—to detect rule changes, signal these changes as a surprise signal, and in turn use the surprise signal to rapidly re-adapt the model's predictions of possible next stimuli. Our bottom-up model presents a concrete hypothesis of a bio-plausible implementation of surprise and makes several specific experimental predictions for future in vivo studies. [ABSTRACT FROM AUTHOR]

Kinase D-interacting substrate of 220 kDa (Kidins220) is a transmembrane protein that participates in neural cell survival, maturation, and plasticity. Mutations in the human KIDINS220 gene are associated with a neurodevelopmental disorder ('SINO' syndrome) characterized by spastic paraplegia, intellectual disability, and in some cases, autism spectrum disorder. To better understand the pathophysiology of KIDINS220-linked pathologies, in this study, we assessed the sensory processing and social behavior of transgenic mouse lines with reduced Kidins220 expression: the CaMKII-driven conditional knockout (cKO) line, lacking Kidins220 in adult forebrain excitatory neurons, and the Kidins220floxed line, expressing constitutively lower protein levels. We show that alterations in Kidins220 expression levels and its splicing pattern cause impaired response to both auditory and olfactory stimuli. Both transgenic lines show impaired startle response to high intensity sounds, with preserved pre-pulsed inhibition, and strongly reduced social odor recognition. In the Kidins220floxed line, olfactory alterations are associated with deficits in social memory and increased aggressive behavior. Our results broaden our knowledge of the SINO syndrome; understanding sensory information processing and its deviations under neuropathological conditions is crucial for devising future therapeutic strategies to enhance the quality of life of affected individuals. [ABSTRACT FROM AUTHOR]

Copper (Cu) is a naturally occurring metal with essential micronutrient properties. However, this metal might also pose increased adverse environmental and health risks due to industrial and agricultural activities. In Brazil, the maximum allowable concentration of Cu in drinking water is 2 mg/L. Despite this standard, the impact of such concentrations on aquatic organisms remains unexplored. This study aimed to evaluate the toxicity of CuSO4 using larval zebrafish at environmentally relevant concentrations. Zebrafish (Danio rerio) larvae at 72 hr post-fertilization (hpf) were exposed to nominal CuSO4 concentrations ranging from 0.16 to 48 mg/L to determine the median lethal concentration (LC50), established at 8.4 mg/L. Subsequently, non-lethal concentrations of 0.16, 0.32, or 1.6 mg/L were selected for assessing CuSO4 -induced toxicity. Morphological parameters, including body length, yolk sac area, and swim bladder area, were adversely affected by CuSO4 exposure, particularly at 1.6 mg/L (3.31 mm ±0.1, 0.192 mm2 ±0.01, and 0.01 mm2 ±0.05, respectively). In contrast, the control group exhibited values of 3.62 mm ±0.09, 0.136 mm2 ±0.013, and 0.3 mm2 ±0.06, respectively. Behavioral assays demonstrated impairments in escape response and swimming capacity, accompanied by increased levels of reactive oxygen species (ROS) and lipid peroxidation. In addition, decreased levels of non-protein thiols and reduced cellular viability were noted. Data demonstrated that exposure to CuSO4 at similar concentrations as those permitted in Brazil for Cu adversely altered morphological, biochemical, and behavioral endpoints in zebrafish larvae. This study suggests that the permissible Cu concentrations in Brazil need to be reevaluated, given the potential enhanced adverse health risks of exposure to environmental metal contamination. [ABSTRACT FROM AUTHOR]

Background and Aims: Acid‐suppressive drugs (ASDs) are widely used in many gastric acid‐associated diseases. Nocturnal acid breakthrough has been a common problem of many ASDs, such as proton‐pump inhibitors (PPIs) and H2‐receptor antagonists (H2RAs). Potassium‐competitive acid blockers (P‐CABs) are expected to solve this continuing conundrum. This article examined major ASDs and compared them with placebo in terms of nocturnal acid‐inhibitory effects, using a network meta‐analysis of randomized controlled trials (RCTs). Methods: To compare the effectiveness of major ASDs, a Bayesian network meta‐analysis (NMA) was applied to process data extracted from RCTs. The plausible ranking for each regimen and some subgroups were assessed by surface under the cumulative ranking curves (SUCRA). Results: Fifty‐five RCTs were conducted with 2015 participants. In terms of nocturnal acid‐inhibitory effects, the overall results showed that tegoprazan (SUCRA 91.8%) and vonoprazan (SUCRA 91.0%) had the best performance, followed by new PPIs (including tenatoprazole and ilaprazole) (SUCRA 76.6%), additional H2RAs once at bedtime (AHB) (SUCRA 61.3%), isomer PPIs (including esomeprazole and dexlansoprazole) (SUCRA 38.6%), revaprazan (SUCRA 34.7%), traditional PPIs (including omeprazole, rabeprazole, pantoprazole, lansoprazole) (SUCRA 32.6%), H2RAs (SUCRA 23.1%), and placebo (SUCRA 0.3%). In some subgroups, the nocturnal acid‐inhibitory effect of vonoprazan or tegoprazan was better than most of the other regimens, even new PPIs and AHB. Conclusions: This is the first study to compare the effect of ASDs on inhibiting nocturnal acid breakthrough. Overall, in terms of nocturnal acid‐inhibitory effect, vonoprazan and tegoprazan had an advantage against other regimens including H2RAs, isomer PPIs, traditional PPIs, AHB, and new PPIs. Even in some subgroups, such as language classification (English), types of study design (crossover‐RCT), age (≤40 years), BMI (18.5–24.9 kg/m2), continent (Asia and North America), disease status (health), the duration of therapy (2 weeks), and time of administration (at daytime or at night‐time), the nocturnal acid‐inhibitory effect of vonoprazan or tegoprazan were better than most regimens, even AHB and new PPIs. [ABSTRACT FROM AUTHOR]

Simple Summary: The possibility of pain occurring in animals is often accepted if various criteria are fulfilled. These criteria include prolonged grooming or rubbing at the site of a wound or tissue damage, or other behaviour involving the site of damage. We also expect to see a reduction in such activities if a local anaesthetic is applied. Here, we report on an experiment that applied caustic soda, a known irritant in humans, to one eyestalk of the glass prawn. This caused immediate escape responses and then nipping and picking at the treated eyestalk rather than at the untreated eyestalk. Prior application of a local anaesthetic reduced the amount of directed behaviour. However, the local anaesthetic also appeared to be an irritant as it too caused immediate escape responses and directed behaviour to the eyestalk. The results provide further support to the idea that these animals can experience pain. Acceptance of the possibility of pain in animals usually requires that various criteria are fulfilled. One such criterion is that a noxious stimulus or wound would elicit directed rubbing or grooming at the site of the stimulus. There is also an expectation that local anaesthetics would reduce these responses to damage. These expectations have been fulfilled in decapod crustaceans but there has been criticism of a lack of replication. Here, we report an experiment on the effects of a noxious chemical, sodium hydroxide, applied to one eyestalk of the glass prawn. This caused an immediate escape tail-flick response. It then caused nipping and picking with the chelipeds at the treated eyestalk but much less so at the alternative eyestalk. Prior treatment with benzocaine also caused an immediate tail-flick and directed behaviour, suggesting that this agent is aversive. Subsequently, however, it reduced the directed behaviour caused by caustic soda. We thus demonstrated responses that are consistent with the idea of pain in decapod crustaceans. [ABSTRACT FROM AUTHOR]

Bioluminescence is widespread among marine organisms and has evolved independently multiple times. While its specific adaptive value is diverse, bioluminescence in most cases mediates fundamental interactions between individuals (predator, prey, mates) and thus impacts ecosystem processes. One hypothesized value of bioluminescence in dinoflagellates is through the 'burglar alarm': Grazers of phytoplankton will make the ambient water 'glow' as they swim, thereby attracting visual predators of the grazer, thus indirectly protecting the dinoflagellates.However, the most important grazers of dinoflagellates, copepods, are generally too small to elicit dinoflagellates to glow. Only individual cells captured by a copepod will flash, which in turn elicits a powerful escape response in the copepod. Here, we test a variant of this hypothesis that may work for copepods. The behavioural response of the grazer to the flashing of a captured dinoflagellate, rather than the flashing itself, attracts the attention of the grazer's flow‐sensing predators.We demonstrate that bioluminescence in three dinoflagellates reduces the clearance and ingestion rate of nauplii of the copepod Temora longicornis. The presence of bioluminescent cells also elicited an increased frequency of high‐speed jumps of the grazers.The increased jump frequency elevated the detectability of the grazers to a flow‐sensing predator, the copepod Centropages typicus, consequently leading to increased predation mortality of T. longicornis nauplii.The consequent behavioural cascade mediated by bioluminescence works for small grazers that cause only single cells to flash, unlike the traditional description of the burglar alarm. The significance of such behavioural mediated indirect interactions in shaping food webs is becoming increasingly recognized, although rarely demonstrated in pelagic food webs.We argue that the burglar alarm is a secondary adaptation, while the defence of individual cells is the primary adaptive value of bioluminescence in dinoflagellates. Read the free Plain Language Summary for this article on the Journal blog. [ABSTRACT FROM AUTHOR]

Aim: The aim of this Swedish study was to evaluate the assessment of clinical signs of perceptual disorder in children with cerebral palsy (CP). Methods: Three experienced raters assessed 56 videos of 19 children from 1 to 18 years of age with bilateral spastic CP, which were recorded by colleagues at an Italian hospital. Six signs were evaluated for inter‐rater reliability and criterion validity. Clinical applicability was evaluated by assessing inter‐rater reliability between 47 Swedish clinicians, who examined 15 of the videos during face‐to‐face and online education seminars. There were 41 physiotherapists, two occupational therapists and four doctors, with 1–37 years of clinical experience and a median of 10 years. Results: The experienced raters demonstrated moderate to almost perfect inter‐rater reliability (kappa 0.54–0.81) and criterion validity (0.54–0.87) for startle reaction, upper limbs in startle position, averted eye gaze and eye blinking. The clinicians recognised these signs with at least moderate reliability (0.56–0.88). Grimacing and posture freezing were less reliable (0.22–0.35) and valid (0.09–0.50). Conclusion: Four of the six signs of perceptual disorder were reliably recognised by experienced raters and by clinicians after education seminars. Extended education and larger study samples are needed to recognise all the signs. [ABSTRACT FROM AUTHOR]

We herein report a 60‐year‐old man with autoimmune glial fibrillary acidic protein astrocytopathy (GFAP‐A) with excessive startle response (ESR), or hyperekplexia. Short‐latency somatosensory evoked potentials (SSEPs) revealed high‐amplitude potentials of the early cortical component. Anti‐GFAPα antibodies in the spinal fluid were positive. The hyperekplexia, other clinical symptoms, and SSEP abnormalities were resolved by corticosteroid therapy. The present case demonstrates that ESR can be associated with GFAP‐A, and its pathophysiology may be cortical hyperexcitability. [ABSTRACT FROM AUTHOR]