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Telemetry techniques are important tools in freshwater fish ecology but are limited by the size of the fish in relation to the size of the electronic tags. The emergence of very small PIT tags (8 mm, mini PIT tags) opens the door to study the individual movement and behavior of small-sized fish species and life stages previously outside the scope of fish telemetry. Although high survival from mini PIT tags have been shown in some groups of fish, suitability assessments are lacking for many taxa, and potential behavioral effects have rarely been evaluated. Here, we evaluate the survival tagging effects in small-sized (35–76 mm) Padanian goby (Padogobius bonelli) implanted with mini PIT tags. PIT-tagging was associated with high survival and tag retention in the tagged fish. No effects of PIT-tagging on volitional swimming activity nor on maximum swimming speed were found. Similar results were obtained implanting larger tags (12 mm) in gobies down to 50 mm in length. Our results indicate that PIT telemetry—using mini PIT tags—is applicable for the study of behavior and movement in small-sized gobies. [ABSTRACT FROM AUTHOR]

Autism spectrum disorder (ASD) is a neurodevelopmental disorder characterized by impairments in social interaction and communication, anxiety, hyperactivity, and interest restricted to specific subjects. In addition to the genetic factors, multiple environmental factors have been related to the development of ASD. Animal models can serve as crucial tools for understanding the complexity of ASD. In this study, a chemical model of ASD has been developed in zebrafish by exposing embryos to valproic acid (VPA) from 4 to 48 h post-fertilization, rearing them to the adult stage in fish water. For the first time, an integrative approach combining behavioral analysis and neurotransmitters profile has been used for determining the effects of early-life exposure to VPA both in the larval and adult stages. Larvae from VPA-treated embryos showed hyperactivity and decreased visual and vibrational escape responses, as well as an altered neurotransmitters profile, with increased glutamate and decreased acetylcholine and norepinephrine levels. Adults from VPA-treated embryos exhibited impaired social behavior characterized by larger shoal sizes and a decreased interest for their conspecifics. A neurotransmitter analysis revealed a significant decrease in dopamine and GABA levels in the brain. These results support the potential predictive validity of this model for ASD research. [ABSTRACT FROM AUTHOR]

Whether the long-term treatment of patients with proton pump inhibitors (PPIs) with different diseases [GERD, Zollinger–Ellison syndrome (ZES), etc.] can result in vitamin B12 (VB12) deficiency is controversial. In this study, in 175 patients undergoing long-term ZES treatment with anti-acid therapies, drug-induced control acid secretory rates were correlated with the presence/absence of VB12 deficiency, determined by assessing serum VB12 levels, measurements of VB12 body stores (blood methylmalonic acid (MMA) and total homocysteine[tHYC]), and other features of ZES. After a mean of 10.2 yrs. of any acid treatment (5.6 yrs. with PPIs), 21% had VB12 deficiency with significantly lower serum and body VB12 levels (p < 0.0001). The presence of VB12 deficiency did not correlate with any feature of ZES but was associated with a 12-fold lower acid control rate, a 2-fold higher acid control pH (6.4 vs. 3.7), and acid control secretory rates below those required for the activation of pepsin (pH > 3.5). Over a 5-yr period, the patients with VB12 deficiency had a higher rate of achlorhydria (73% vs. 24%) and a lower rate of normal acid secretion (0% vs. 49%). In conclusion, in ZES patients, chronic long-term PPI treatment results in marked acid hyposecretion, resulting in decreased serum VB12 levels and decreased VB12-body stores, which can result in VB12 deficiency. [ABSTRACT FROM AUTHOR]

In this study, we investigate the potential of cold atmospheric plasma (CAP) as a non-contact excitation device, comparing its performance with an ultrasound transmitter. Utilizing a scanning Laser Doppler Vibrometer (LDV), we visualize the acoustic wavefront generated by a CAP probe and an ultrasound sensor within a designated 50 mm × 50 mm area in front of each probe. Our focus lies in assessing the applicability of a CAP probe for exciting a small polymethyl methacrylate (PMMA) sample. By adjusting the dimensions of the sample to resonate at the excitation frequency of the probe, we can achieve high vibrational velocities, enabling further mechanical analysis. In contrast with traditional vibration excitation techniques such as electrodynamical shakers and hammer impact excitation, a plasma probe can offer distinct advantages without altering the structure's dynamics since it is contactless. Furthermore, in comparison with laser excitation, plasma excitation provides a higher power level. Additionally, while pressurized air systems are applicable for limited low frequencies, plasma probes can perform at higher frequencies. Our findings in this study suggest that CAP is comparable with acoustic excitation, indicating its potential as an effective mechanical excitation method. [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]

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]

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]

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]

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]

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]

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]

Evidence suggests that sex differences commonly occur in trauma-related disorders. The current study aims to explore sex differences in complex posttraumatic stress disorder (CPTSD) symptom networks among Chinese young adults with childhood trauma. The current study utilized a representative sample of college students in Beijing and included 1416 participants (409 men and 907 women) who had childhood trauma experience. CPTSD symptoms were evaluated using the International Trauma Questionnaire. Regularized partial correlation network analysis and Bayesian network analysis were used to estimate the network structure and possible causality of CPTSD symptoms for both sexes. Male and female CPTSD symptom networks had differences in strength centrality and bridge centrality. Nightmares and feelings of failure had the highest strength centrality, and long-term upset and nightmares had the highest bridge centrality for men. Hypervigilance and feelings of failure had the highest strength centrality, and long-term upset and exaggerated startle response had the highest bridge centrality for women. The current study provides the first evidence of sex differences in the CPTSD symptom network among Chinese young adults with childhood trauma. Young men and women differed in highly central symptoms, which may speak to sex specificity in the main manifestations of CPTSD symptoms. [ABSTRACT FROM AUTHOR]

Koumine is one of the most abundant alkaloids found in Gelsemium elegans, and it has a wide range of pharmacological effects including antitumor, anti-inflammatory, analgesic treatment effects, and antianxiety. However, its high toxicity and unclear mechanism of action have greatly limited the medicinal development and use of koumine. We investigated the toxic effects of koumine on the developmental toxicity and behavioral neurotoxicity of zebrafish embryos and larvae. Embryos at 6 h postfertilization (hpf) were exposed to 12.5, 25, 50, 75, and 100 mg/L of koumine until 120 hpf. Koumine affected the hatching and heartbeats of the embryos. The morphological analysis also revealed many abnormalities, such as shortened bodies, yolk sac edemas, tail malformations, and pericardial edemas. To identify the neurotoxicity of koumine, the behavior of the larvae was measured. Koumine at 50 and 100 mg/L affect the escape response. The embryos exhibited uncoordinated muscle contractions along the body axis in response to touch at 36 hpf. More importantly, we found that the neurotoxicity of koumine is mainly caused by influencing the ACh content and the activity of AChE without impairing motor neuron development. A comprehensive analysis shows that a high concentration of koumine has obvious toxic effects on zebrafish, and the safe concentration of koumine for zebrafish should be less than 25 mg/L. These results will be valuable for better understanding the toxicity of koumine and provide new insights into the application of koumine. [ABSTRACT FROM AUTHOR]

Simple Summary: Respiratory viral infections are among the most common diseases that affect children. Respiratory syncytial virus (RSV) is the most common pathogen causing lower tract infections in children and is responsible for a significant number of hospital admissions, whereas, in adults, its clinical importance is less significant. In contrast, SARS-CoV-2, the virus responsible for the COVID-19 pandemic, rarely causes severe disease in children. In this review, we discuss the differences in susceptibility between these two viruses in children with a focus on the immune response. A better understanding of the immune responses induced by SARS-CoV-2 and RSV, as well as their unique roles in viral evasion, is essential for the development of vaccines and new drugs. Viral respiratory tract infections are a significant public health concern, particularly in children. RSV is a prominent cause of lower respiratory tract infections among infants, whereas SARS-CoV-2 has caused a global pandemic with lower overall severity in children than in adults. In this review, we aimed to compare the innate and adaptive immune responses induced by RSV and SARS-CoV-2 to better understand differences in the pathogenesis of infection. Some studies have demonstrated that children present a more robust immune response against SARS-CoV-2 than adults; however, this response is dissimilar to that of RSV. Each virus has a distinctive mechanism to escape the immune response. Understanding the mechanisms underlying these differences is crucial for developing effective treatments and improving the management of pediatric respiratory infections. [ABSTRACT FROM AUTHOR]

Simple Summary: Negative interactions between humans and wildlife pose a significant challenge to their coexistence. Although dog walking brings millions of people to public open spaces, roaming unleashed dogs threaten urban birds. Leashes for dogs in public parks remain controversial, with low compliance rates. As a practical solution, leashes could reduce fear among urban birds and enhance their coexistence with humans and dogs. Park leashing laws would be more likely to be enforced if there was a better understanding of how leashing laws benefit birds and wildlife. There is, however, no evidence that birds are less fearful of dogs because they understand the function of a dog's leash. Using a common urban bird in public parks in a major Australian city, we standardized human and dog approaches, both leashed and unleashed. The birds demonstrated an increased intensity of escape responses (for example, flight) when dogs were unleashed compared to leashed. By leashing dogs in parks, coexistence between people and birds would be enhanced. Controversy exists around owned dogs' impacts in public open spaces, with concerns about dogs' impact on wildlife, including birds. Leashing dogs in public open spaces offers a tractable way of reducing dogs' deleterious impacts on birds. Although dogs in public spaces are often unleashed, some dogs roam freely, whilst other unleashed dogs remain close to their owners. It is currently unknown whether birds can perceive and incorporate subtle differences in the leash status of approaching, but non-roaming, dogs into their escape decisions. We compare escape responses of a common urban bird, the magpie-lark Grallina cyanoleuca, in parks in Melbourne, Australia, to standardized approaches by a walker and a dog, which was either leashed or not leashed (but with the dog at the same distance from the walker). Flight-initiation distances, the distance between the lark and dog when escape commenced, did not vary between treatments. However, the unleashed dog evoked more intense responses (mostly flying away) than the leashed dog (mostly walking away). Thus, this species appears to perceive unleashed dogs as especially threatening, independent of their roaming behavior. Our findings suggest that leashing may be an effective way to reduce dog disturbance to wildlife, even for non-roaming dogs. [ABSTRACT FROM AUTHOR]

Traumatic brain injury (TBI) affects millions of people annually, and most cases are classified as mild TBI (mTBI). Ketamine is a potent trauma analgesic and anesthetic with anti-inflammatory properties. However, ketamine's effects on post-mTBI outcomes are not well characterized. For the current study, we used the Closed-Head Impact Model of Engineered Rotational Acceleration (CHIMERA), which replicates the biomechanics of a closed-head impact with resulting free head movement. Adult male Sprague–Dawley rats sustained a single-session, repeated-impacts CHIMERA injury. An hour after the injury, rats received an intravenous ketamine infusion (0, 10, or 20 mg/kg, 2 h period), during which locomotor activity was monitored. Catheter blood samples were collected at 1, 3, 5, and 24 h after the CHIMERA injury for plasma cytokine assays. Behavioral assays were conducted on post-injury days (PID) 1 to 4 and included rotarod, locomotor activity, acoustic startle reflex (ASR), and pre-pulse inhibition (PPI). Brain tissue samples were collected at PID 4 and processed for GFAP (astrocytes), Iba-1 (microglia), and silver staining (axonal injury). Ketamine dose-dependently altered locomotor activity during the infusion and reduced KC/GRO, TNF-α, and IL-1β levels after the infusion. CHIMERA produced a delayed deficit in rotarod performance (PID 3) and significant axonal damage in the optic tract (PID 4), without significant changes in other behavioral or histological measures. Notably, subanesthetic doses of intravenous ketamine infusion after mTBI did not produce adverse effects on behavioral outcomes in PID 1–4 or neuroinflammation on PID 4. A further study is warranted to thoroughly investigate beneficial effects of IV ketamine on mTBI given multi-modal properties of ketamine in traumatic injury and stress. [ABSTRACT FROM AUTHOR]

This article presents a low-cost and flexible software solution for acoustic startle response (ASR) test that can be used with a Spike2-based interface. ASR is a reflexive response to an unexpected, loud acoustic stimulus, and prepulse inhibition (PPI) is a phenomenon in which the startle response is reduced when preceded by a weak prestimulus of the same modality. Measuring PPI is important because changes in PPI have been observed in patients with various psychiatric and neurological disorders. Commercial ASR testing systems are expensive, and their closed source code affects their transparency and result reproducibility. The proposed software is easy to install and use. The Spike2 script is customizable and supports a wide range of PPI protocols. As an example of PPI recording, the article presents data obtained in female rats, both wild-type (WT) and dopamine transporter knockout (DAT-KO), showing the same tendency as the data obtained in males, with ASR on a single pulse higher than ASR on prepulse+pulse, and PPI reduced in DAT-KO rats compared to WT. [ABSTRACT FROM AUTHOR]

Bisphenol F (BPF; 4,4′-dihydroxydiphenylmethane) is one of the most frequently used compounds in the manufacture of plastics and epoxy resins. Previous studies have demonstrated that BPF affects locomotor behavior, oxidative stress, and neurodevelopment in zebrafish. However, its neurotoxic effects are controversial, and the underlying mechanisms are unclear. In order to determine whether BPF affects the motor system, we exposed zebrafish embryos to BPF and assessed behavioral, histological, and neurochemical changes. Spontaneous locomotor behavior and startle response were significantly decreased in BPF-treated zebrafish larvae compared with control larvae. BPF induced motor degeneration and myelination defects in zebrafish larvae. In addition, embryonic exposure to BPF resulted in altered metabolic profiles of neurochemicals, including neurotransmitters and neurosteroids, which may impact locomotion and motor function. In conclusion, exposure to BPF has the potential to affect survival, motor axon length, locomotor activity, myelination, and neurochemical levels of zebrafish larvae. [ABSTRACT FROM AUTHOR]

Mycobacterium tuberculosis (Mtb) modulates diverse cell death pathways to escape the host immune responses and favor its dissemination, a complex process of interest in pathogenesis-related studies. The main virulence factors of Mtb that alter cell death pathways are classified according to their origin as either non-protein (for instance, lipomannan) or protein (such as the PE family and ESX secretion system). The 38 kDa lipoprotein, ESAT-6 (early antigen-secreted protein 6 kDa), and another secreted protein, tuberculosis necrotizing toxin (TNT), induces necroptosis, thereby allowing mycobacteria to survive inside the cell. The inhibition of pyroptosis by blocking inflammasome activation by Zmp1 and PknF is another pathway that aids the intracellular replication of Mtb. Autophagy inhibition is another mechanism that allows Mtb to escape the immune response. The enhanced intracellular survival (Eis) protein, other proteins, such as ESX-1, SecA2, SapM, PE6, and certain microRNAs, also facilitate Mtb host immune escape process. In summary, Mtb affects the microenvironment of cell death to avoid an effective immune response and facilitate its spread. A thorough study of these pathways would help identify therapeutic targets to prevent the survival of mycobacteria in the host. [ABSTRACT FROM AUTHOR]

Inflammasomes are cytosolic sensors of pathogens. Their activation can lead to the induction of caspase-1-mediated inflammatory responses and the release of several proinflammatory cytokines, including IL-1β. There is a complex relationship between viral infection and the nucleotide-binding oligomerization domain-like receptors family pyrin domain-containing 3 (NLRP3) inflammasome. The activation of the NLRP3 inflammasome is essential for antiviral immunity, while excessive NLRP3 inflammasome activation may lead to excessive inflammation and pathological damage. Meanwhile, viruses have evolved strategies to suppress the activation of inflammasome signaling pathways, thus escaping immune responses. In this study, we investigated the inhibitory effect of coxsackievirus B3 (CVB3), a positive single-strand RNA virus, on the activation of the NLRP3 inflammasome in macrophages. CVB3-infected mice had significantly lower production of IL-1β and a lower level of NLRP3 in the small intestine after LPS stimulation. Furthermore, we found that CVB3 infection inhibited NLRP3 inflammasome activation and IL-1β production in macrophages by suppressing the NF-κB signaling pathway and ROS production. Additionally, CVB3 infection increased the susceptibility of mice to Escherichia coli infection by decreasing IL-1β production. Collectively, our study revealed a novel mechanism of NLRP3 inflammasome activation by suppressing the NF-κB pathway and ROS production in LPS-induced macrophages. Our findings may provide new ideas for antiviral treatment and drug development for CVB3 infection. [ABSTRACT FROM AUTHOR]

Lung cancer is a highly heterogeneous disease. Cancer cells and other cells within the tumor microenvironment interact to determine disease progression, as well as response to or escape from treatment. Understanding the regulatory relationship between cancer cells and their tumor microenvironment in lung adenocarcinoma is of great significance for exploring the heterogeneity of the tumor microenvironment and its role in the genesis and development of lung adenocarcinoma. This work uses public single-cell transcriptome data (distant normal, nLung; early LUAD, tLung; advanced LUAD, tL/B), to draft a cell map of lung adenocarcinoma from onset to progression, and provide a cell-cell communication view of lung adenocarcinoma in the different disease stages. Based on the analysis of cell populations, it was found that the proportion of macrophages was significantly reduced in the development of lung adenocarcinoma, and patients with lower proportions of macrophages exhibited poor prognosis. We therefore constructed a process to screen an intercellular gene regulatory network that reduces any error generated by single cell communication analysis and increases the credibility of selected cell communication signals. Based on the key regulatory signals in the macrophage-tumor cell regulatory network, we performed a pseudotime analysis of the macrophages and found that signal molecules (TIMP1, VEGFA, SPP1) are highly expressed in immunosuppression-associated macrophages. These molecules were also validated using an independent dataset and were significantly associated with poor prognosis. Our study provides an effective method for screening the key regulatory signals in the tumor microenvironment and the selected signal molecules may serve as a reference to guide the development of diagnostic biomarkers for risk stratification and therapeutic targets for lung adenocarcinoma. [ABSTRACT FROM AUTHOR]

Use of proton-pump inhibitors (PPIs) is common in patients with chronic kidney disease (CKD). PPIs and many uremic toxins (UTs) are eliminated by the kidney's tubular organic anion transporter system. In a cross-sectional study, we sought to evaluate the association between PPI prescription and serum concentrations of various UTs. We studied a randomly selected sub-group of participants in the CKD-REIN cohort (adult patients with a confirmed diagnosis of CKD and estimated glomerular filtration rate (eGFR) < 60 mL/min/1.73 m2) with available frozen samples collected at baseline. PPI prescription was recorded at baseline. Serum concentrations of 10 UTs were measured using a validated liquid chromatography tandem mass spectrometry technique. Multiple linear regression was performed, with the log UT concentration as the dependent variable. Of the 680 included patients (median age: 68 years; median eGFR: 32 mL/min/1.73 m2), 31% had PPI prescriptions at baseline. Patients using PPIs had higher levels of certain UTs in comparison to other patients, including total and free indoxyl sulfate (IS), total and free p-cresylsulfate, total and free p-cresylglucuronide (PCG), phenylacetylglutamine (PAG), free kynurenine, and free hippuric acid. After adjustment for baseline co-morbidities, number of co-prescribed drugs, and laboratory data, including eGFR, associations between PPI prescription and elevated serum concentrations of free and total IS, free and total PCG, and PAG remained significant. Our results indicate that PPI prescription is independently associated with serum UT retention. These findings are interesting to better understand the factors that may modulate serum UT concentration in CKD patients, however, they will need to be confirmed by longitudinal studies. [ABSTRACT FROM AUTHOR]

In the clinic, the death certificate is issued if brain electrical activity is no longer detectable. However, recent research has shown that in model organisms and humans, gene activity continues for at least 96 h postmortem. The discovery that many genes are still working up to 48 h after death questions our definition of death and has implications for organ transplants and forensics. If genes can be active up to 48 h after death, is the person technically still alive at that point? We discovered a very interesting parallel between genes that were upregulated in the brain after death and genes upregulated in the brains that were subjected to medically-induced coma, including transcripts involved in neurotransmission, proteasomal degradation, apoptosis, inflammation, and most interestingly, cancer. Since these genes are involved in cellular proliferation, their activation after death could represent the cellular reaction to escape mortality and raises the question of organ viability and genetics used for transplantation after death. One factor limiting the organ availability for transplantation is religious belief. However, more recently, organ donation for the benefit of humans in need has been seen as "posthumous giving of organs and tissues can be a manifestation of love spreading also to the other side of death". [ABSTRACT FROM AUTHOR]

The startle response can be defined as a reflexive reaction to the sudden appearance of a novel stimulus that influences the survival and resilience of animals. In domesticated species, the behavioral component of the startle response can, in some cases, cause serious injury to the animal or human handlers if inappropriately expressed. Here, we describe a longitudinal study in a population of stock-type horses that quantified behavioral startle responses elicited by the presentation of a sudden novel object (rapidly opening umbrella). The study was performed in weanling foals across four consecutive years (n = 74, mean age = 256 days). Behavioral assays for the startle response phenotype focused on six behavioral variables: latency to return to the feed pan (seconds), maximum distance fled (meters), proportion of time spent walking or trotting (seconds), and how long a horse spent standing facing away from or toward the novel object. We observed behavioral startle response variables in relation to cardiac response, age, and sex for each individual. Each horse's cardiac startle response pattern was determined and categorized into heart rate response cluster groups identified as accelerators and decelerators. Using principal component analysis (PCA) with a factor rotation, we identified "startle response" phenotypes that summarize the behavioral and physiological variables. The largest component of variation, Factor 1, comprised 32.5% of the behavioral variable with a positive correlation with latency and distance, and was not influenced by sex or age. Factor 2 comprised 23.2% of the variation, and was positively correlated with activity level performed such as proportion of time spent walking and/or trotting. Horses with the accelerator type cardiac response had significantly higher Factor 1 scores than decelerators but did not differ in Factor 2. Future work includes expanding our sample size to conduct a genome-wide association study (GWAS) to identify novel genetic loci influencing behavioral startle reactions using recorded behavioral and physiological phenotypes. [ABSTRACT FROM AUTHOR]

Northern white cedar (Thuja occidentalis L.) is a species of high ecological and economic value whose abundance has been declining since the pre-industrial period. It is an important element of white-tailed deer (Odocoileus virginianus Zimmerman) habitat, but its regeneration can be compromised by excessive browsing. This situation is especially critical in deeryards, where deer concentrate during winter. In 2018 and 2019, deer culling operations were carried out by the Ministry of Forests, Wildlife and Parks of Québec over 400 km2 in response to the occurrence of chronic wasting disease cases on a red deer farm. This operation offered an opportunity to look at how variations in deer pressure influence cedar regeneration and how cedar responds to a sudden reduction in browsing. We conducted regeneration surveys within and outside mapped deeryards both in the deer reduction zone and in a control zone. We performed dendrochronological analyses of cedar seedlings and saplings to quantify radial growth response to a reduction in browsing pressure. The results show that cedar basal area influences the abundance of small seedlings but that the effect of browsing becomes dominant for seedlings taller than 50 cm. Cedar growth responds to a reduction in browsing, but a two-year period was not sufficient to translate into changes in regeneration structure. The duration of the windows of opportunity at low browsing pressure required for cedar to reach a safe height remains to be determined. However, canopy openness had a significant influence on growth, suggesting that silvicultural measures could be taken to shorten the period of vulnerability to deer browsing. [ABSTRACT FROM AUTHOR]

Simple Summary: The neurodegenerative disorder Parkinson's disease (PD) has a multifactorial etiology, and recent large-scale genetic studies have identified more than one hundred regions in the human genome that display statistical association with the risk of developing PD. To understand the disease mechanism better, biological validation of the identified genomic regions is warranted. However, in most studies such validation is absent. The aim of the study was to identify PD-genes that are evolutionary conserved between humans and the vinegar fly, and phenotypically investigate the effect of gene expression knockdown of those genes in the fly model. We identified eleven PD-genes that display strong evolutionary conservatism, and we successfully reduced gene expression in nine of the knockdown lines. A phenotype that previously has been used to investigate PD in a fly model is the flies' innate escape response. We found that gene expression knockdown resulted in a disrupted escape response in eight of the nine knockdown lines. These results provide additional support for potential involvement of these genes in the disease pathology underlying PD. Parkinson's disease (PD) is a heterogeneous and complex neurodegenerative disorder and large-scale genetic studies have identified >130 genes associated with PD. Although genomic studies have been decisive for our understanding of the genetic contributions underlying PD, these associations remain as statistical associations. Lack of functional validation limits the biological interpretation; however, it is labour extensive, expensive, and time consuming. Therefore, the ideal biological system for functionally validating genetic findings must be simple. The study aim was to assess systematically evolutionary conserved PD-associated genes using Drosophila melanogaster. From a literature review, a total of 136 genes have found to be associated with PD in GWAS studies, of which 11 are strongly evolutionary conserved between Homo sapiens and D. melanogaster. By ubiquitous gene expression knockdown of the PD-genes in D. melanogaster, the flies' escape response was investigated by assessing their negative geotaxis response, a phenotype that has previously been used to investigate PD in D. melanogaster. Gene expression knockdown was successful in 9/11 lines, and phenotypic consequences were observed in 8/9 lines. The results provide evidence that genetically modifying expression levels of PD genes in D. melanogaster caused reduced climbing ability of the flies, potentially supporting their role in dysfunctional locomotion, a hallmark of PD. [ABSTRACT FROM AUTHOR]

Simple Summary: In several Asian and Latin American nations, severe dengue is the main cause of serious disease and death. Dengue viruses are transmitted to humans via the bite of an infected Aedes species. Personal protection measures may be an effective method of avoiding mosquito bites. Nowadays, consumers are increasingly interested in commercial repellent products containing plant-based ingredients because they are perceived as "safe" in comparison to long-established synthetic repellents. We tested a binary plant-based mixture formulation of Cananga odorata, Vetiveria zizanioides, and the crude extract of Andrographis paniculata on laboratory and field strains of Aedes aegypti using an excito-repellency test system. The results showed that a mixture of V. zizanioides and A. paniculata at a 1:4 ratio was better than DEET. These results could lead to the further development of a combination of V. zizanioides and A. paniculata as active ingredients in a repellent that could be tested in human trials. Each binary mixture formulation of Vetiveria zizanioides (L.) Nash (VZ) with Andrographis paniculata (Burm.f.) Wall. ex Nees (AP) or Cananga odorata (Lam.) Hook.f. & Thomson (CO) and AP with CO at 1:1, 1:2, 1:3, and 1:4 ratios (v:v) was investigated for behavioral responses on laboratory and field strains of Aedes aegypti. Irritant and repellent activities of each formulation were compared with N,N-diethyl-3-methylbenzamide (DEET) using an excito-repellency test system. The result demonstrated that the mixture of VZ:AP in all combination ratios was the most effective in inducing an irritancy response against the laboratory strain (56.57–73.33%). The highest percentage of escaped mosquitoes exposed to the mixture at a 1:4 ratio (73.33%) was significantly different from DEET (26.67%) (p < 0.05). Against the field strain, the strongest escape response of AP:CO at a 1:1 ratio in the contact trial (70.18%) was significantly different compared with DEET (38.33%) (p < 0.05). There was a weak non-contact escape pattern in all combinations of VZ:CO against the laboratory strains (6.67–31.67%). These findings could lead to the further development of VZ and AP as active ingredients in a repellent that could advance to human use trials. [ABSTRACT FROM AUTHOR]

Williams–Beuren syndrome (WBS) is a neurodevelopmental disorder caused by a chromosomic microdeletion (7q11.23). WBS has been modeled by a mouse line having a complete deletion (CD) of the equivalent mouse locus. This model has been largely used to investigate the etiopathological mechanisms of WBS, although pharmacological therapies have not been identified yet. Surprisingly, CD mice were so far mainly tested in adulthood, despite the developmental nature of WBS and the critical relevance of early timing for potential treatments. Here we provide for the first time a phenotypic characterization of CD mice of both sexes during infancy and adolescence, i.e., between birth and 7 weeks of age. CD pups of both sexes showed reduced body growth, delayed sensory development, and altered patterns of ultrasonic vocalizations and exploratory behaviors. Adolescent CD mice showed reduced locomotion and acoustic startle response, and altered social interaction and communication, the latter being more pronounced in female mice. Juvenile CD mutants of both sexes also displayed reduced brain weight, cortical and hippocampal dendritic length, and spine density. Our findings highlight the critical relevance of early neurobehavioral alterations as biomarkers of WBS pathology, underlying the importance of adolescence for identifying novel therapeutic targets for this neurological disorder. [ABSTRACT FROM AUTHOR]

Simple Summary: In-water behavioral observation studies of sea turtles are lacking primarily because they are highly migratory throughout their lifecycles. However, utilizing new technology, such as remote stereo-video cameras, allows researchers to collect size-specific data and view relatively natural sea turtle behavior. In this study, we completed stereo-video camera surveys at local artificial reefs, piers, and jetties within the northern Gulf of Mexico from May 2019 to August 2021. We remotely measured sea turtle straight carapace length, assessed wariness using minimum approach distance (MAD) between the turtle and camera operator, and documented behaviors during encounters. Our results indicated that green sea turtles had the smallest mean MAD before a startle response occurred, but the largest range compared to loggerhead and Kemp's ridley sea turtles. Using a linear mixed model, we found that the size of the turtle was an important predictor of MAD. Overall, our results suggest that larger sea turtles became startled at longer distances compared to the smaller individuals surveyed across all the species studied. This study supports the use of stereo-video camera systems as a non-invasive tool to conduct surveys to assess sea turtle behavioral observations in relation to body size. Our understanding of size-specific sea turtle behavior has lagged due to methodological limitations. However, stereo-video cameras (SVC) are an in-water approach that can link body-size and allow for relatively undisturbed behavioral observations. In this study, we conducted SVC dive surveys at local artificial reefs, piers, and jetties in the northern Gulf of Mexico (nGOM) from May 2019 to August 2021. Using SVCs, we measured sea turtle straight carapace length, documented behaviors, and quantified wariness by assessing minimum approach distance (MAD). In green sea turtles (Chelonia mydas), the observed MAD ranged from 0.72 to 5.99 m (mean 2.10 m ± 1.10 standard deviation (SD), n = 73). For loggerhead sea turtles (Caretta caretta), the MAD ranged between 0.93 and 3.80 m (mean 2.12 m ± 0.99 SD, n = 16). Kemp's ridley sea turtles (Lepidochelys kempii) were similar to loggerheads, and MAD ranged from 0.78 to 3.63 m (mean 2.35 m ± 0.99 SD, n = 8). We then evaluated what biological factors could impact the MAD observed by species, but we excluded Kemp's ridleys as the sample size was small. Using a linear mixed model and model selection based on AICc, the top ranked model for both green and loggerhead sea turtles included SCL as the most important factor influencing MAD. MAD did not vary with habitat type for either species. Our results showed that larger individuals, regardless of species, have a greater wariness response, becoming startled at greater distances than smaller individuals. The findings of our study support the use of SVC as an accessible, non-invasive tool to conduct ecologically relevant in-water surveys of sea turtles to link behavioral observations to body size. [ABSTRACT FROM AUTHOR]

Simple Summary: The socialisation period in dog puppies (approx. 3–12 weeks) is one of the most important periods in determining later behaviour. Nonetheless, only a few studies investigated how socialisation can be optimised. Here, we tested whether providing small "challenge" exercises to puppies early in the socialisation period (between 3 and 6 weeks of age) enables puppies to cope better with stressful stimuli later. Eighty-three puppies from 12 litters of various breeds were enrolled. Half of each litter was assigned to the treatment group and was carefully exposed to potentially startling stimuli, novel objects, and problem-solving tasks over a period of three weeks. The other half of the litter served as a control group and received no additional exercises. All puppies were tested in a behaviour test at 6–7 weeks of age. Puppies from the treatment group were bolder towards a novel object, startled less after a loud noise, solved the problem-solving task faster, and showed higher persistence in problem-solving task than the control group. These findings demonstrate beneficial effects of the exercises. However, at the age of six months, there were no differences in owner-reported personality measures between the groups. To achieve lasting effects, it may be necessary to continue with the training exercises for a longer time period. The socialisation period in dog puppies is one of the most important periods determining behavioural development in dogs. Here, we aimed to test the effect of providing stimulation (beyond mere exposure) early during the socialisation period (approx. 3–6 weeks) on puppies' behaviour. Each of 12 litters (83 puppies) of various breeds was divided into a treatment and a control group. Between 3–6 weeks, the treatment group received age-appropriate "challenge" exercises (carefully graded noise exposure, novel objects, and problem-solving tasks) four times per week (total 12 times). The control group spent the same time with the trainer, who cuddled or played with the puppies. In a behaviour test at 6–7 weeks, two of four principal components, "social-startle" and "response to novelty", differed significantly between the groups. Treatment puppies were bolder towards the novel object, showed a reduced startle reaction, and recovered more quickly after a loud noise. Furthermore, they accomplished the problem-solving task faster and were more persistent during problem-solving than the control group. The control group showed a higher interest in a friendly stranger. It is a possibility that increased handling experienced by the control group had beneficial effects on their sociability. No long-term effects of the treatment were found, as determined by a validated dog personality questionnaire, available for 67 dogs at the age of six months. Likely, a continuation of the treatment over a longer time period would be necessary to obtain lasting effects, since the training took place only during the first third of the socialisation period. [ABSTRACT FROM AUTHOR]

To date, the effect of resveratrol on tinnitus has not been reported. The attenuative effects of resveratrol (RSV) on a salicylate-induced tinnitus model were evaluated by in vitro and in vivo experiments. The gene expression of the activity-regulated cytoskeleton-associated protein (ARC), tumor necrosis factor-alpha (TNFα), and NMDA receptor subunit 2B (NR2B) in SH-SY5Y cells was examined using qPCR. Phosphorylated cAMP response element-binding protein (p-CREB), apoptosis markers, and reactive oxygen species (ROS) were evaluated by in vitro experiments. The in vivo experiment evaluated the gap-prepulse inhibition of the acoustic startle reflex (GPIAS) and auditory brainstem response (ABR) level. The NR2B expression in the auditory cortex (AC) was determined by immunohistochemistry. RSV significantly reduced the salicylate-induced expression of NR2B, ARC, and TNFα in neuronal cells; the GPIAS and ABR thresholds altered by salicylate in rats were recovered close to their normal range. RSV also reduced the salicylate-induced NR2B overexpression of the AC. These results confirmed that resveratrol exerted an attenuative effect on salicylate-induced tinnitus and may have a therapeutic potential. [ABSTRACT FROM AUTHOR]

Protist grazing pressure plays a major role in controlling aquatic bacterial populations, affecting energy flow through the microbial loop and biogeochemical cycles. Predator-escape mechanisms might play a crucial role in energy flow through the microbial loop, but are yet understudied. For example, some bacteria can use planktonic as well as surface-associated habitats, providing a potential escape mechanism to habitat-specific grazers. We investigated the escape response of the marine bacterium Marinobacter adhaerens in the presence of either planktonic (nanoflagellate: Cafeteria roenbergensis) or surface-associated (amoeba: Vannella anglica) protist predators, following population dynamics over time. In the presence of V. anglica, M. adhaerens cell density increased in the water, but decreased on solid surfaces, indicating an escape response towards the planktonic habitat. In contrast, the planktonic predator C. roenbergensis induced bacterial escape to the surface habitat. While C. roenbergensis cell numbers dropped substantially after a sharp initial increase, V. anglica exhibited a slow, but constant growth throughout the entire experiment. In the presence of C. roenbergensis, M. adhaerens rapidly formed cell clumps in the water habitat, which likely prevented consumption of the planktonic M. adhaerens by the flagellate, resulting in a strong decline in the predator population. Our results indicate an active escape of M. adhaerens via phenotypic plasticity (i.e., behavioral and morphological changes) against predator ingestion. This study highlights the potentially important role of behavioral escape mechanisms for community composition and energy flow in pelagic environments, especially with globally rising particle loads in aquatic systems through human activities and extreme weather events. [ABSTRACT FROM AUTHOR]

p-Toluene sulfonamide (p-TSA), a small molecular drug with antineoplastic activity is widely gaining interest from researchers because of its pharmacological activities. In this study, we explored the potential cardio and neural toxicity of p-TSA in sublethal concentrations by using zebrafish as an in vivo animal model. Based on the acute toxicity assay, the 96hr LC50 was estimated as 204.3 ppm, suggesting the overall toxicity of p-TSA is relatively low in zebrafish larvae. For the cardiotoxicity test, we found that p-TSA caused only a minor alteration in treated larvae after no overall significant alterations were observed in cardiac rhythm and cardiac physiology parameters, as supported by the results from expression level measurements of several cardiac development marker genes. On the other hand, we found that acute p-TSA exposure significantly increased the larval locomotion activity during the photomotor test while prolonged exposure (4 days) reduced the locomotor startle reflex activities in zebrafish. In addition, a higher respiratory rate and blood flow velocity was also observed in the acutely treated fish groups compared to the untreated group. Finally, by molecular docking, we found that p-TSA has a moderate binding affinity to skeletal muscle myosin II subfragment 1 (S1), ATPase activity, actin- and Ca2+-stimulated myosin S1 ATPase, and v-type proton ATPase. These binding interactions between p-TSA and proteins offer insights into the potential molecular mechanism of action of p-TSA on observed altered responses toward photo and vibration stimuli and minor altered vascular performance in the zebrafish larvae. [ABSTRACT FROM AUTHOR]

Inhibition of fatty acid amide hydrolase (FAAH), which increases anandamide levels, has been suggested as a potential treatment for stress-related conditions. We examined whether the stress-preventing effects of the FAAH inhibitor URB597 on behavior are mediated via β-catenin in the nucleus accumbens (NAc). Male rats were exposed to the shock and reminders model of PTSD and then treated with URB597 (0.4 mg/kg; i.p.). They were tested for anxiety- (freezing, startle response), depression-like behaviors (despair, social preference, anhedonia), and memory function (T-maze, social recognition). We also tested the involvement of the CB1 receptor (CB1r), β-catenin, and metabotropic glutamate receptor subtype 5 (mGluR5) proteins. URB597 prevented the shock- and reminders-induced increase in anxiety- and depressive-like behaviors, as well as the impaired memory via the CB1r-dependent mechanism. In the NAc, viral-mediated β-catenin overexpression restored the behavior of rats exposed to stress and normalized the alterations in protein levels in the NAc and the prefrontal cortex. Importantly, when NAc β-catenin levels were downregulated by viral-mediated gene transfer, the therapeutic-like effects of URB597 were blocked. We suggest a potentially novel mechanism for the therapeutic-like effects of FAAH inhibition that is dependent on β-catenin activation in the NAc in a PTSD rat model. [ABSTRACT FROM AUTHOR]

The present study investigates whether predator scent-stress (PSS) shifts the microglia from a quiescent to a chronically activated state and whether morphological alterations in microglial activation differ between individuals displaying resilient vs. vulnerable phenotypes. In addition, we examined the role that GC receptors play during PSS exposure in the impairment of microglial activation and thus in behavioral response. Adult male Sprague Dawley rats were exposed to PSS or sham-PSS for 15 min. Behaviors were assessed with the elevated plus-maze (EPM) and acoustic startle response (ASR) paradigms 7 days later. Localized brain expression of Iba-1 was assessed, visualized, and classified based on their morphology and stereological counted. Hydrocortisone and RU486 were administered systemically 10 min post PSS exposure and behavioral responses were measured on day 7 and hippocampal expression of Ionized calcium-binding adaptor molecule 1 (Iba-1) was subsequently evaluated. Animals whose behavior was extremely disrupted (PTSD-phenotype) selectively displayed excessive expression of Iba-1 with concomitant downregulation in the expression of CX3C chemokine receptor 1 (CX3CR1) in hippocampal structures as compared with rats whose behavior was minimally or partially disrupted. Changes in microglial morphology have also been related only to the PTSD-phenotype group. These data indicate that PSS-induced microglia activation in the hippocampus serves as a critical mechanistic link between the HPA-axis and PSS-induced impairment in behavioral responses. [ABSTRACT FROM AUTHOR]

The Heidenhain Variant of Creutzfeldt–Jakob disease (CJD) is an uncommon early clinical syndrome of the otherwise regular sporadic CJD, which belongs to the group of prion diseases caused by a transmissible agent, the misfolded form of the prion protein. The most characteristic symptoms of CJD are rapidly progressive cognitive impairment, typical motor manifestations and mental and behavioural changes. Conversely, in the Heidenhain Variant, different kinds of visual disturbances are observed at onset due to microvacuolar spongiform degeneration or, less frequently, confluent spongiform changes in the parieto-occipital area, detectable through brain MRI with hyperintensity in T2-FLAIR or DWI in the same areas. Since this an extremely rare condition with a heterogeneous clinical presentation, it may easily be misdiagnosed with other diseases at the earlier stages. Here, we describe the case of a patient initially diagnosed with posterior reversible encephalopathy syndrome (PRES), presenting with visual disturbances and headache at onset in a context of poorly controlled arterial hypertension. Subsequently, a rapid worsening of cognitive decline, associated with myoclonus and startle reaction led to further investigations, shifting the diagnosis toward a rapidly evolving neurodegenerative form. This hypothesis was also supported by EEG traces, MRI and CSF analysis. Finally, the clinical–instrumental evolution confirmed the diagnosis of Heidenhain Variant of CJD. [ABSTRACT FROM AUTHOR]

Taurine (2-aminoethanesulfonic acid) plays an important role in various physiological functions and is abundant in the brain and skeletal muscle. Extracellular taurine is an endogenous agonist of gamma-aminobutyric acid type A and glycine receptors. Taurine actively accumulates in cells via the taurine transporter (TauT). Adult taurine-knockout (TauT−/−) mice exhibit lower body weights and exercise intolerance. To further examine the physiological role of taurine, we examined the effect of its depletion on mouse behavior, startle responses, muscular endurance, and body weight during development from postnatal day 0 (P0) until P60. In the elevated plus maze test, TauT−/− mice showed decreased anxiety-like behavior. In addition, TauT−/− mice did not show a startle response to startle stimuli, suggesting they have difficulty hearing. Wire-hang test revealed that muscular endurance was reduced in TauT−/− mice. Although a reduction of body weight was observed in TauT−/− mice during the developmental period, changes in body weight during 60% food restriction were similar to wild-type mice. Collectively, these results suggest that taurine has important roles in anxiety-like behavior, hearing, muscular endurance, and maintenance of body weight. [ABSTRACT FROM AUTHOR]

Prepulse inhibition (PPI) is the reduction in the acoustic startle reflex (ASR) when the startling stimulus (pulse) is preceded by a weaker, non-starting stimulus. This can be enhanced by facilitating selective attention to the prepulse against a noise-masking background. On the other hand, the facilitation of selective attention to a target speech can release the target speech from masking, particularly from speech informational masking. It is not clear whether attentional regulation also affects PPI in this kind of auditory masking. This study used a speech syllable as the prepulse to examine whether the masker type and perceptual spatial attention can affect the PPI or the scalp EEG responses to the prepulse in healthy younger-adult humans, and whether the ERPs evoked by the prepulse can predict the PPI intensity of the ASR. The results showed that the speech masker produced a larger masking effect than the noise masker, and the perceptual spatial separation facilitated selective attention to the prepulse, enhancing both the N1 component of the prepulse syllable and the PPI of the ASR, particularly when the masker was speech. In addition, there was no significant correlation between the PPI and ERPs under any of the conditions, but the perceptual separation-induced PPI enhancement and ERP N1P2 peak-to-peak amplitude enhancement were correlated under the speech-masking condition. Thus, the attention-mediated PPI is useful for differentiating noise energetic masking and speech informational masking, and the perceptual separation-induced release of the prepulse from informational masking is more associated with attention-mediated early cortical unmasking processing than with energetic masking. However, the processes for the PPI of the ASR and the cortical responses to the prepulse are mediated by different neural mechanisms. [ABSTRACT FROM AUTHOR]

Exposure to high ambient temperature is a stressor that influences both biological and behavioral functions and has been previously shown to have an extensive impact on brain structure and function. Physiological, cellular and behavioral responses to heat-stress (HS) (40–41 °C, 2 h) were evaluated in adult male Sprague-Dawley rats. The effect of HS exposure before predator-scent stress (PSS) exposure (i.e., HS preconditioning) was examined. Finally, a possible mechanism of HS-preconditioning to PSS was investigated. Immunohistochemical analyses of chosen cellular markers were performed in the hippocampus and in the hypothalamic paraventricular nucleus (PVN). Plasma corticosterone levels were evaluated, and the behavioral assessment included the elevated plus-maze (EPM) and the acoustic startle response (ASR) paradigms. Endogenous levels of heat shock protein (HSP)-70 were manipulated using an amino acid (L-glutamine) and a pharmacological agent (Doxazosin). A single exposure to an acute HS resulted in decreased body mass (BM), increased body temperature and increased corticosterone levels. Additionally, extensive cellular, but not behavioral changes were noted. HS-preconditioning provided behavioral resiliency to anxiety-like behavior associated with PSS, possibly through the induction of HSP-70. Targeting of HSP-70 is an attractive strategy for stress-related psychopathology treatment. [ABSTRACT FROM AUTHOR]

Over the past two years, several variants of SARS-CoV-2 have emerged and spread all over the world. However, infectivity, clinical severity, re-infection, virulence, transmissibility, vaccine responses and escape, and epidemiological aspects have differed between SARS-CoV-2 variants. Currently, very few treatments are recommended against SARS-CoV-2. Identification of effective drugs among repurposing FDA-approved drugs is a rapid, efficient and low-cost strategy against SARS-CoV-2. One of those drugs is ivermectin. Ivermectin is an antihelminthic agent that previously showed in vitro effects against a SARS-CoV-2 isolate (Australia/VI01/2020 isolate) with an IC50 of around 2 µM. We evaluated the in vitro activity of ivermectin on Vero E6 cells infected with 30 clinically isolated SARS-CoV-2 strains belonging to 14 different variants, and particularly 17 strains belonging to six variants of concern (VOC) (variants related to Wuhan, alpha, beta, gamma, delta and omicron). The in vitro activity of ivermectin was compared to those of chloroquine and remdesivir. Unlike chloroquine (EC50 from 4.3 ± 2.5 to 29.3 ± 5.2 µM) or remdesivir (EC50 from 0.4 ± 0.3 to 25.2 ± 9.4 µM), ivermectin showed a relatively homogeneous in vitro activity against SARS-CoV-2 regardless of the strains or variants (EC50 from 5.1 ± 0.5 to 6.7 ± 0.4 µM), except for one omicron strain (EC50 = 1.3 ± 0.5 µM). Ivermectin (No. EC50 = 219, mean EC50 = 5.7 ± 1.0 µM) was, overall, more potent in vitro than chloroquine (No. EC50 = 214, mean EC50 = 16.1 ± 9.0 µM) (p = 1.3 × 10−34) and remdesivir (No. EC50 = 201, mean EC50 = 11.9 ± 10.0 µM) (p = 1.6 × 10−13). These results should be interpreted with caution regarding the potential use of ivermectin in SARS-CoV-2-infected patients: it is difficult to translate in vitro study results into actual clinical treatment in patients. [ABSTRACT FROM AUTHOR]

Simple Summary: Spiders are common predators found in almost every type of environment, and are used as model organisms in studies ranging from communication and signalling to biochemical studies on their silk. Orb spiders are particularly interesting, as their web provides a cost-effective way to obtain information on their foraging behaviour. However, studies on short-term behaviours including prey capture and escape behaviours are rare and usually take place in artificial settings, such as laboratories. In this study, we tested a simple methodology using tuning forks that can be used consistently and reliably in the field. The two tuning forks are capable of producing attack (440 Hz) and escape (256 Hz) responses from the spiders. We also used a metal wire as a mechanical stimulus for comparison, which as predicted, was less reliable. We demonstrate the usefulness of the methodology by quantitatively investigating how the size of the spider and the size of its web affect predatory and escape response rates in the autumn spider, although no significant effects of either were found. However, our results confirm the ease by which this simple method can be used to conduct behavioural studies of orb spiders in the wild. Spiders and their webs are often used as model organisms to study a wide range of behaviours. However, these behavioural studies are often carried out in the laboratory, and the few field studies usually result in large amounts of video footage and subsequent labour-intensive data analysis. Thus, we aimed to devise a cost- and time-effective method for studying the behaviour of spiders in the field, using the now almost forgotten method of stimulating webs with tuning forks. Our study looked at the viability of using 256 Hz and 440 Hz tuning forks to stimulate, anti-predatory and predatory responses in the orb web spider Metellina segmentata, respectively. To assess the consistency of the behaviours produced, we compared these to direct mechanical stimulation with a metal wire. The results suggest that the tuning forks produce relatively consistent behaviours within and between two years in contrast to the metal wire. We furthermore found no significant effects of spider length or web area on spider reaction times. However, we found significant differences in reaction times between escape and prey capture behaviours, and between tuning forks and the wire. Thus, we demonstrated the potential of tuning forks to rapidly generate quantitative data in a field setting. [ABSTRACT FROM AUTHOR]

Simple Summary: The onion thrips (Thrips tabaci), which is a key pest worldwide, includes three characteristic, distinct groups (i.e., lineages) under the same species name. In the current report, we addressed the question of whether individuals from these lineages recognize and assess each other as potential mating partners. We demonstrated that at least two of these lineages do not belong to the same species, since under our laboratory conditions no mating occurred between them. Moreover, specimens from these cross pairings often exhibited an escape response upon contact with the other thrips, while most of the pairs from the same lineages readily mated at their first interaction. The behaviour of males clearly indicated that they can assess the mating status of a female and usually only try to copulate with virgins. Our findings are important not only because in agriculture it is vital to know whether morphologically similar entities belong to the same species, but also because knowledge about the communication of insects and the possible role of the cues involved can help the development of new plant protection techniques. Thrips tabaci Lindeman is a serious pest of various cultivated plants, with three, distinct lineages within a cryptic species complex. Despite the well-known significance of this pest, many attributes of these lineages are not yet fully understood, including their reproductive behaviour. We performed no-choice-design cross-mating experiments under a controlled laboratory environment with virgin adult individuals from all three lineages. The behaviour of thrips was recorded with a camera mounted on a stereomicroscope, and the recordings were analysed in detail. We found that the so-called leek-associated lineages of this cryptic species complex are reproductively isolated from the tobacco-associated lineage; therefore, they represent different species. Divergence in the behaviour of conspecific and heterospecific pairs became evident only after contact. There were no marked differences between the lineages in their precopulatory and copulatory behaviour, except in the duration of the latter. We confirmed mating between thelytokous females and arrhenotokous males; however, we assume some form of loss of function in the sexual traits of asexual females. The post-mating behaviour of males indicated the presence and role of an anti-aphrodisiac pheromone. We also demonstrated differences between lineages regarding their activity and their propensity for exhibiting an escape response upon interaction with heterospecific thrips. [ABSTRACT FROM AUTHOR]

Devil facial tumour disease (DFTD) is a transmissible cancer that has circulated in the Tasmanian devil population for >25 years. Like other contagious cancers in dogs and devils, the way DFTD escapes the immune response of its host is a central question to understanding this disease. DFTD has a low major histocompatibility complex class I (MHC-I) expression due to epigenetic modifications, preventing host immune recognition of mismatched MHC-I molecules by T cells. However, the total MHC-I loss should result in natural killer (NK) cell activation due to the 'missing self'. Here, we have investigated the expression of the nonclassical MHC-I, Saha-UD as a potential regulatory or suppressive mechanism for DFTD. A monoclonal antibody was generated against the devil Saha-UD that binds recombinant Saha-UD by Western blot, with limited crossreactivity to the classical MHC-I, Saha-UC and nonclassical Saha-UK. Using this antibody, we confirmed the expression of Saha-UD in 13 DFTD tumours by immunohistochemistry (n = 15) and demonstrated that Saha-UD expression is heterogeneous, with 12 tumours showing intratumour heterogeneity. Immunohistochemical staining for the Saha-UD showed distinct patterns of expression when compared with classical MHC-I molecules. The nonclassical Saha-UD expression by DFTD tumours in vivo may be a mechanism for immunosuppression, and further work is ongoing to characterise its ligand on immune cells. [ABSTRACT FROM AUTHOR]

The first exposure to an unexpected, rapid displacement of a light touch reference induces a balance reaction in naïve participants, whereas an arm-tracking behaviour emerges with subsequent exposures. The sudden behaviour change suggests the first trial balance reaction arises from the startling nature of the unexpected stimulus. We investigated how touch-induced balance reactions interact with startling acoustic stimuli. Responses to light touch displacements were tested in 48 participants across six distinct combinations of touch displacement (DISPLACEMENT), acoustic startle (STARTLE), or combined (COMBINED) stimuli. The effect of COMBINED depended, in part, on the history of the preceding stimuli. Participants who received 10 DISPLACEMENT initially, produced facilitated arm-tracking responses with subsequent COMBINED. Participants who received 10 COMBINED initially, produced facilitated balance reactions, with arm-tracking failing to emerge until the acoustic stimuli were discontinued. Participants who received five DISPLACEMENT, after initially habituating to 10 STARTLE, demonstrated re-emergence of the balance reaction with the subsequent COMBINED. Responses evoked by light touch displacements are influenced by the startling nature of the stimulus, suggesting that the selection of a balance reaction to a threatening stimulus is labile and dependent, in part, on the context and sensory state at the time of the disturbance. [ABSTRACT FROM AUTHOR]

Background: Altered sensorimotor gating has been demonstrated by Prepulse Inhibition (PPI) tests in patients with psychosis. Recent advances in signal processing methods allow assessment of neural PPI through electroencephalogram (EEG) recording during acoustic startle response measures (classic muscular PPI). Simultaneous measurements of muscular (eye-blink) and neural gating phenomena during PPI test may help to better understand sensorial processing dysfunctions in psychosis. In this study, we aimed to assess simultaneously muscular and neural PPI in early bipolar disorder and schizophrenia patients. Method: Participants were recruited from a population-based case-control study of first episode psychosis. PPI was measured using electromyography (EMG) and EEG in pulse alone and prepulse + pulse with intervals of 30, 60, and 120 ms in early bipolar disorder (n = 18) and schizophrenia (n = 11) patients. As control group, 15 socio-economically matched healthy subjects were recruited. All subjects were evaluated with Rating Scale, Hamilton Rating Scale for Depression, and Young Mania Rating Scale questionnaires at recruitment and just before PPI test. Wilcoxon ranked sum tests were used to compare PPI test results between groups. Results: In comparison to healthy participants, neural PPI was significantly reduced in PPI 30 and PPI60 among bipolar and schizophrenia patients, while muscular PPI was reduced in PPI60 and PPI120 intervals only among patients with schizophrenia. Conclusion: The combination of muscular and neural PPI evaluations suggested distinct impairment patterns among schizophrenia and bipolar disorder patients. Simultaneous recording may contribute with novel information in sensory gating investigations. [ABSTRACT FROM AUTHOR]

The ubiquitin proteasome system (UPS) is a protein degradation machinery that is crucial for cellular homeostasis in eukaryotes. Therefore, it is not surprising that the UPS coordinates almost all host cellular processes, including host–pathogen interactions. This protein degradation machinery acts predominantly by tagging substrate proteins designated for degradation with a ubiquitin molecule. These ubiquitin tags have been involved at various steps of the innate immune response. Hence, herpesviruses have evolved ways to antagonize the host defense mechanisms by targeting UPS components such as ubiquitin E3 ligases and deubiquitinases (DUBs) that establish a productive infection. This review delineates how herpesviruses usurp the critical roles of ubiquitin E3 ligases and DUBs in innate immune response to escape host-antiviral immune response, with particular focus on retinoic acid-inducible gene I (RIG-I)-like receptors (RLR), cyclic-GMP-AMP (cGAMP) synthase (cGAS), stimulator of interferon (IFN) genes (STING) pathways, and inflammasome signaling. [ABSTRACT FROM AUTHOR]

Simple Summary: Feline coronavirus (FCoV) and feline herpesvirus-1 (FeHV-1) can induce infections that are difficult to prevent and to treat due to the involvement of host genetic factors and immune mechanisms. These two viruses areimportant examples of viral immune evasion of the host's innate immune response. The innate immune system provides an early form of host protection from infectious diseases without pre-exposure and plays an essential role in determining the outcome of viral infections. The mechanisms that the innate immune system utilizes to counteract infections are based on therecognition of a relatively limited set of molecular structures that are either products of microbes (virus, bacteria, fungi, parasites) or expressed by injured or dead host cells. This review provides a brief overview of the main mechanisms achieved by host's innate immunity, focusing primarily on the immune escape mechanisms developed and carried out by FCoV and FeHV-1 during infection. Over time, feline viruses have acquired elaborateopportunistic properties, making their infections particularly difficult to prevent and treat. Feline coronavirus (FCoV) and feline herpesvirus-1 (FeHV-1), due to the involvement of host genetic factors and immune mechanisms in the development of the disease and more severe forms, are important examples of immune evasion of the host's innate immune response by feline viruses.It is widely accepted that the innate immune system, which providesan initial universal form of the mammalian host protection from infectious diseases without pre-exposure, plays an essential role in determining the outcome of viral infection.The main components of this immune systembranchare represented by the internal sensors of the host cells that are able to perceive the presence of viral component, including nucleic acids, to start and trigger the production of first type interferon and to activate the cytotoxicity by Natural Killercells, often exploited by viruses for immune evasion.In this brief review, we providea general overview of the principal tools of innate immunity, focusing on the immunologic escape implemented byFCoVand FeHV-1 duringinfection. [ABSTRACT FROM AUTHOR]

Both in utero exposure to maternal immune activation and cannabis use during adolescence have been associated with increased risk for the development of schizophrenia; however, whether these exposures exert synergistic effects on brain function is not known. In the present study, mild maternal immune activation (MIA) was elicited in mice with prenatal exposure to polyinosinic-polycytidylic acid (poly(I:C)), and ∆9-tetrahydrocannabinol (THC) was provided throughout adolescence in cereal (3 mg/kg/day for 5 days). Neither THC nor MIA pretreatments altered activity in assays used to characterize hyperdopaminergic states in adulthood: amphetamine hyperlocomotion and prepulse inhibition of the acoustic startle reflex. Adolescent THC treatment elicited deficits in spatial memory and enhanced spatial reversal learning in adult female mice in the Morris water maze, while exposure to MIA elicited female-specific deficits in fear extinction learning in adulthood. There were no effects in these assays in adult males, nor were there interactions between THC and MIA in adult females. While doses of poly(I:C) and THC were sufficient to elicit behavioral effects, particularly relating to cognitive performance in females, there was no evidence that adolescent THC exposure synergized with the risk imposed by MIA to worsen behavioral outcomes in adult mice of either sex. [ABSTRACT FROM AUTHOR]