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The orbitofrontal cortex (OFC)-dorsal striatum (DS) is an important neural circuit that contributes to addictive behavior, including compulsive reinforcement, yet the specific types of neurons that play a major role still need to be further elucidated. Here, we used a place conditioning paradigm to measure the conditioned responses to methamphetamine (MA). The results demonstrated that MA increases the expression of c-Fos, synaptic plasticity in OFC and DS. Patch-clamp recording showed that MA activated projection neurons from the OFC to the DS, and chemogenetic manipulation of neuronal activity in OFC-DS projection neurons affects conditioned place preference (CPP) scores. And the combined patch-electrochemical technique was used to detect the DA release in OFC, the data indicated that the DA release was increased in MA group. Additionally, SCH23390, a D1R antagonist, was used to verify the function of D1R projection neurons, showing that SCH23390 reversed MA addiction-like behavior. Collectively, these findings provide evidence for the D1R neuron is sufficient to regulate MA addiction in the OFC-DS pathway, and the study provides new insight into the underlying mechanism of pathological changes in MA addiction. • MA enhanced the excitability of OFC-DS pathway detected by patch clamp in MA-induced mice. • Inhibition of OFC-DS projection neurons alleviates MA-induced CPP behavior. • Blocking of D1R projection neurons in OFC-DS pathway reverse MA-induced CPP behavior. [ABSTRACT FROM AUTHOR]

Cloud computing environments are indispensable components of the majority of information technology organizations and users' lives. Despite multiple benefits of cloud computing environments, cloud users (CUs) as well as cloud service providers (CSPs) may experience unpleasant conditions by detrimental results of distributed denial of service (DDoS) attacks such as unavailability of cloud services or lengthy response times of the services. In this paper, we provide a threshold anomaly-based DDoS attack detection method to protect cloud environments against DDoS attack. Our proposed method is introduced to reduce DDoS attack consequences in CSPs. Our suggested method includes three newly defined components: 1. A third party auditor (TPA) which acquires direct interaction with each datacenter of the CSP, 2. A zone delimiter (ZD) which encapsulates the sensitive internal specifications of a CSP from TPA, and 3. A protocol which is defined to coordinate TPA, ZD, and CSPs for DDoS attack detection via TPA. We analyze our proposed method by determining and conducting a simulation strategy for an intrusion detection system in CSPs. Results illustrate that interactive communication between TPA and datacenters of CSPs improves the user experience of CUs in the time of DDoS attacks by reducing excessive attack filtering stages. Moreover, by using an intrusion detection system (IDS), we investigate efficiency of the proposed method to recover CSPs from DDoS attacks. We further indicate the efficiency of our proposed method by providing accuracy and qualitative comparisons with other existing methods. • A cloud auditor detects Denial of Service or Distributed Denial of Service attacks in services of a Cloud Service Provider. • Interactive communication between cloud auditor and datacenters improves the user experience in the time of attacks. • When attacks remain undetected, cloud users will not experience any unusual condition such as long response time. • When attacks remain undetected, hosts will not experience any unusual condition such as overheating the hardware. • This method functions completely independent from any other intrusion detection mechanism or filtration method. [ABSTRACT FROM AUTHOR]

This article examines the promotion of private tree planting, in particular by farmers, by the New Zealand State Forest Service (SFS) as a solution to a timber shortage in the 1920s. While previous research has detailed the SFS's efforts to ensure a stable supply of timber by placing New Zealand's native forests under a system of sustained yield management and through the establishment of exotic plantations, it overlooks the importance the SFS placed on private tree plantations as a source of timber, expecting it to supply a third of New Zealand's timber demand. In its propaganda, the SFS portrayed tree planting as a mean to improve the productivity of the farm and as a financial investment. To assist farmers, the SFS also sold trees and seedlings to farmers, a practice that met with major resistance from private nurserymen and political lobby organisations. By exploring the SFS's promotion of private tree planting to farmers, this article demonstrates how the SFS built upon a tradition of experimental tree planting and promotion of exotic afforestation. Moreover, by examining the opposition to the policy of the SFS selling trees and seedlings to farmers, the article highlights the contesting notions of the state's role in promoting private tree planting; whether it was a responsibility of the state, or an invasion on the private market. On a broader scale, this paper demonstrates how local environmental and political conditions shaped responses to a perceived global timber shortage. • The notion of private tree planting by farmers as a remedy against a wood shortage in New Zealand. • The means and arguments employed by scientific foresters to encourage farmers to engage in private tree planting. • The collaboration and tension between state and private firms in the promotion of private tree planting. [ABSTRACT FROM AUTHOR]

• Acute inflammation impacts on neural circuitry during interoceptive fear extinction. • Timing of inflammatory insult relative to fear learning and extinction is critical. • Altered fear extinction circuitry may contribute to enhanced interoceptive perception. • Inflammation as risk factor for atypical interoception in psychiatric conditions. Inflammation could impact on the formation and persistence of interoceptive fear and hypervigilance, with relevance to psychiatric disorders and chronic pain. To systematically analyze effects of inflammation on fear learning and extinction, we performed two complementary randomized, double-blind, placebo-controlled functional magnetic resonance imaging (fMRI) studies combining experimental endotoxemia as a translational model of acute systemic inflammation with a two-day multiple-threat fear conditioning paradigm involving interoceptive and exteroceptive unconditioned stimuli (US). Healthy volunteers (N = 95) were randomized to receive intravenous injections of either endotoxin (lipopolysaccharide, LPS; 0.4 ng/kg) or placebo prior to fear acquisition (study 1) or extinction training (study 2). Treatment effects on behavioral and neural responses to conditioned stimuli (CS) predicting interoceptive or exteroceptive threat were assessed during fear learning and extinction phases, along with US valence ratings. Despite robust inflammatory and emotional responses triggered by LPS, no direct effects of inflammation on US ratings or on the formation or extinction of conditioned fear, as assessed with CS valence ratings, were observed. However, in the group treated with LPS prior to acquisition (i.e., study 1), we found enhanced neural responses to the interoceptive but not the exteroceptive CS in key regions of the central fear circuitry during extinction learning. After extinction, this group further showed enhanced negative valence ratings selectively for the interoceptive US during unexpected US re-exposure when compared to the placebo group. Together, inflammation during fear acquisition may promote the establishment of a more robust neural signature of the interoceptive fear memory trace, which may contribute to altered interoceptive pain perception. The fear extinction circuitry engaged during interoceptive fear memory processing may be particularly vulnerable to inflammation, with transdiagnostic implications for gut-brain mechanisms underlying disturbed interoception in psychiatric conditions and chronic visceral pain. [ABSTRACT FROM AUTHOR]

• Depletion of the gut microbiota altered reward responses to both cocaine and social stimuli. • The combination of depleting the gut microbiota in the presence of social stimulus attenuates cocaine reward. • Reductions in proinflammatory cytokines in the ileum of animals with a depleted microbiota may modulate brain reward responses. The gut microbiota is a key factor in the maintenance of physiological homeostasis and immunity. Correlational studies have demonstrated that alterations in microbiota composition have been associated with addiction. Moreover, animal studies have confirmed a link between reward and social processes, which may be shaped by the gut microbiota thus influencing neurodevelopment and the programming of social behaviors across diverse animal species. However, whether there is an interaction between the microbiota and social reward processes in the context of drug reward remains unclear. To this end, we explored the influence of gut microbiota in regulating behaviourally conditioned responses to different rewards (cocaine and social interactions). Depletion of the intestinal microbiota resulted in differential reward responses to both drug and social stimuli with an attenuation of the former and enhancement of the latter independent of concomitant immune changes. Moreover, the combination of depleting the gut microbiota in the presence of a positive social stimulus attenuates cocaine reward. Together these data suggest that the two-pronged approach of targeting the microbiota and enhancing social behaviour could constitute a valuable component in reducing harm in drug use by altering the salient effects of cocaine. [ABSTRACT FROM AUTHOR]

• New evidence demonstrates that Pavlovian conditioning and extinction trials have different effects on the spatial and temporal distribution of conditioned responding. • This evidence is beyond the scope of influential theoretical models of Pavlovian conditioning, including the Rescorla and Wagner (1972) model. • Formal simulations demonstrate how a recent model, HeiDI, accommodates this new evidence. Rat autoshaping procedures generate two readily measurable conditioned responses: During lever presentations that have previously signaled food, rats approach the food well (called goal-tracking) and interact with the lever itself (called sign-tracking). We investigated how reinforced and nonreinforced trials affect the overall and temporal distributions of these two responses across 10-second lever presentations. In two experiments, reinforced trials generated more goal-tracking than sign-tracking, and nonreinforced trials resulted in a larger reduction in goal-tracking than sign-tracking. The effect of reinforced trials was evident as an increase in goal-tracking and reduction in sign-tracking across the duration of the lever presentations, and nonreinforced trials resulted in this pattern transiently reversing and then becoming less evident with further training. These dissociations are consistent with a recent elaboration of the Rescorla-Wagner model, HeiDI (Honey, R.C., Dwyer, D.M., & Iliescu, A.F. (2020a). HeiDI: A model for Pavlovian learning and performance with reciprocal associations. Psychological Review , 127 , 829–852.), a model in which responses related to the nature of the unconditioned stimulus (e.g., goal-tracking) have a different origin than those related to the nature of the conditioned stimulus (e.g., sign-tracking). [ABSTRACT FROM AUTHOR]

Meat co-products are a promising alternative for meeting the increasing demand for protein, especially for the formulation of meat products. The present study aims to determine the optimal conditions under which two innovative bovine co-products, resulting from the fat rendering process, can mimic the gelling and emulsifying properties of commercial gelatines and sodium caseinate (NaCas), respectively, using Response Surface Methodology (RSM). The desirability function was used to determine the values for protein concentration, pH and NaCl content that enable the two co-products to effectively mimic gelatine and NaCas. The co-product obtained from water recovered during the fat rendering process proved to be the most suitable to mimic commercial gelatines. Very high desirability scores were obtained with this ingredient on 4 criteria out of 7, and a high overall score as well, provided 90 g/L protein was used to mimic a 50 g/L gelatine 150 Bloom. Both co-products appeared as effective alternatives to NaCas as emulsifiers, especially regarding their capacity in stabilizing emulsions. The co-product made of greasy greaves can be even regarded as more effective than NaCas, as less proteins are needed to obtain the same performances (110 g/L vs 125 g/L, respectively). • The soluble proteins extracted from beef fat melting are gelling agents similar to gelatin. • The greaves extracted from beef fat melting stabilize emulsions more efficiently than caseinate. • Both coproducts are efficient alternatives to sodium caseinate as emulsifiers. [ABSTRACT FROM AUTHOR]

Flux balance analysis (FBA) and associated techniques operating on stoichiometric genome-scale metabolic models play a central role in quantifying metabolic flows and constraining feasible phenotypes. At the heart of these methods lie two important assumptions: (i) the biomass precursors and energy requirements neither change in response to growth conditions nor environmental/genetic perturbations, and (ii) metabolite production and consumption rates are equal at all times (i.e., steady-state). Despite the stringency of these two assumptions, FBA has been shown to be surprisingly robust at predicting cellular phenotypes. In this paper, we formally assess the impact of these two assumptions on FBA results by quantifying how uncertainty in biomass reaction coefficients, and departures from steady-state due to temporal fluctuations could propagate to FBA results. In the first case, conditional sampling of parameter space is required to re-weigh the biomass reaction so as the molecular weight remains equal to 1 g mmol−1, and in the second case, metabolite (and elemental) pool conservation must be imposed under temporally varying conditions. Results confirm the importance of enforcing the aforementioned constraints and explain the robustness of FBA biomass yield predictions. • The propagation of biomass coefficient uncertainty and metabolite imbalances is systematically assessed in FBA. • The importance of sampling biomass coefficients so as the biomass molecular weight is always scaled to one is highlighted. • Conservation of metabolite pools and elemental balances is demonstrated to be necessary in modeling steady-state departure. • FBA-predicted biomass yield, but not metabolic fluxes, was found to be insensitive to noise in biomass coefficients. • Departures from metabolite steady-state almost always led to a drastic reduction in biomass yield. [ABSTRACT FROM AUTHOR]

The high prevalence of hay fever in Europe has raised concerns about the implications of climate change-induced higher temperatures on pollen production. Our study focuses on downy birch pollen production across Europe by analyzing 456 catkins during 2019–2021 in 37 International Phenological Gardens (IPG) spanning a large geographic gradient. As IPGs rely on genetically identical plants, we were able to reduce the effects of genetic variability. We studied the potential association with masting behavior and three model specifications based on mean and quantile regression to assess the impact of meteorology (e.g., temperature and precipitation) and atmospheric gases (e.g., ozone (O 3) and carbon-dioxide (CO 2)) on pollen and catkin production, while controlling for tree age approximated by stem circumference. The results revealed a substantial geographic variability in mean pollen production, ranging from 1.9 to 2.5 million pollen grains per catkin. Regression analyses indicated that elevated average temperatures of the previous summer corresponded to increased pollen production, while higher O 3 levels led to a reduction. Additionally, catkins number was positively influenced by preceding summer's temperature and precipitation but negatively by O 3 levels. The investigation of quantile effects revealed that the impacts of mean temperature and O 3 levels from the previous summer varied throughout the conditional response distribution. We found that temperature predominantly affected trees characterized by a high pollen production. We therefore suggest that birches modulate their physiological processes to optimize pollen production under varying temperature regimes. In turn, O 3 levels negatively affected trees with pollen production levels exceeding the conditional median. We conclude that future temperature increase might exacerbate pollen production while other factors may modify (decrease in the case of O 3 and amplify for precipitation) this effect. Our comprehensive study sheds light on potential impacts of climate change on downy birch pollen production, which is crucial for birch reproduction and human health. [Display omitted] • Effects of climate change on birch pollen production across Europe are evaluated. • Pollen production tends to increase with average temperatures. • Pollen production tends to decrease with O 3 concentration levels. • Effects of temperatures and O 3 vary across response distribution. [ABSTRACT FROM AUTHOR]

Selenium (Se) biofortification of staple crops can be used as a valuable pathway to prevent Se deficiency in human diet. In this study, a pot experiment was performed under semi-controlled conditions to investigate the response of indigenous wheat cultivars to different Se concentrations (0 to 100 mg L-1) and to also assess the effects of Se foliar application on the storage proteins in wheat grains. A linear increase in Se concentrations in the grains of various wheat cultivars was observed (up to 158 μg kg-1) in response to Se application rates. It was observed that Gandum-1, Fakhar-e-Bhakkar-17, Ujala-16 and Anaj-17 were the most responsive wheat cultivars to Se application rates and accumulated the highest Se concentrations in grains. Though Se foliar treatments did not significantly affect the wheat yield, a highly significant correlation was observed between the Se application rates and the concentration of mineral nutrients (iron, zinc, calcium and potassium). Moreover, the exogenous Se supply considerably enhanced the concentrations of different storage proteins viz. albumin, globulin, prolamin and glutelin in wheat grains. The target hazard quotient of all Se application rates was found less than the toxic levels. In conclusion, wheat cultivars differ in their ability to accumulate Se concentrations in grains and biofortifying the most responsive wheat cultivars could be used as an efficient agronomic strategy to overcome widespread Se deficiency in human population. • The effects of different selenium (Se) concentrations on nutritional quality of wheat grain were investigated. • Foliar spray of Se increased the concentration of albumin, globulin, prolamin and glutelin in wheat grains. • Se application significantly increased iron, zinc, calcium and potassium content but did not affect yield. • Wheat genotypes differ in their response to Se application. [ABSTRACT FROM AUTHOR]

Stimuli in our environment are not always associated with an outcome. Some of these stimuli, depending on how they are presented, may gain inhibitory value or simply be ignored. If experienced in the presence of other cues predictive of appetitive or aversive outcomes, they typically gain inhibitory value and become predictive cues indicating the absence of appetitive or aversive outcomes. In this case, these cues are referred to as conditioned inhibitors. Here, male and female Long Evans rats underwent cue discrimination training where a reward cue was paired with sucrose, a fear cue with footshock, and an inhibitor cue resulted in neither sucrose or footshock. During a subsequent summation test for conditioned inhibition of fear and reward, the inhibitor cue was presented concurrently with the reward and fear cues without any outcome, intermixed with trials of reinforced reward and fear trials. Males showed significant conditioned inhibition of freezing, while females did not, which was not dependent on estrous. Both males and females showed significant conditioned inhibition of reward. During a retardation of fear acquisition test, the inhibitor was paired with footshock and both males and females showed delayed acquisition of fear. During a retardation of reward acquisition test, the inhibitor was paired with sucrose, and females showed delayed acquisition of reward, while males did not. In summary, males and females showed significant reward-fear-inhibitor cue discrimination, conditioned inhibition of reward, and retardation of fear acquisition. The main sex difference, which was not estrous-dependent, was the lack of conditioned inhibition of freezing in females. These data imply that while the inhibitor cue gained some inhibitory value in the females, the strength of this inhibitory value may not have been great enough to effectively downregulate freezing elicited by the fear cue. [ABSTRACT FROM AUTHOR]

Conditional responses of the abundance of native and non-native plants to processes controlling community dominance remain little explored. Here, we studied how the environmental context alters relative abundances of those species in communities growing after disturbance. We addressed that question by conducting field sampling, where we seasonally estimated species cover and soil moisture in dunes and non-dune environments subjected to plowing, a common disturbance in our study site, the Argentinean Caldenal. We also measured texture, nutrients, and pH in dune and non-dune soils. We found that natives consistently dominated communities in dunes. In non-dunes, non-natives dominated communities soon after disturbance, but exhibited lower abundance than natives toward the end of the growing season, resulting in no differences between biogeographical origins when seasonal samplings were combined within the year. Panicum urvilleanum , a native grass, quickly dominated communities in dunes, but it was virtually absent in non-dunes. In addition, soils were coarser and lower in resources and pH in dunes than non-dunes. Our results suggest that native versus non-native dominance after disturbance varies with the environment. Moreover, the strong community dominance displayed by natives after plowing in dunes questions the common perspective that considers human disturbance as favoring non-native over native species. • Native versus non-native dominance after disturbance varies with the environment. • Human disturbance fails to favor non-native over native plants under some conditions. • Disturbance effects on invasion may depend on environmental conditions. [ABSTRACT FROM AUTHOR]

The degree to which miniature-brained insects make individual adjustments in response to changing conditions remains unclear. Honey bees, Apis mellifera , are an important insect model and have been shown to make individual speed–accuracy trade-offs, but it is currently not known whether they can adjust speed–accuracy strategies to solve tasks in dynamic ecological contexts. Further, it is unclear how they may behave when facing unsolvable or impossible tasks. We therefore tested whether honey bees flexibly allocate time in a colour discrimination task with four levels of task difficulty, and how such differences in time allocation affect accuracy. We found that response time differed between task difficulties, although accuracy did not appear to be influenced by response time. Specifically, bees allocated less time when facing an impossible task than when addressing easier tasks. Our findings suggest that honey bees demonstrate a time allocation strategy depending on context, and that there was little effect of speed on accuracy in both the easy and impossible tasks. • Honey bees spent less time in impossible tasks compared to easier tasks. • Fast choices do not cost accuracy if the task is very easy or impossible to solve. • Honey bees may favour a fast guessing strategy in low-risk foraging contexts. • This contrasts with bumble bee behaviour and may be due to differences in ecology. [ABSTRACT FROM AUTHOR]

• We aimed at sustaining conditioned properties of the mTOR inhibitor rapamycin. • Sub-effective doses of rapamycin (US) were applied with the taste (CS) at retrieval. • Conditioned immunopharmacological responses persisted peripherally and centrally. • Sub-effective US doses strengthen conditioned associations between taste and drug. Peripheral immune responses can be modulated by taste-immune associative learning where the presentation of a sweet taste as conditioned stimulus (CS) is paired with the injection of an immunosuppressive substance as unconditioned stimulus (US). Previous findings demonstrate conditioned immunopharmacological properties of the mechanistic target of rapamycin (mTOR)-inhibitor rapamycin, a drug used to ameliorate neurological diseases and for the prevention of graft rejection. However, conditioned responses gradually weaken over time and eventually disappear following repeated exposure to the CS in the absence of the US. Thus, in order to employ learning paradigms in clinical conditions as supportive immunopharmacological therapy it is important to understand the central and peripheral mechanisms of how learned immune responses can be protected from extinction. Against this background, the present study used a taste-immune learning paradigm with rapamycin as US (5 mg/kg). By applying only 10% (0.5 mg/kg) of the therapeutic dose rapamycin together with the CS (taste stimulus) during eight retrieval trials, conditioned animals still displayed suppressed interleukin-10 production and T cell proliferation in splenocytes as well as diminished activity of the mTOR target protein p70s6k in amygdala tissue samples. Together, these findings indicate that reminder cues in form of only 10% (0.5 mg/kg) of the therapeutic dose rapamycin together with the CS (taste stimulus) at retrieval preserved the memory of conditioned properties of rapamycin, characterizing this approach as a potential supportive tool in peripheral and central pharmacotherapy with the aim to maximize the therapeutic outcome for the patient's benefit. [ABSTRACT FROM AUTHOR]

The frequency–time domain method is a very powerful tool for analyzing nonlinear aeroelastic systems; however, it is limited to obtaining steady-state solutions. To investigate nonlinear dynamic behaviors with initial conditions, a modified frequency–time domain method is proposed. Initial conditions, represented as pseudo forces, are introduced into the nonlinear feedback loops and are subsequently transformed from the time domain into the frequency domain. Hence, the proposed method allows nonlinear responses with initial conditions. Owing to the characteristics and limitations of this method, certain skills are presented to simulate both accurately and efficiently. Numerical results are provided for, in addition to the Van Der Pol equation, a two-degree-of-freedom airfoil section, and a three-degree-of-freedom aeroelastic typical section with control surface freeplay. Consequently, the feasibility of introducing initial conditions is validated. The comparison with the Runge–Kutta algorithm demonstrates the accuracy and efficiency of the proposed method, as an alternative to time-marching approaches. Furthermore, several key parameters, such as the sampling frequency and ending time of convolution integral, are investigated to explore the efficiency. The sensitivity of parameters and calculation methods of convolution integral is observed, which contributes to the strategies for adequate accuracy. • The modification of the increased-order modeling method. • An alternative to time-marching approaches. • Pseudo forces of initial conditions introduced into the nonlinear feedback loops. • Obtaining nonlinear responses with initial conditions. [ABSTRACT FROM AUTHOR]

We examined whether ABA, ABC, and AAB renewal effects could be observed using fear conditioning with social stimuli as both conditioned stimulus (CS) and unconditioned stimulus (US) to investigate the possibility of relapse following exposure interventions for social anxiety in a laboratory setting. Sixty-four participants were randomly allocated to four groups (AAA, ABA, ABC, and AAB). They received nine pairings with a neutral face (CS) and aggressive facial expressions and insults (US) during the acquisition phase, and then received 18 pairings with the same CS and a neutral comment in the extinction phase. Following the extinction, the testing phase (three trials) was conducted. The background colors presented in each phase were manipulated to serve as the contextual stimuli. ANOVA showed the occurrence of the three types of renewals, but there were no consistent results showing differences between the renewals. Bayesian modeling demonstrated that there are some relationships between each parameter in the learning curves and social anxiety. The participants were non-clinical populations; therefore, it remains unclear whether the findings can be generalized to clinical populations. The results suggest that relapse following exposure therapy is related to a contextual change from the therapeutic environment and that individual differences in learning are related to social anxiety symptoms. [ABSTRACT FROM AUTHOR]

• Cortisol administration resulted in higher renewal rates compared to placebo. • CORT group showed context-dependent impairment of extinction memory recall. • Cortisol affected functioning of extinction-related brain areas. • Cortisol reduced BOLD activation of hippocampus and prefrontal areas. Conditioned responding gradually stops during successful extinction learning. The renewal effect is defined as the recovery of a extinguished conditioned response when the context of extinction is different from acquisition. The stress hormone cortisol is known to have an influence on extinction memory and associative learning. Different effects of cortisol on behaviour and brain activity have been observed with respect to stress timing, duration, and intensity. However, the influence of cortisol prior to the initial encoding of stimulus-outcome associations on extinction learning, renewal and its behavioural and neurobiological correlates is still largely unknown. In our study, 60 human participants received 20 mg cortisol or placebo and then learned, extinguished, and recalled the associations between food stimuli presented in distinct contexts and different outcomes in three subsequent task phases. Learning performance during acquisition and extinction phases was equally good for both treatment groups. In the cortisol group, significantly more participants showed renewal compared to placebo. In the subgroup of participants with renewal, cortisol treated participants showed significantly better extinction learning performance compared to placebo. Participants showing renewal had in general difficulties with recalling extinction memory, but in contrast to placebo, the cortisol group exhibited a context-dependent impairment of extinction memory recall. Imaging analyses revealed that cortisol decreased activation in the hippocampus during acquisition. The cortisol group also showed reduced dorsolateral prefrontal cortex activation when extinction learning took place in a different context, but enhanced activation in inferior frontal gyrus during extinction learning without context change. During recall, cortisol decreased ventromedial prefrontal cortex activation. Taken together, our findings illustrate cortisol as a potent modulator of extinction learning and recall of extinction memory which also promotes renewal. [ABSTRACT FROM AUTHOR]

There is now ample evidence that the strength and underlying mechanisms of memory formation can be drastically altered by prior experience. However, the prior work using rodent models on this topic has used only males as subjects, and as a result, we do know whether or not the effects of prior experience on subsequent learning are similar in both sexes. As a first step towards addressing this shortcoming, rats of both sexes were given auditory fear conditioning, or fear conditioning with unsignaled shocks, followed an hour or a day later by a single pairing of light and shock. Fear memory for each experience was assessed by measuring freezing behavior to the auditory cue and fear-potentiated startle to the light. Results showed that males trained with auditory fear conditioning showed facilitated learning to the subsequent visual fear conditioning session when the two training sessions were separated by one hour or one day. Females showed evidence of facilitation in rats given auditory conditioning when they were spaced by an hour but not when they were spaced by one day. Contextual fear conditioning did not support the facilitation of subsequent learning under any conditions. These results indicate that the mechanism by which prior fear conditioning facilitates subsequent learning differs between sexes, and they set the stage for mechanistic studies to understand the neurobiological basis of this sex difference. [ABSTRACT FROM AUTHOR]

To effectively manage species and habitats at multiple scales, population and land managers require rapid information on wildlife use of managed areas and responses to landscape conditions and management actions. GPS tracking studies of wildlife are particularly informative to species ecology, habitat use, and conservation. Combining GPS data with administrative data and a diverse suite of remotely sensed, geo-referenced environmental (e.g., climatic) data, would more comprehensively inform how animals interact with and utilize habitats and ecosystems and our goal was to create a conceptual model for a system that would accomplish this – the 'Automated Interactive Monitoring System (AIMS) for Wildlife'. Our objective for this study was to develop a Customized Wildlife Report (CWR) - the first AIMS for Wildlife deliverable product. CWRs collate and summarize our 8-year GPS tracking dataset of ∼11 million locations from 1338 individual (16 species) avifauna and make actionable, real-time data on animal movements and trends in a specific area of interest available to managers and stakeholders for rapid application in day-to-day management. The CWR exemplar presented in this paper was developed to address needs identified by habitat managers of Sacramento National Wildlife Refuge and illustrates the highly specific, information offered and how it contributes to assessing the efficacy of conservation actions while allowing for near real-time adaptive management. The report can be easily customized for any of the thousands of wildlife refuges or regional areas of interest in the United States, emphasizing the broad application of an animal movement data stream. Utilizing diverse, extensive telemetry data streams through scientific collaboration can aid managers and conservation stakeholders with short and long-term research and conservation planning and help address a cadre of issues from local-scale habitat management to improving the understanding of landscape level impacts like drought, wildfire, and climate change on wildlife populations. [Display omitted] • Our Automated Interactive Monitoring System (AIMS) for Wildlife utilizes animal GPS data. • We developed proof-of-concept Customized Wildlife Reports (CWRs) with 11 million locations. • CWRs inform wildlife managers' decision-making in near real-time. • We conceptualize a multi-tool AIMS for Wildlife incorporating remote-sensing data. • Automated delivery of animal movement data will allow for true adaptive management. [ABSTRACT FROM AUTHOR]

The present study was designed to determine the modulatory effects of arginine and citrulline dietary supplementation on the immune condition and inflammatory response of European seabass, Dicentrarchus labrax. Four diets were manufactured: a control diet (CTRL) was formulated to meet the indispensable amino acids profile established for seabass. Based on this formulation, three other diets were supplemented with l -arginine at two different levels (0.5% and 1%, ARG1 and ARG2, respectively) and l -citrulline at 0.5% (CIT). Fish were fed these diets for 2 or 4 weeks under controlled conditions. At the end of 4 weeks, fish from all dietary treatments were intraperitoneally-injected with Photobacterium damselae piscicida and sampled after 4, 24 our 48 h. Immune status was characterized by a lymphocyte time-dependent decrease regardless of dietary treatment, whereas peroxidase values dropped in time in fish fed ARG1 and ARG2 and was lower at 4 weeks in fish fed ARG1 than in fish fed CTRL. Up-regulation of several genes was more evident in ARG1-and CIT-fed fish, though pro-inflammatory cytokines were down-regulated by CIT dietary treatment. Following immune stimulation, seabass fed ARG1 showed a decrease in neutrophils and monocytes circulating numbers. On the other hand, expression of 17 selected immune and inflammatory responses genes was barely affected by dietary treatments. Based on the analyzed parameters, results suggest an active role of dietary arginine/citrulline supplementation in modulating immune defences that seem to translate into a suppressed immune repertoire, mostly at the cell response level. The observed changes due to citrulline dietary supplementation were in part similar to those caused by arginine, suggesting that citrulline might have been used by macrophages as an arginine precursor and then engaged in similar immune-impairment leading mechanisms. • European seabass immune status is modulated by dietary arginine and citrulline surplus mostly at the transcription level. • Dietary citrulline modulatory effects on fish immunity suggest it is perceived by fish as an arginine precursor. • Arginine supplementation decreased neutrophil and monocyte peripheral concentrations in immune-stimulated European seabass. [ABSTRACT FROM AUTHOR]

BipA is a conserved translational GTPase of bacteria recently implicated in ribosome biogenesis. Here we show that Escherichia coli ΔbipA cells grown at suboptimal temperature accumulate immature large subunit particles missing several proteins. These include L17 and L17-dependent binders, suggesting that structural block 3 of the subunit folds late in the assembly process. Parallel analysis of the control strain revealed accumulation of nearly identical intermediates, albeit at lower levels, suggesting qualitatively similar routes of assembly. This came as a surprise, because earlier analogous studies of wild-type E. coli showed early binding of L17. Further investigation showed that the main path of 50S assembly differs depending on conditions of growth. Either supplementation of the media with lysine and arginine or suboptimal temperature appears to delay block 3 folding, demonstrating the flexible nature of the assembly process. We also show that the variant BipA-H78A fails to rescue phenotypes of the ΔbipA strain, indicating a critical role for GTP hydrolysis in BipA function. In fact, BipA-H78A confers a dominant negative phenotype in wild-type cells. Controlled production of BipA-H78A causes accumulation of 70S monosomes at the expense of polysomes, suggesting that the growth defect stems from a shutdown of translation. Unlabelled Image • In E. coli , the landscape of 50S assembly changes in response to growth conditions. • BipA facilitates assembly of the 50S subunit at suboptimal growth temperature. • A GTPase-deficient variant of BipA shuts down translation and cell growth. [ABSTRACT FROM AUTHOR]

We study the theoretical underpinning of a robust empirical risk minimization (RERM) scheme which has been finding numerous successful applications across various data science fields owing to its robustness to outliers and heavy-tailed noises. The specialties of RERM lie in its nonconvexity and that it is induced by a loss function with an integrated scale parameter trading off the robustness and the prediction accuracy. The nonconvexity of RERM and the integrated scale parameter also bring barriers when assessing its learning performance theoretically. In this paper, concerning the study of RERM, we make the following main contributions. First, we establish a no-free-lunch result, showing that there is no hope of distribution-free learning of the truth without adjusting the scale parameter. Second, by imposing the (1 + ϵ) -th (with ϵ > 0) order moment condition on the response variable, we establish a comparison theorem that characterizes the relation between the excess generalization error of RERM and its prediction error. Third, with a diverging scale parameter, we establish almost sure convergence rates for RERM under the (1 + ϵ) -moment condition. Notably, the (1 + ϵ) -moment condition allows the presence of noise with infinite variance. Last but not least, the learning theory analysis of RERM conducted in this study, on one hand, showcases the merits of RERM on robustness and the trade-off role that the scale parameter plays, and on the other hand, brings us inspirational insights into robust machine learning. [ABSTRACT FROM AUTHOR]

• Visceral pain-related learning establishes a robust aversive memory trace. • Re-exposure to visceral pain induces return of extinguished conditioned fear. • Acute inflammation does not impair the extinction of aversive gut memories. • Inflammation is not a vulnerability factor for increased return of fear. Impaired extinction of pain-related fear memories can lead to persistent or resurging fear of pain, contributing to the development and maintenance of chronic pain conditions. The mechanisms underlying maladaptive pain-related learning and memory processes remain incompletely understood, particularly in the context of interoceptive, visceral pain. Inflammation is known to interfere with learning and memory, but its effects on the extinction of pain-related fear memories have never been tested. In a randomized, double-blind, placebo-controlled study, we assessed the impact of experimental acute inflammation on the extinction and reinstatement of conditioned visceral pain-related fear. Forty healthy male volunteers underwent differential fear conditioning with visceral pain as clinically relevant unconditioned stimulus (US). Participants then received an intravenous injection of either 0.8 ng/kg lipopolysaccharide (LPS) as inflammatory stimulus or physiological saline as placebo, and extinction training was conducted at the peak of the inflammatory response. Extinction recall and reinstatement test were performed after overnight consolidation. Results showed that visceral pain represents an effective US, eliciting pronounced conditioned pain-related fear responses. Repeated unreinforced presentation of the pain-predictive cue during extinction training resulted in full extinction of the conditioned behavioral response. However, unexpected re-exposure to the US during reinstatement test resulted in return of fear. Despite pronounced LPS-induced effects on inflammatory markers, cortisol, and negative affect, we did not find evidence that acute inflammation resulted in altered fear extinction. The findings support the notion that visceral pain-related fear learning establishes a robust aversive memory trace that remains preserved during inhibitory learning, leaving a latent vulnerability for the return of fear. Inflammation during inhibitory learning did neither weaken nor further amplify this aversive memory trace, suggesting that it is rather resistant to acute inflammation-induced effects, at least in healthy individuals with no additional vulnerability factors. [ABSTRACT FROM AUTHOR]

• Effect of lifelong omega-3 deficiency on sleep in physiology and under inflammation. • Omega-3 deficiency affects the architecture of sleep-wake activity. • Omega-3 deficiency decreases the amplitude of delta oscillations during NREM sleep. • Omega-3 deficiency affects the REM sleep response to an acute inflammatory challenge. Essential polyunsaturated fatty acids (PUFA) from the n-3 and n-6 series constitute the building blocks of brain cell membranes where they regulate most aspects of cell physiology. They are either biosynthesized from their dietary precursors or can be directly sourced from the diet. An overall increase in the dietary n-6/n-3 PUFA ratio, as observed in the Western diet, leads to reduced n-3 PUFAs in tissues that include the brain. Some clinical studies have shown a positive correlation between dietary n-3 PUFA intake and sleep quantity, yet evidence is still sparse. We here used a preclinical model of dietary n-3 PUFA deficiency to assess the precise relationship between dietary PUFA intake and sleep/wake activity. Using electroencephalography (EEG)/electromyography (EMG) recordings on n-3 PUFA deficient or sufficient mice, we showed that dietary PUFA deficiency affects the architecture of sleep-wake activity and the oscillatory activity of cortical neurons during sleep. In a second part of the study, and since PUFAs are a potent modulator of inflammation, we assessed the effect of dietary n-3 PUFA deficiency on the sleep response to an inflammatory stimulus known to modulate sleep/wake activity. We injected mice with the endotoxin lipopolysaccharide (LPS) and quantified the sleep response across the following 12 h. Our results revealed that n-3 PUFA deficiency affects the sleep response in basal condition and after a peripheral immune challenge. More studies are now required aimed at deciphering the molecular mechanisms underlying the intimate relationship between n-3 PUFAs and sleep/wake activity. [ABSTRACT FROM AUTHOR]

Fear renewal is defined as return of the conditioned fear responses after extinction when a conditioned stimulus (CS) is given outside of the extinction context. Previously, we have suggested that extinction induces S-nitrosylation of GluA1 in the lateral amygdala (LA), and that the extinction-induced S-nitrosylation of GluA1 lowers the threshold of GluA1 phosphorylation (at Ser 831) which is required for fear renewal. This fits nicely with the fact that fear renewal is induced by weak stimuli. However, it has not been tested whether S-nitrosylation of GluA1 in the LA is indeed required for fear renewal. In the present study, we used three different chemicals to impede protein S-nitrosylation via distinct mechanisms. Fear renewal was inhibited by microinjection of 7-Nitroindazole (nNOS inhibitor), and ZL006 (a blocker of PSD-95-nNOS interaction) before fear renewal. Furthermore, fear renewal was also attenuated by microinjection of a strong antioxidant (N-acetyl cysteine), which scavenges reactive oxygen including nitric oxide, into the LA before each extinction training. These findings suggest that protein S-nitrosylation is required for fear renewal. • Inhibition of nNOS in the LA attenuated fear renewal. • Disruption of PSD-95-nNOS interaction in the LA inhibited fear renewal. • NO scavenging in the LA during extinction inhibited subsequent fear renewal. [ABSTRACT FROM AUTHOR]

Autophagy is dependent on appropriate lipid supply for autophagosome formation. The regulation of lipid acquisition and the autophagy network response to lipid-limiting conditions are mostly elusive. Here, we show that the knockout of the RAB GTPase RAB18 interferes with lipid droplet catabolism, causing an impaired fatty acid release. The resulting reduced lipid-droplet-derived lipid availability influences autophagy and provokes adaptive modifications of the autophagy network. These adjustments include increased expression and phosphorylation of ATG2B as well as augmented formation of the ATG12-ATG5 conjugate. Moreover, ATG9A shows an enhanced phosphorylation at amino acid residues tyrosine 8 and serine 14, resulting in an increased ATG9A trafficking. Via pharmacological inhibition of Y8 phosphorylation, we demonstrate that this ATG9A modification is important to maintain basal autophagy under RAB18 knockout conditions. However, while the network adaptations are sufficient to maintain basal autophagic activity, they are incapable of ensuring autophagy induction upon starvation, which is characterized by an enhanced lipid demand. Thus, here, we define the molecular role of RAB18 in connecting lipid droplets and autophagy, emphasize the significance of lipid droplets as lipid sources for the degradative pathway, and uncover a remarkable autophagy network plasticity, including phosphorylation-dependent ATG9A activation, to compensate reduced lipid availability in order to rescue basal autophagic activity. Image 1 • The knockout of RAB18 impedes lipid droplet catabolism. • Insufficient LD-derived lipid availability affects autophagy. • The autophagy network adapts to maintain autophagic activity. • Prominent adaptations include enhanced ATG9A phosphorylation. • Increased ATG9A trafficking rescues basal autophagy under lipid-limiting conditions. [ABSTRACT FROM AUTHOR]

Dimethylarginine dimethylamino hydrolase-1 (DDAH-1) as an indirect regulator of nitric oxide (NO) metabolism, its role in hypoxic preconditioning (HPC) and ischemic tolerance (IT) of ischemic stroke has still been unknown and needs to be elucidated. Herein, DDAH-1 knock-out (KO) and wild-type (WT) rats underwent HPC and middle cerebral artery occlusion/reperfusion (MCAO/R) model. After 24 h, neurological severity scores, TTC staining and TUNEL assay were used to evaluate neurological damages. To explore the mechanism, the expression of hypoxia inducible factor (HIF-1α) and its target genes were assessed by Western blot and RT-qPCR. NO and ADMA contents were also tested. In addition, supplementation of l -arginine to DDAH-1 KO rats was used to explore the role of DDAH-1 in regulating NO. After HPC the ischemic outcome improved in both KO and WT rats, while KO rats showed attenuated IT exhibiting less expression of HIF-1α and its target genes, lower NO but higher ADMA content. The supplement of l -arginine to KO rats partly alleviated neurological damages accompanied with higher expression of HIF-1α. To sum up, DDAH-1 could regulate the level of NO and enhance IT following HPC and MCAO model via activating the expression of HIF-1α and its target genes. • DDAH-1 gene deletion alleviated cerebral ischemic tolerance after hypoxic preconditioning and MCAO/R model. • DDAH-1 gene deletion alleviated the activation of HIF-1α and its target genes in hypoxic preconditioning. • DDAH-1 gene deletion down-regulated the level of NO in hypoxic preconditioning. • DDAH-1 may enhance ischemic tolerance by regulating the level of NO. [ABSTRACT FROM AUTHOR]

As molecular chaperones, heat shock proteins (HSPs) play essential roles in cells in response to stress conditions. Recent studies about immune functions of HSPs in fish have also been reported. In this study, based on the reported cDNA sequences of the four HSP genes, HSP70, HSC70, HSP90α and HSP90β, the temporal expression patterns of the four genes during embryonic development of dojo loach(Misgurnus anguillicaudatus) was assayed with qRT-PCR. All of the four genes were ubiquitously expressed in all detected embryonic developmental stages. Among of them, HSP70, HSC70 and HSP90β were highly expressed in the organ formation stage, while HSP90α was the highest expressed in myotome formation stage. Further, the immune responses of the four HSP genes were assayed when loach were infected with three different pathogens, bacterium (Flavobacterium cloumnare G4), parasite (Ichthyophthirius multifiliis) and fungus (Saprolegnia). All of the four genes were differentially expressed in four tissues such as skin, gills, spleen and kidney in response to the pathogenic invasion, but both HSP70 and HSP90α expressions were dramatically up-regulated. Further, the cellular responses of the loach skinand gill tissues were observed, in which the number of the skin goblet cells were significantly increased, and the gill lamellae became shorter and wider after infected. Thus, our work indicated that the HSPs may directly or indirectly involved in immune defense in fish, at least in the loach. • The expression patterns of HSP70, HSC70, HSP90α and HSP90β in different embryonic development stages of loach were analyzed. • The HSP proteins exhibited deferentially expressed in response to the different pathogenic invasion of loach. • Our work indicated that the HSPs may directly or indirectly involved in immune defense in fish, at least in the loach. [ABSTRACT FROM AUTHOR]

Social learning about predation threat during early ontogeny can be beneficial in developing appropriate antipredator behaviours. While such learning can be achieved through direct interactions between offspring and parents, it is unknown whether young animals can also learn appropriate responses towards different heterospecifics posing different levels of threat through inadvertent information obtained from witnessing parental interactions with these heterospecifics. In this study, we split sibling groups of the cooperatively breeding cichlid Neolamprologus pulcher and raised them with or without parents. Both rearing groups repeatedly received visual and olfactory cues from four types of fish (predators, egg predators, herbivores and conspecifics) during a 4-week experience phase. After a 'neutral phase' of 4 months under identical conditions and without further fish stimuli, individuals from both rearing conditions were tested for their response towards the same four stimulus species. Unlike those reared with parents, the fish reared without parents spent significantly more time in safety and were more vigilant towards the predator, whereas responses to the other three species did not differ. As during the experience phase parental responses towards the stimulus fish were unexpectedly low and indiscriminate, our results suggest that young N. pulcher reverse their innate fear of predators when observing parents being unresponsive to a threat ('observational conditioning'). We suggest that learned reduction of fear can be a potent mechanism to prevent responding to false alarms and mitigate potentially harmful effects of chronically elevated predation stress. • We studied social learning of antipredator behaviour by offspring in a cichlid. • Indiscriminate parental response towards different species reduces innate fear. • Lack of experience of parental response preserves innate fear. • Conditional learning can help mitigate effects of chronic predation stress. [ABSTRACT FROM AUTHOR]

Hippocampal SIRT1 dysfunction and gene variation have previously been found potentially involved in depressive and anxiety disorders. However, the exact role of SIRT1 in post-traumatic stress disorder (PTSD) is not well understood. Here, we employed multiple genetic and pharmacological approaches targeting SIRT1 to verify the effects of SIRT1 on SPS-induced PTSD-like behaviors and its potential cellular and molecular mechanisms. We first demonstrated that Sirt1 knockout mice showed milder PTSD-like behavior after single prolonged stress (SPS) induction than wild type mice. Moreover, the expression of SIRT1 in the ventral CA1 (vCA1) region of hippocampus showed no significant changes following SPS induction, but the activity of SIRT1 enzyme was significantly increased post-SPS. Osmotic administration of EX527 in vCA1, a SIRT1 inhibitor, was shown to normalize the SIRT1 activity in SPS mice. Mechanically, EX527 rescued the acetylation of helix-loop-helix transcription factor 2 (NHLH2) and transcriptionally inhibited the increase of MAO-A expression in the vCA1, which thus suppressed the decomposition of the neurotransmitter serotonin into 5-hydroxydoleacetic acid (5-HIAA). Morphologically, Golgi staining showed that EX527 treatment improved the abnormal neuronal structure plasticity in the vCA1 region after SPS, including reversing the atrophic dendrites and the decreased dendritic spines. Finally, SIRT1 inhibitor effectively alleviated fear conditioning responses and anxiety-like behaviors. Our study first demonstrated that the development of PTSD-like behaviors was causatively related to the abnormal increase of SIRT1 activity in the ventral hippocampal CA1 region. And we also provided evidence that SIRT1 inhibition might exert therapeutic effects on PTSD by maintaining serotonin homeostasis through transcriptional inhibition of MAO-A, and thereby remodeled synaptic plasticity in the vCA1 region. • Sirt1 deletion increased resistance to PTSD-like stress stimuli in mice. • SIRT1 activity in ventral CA1 was negatively involved with PTSD. • EX527 protected 5-HT homeostasis in ventral CA1 of PTSD mice via inhibiting MAO-A. • EX527 remodeled synaptic plasticity in the ventral CA1 of PTSD mice. • SIRT1 inhibition alleviated PTSD symptoms in mice. [ABSTRACT FROM AUTHOR]

The auditory cortex is sensitive to many forms of acoustic regularity, resulting in suppressed neural activity for expected auditory events. It is unclear whether this activity reduction for expected events is the result of suppression of neurons that are tuned to the expected stimulus (i.e., dampening), or alternatively suppression of neurons that are tuned away from the expected stimulus (i.e., sharpening). In the present study, we adjudicated between these models by characterizing the effect of expectation on the ability to classify the identity of auditory stimuli from auditory neural activity patterns, using magnetoencephalography (MEG) in healthy human observers. Participants listened to pure tone pairs, in which the identity of the second tone was either expected or unexpected. The task of the participants was to detect a target tone, which deviated strongly from both the expected and unexpected tones. We found a strong suppression of the overall neural response in the expected condition compared to the unexpected condition. Linear classifiers showed a reduced ability to decode stimulus identity from event-related auditory fields in the expected condition compared to the unexpected condition. This suggests that stimulus-specific event-related activity is dampened for expected tones in auditory cortex. [ABSTRACT FROM AUTHOR]

Pre-grafting conditioning is a crucial procedure before transplant surgery during pearl production. To investigate the molecular response of the pearl oyster Pinctada fucata martensii to conditioning, we constructed two hemocyte transcriptomes from pearl oysters with and without conditioning. A total of 134,222,686 raw reads were generated and assembled using the reference genome of the pearl oyster. Transcriptome analysis revealed 3,074 differentially expressed genes (DEGs). Gene ontology and pathway enrichment analyses revealed that these DEGs were mainly associated with "microtubule-based process", "regulation of actin cytoskeleton", and "cell cycle". All related genes were over-expressed in pearl oysters after conditioning. Some nucleotide-binding oligomerization domain-like receptors (NLR), toll-like receptor, myd88, proinflammatory cytokine interleukin-17 (IL-17), and apoptosis-related genes were highly expressed in pearl oysters after conditioning, indicating that conditioning induced the immune response of pearl oysters. "Fatty acid biosynthesis" (FA biosynthesis) was included in the enriched terms, and all eight FA synthase genes in this pathway were highly induced after conditioning. Four tandemly duplicated arginine kinase genes (PmAK) were found in the genome of P. f. martensii , gene structure and sequence analysis indicated PmAK genes were more diverse compared with that from human and zebra fish. The four tandemly duplicated PmAKs were highly up-regulated after conditioning. These findings will help to elucidate the responding molecular events after conditioning and explain the high pearl oyster survival rate with conditioning after transplantation, thereby providing useful information in perfecting the conditioning method to improve pearl oyster survival rate after transplantation. • Immune response was induced after pre-grafting conditioning. • Fatty acid biosynthesis were involved in the response to conditioning. • Four tandemly duplicated AK were found in the genome of P. f. martensii. • AK was functional in the energy production after conditioning. [ABSTRACT FROM AUTHOR]

Strong turbulence in temperate shelves during winter months enhances the vertical mixing of the water column, consequently pumps up nutrients and induces high turbidity in the upper ocean. Thus, light availability often becomes an important factor to impact phytoplankton biomasses and their spatial patterns in winter. To quantitatively assess the effect of light availability on the spatial pattern of phytoplankton in the Yellow Sea in winter, we used vertical average irradiance (I m) as a light index which denotes the average irradiance received by phytoplankton during their vertical motion, and then analyzed the spatial correlation between winter climatological I m and chlorophyll-a (Chl-a). The result from a set of high-resolution satellite-derived climatological data (2003–2016) demonstrated that there is a significantly positive correlation (R = 0.71, p < 0.0001) between Chl-a and I m in space. The observational data of 2016 winter further showed that I m is much more important in determining the spatial pattern of Chl-a concentrations than nutrients, due to the availability of sufficient nutrients but very limited light availability for almost the entire sea area. Relatively high Chl-a regions (>1 mg/m3) are in response to an environmental condition of I m > 50 μmol photons/m2/s, total suspended matter concentration (TSM) < 10 mg/L, and mixed layer depth (MLD) < 40 m. In coastal waters, TSM is the key factor to cause low I m ; while MLD is more important in deep offshore waters to determine the I m values. 1. Strong spatial correlation between winter Chl-a and I m exists in the Yellow Sea. 2. PCA analysis on field observed data confirms the dominating role of I m in Chl-a. 3. Winter sufficient nutrients but limited light lead to the critical role of I m. [ABSTRACT FROM AUTHOR]

• Reduced spatial learning ability in female, but not male Tg26(+/−) mice. • Short-term and long-term memory deficits in male Tg26(+/−) mice. • Short-term, but not long-term memory deficits in female Tg26(+/−) mice. • Sex-specific adult neurogenic impairments in Tg26(+/−) mice. Varying degrees of cognitive deficits affect over half of all HIV-1 infected patients. Because of antiretroviral treatment (ART) regimens, the HIV-1 patient population is increasing in age. Very few epidemiological studies have focused on sex-specific differences in HIV-1-associated neurocognitive disorders (HAND). The purpose of this study is to examine any possible differences between male and female mice in the progression of cognitive dementia during persistent low-level HIV-1 protein exposure, mimicking the typical clinical setting in the post-ART era. Eight to ten-month old HIV-1 Tg26(+/−) transgenic mice were utilized to assess for specific learning and memory modalities. Initial physiological screening and fear conditioning assessments revealed that Tg26 mice exhibited no significant differences in general behavioral function, contextual fear conditioning, or cued fear conditioning responses when compared to their wild-type (WT) littermates, regardless of sex. However, Barnes maze testing revealed significantly impaired short and long-term spatial memory in males, while females had impaired spatial learning abilities and short-term spatial memory. The potential cellular mechanism underlying these sex-specific neurocognitive deficits was explored with hippocampal neurogenic analysis. Compared to WT mice, both male and female Tg26(+/−) mice had fewer quiescent neural stem cells and neuroblasts in their hippocampi. Male Tg26(+/−) mice had a more robust reduction of the quiescent neural stem cell pool than female Tg26(+/−) mice. While female WT mice had a higher number of neural progenitor cells than male WT mice, only female Tg26(+/−) mice exhibited a robust reduction in the number of neural progenitor cells. Altogether, these results suggest that middle-aged male and female Tg26(+/−) mice manifest differing impairments in cognitive functioning and hippocampal neurogenesis. This study emphasizes the importance of understanding sex related differences in HAND pathology, which would aid in designing more optimized therapeutic regimens for the treatment of HAND. [ABSTRACT FROM AUTHOR]

Highlights • An enhanced sparse regularization method is developed for improving impact force identification. • A weighted l 1 -norm convex optimization model for impact force identification is developed. • Iteratively reweighted l 1 -norm minimization algorithm is proposed for solving impact force identification. • Compared with existing regularizations, the enhanced sparse regularization has much sparser and more accurate result. Abstract The standard sparse regularization method based on l 1 -norm minimization for impact force identification has already proved to be an interesting alternative to the classical regularization method based on l 2 -norm minimization. However, choosing the l 1 -norm as a convex relaxation of the l 0 -norm, the corresponding sparse regularization model generally offers a sparse but underestimated solution. In this paper, considering the sparsity of impact force, an enhanced sparse regularization method based on reweighted l 1 -norm minimization is developed for reducing the peak force error and improving the identification accuracy of impact force. First, a weighted l 1 -norm convex optimization model is presented to overcome the ill-posed nature of the inverse problem of impact force identification. Second, to solve such a regularized model efficiently, an iteratively reweighted l 1 -norm minimization algorithm is introduced, where the weights are adaptively updated from the previous solution. The application of the iteratively reweighted scheme is to overcome the mismatch between l 1 -norm minimization and l 0 -norm minimization, while keeping the enhanced sparse regularization problem solvable and convex. Finally, numerical simulation and experimental verification including the single and double impact force identification on a plate structure are presented to illustrate the superior performance of the enhanced sparse regularization method compared to classical regularization approaches. Effects of reweighting iteration number, tuning parameters, initial conditions and response locations are successfully investigated in detail. Results demonstrate that compared with the standard l 1 -norm regularization method and the classical l 2 -norm regularization method, the enhanced sparse regularization method based on reweighted l 1 -norm minimization whose solution is much sparser, can greatly improve the identification accuracy of impact force. Moreover, the proposed method is much more robust to the choice of tuning parameters and noisy measurements. [ABSTRACT FROM AUTHOR]

Understanding how animals learn is crucial to interpreting animal behaviour. Flower-visiting insects, such as bees and parasitoids, are excellent animal models to study visual and olfactory learning, including memory phenomena. The diversity of resources flower-visiting insects exploit predisposes them to learn and remember the colours, shapes and odours associated with rewarding experiences (e.g. flowers), allowing them to focus on the most rewarding resources. Recent research has shown that nectar-living microbes release volatile organic compounds (VOCs) that contribute to overall flower scent. Nevertheless, little is known about the extent to which nectar microbiota mediate insect learning of floral preferences. In this study, we investigated whether VOCs produced by nectar microbes serve as a learning cue to parasitoids and how long any developed preference is maintained. Experiments were performed using the generalist aphid parasitoid Aphidius ervi and three nectar yeasts, including the nectar specialist Metschnikowia reukaufii and the generalist species Hanseniaspora uvarum and Sporobolomyces roseus. Results showed that naïve parasitoids had an innate preference for nectar fermented by the nectar specialist M. reukaufii , but not by the other two yeasts which had either a neutral (H. uvarum) or deterrent (S. roseus) effect. When parasitoids were conditioned with yeast-fermented nectar, they were strongly attracted to their odours 2 and 24 h after conditioning, but not after 48 h. Furthermore, when parasitoids were conditioned to one yeast-fermented nectar, they also showed increased attraction to other yeast-fermented nectars. This generalization suggests that their learning ability may have broader ecological consequences. However, this generalized response to other yeast VOCs lasted for only 2 h. We conclude that parasitoids show conditioned responses to the scent of yeast-fermented nectar, and yeasts, therefore, may play an important but understudied role in shaping their foraging behaviour. • Aphidius ervi has an innate preference for nectar fermented by specialist yeasts. • Nectar foraging can be optimized by associative learning of nectar yeast VOCs. • Trained A. ervi respond to conditioned yeast VOCs at 2 and 24 h after conditioning. • Conditioned responses can be generalized to odours different from the training odour. [ABSTRACT FROM AUTHOR]

The present work examines whether the variability of attitude objects at attitude acquisition increases the generalization of likes and dislikes. In particular, variability might enhance the discriminative learning of cues, resulting in attitudes towards abstract entities rather than concrete instances. Using evaluative conditioning as an experimental paradigm to study attitude acquisition, we manipulated the variability of conditioned stimuli (CSs) that were paired with unconditioned stimuli (USs) of negative or positive valence. CSs resembled Chinese characters that could be grouped into categories by one common component. In the invariable condition, one item per category served as CSs. In the variable condition, multiple items per category were used as CSs. We measured participants' evaluations of the CSs and novel Chinese characters (generalization stimuli), and included a recognition memory task and evaluative measures of CS components. As compared to the invariable condition, the learning condition that introduced variability among CSs facilitated generalization towards novel stimuli, diminished recognition memory performance, and produced evaluative ratings of CS components that were more extreme for common components. The findings suggest the formation of attitudes towards abstract cues rather than concrete instances in the variable relative to the invariable condition, and propose that high variability facilitates the generalization of likes and dislikes. We discuss mechanistic explanations as well as practical implications with regard to the formation of prejudice and intergroup biases. [ABSTRACT FROM AUTHOR]

The circadian clock mechanism, which is evolutionarily conserved across various organisms, plays a crucial role in synchronizing physiological responses to external conditions, primarily in response to light availability. By maintaining homeostasis of biological processes and behavior, the circadian clock serves as a key regulator. This biological mechanism also coordinates diurnal oscillations of the immune response during infections. However there is limited information available regarding the influence of circadian oscillation on immune regulation, especially in lower vertebrates like teleost fish. Therefore, the present study aimed to investigate the effects of light and the timing of infection induction on the antiviral immune response in zebrafish. To explore the relationship between the timing of infection and the response activated by viral pathogens, we used a zebrafish model infected with tilapia lake virus (TiLV). Our findings demonstrated that light availability significantly affects the antiviral immune response and the functioning of the molecular clock mechanism during TiLV infection. This is evident through alterations in the expression of major core clock genes and the regulation of TiLV replication and type I IFN pathway genes in the kidney of fish maintained under LD (light-dark) conditions compared to constant darkness (DD) conditions. Moreover, infection induced during the light phase of the LD cycle, in contrast to nocturnal infection, also exhibited similar effects on the expression of genes associated with the antiviral response. This study indicates a more effective mechanism of the zebrafish antiviral response during light exposure, which inherently involves modification of the expression of key components of the molecular circadian clock. It suggests that the zebrafish antiviral response to infection is regulated by both light and the circadian clock. • Light conditions regulate clock genes expression in the brain and kidney. • Disruption of the day/night rhythm deregulate the functioning of the feedback loops. • Light enhances the antiviral immune response. • Rhythmicity of the clock genes is independent of the time of infection. [ABSTRACT FROM AUTHOR]

• Pavlovian learning can induce sign-tracking or goal-tracking responses. • Sign-tracking is reduced by reward devaluation, while goal-tracking is not. • Goal-tracking can be blocked by a competing cue, but sign-tracking resists blocking. • Thus some types of learning are sensitive to reward value; others predictive value. When a neutral stimulus is repeatedly paired with an appetitive reward, two different types of conditioned approach responses may develop: a sign-tracking response directed toward the neutral cue, or a goal-tracking response directed toward the location of impending reward delivery. Sign-tracking responses have been postulated to result from attribution of incentive value to conditioned cues, while goal-tracking reflects the assignment of only predictive value to the cue. We therefore hypothesized that sign-tracking rats would be more sensitive to manipulations of incentive value, while goal-tracking rats would be more responsive to changes in the predictive value of the cue. We tested sign- and goal-tracking before and after devaluation of a food reward using lithium chloride, and tested whether either response could be learned under negative contingency conditions that precluded any serendipitous reinforcement of the behavior that might support instrumental learning. We also tested the effects of blocking the predictive value of a cue using simultaneous presentation of a pre-conditioned cue. We found that sign-tracking was sensitive to outcome devaluation, while goal-tracking was not. We also confirmed that both responses are Pavlovian because they can be learned under negative contingency conditions. Goal-tracking was almost completely blocked by a pre-conditioned cue, while sign-tracking was much less sensitive to such interference. These results indicate that sign- and goal-tracking may follow different rules of reinforcement learning and suggest a need to revise current models of associative learning to account for these differences. [ABSTRACT FROM AUTHOR]

The brain-derived neurotrophic factor (BDNF) Val66Met polymorphism is associated with reduced activity-dependent BDNF release in the brain and has been implicated in fear and anxiety disorders, including post-traumatic stress disorder. Exercise has been shown to have benefits in affective disorders but the role of BDNF Val66Met remains unclear. Male and female BDNF Val66Met rats were housed in automated running-wheel cages from weaning while controls were housed in standard cages. During adulthood, all rats underwent standard three-day fear conditioning testing, with three tone/shock pairings on day 1 (acquisition), and extinction learning and memory (40 tones/session) on day 2 and day 3. Expression of BDNF and stress-related genes were measured in the frontal cortex. Extinction testing on day 2 revealed significantly lower freezing in response to initial cue exposure in control Met/Met rats, reflecting impaired fear memory. This deficit was reversed in both male and female Met/Met rats exposed to exercise. There were no genotype effects on acquisition or extinction of fear, however chronic exercise increased freezing in all groups at every stage of testing. Exercise furthermore led to increased expression of Bdnf in the prefrontal cortex of females and its isoforms in both sexes, as well as increased expression of FK506 binding protein 51 (Fkpb5) in females and decreased expression of Serum/glucocorticoid-regulated kinase (Sgk1) in males independent of genotype. These results show that the Met/Met genotype of the Val66Met polymorphism affects fear memory, and that chronic exercise selectively reverses this genotype effect. Chronic exercise also led to an overall increase in freezing in all genotypes which may contribute to results. [ABSTRACT FROM AUTHOR]

• Blockade of octopaminergic transmission impairs conditioning and execution of a conditioned response (CR) in cockroaches. • Blockade of octopaminergic (OAergic) transmission in the vertical lobes of the mushroom body impairs execution of the CR. • The roles of OA neurons in conditioning and execution of the CR in cockroaches are analogous to those of midbrain dopamine neurons in mammals. Aminergic neurons mediate reward signals in mammals and insects. In crickets, we showed that blockade of synaptic transmission from octopamine neurons (OANs) impairs conditioning of an odor (conditioned stimulus, CS) with water or sucrose (unconditioned stimulus, US) and execution of a conditioned response (CR) to the CS. It has not yet been established, however, whether findings in crickets can be applied to other species of insects. In this study, we investigated the roles of OANs in conditioning of salivation, monitored by activities of salivary neurons, and in execution of the CR in cockroaches (Periplaneta americana). We showed that injection of epinastine (an OA receptor antagonist) into the head hemolymph impaired both conditioning and execution of the CR, in accordance with findings in crickets. Moreover, local injection of epinastine into the vertical lobes of the mushroom body (MB), the center for associative learning and control of the CR, impaired execution of the CR, whereas injection of epinastine into the calyces of the MB or the antennal lobes (primary olfactory centers) did not. We propose that OANs in the MB vertical lobes play critical roles in the execution of the CR in cockroaches. This is analogous to the fact that midbrain dopamine neurons govern execution of learned actions in mammals. [ABSTRACT FROM AUTHOR]

The contextual fear conditioning (CFC) paradigm is the most productive approach for understanding the neurobiology of learning and memory as it allows to follow the evolution of memory trace s of a conditioned stimulus and a specific context. The formation of long-term memory involves alterations in synaptic efficacy and neural transmission. It is known that the prefrontal cortex (PFC) exerts top-down control over subcortical structures to regulate behavioural responses. Moreover, cerebellar structures are involved in storing conditioned responses. The purpose of this research was to determine if the response to conditioning and stressful challenge is associated with alterations in synapse-related genes mRNA levels in the PFC, cerebellar vermis (V), and hemispheres (H) of young adult male rats. Four groups of Wistar rats were examined: naïve, CFC, shock only (SO), and exploration (EXPL). The behavioural response was evaluated by measuring the total freezing duration. Real-Time PCR was employed to quantify mRNA levels of some genes involved in synaptic plasticity. The results obtained from this study showed alterations in gene expression in different synapse-related genes after exposure to stressful stimuli and positioning to new environment. In conclusion, conditioning behavioural stimuli change the expression profile of molecules involved in neural transmission. [ABSTRACT FROM AUTHOR]

• Neural substrates of conditioned inhibition and other inhibitory discriminations. • Inhibitors signal safety for aversive outcomes, frustration for appetitive outcomes. • Neural substrates include mesocorticolimbic, retrosplenial cortex and hippocampus. • Further neural substrates relate to task motivation and modality of learning cues. • Translational implications of inhibitory learning extend beyond anxiety disorders. Inhibitory associative learning counters the effects of excitatory learning, whether appetitively or aversively motivated. Moreover, the affective responses accompanying the inhibitory associations are of opponent valence to the excitatory conditioned responses. Inhibitors for negative aversive outcomes (e.g. shock) signal safety, while inhibitors for appetitive outcomes (e.g. food reward) elicit frustration and/or disappointment. This raises the question as to whether studies using appetitive and aversive conditioning procedures should demonstrate the same neural substrates for inhibitory learning. We review the neural substrates of appetitive and aversive inhibitory learning as measured in different procedural variants and in the context of the underpinning excitatory conditioning on which it depends. The mesocorticolimbic dopamine pathways, retrosplenial cortex and hippocampus are consistently implicated in inhibitory learning. Further neural substrates identified in some procedural variants may be related to the specific motivation of the learning task and modalities of the learning cues. Finally, we consider the translational implications of our understanding of the neural substrates of inhibitory learning, for obesity and addictions as well as for anxiety disorders. [ABSTRACT FROM AUTHOR]

Holistic ecosystem health indices are urgently needed for conserving and managing rapidly dwindling mangrove ecosystems. The appropriate indices should provide consistent outcomes that enable both the assessment of current conditions and assist future planning. The previous approaches mostly focus on the structural condition of trees, with mangrove ecosystems often treated as terrestrial forests. Structural features are too insensitive as representatives of negative internal creeping changes. Some unique mangrove ecosystem attributes can react to anthropogenic pressures much faster than tree or forest structures do, making them more useful as early warning indicators. The development of holistic indicators requires a multidimensional approach engaging specific functions and services underpinning the characteristics of mangrove ecosystems. We present an approach to identify potential variables ranging from assemblage structure to physiological and biochemical variables for reliably indicating mangrove condition. These indicators could then be tested against a range of ecosystem conditions (e.g. disturbance levels) to reveal their response to different degrees of pressures. These variables were first nominated based on the driver-response model relating changes in environmental conditions and ecosystem responses. The nominated variables were then prioritised through an expert questionnaire survey, in which the experts scored every nominated variable on the efficiency, the number of pertinent ecosystem services and the time required them to reflect the impact of the pressure. Sediment properties and elements of forest structure featured strongly in the survey, followed by variables pertaining to biomass, vegetation status and carbon cycling. With respect to community composition, components of the higher trophic levels (e.g. crabs, other macrofauna) were ranked higher by the experts. The mangrove-tree-related variables (e.g. Importance Value Index, IVI), associated biotic components of insects, annelids and moss were ranked lowest. These results provide the basis for establishing a specific framework for mangrove ecosystem assessment. [ABSTRACT FROM AUTHOR]

Abstract In the present study, the effects of mild air oxidation of a biochar produced by the Pyrovac Inc. pyrolysis process, on the adsorption of lead(II) from synthetic wastewater under batch experimental conditions have been investigated. The adsorption experiments were performed under several conditions suggested by the response surface methodology, which allowed finding the optimal conditions, in order to maximize the adsorption capacity (Q (mg g − 1 )) , as well as the extraction efficiency (E (%)). The optimal conditions of lead ions adsorption were as follows: pH = 5, agitation time = 300 min, adsorbent mass = 0.5 g (per 50 cm3 of solution), and lead initial concentration = 100 g m − 3 , resulted in an adsorption capacity of 7.9 mg g−1. Equilibrium adsorption was then obtained by keeping pH and adsorbent mass at the optimal values and changing the lead initial concentration for a sufficient agitation time. Results showed that mild air oxidation increased the equilibrium adsorption capacity of biochar from 2.5 to 44 mg g−1. Oxidized biochar after equilibrium adsorption was submitted to SEM/EDX and XPS analysis. From SEM it was found that lead particles were distributed heterogeneously after adsorption. From XPS analysis, it was revealed that the external surface of oxidized biochar particles becomes saturated for the initial point of equilibrium diagram, obtained at lead initial concentration of 100 g m − 3 , suggesting that for a higher concentration, the internal surfaces of particles participate in the cations adsorption. The participation of surface functional groups in the adsorption process showed that carbonyl, carboxylic, and aromatic rings of oxidized biochar were involved in the adsorption. This work suggests that the very simple process of mild air oxidation can be used instead of the usual costly chemical activation, in order to improve biochar cation exchange capacity. Graphical abstract Image 1 Highlights • Increasing biochar cation exchange capacity by using simple mild air oxidation. • Involvement of oxygen-containing functional groups in lead cations adsorption. • Correlating processing parameters with oxidized biochar adsorption capacity. [ABSTRACT FROM AUTHOR]

The mechanisms whereby autoreactive T cells escape peripheral tolerance establishing thus autoimmune diseases in humans remain an unresolved question. Here, we demonstrate that autoreactive polyfunctional CD8+ T cells recognizing self-antigens (i.e., vimentin, actin cytoplasmic 1, or non-muscle myosin heavy chain 9 epitopes) with high avidity, counter-regulate Tregs by killing them, in a consistent percentage of rheumatoid arthritis (RA) patients. Indeed, these CD8+ T cells express a phenotype and gene profile of effector (eff) cells and, upon antigen-specific activation, kill Tregs indirectly in an NKG2D-dependent bystander fashion in vitro. This data provides a mechanistic basis for the finding showing that AE-specific (CD107a+) CD8+ T killer cells correlate, directly with the disease activity score, and inversely with the percentage of activated Tregs, in both steady state and follow-up studies in vivo. In addition, multiplex immunofluorescence imaging analyses of inflamed synovial tissues in vivo show that a remarkable number of CD8+ T cells express granzyme-B and selectively contact FOXP3+ Tregs, some of which are in an apoptotic state, validating hence the possibility that CD8+ Teff cells can counteract neighboring Tregs within inflamed tissues, by killing them. Alternatively, the disease activity score of a different subset of patients is correlated with the expansion of a peculiar subpopulation of autoreactive low avidity, partially-activated (pa)CD8+ T cells that, despite they conserve the conventional naïve (N) phenotype, produce high levels of tumor necrosis factor (TNF)-α and exhibit a gene expression signature of a progressive activation state. Tregs directly correlate with the expansion of this autoreactive (low avidity) paCD8+ TN cell subset in vivo , and efficiently control their differentiation rather their proliferation in vitro. Interestingly, autoreactive high avidity CD8+ Teff cells or low avidity paCD8+ TN cells are significantly expanded in RA patients who would become non-responders or patients who would become responders to TNF-α inhibitor therapy, respectively. These data provide evidence of a previously undescribed role of such mechanisms in the progression and therapy of RA. • Autoreactive CD8+ TN or eff cells differently affect Tregs to their vantage in RA. • Autoreactive low avidity CD8+ TN cells producing TNF-α are sustained by Tregs. • Autoreactive high avidity CD8+ Teff cells resist Tregs by killing them. • These distinctive mechanisms condition the response to anti-TNF therapy. • They could contribute for designing innovative therapeutic strategies. [ABSTRACT FROM AUTHOR]

Three experiments were conducted to test the following hypothesis: the taste, smell, and sight of non-alcoholic beer (alcohol cue) will induce a conditioned response even when participants know that the beer is non-alcoholic. In Experiments 1A and 1B, the participants who drank beer at least once a month were divided into a non-alcoholic beer group and a water group. After being told that their beverage was alcohol-free, participants in the experiment group drank non-alcoholic beer, while those in the control group drank water. Subsequently, all participants completed a Go/No-Go task. In Experiment 1A, the change from baseline in false alarms did not significantly differ between the groups; however, in Experiment 1B, the change from baseline in false alarms was greater in the non-alcoholic beer group than in the water group. That is, an alcohol-like effect only occurred in Experiment 1B. A correlation analysis combining the results of Experiments 1A and 1B revealed a significant positive correlation between the change from baseline in false alarms and age (an estimate of beer intake experience) in the non-alcoholic beer group only. Then, to examine the effect of age on the results more precisely, an older sample (mean age, 50 years) was recruited for Experiment 2. Among the older participants, the change from baseline in false alarms was greater in the non-alcoholic beer group than in the water group. Taken together, the results suggest that non-alcoholic beer impairs inhibitory responses (i.e., produces a conditioned response) in older drinkers because these drinkers more strongly associate the alcohol conditioned stimulus with the unconditioned stimulus than do younger participants. [ABSTRACT FROM AUTHOR]

Graphical abstract Abstract Vortioxetine is a novel multimodal antidepressant approved in 2013 by the Food and Drug Administration and the European Medicines Agency for the treatment of major depressive disorder (MDD). It combines the modulation of serotonin receptors activity with the inhibition of serotonin transporter (SERT). In this study, we aim at establishing the effect of chronic vortioxetine treatment (5 mg/kg twice/daily) in modulating neuroplastic mechanisms as well as hypothalamic pituitary adrenal axis (HPA) activity under basal condition and in response to an acute challenge. We found that prolonged vortioxetine administration significantly increased total Bdnf expression in the dorsal and ventral hippocampus of adult male rats and affected the stress-induced modulation of the immediate early genes Arc and Zif268, mainly in the ventral sub-region. Moreover, we also found that, within this brain area, chronic drug treatment was able to modulate glucocorticoid responsiveness at genomic level by enhancing the translocation of the glucocorticoid receptor (GR) in the nuclear compartment in response to the acute stress. Interestingly, this effect was mirrored by the up-regulation of different GR responsive-genes. Taken together, our data suggest that repeated exposure to vortioxetine specifically targets the ventral hippocampus by improving the ability to cope with stressful conditions. Moreover, its ability to facilitate HPA axis function might provide an indication to use this drug in patients characterized by glucocorticoid resistance. [ABSTRACT FROM AUTHOR]

Abstract The contributions of the cerebral cortex to human balance control are clearly demonstrated by the profound impact of cortical lesions on the ability to maintain standing balance. The cerebral cortex is thought to regulate subcortical postural centers to maintain upright balance and posture under varying environmental conditions and task demands. However, the cortical mechanisms that support standing balance remain elusive. Here, we present an EEG-based analysis of cortical oscillatory dynamics during the preparation and execution of balance responses with distinct postural demands. In our experiment, participants responded to backward movements of the support surface either with one forward step or by keeping their feet in place. To challenge the postural control system, we applied participant-specific high accelerations of the support surface such that the postural demand was low for stepping responses and high for feet-in-place responses. We expected that postural demand modulated the power of intrinsic cortical oscillations. Independent component analysis and time-frequency domain statistics revealed stronger suppression of alpha (9–13 Hz) and low-gamma (31–34 Hz) rhythms in the supplementary motor area (SMA) when preparing for feet-in-place responses (i.e., high postural demand). Irrespective of the response condition, support-surface movements elicited broadband (3–17 Hz) power increase in the SMA and enhancement of the theta (3–7 Hz) rhythm in the anterior prefrontal cortex (PFC), anterior cingulate cortex (ACC), and bilateral sensorimotor cortices (M1/S1). Although the execution of reactive responses resulted in largely similar cortical dynamics, comparison between the bilateral M1/S1 showed that stepping responses corresponded with stronger suppression of the beta (13–17 Hz) rhythm in the M1/S1 contralateral to the support leg. Comparison between response conditions showed that feet-in-place responses corresponded with stronger enhancement of the theta (3–7 Hz) rhythm in the PFC. Our results provide novel insights into the cortical dynamics of SMA, PFC, and M1/S1 during the control of human balance. Highlights • We evaluated the cortical control of balance from EEG-derived source-level activity. • We compared two distinct reactive balance responses with different postural demands. • Stronger preparatory SMA activity corresponded with higher postural demand. • Midfrontal theta activity may signify instability detection and/or motor inhibition. • Lateralized M1/S1 beta rhythm suggests contributions to support side stabilization. [ABSTRACT FROM AUTHOR]