Conditioning Trials Research Articles

Lipopolysaccharide (LPS) attenuates the primary conditioning of lithium chloride (LiCl)-induced context aversion but not the secondary conditioning of context aversion or taste avoidance

A first-order association can be formed between toxin-induced nausea and a context, as well as nausea and a taste cue. However, comparatively little is understood about second-order associations. The present study examined if the bacterial endotoxin, LPS, could impair the first- and second-order conditioning of context aversion (anticipatory nausea paradigm) and subsequent conditioned taste avoidance (two-bottle task). Adult male Long Evans rats were treated with LiCl (127 mg/kg, intraperitoneal [i.p.]) or vehicle control (NaCl) and then exposed to a distinct context for 4 first-order conditioning trials. LPS (200 μg/kg, i.p.) or NaCl were administered 24 h after each trial. Seventy-two h after the final first-order conditioning trial, rats underwent 2 second-order conditioning trials where they were treated with 2% saccharin (i.p.) and then exposed to the same context. Twenty-four h after the final second-order conditioning trial, rats were tested in a two-bottle task (2 trials), where they were given a choice between water and a palatable 0.2% saccharin solution. LiCl-treated rats demonstrated a context aversion by the 3rd conditioning trial in the anticipatory nausea paradigm. Rats previously exposed to LiCl also displayed a conditioned taste avoidance of saccharin within the two-bottle task. LPS attenuated first-order context aversion but did not alter either second-order context aversion or conditioned taste avoidance in the two-bottle task. This study demonstrated that a secondary association formed within an aversive context could result in a conditioned taste avoidance. Further, LPS may be able to attenuate primary conditioning, but not secondary conditioning.

Movement of the stimulated finger in a Go/NoGo task enhances attention directed to that finger as evidenced by P300 amplitude modulation.

Somatosensory cues and the optimal allocation of attentional resources are critical for motor performance, but it is uncertain how movement of a body part modulates directed attention and the processing of somatosensory signals originating from that same body part. The current study measured motor reaction time (RT) and the P300 event-related potential during a required movement response to stimulation of the same body part in a Go/NoGo task under multiple response. In the Movement Condition, participants were instructed to extend their right index finger in response to mild electrical stimulation of the same finger (Go signal) or remain still when receiving electrical stimulation to the fifth right finger (NoGo signal). Movement RTs and P300 amplitudes and latencies were measured under varying Go signal 50% probabilities. In other trial blocks, participants were required to count Go signals but not respond with movement or to ignore all signals while engaged in an unrelated task. Mean RT in the Movement Condition was 234.5 ms. P300 response amplitudes at midline electrodes (Fz, Cz, Pz) were the largest in the Movement Condition. The P300 amplitude at parietal electrode site Pz was significantly greater during Movement Condition trials than during Count Condition trials. The increase in P300 amplitude during trials requiring movement of the same body part receiving somatosensory stimulation suggests that movement itself modulates the attentional resources allocated to that body part.

Energy efficiency, reproductive performance, and metabolic parameters of grazing Hereford heifers

Feed and energy efficiency have been topics of extensive research in recent years, with residual feed intake (RFI) being the preferred index to determine feed efficiency in beef cattle. Nevertheless, the biggest downside of RFI is that its measurement requires accurately determining individual feed intake, which leads to the need to carry out RFI trials in confinement conditions. In this context, residual heat production (RHP), defined as the difference between observed and predicted heat production, presents an alternative to determine efficiency in grazing conditions as it is independent of feed intake. This work aimed to evaluate the repeatability of RHP and study its relationship with metabolic, endocrine, and reproductive variables. Seventy-four Hereford heifers were used, and at the beginning of the experimental period, heifers were 18 ± 0.7-month-old and weighed on average 278 ± 26 kg. Heat production (HP) was determined at the beginning (March to May; fall) and at the end (September to November; spring) of the experiment using the heart rate-O2 pulse technique to classify heifers according with the residual heat production (RHP). Efficient heifers showed lower HP (P < 0.01), ME (P < 0.01), and DM intake (P < 0.01) without differences in retained energy (RE; only in spring). During fall, average daily gain (ADG) was not included in the estimated HP model; therefore, although, as in RFI, RHP should be independent of BW and ADG, a trend for greater ADG and RE was found for efficient when compared with inefficient heifers. Decreased maintenance requirements (NEm and MEm) as well as higher partial efficiency of use of consumed ME (k) were estimated for more efficient heifers (low RHP; HH), while efficient heifers showed an earlier luteal phase and a shorter service-conception interval and calved earlier in the season, probably associated to an earlier development of fat tissue. Excluding glucose, no major differences were found in the plasma metabolites between groups. However, high-efficiency animals showed positive correlations with cholesterol and negative ones with NEFA plasma concentrations during fall.

Differences in Absolute Neutrophil Count Eligibility Criteria of Pediatric Phase I and Phase I/II Oncology Clinical Trials According to Sponsorship

Introduction: Racial clinical trial enrollment disparities in oncology are well documented ( Pediatr Blood Cancer. 2020 10.1002/pbc.28296). Barriers to enrollment are multifactorial and include structural and clinical barriers like restrictive eligibility criteria ( Am Soc Clin Oncol Educ Book. 2016 10.1200/EDBK_156686). Many phase I/II oncology clinical trials have laboratory criteria such as a minimum threshold for absolute neutrophil count (ANC). The Common Terminology Criteria for Adverse Events (CTCAE) defines an ANC of less than 1500 cells/µL as the upper limit of a grade 2 toxicity ( J Clin Oncol. 2010 10.1200/JCO.2009.24.3881), and this has become the minimum eligibility threshold in many oncology trials ( J Clin Oncol. 2017 10.1200/JCO.2017.73.4186). Using a minimum ANC of 1500 cells/µL may contribute to further racial enrollment disparities due to the Duffy null phenotype, which has a prevalence of ~65% in Black/African American individuals ( PLoS Genet. 2011 10.1371/journal.pgen.1002108) and results in a lower number of circulating neutrophils compared to people without the Duffy null phenotype ( Blood. 2021 10.1182/blood.2020008600). Up to 23% of pediatric patients with the Duffy null phenotype have ANCs &amp;lt;1500 cells/µL ( Blood Adv. 2023 10.1182/bloodadvances.2022007680). A recent adult multiple myeloma study found that the most common reason for ineligibility among Black patients was failure to meet hematologic laboratory criteria ( Blood. 2023 10.1182/blood.2022018657). Less is known about eligibility criteria as a barrier to enrollment in the pediatric cancer population. We hypothesized industry-sponsored trials would have more restrictive eligibility criteria than non-industry-sponsored trials. To explore this further we describe ANC eligibility criteria of pediatric oncology phase I/II clinical trials according to sponsorship. Methods: We analyzed ANC eligibility criteria of interventional phase I and phase I/II oncology trials opened in the United States from January 2010 to May 2023 using the ClinicalTrials.gov registry. Trials that included pediatric participants only (up to age 18), pediatric and adolescent young adult participants (up to age 39), and adult studies that allowed pediatric participants were included. We excluded trials for non-malignant conditions and trials that did not report ANC eligibility criteria. ANC eligibility criteria were categorized as ≥1500 cells/µL and &amp;lt;1500 cells/µL. Trials were compared according to primary sponsorship (industry vs non-industry). Secondary objective was to describe language requirements explicitly mentioned for these trials. Distribution of trial characteristics were compared using Fisher's exact or Chi-squared tests. Logistic regression was used to evaluate potential changes in ANC criteria over time (in years), using ANC&amp;lt;1500 cells/µL as the reference group. Results: We identified 861 interventional trials that met our initial inclusion criteria. After review of the trials, 36 were excluded for enrolling participants with non-malignant diagnoses. Of the remaining 825 studies, 438 (53%) had ANC eligibility criteria reported. 89 (20%) studies were industry-sponsored (Table 1). Trial phase, age eligibility, diagnosis, and results reported differed statistically significantly by sponsor type. 76 (17%) studies required ANC ≥1500 cells/µL for enrollment. For industry sponsored trials, 26 (29%) required ANC ≥1500, while 50 (14%) non-industry sponsored trials required ANC ≥1500, with a risk ratio of 2.04 (95% CI 1.35-3.08, p=0.002) (Figure 1). Almost all studies (96%) did not explicitly state language requirements, and this did not vary by sponsor type. There was no significant change in odds of a trial requiring ANC ≥1500 cells/µL over time (odds ratio 1.05, 95% CI 0.98-1.12, p=0.138). Conclusion: A minority of trials (17%) required an ANC ≥1500 cells/µL for enrollment on a phase I or phase I/II interventional clinical oncology trial; however, industry-sponsored trials were twice as likely than non-industry trials to require this higher ANC threshold. Further studies are needed to investigate laboratory criteria as a possible reason for racial enrollment disparities in pediatric cancer trials.

Degrader progresses in clinical trials for skin conditions

Degrader progresses in clinical trials for skin conditions

Investigating the agreement between force platform and plantar pressure insole data in barefoot and skating-specific footwear conditions across four different movement patterns

Conducting applied sport research in real-world settings is challenged by the lack of portable instrumentation capable of producing valid and reliable data that is collected without interfering with the athletes’ movement and is meaningful to sport performance. The purpose of this study was to compare and contrast data collected simultaneously from a force platform and a plantar pressure insole to provide support for the use of the XSENSOR® plantar pressure insoles in a skating-performance application. Data was collected in two conditions. The barefoot condition consisted of the insole on a force platform in isolation and the in-skate condition consisted of the insole inside a speed skate boot on a force platform. A single-participant design was conducted whereby an injury-free female completed multiple trials in both conditions. A P6000 Force Platform (BTS Bioengineering Corp., MI, Italy) was used to collect force data and an X4 Foot and Gait Measurement Systems plantar pressure insole (XSENSOR® Technology Corporation, AB, Canada) was used to collect pressure data in the two conditions across four movement patterns; static stance (SS), anterior-posterior sway (AP), medial-lateral sway (ML), and lateral jump (LJ). Intraclass correlation coefficients (ICC) and Bland-Altman plots revealed excellent agreement between the cumulative centre of pressure path length (mm) measured from the force platform and insole in the barefoot condition and moderate to excellent agreement between impulse (Ns) measured from the force platform and insole, in both conditions. These outcomes provide researchers and practitioners with empirical support and confidence to employ the XSENSOR® plantar pressure insoles outside of a laboratory setting in a real-world skating environment to collect and analyse in-skate kinetic data during on ice performance.

Hippocampal firing fields anchored to a moving object predict homing direction during path-integration-based behavior

Homing based on path integration (H-PI) is a form of navigation in which an animal uses self-motion cues to keep track of its position and return to a starting point. Despite evidence for a role of the hippocampus in homing behavior, the hippocampal spatial representations associated with H-PI are largely unknown. Here we developed a homing task (AutoPI task) that required a mouse to find a randomly placed lever on an arena before returning to its home base. Recordings from the CA1 area in male mice showed that hippocampal neurons remap between random foraging and AutoPI task, between trials in light and dark conditions, and between search and homing behavior. During the AutoPI task, approximately 25% of the firing fields were anchored to the lever position. The activity of 24% of the cells with a lever-anchored field predicted the homing direction of the animal on each trial. Our results demonstrate that the activity of hippocampal neurons with object-anchored firing fields predicts homing behavior.

Multilingual Language Diversity Protects Native Language Production under Different Control Demands.

The use of multiple languages has been found to influence individuals' cognitive abilities. Although some studies have also investigated the effect of multilingualism on non-native language proficiency, fewer studies have focused on how multilingual experience affects native language production. This study investigated the effect of multilingualism on native language production, specifically examining control demands through a semantic Go/No-Go picture naming task. The multilingual experience was quantified using language entropy, which measures the uncertainty and diversity of language use. Control demands were achieved by manipulating the proportion of Go (i.e., naming) trials in different conditions. Results showed that as control demands increased, multilingual individuals exhibited poorer behavioral performance and greater brain activation throughout the brain. Moreover, more diverse language use was associated with higher accuracy in naming and more interconnected brain networks with greater involvement of domain-general neural resources and less domain-specific neural resources. Notably, the varied and balanced use of multiple languages enabled multilingual individuals to respond more efficiently to increased task demands during native language production.

A core domain set for pyoderma gangrenosum trial outcomes: an international eDelphi and consensus study from the UPGRADE initiative.

Pyoderma gangrenosum (PG) is a rare ulcerative skin condition with no current standardized outcomes or outcome measures. With a rich investigational therapeutic pipeline, standardization of outcomes and improvement of data quality and interpretability will promote the appropriate and consistent evaluation of potential new therapies. Core outcome sets (COS) are agreed, standardized sets of outcomes that represent the minimum that should be measured and reported in all clinical trials of a specific condition. To identify and reach a consensus on which domains (what to be measured) should be included in the Understanding Pyoderma Gangrenosum: Review and Analysis of Disease Effects (UPGRADE) core domain set for clinical trials in PG. Collaborative discussions between patients and PG experts, and a systematic review of the literature identified items and prospective domains. A three-round international eDelphi exercise was performed to prioritize the domains and refine the provisional items (consensus: ≥ 70% of participants rating a domain as 'extremely important' and < 15% of participants voting 'not important'), followed by an international meeting to reach consensus on the core domain set (consensus: < 30% disagreement). Item-generation discussions and consensus meetings were hosted via online videoconferences. The eDelphi exercise and consensus voting were performed using Qualtrics survey software. Participants were adults with PG, healthcare professionals, researchers and industry representatives. Collaborative discussions and systematic reviews yielded 115 items, which were distilled into 15 prospective domains. The eDelphi exercise removed the three lowest-priority domains ('laboratory tests', 'treatment costs' and 'disease impact on family') and ranked 'pain', 'quality of life' and 'physical symptoms' as the highest-priority prospective domains. Consensus was reached on the domains of 'pain', 'quality of life' and 'clinical signs'. The domain of 'disease course/disease progression' narrowly failed to reach consensus for inclusion in the core set (32% of participants voted 'no'). Refinement of this domain definition will be required and presented for consideration at future consensus meetings. The UPGRADE core domain set for clinical trials in PG has been agreed by international multistakeholder consensus. Future work will develop and/or select outcome measurement instruments for these domains to establish a COS.

Design and evaluation of microencapsulation technology to reduce the environmental impact of copper fungicides in vineyards

Grapevine is a relevant crop in the European area, that has been traditionally linked to the use of copper fungicides for downy mildew control (Plasmopara viticola). The continued use among the years of this type of copper fungicides has caused an environmental impact, mainly accumulating copper ions in the soil and also resulting in surface and groundwater pollution. To reduce the amount of copper used in vineyard crop protection strategies, and for instance, the contamination, a microencapsulated copper product has been developed. Deposition trials in artificial vegetation were assessed in order to define the optimal formulation characteristics linked with leaf deposit. Also, field trials in real conditions were performed to compare the newly developed copper product with a conventional one. These studies were completed with an evaluation of the microencapsulated product behaviour into two different soil types and its leaching that can consequently be potential groundwater contamination. Microencapsulated formulation resulted in higher deposition compared to the reference product. The obtained results are a relevant drawing up on a way to reduce the amount of copper used, due to the microencapsulated product having the potential to reduce the amount of copper used in vineyard crop protection and the environmental impact they cause.

Randomized feasibility trial of remote ischemic conditioning to enhance resuscitation (RICE)

RationaleRestoration of blood flow after out-of-hospital cardiac arrest (OHCA) is associated with inflammation that causes cellular injury. The extent of this reperfusion injury (RI) is associated with the duration of ischemia and adequacy of resuscitation. Remote ischemic conditioning (RIC) consists of repeated application of non-lethal ischemia then reperfusion to a limb distal to the heart by inflating a blood pressure (BP) cuff. Trials in animal models in cardiac arrest and in humans with acute infarction show RIC reduces RI. ObjectiveWe sought to demonstrate the feasibility and safety of RIC in patients resuscitated from OHCA and transported to hospital. MethodsThis study was conducted under exception from informed consent (EFIC) for emergency research. Eligible subjects were randomized with masked allocation to control (standard care) versus intervention (standard care and RIC). Included were adults with non-traumatic OHCA. The primary outcome was attrition, the proportion of patients enrolled and not on allocated therapy for the study duration. Key secondary outcomes were survival to discharge, neurologic status at discharge, hospital-free survival, and adverse events. Results were summarized descriptively as recommended for pilot studies. ResultsN = 30 patients were enrolled (n = 14 control, n = 16 intervention). Mean age of enrolled patients was 52.5 ± 16.2 years. Eight (27%) were female gender and 7 (23%) had a shockable first recorded rhythm. 100% of enrolled patients completed their allocated study intervention (i.e., 0% attrition). The RIC group had 7 (44%) survival to discharge and median Rankin score of 6 (IQR 1, 6) at discharge as compared to the standard care group which had 6 (43%) survival to discharge and median Rankin score of 6 (IQR 1.5, 6) at discharge. A single patient (6%) in the intervention group had transient occlusion of their upper extremity intravenous line, which immediately resolved on repositioning of the blood pressure cuff. ConclusionApplication of RIC to patients resuscitated from CA and transported to an ED is feasible and safe. An adequately powered trial is required to assess whether RIC is effective at decreasing morbidity and mortality after CA.

Biomechanical role can vary depending on the conditions of the motor task

Expert players in throwing sports may reduce the variability of projectile arrival position by systematically relating release parameters (e.g., release position, velocity, and angular velocity of the projectile). Reducing the variability of the projectile arrival position is often believed to increase the success rate of throwing task, but it may not be always true. Here, we experimentally illustrate that the systematic relationship between release parameters that reduce the variability of the ball arrival position may not increase the number of hitting trials during a throwing task. Furthermore, we demonstrate that the role of the release parameters in increasing successful trials can vary depending on the target size. Each participant threw balls at two different-sized targets (small and large target conditions). Additionally, they alternately threw balls with overhead and sidearm throwing for both the small and large targets. Our results showed that the release position and velocity in the left-right direction reduced the variability of the ball arrival position and increased the successful trials in the small target condition. In the large target condition, the two release parameters reduced the variability of the ball arrival position, but they did not increase the successful trials. Consequently, reducing the variability of the ball arrival position did not always equate to an increase in successful trials, as it depended on the target size. These findings indicate that the role of the release parameters in increasing hitting trials is not constant but varies depending on the condition of the motor task.

Development of Solid Termite Bait Matrix; Its Efficacy Trials in Lab and Semi Field Condition

The study on development of solid termite bait matrix and its efficacy against the Heterotermes indicola was performed in the Termite Laboratory, Entomology Division, Nuclear Institute for Food and Agriculture (NIFA), Peshawar, during 2023. The study was performed with completely randomized design (CRD) with different treatments i.e., developed bait, patent bait, popular wood and blotting paper. Each treatment was replicated three times. The laboratory experiment consisted of no-choice, free choice and aggregation test. While the semi-field experiment consisted of free choice test. During the no-choice test of the laboratory experiment, H. indicola showed a consumption rate of 6.29% for the popular wood and developed bait. However, in the blotting paper treatment, the termites consumed only 2.81%. In terms of choice test conducted in the lab, the popular wood exhibited the highest weight consumption percentage of 2.87%, while the patent bait displayed the lowest weight consumption percentage of 2.25%. Under the choice test maximum number of termites were attracted towards popular wood (77.00 Number of termites) while minimum number of termites were attracted towards patent bait (54.66 Number of termites). Whereas, in aggregation test, of the lab experiment, maximum number of termites were also aggregated towards popular wood (37.77 Number of termites) while minimum termites were aggregated for patent bait (25.22 Number of termites). In the case of free choice under semi-field conditions, the highest number of termites were observed on popular wood i.e., 380.00 followed by the developed bait, which recorded 293.50 termites. On the other hand, the lowest number of termites were recorded on the patent bait i.e., 231.50. Similarly, when considering the maximum consumed weight in percentage, popular wood exhibited the highest value at 16.24%, closely followed by the developed bait at 15.67% while the patent bait displayed minimum consumed weight percentage of 12.89%. In overall experiments it is concluded that among all the tested treatments, termites mostly consumed popular wood and developed bait. Since the developed bait showed promising results in attracting termites, it is recommended to continue refining its formulation. Conduct additional research to identify the key components or additives that enhance its attractiveness and consumption by termites. This optimization process can help maximize the effectiveness of the bait as a termite control strategy. Adding more popular wood saw dust in the bait may achieve more significant and desired results and can also prove to be cost efficient rather than adding more cellulosic material.

Trial arm outcome variance difference after dropout as an indicator of missing-not-at-random bias in randomized controlled trials.

Randomized controlled trials (RCTs) are vulnerable to bias from missing data. When outcomes are missing not at random (MNAR), estimates from complete case analysis (CCA) and multiple imputation (MI) may be biased. There is no statistical test for distinguishing between outcomes missing at random (MAR) and MNAR. Current strategies rely on comparing dropout proportions and covariate distributions, and using auxiliary information to assess the likelihood of dropout being associated with the outcome. We propose using the observed variance difference across trial arms as a tool for assessing the risk of dropout being MNAR in RCTs with continuous outcomes. In an RCT, at randomization, the distributions of all covariates should be equal in the populations randomized to the intervention and control arms. Under the assumption of homogeneous treatment effects and homoskedastic outcome errors, the variance of the outcome will also be equal in the two populations over the course of follow-up. We show that under MAR dropout, the observed outcome variances, conditional on the variables included in the model, are equal across trial arms, whereas MNAR dropout may result in unequal variances. Consequently, unequal observed conditional trial arm variances are an indicator of MNAR dropout and possible bias of the estimated treatment effect. Heterogeneous treatment effects or heteroskedastic outcome errors are another potential cause of observing different outcome variances. We show that for longitudinal data, we can isolate the effect of MNAR outcome-dependent dropout by considering the variance difference at baseline in the same set of patients who are observed at final follow-up. We illustrate our method in simulation for CCA and MI, and in applications using individual-level data and summarydata.

Investigating the role of task relevance during rhythmic sampling of spatial locations

Recently it has been discovered that visuospatial attention operates rhythmically, rather than being stably employed over time. A low-frequency 7–8 Hz rhythmic mechanism coordinates periodic windows to sample relevant locations and to shift towards other, less relevant locations in a visual scene. Rhythmic sampling theories would predict that when two locations are relevant 8 Hz sampling mechanisms split into two, effectively resulting in a 4 Hz sampling frequency at each location. Therefore, it is expected that rhythmic sampling is influenced by the relative importance of locations for the task at hand. To test this, we employed an orienting task with an arrow cue, where participants were asked to respond to a target presented in one visual field. The cue-to-target interval was systematically varied, allowing us to assess whether performance follows a rhythmic pattern across cue-to-target delays. We manipulated a location’s task relevance by altering the validity of the cue, thereby predicting the correct location in 60%, 80% or 100% of trials. Results revealed significant 4 Hz performance fluctuations at cued right visual field targets with low cue validity (60%), suggesting regular sampling of both locations. With high cue validity (80%), we observed a peak at 8 Hz towards non-cued targets, although not significant. These results were in line with our hypothesis suggesting a goal-directed balancing of attentional sampling (cued location) and shifting (non-cued location) depending on the relevance of locations in a visual scene. However, considering the hemifield specificity of the effect together with the absence of expected effects for cued trials in the high valid conditions we further discuss the interpretation of the data.

Be careful what you explain: Benefits and costs of explainable AI in a simulated medical task

We investigated the impact of explainability instructions with respect to system limitations on trust behavior and trust attitude when using an artificial intelligence (AI) support agent to perform a simulated medical task. In an online experiment (N = 128), participants performed a visual estimation task in a simulated medical setting (i.e., estimate the percentage of bacteria in a visual stimulus). All participants were supported by an AI that gave perfect recommendations for all but one color of bacteria (i.e., error-prone color with 50% reliability). We manipulated between-subjects whether participants knew about the error-prone color (XAI condition) or not (nonXAI condition). The analyses revealed that participants showed higher trust behavior (i.e., lower deviation from the AI recommendation) for the non-error-prone trials in the XAI condition. Moreover, participants showed lower trust behavior for the error-prone color in the XAI condition than in the nonXAI condition. However, this behavioral adaptation only applied to the subset of error-prone trials in which the AI gave correct recommendations, and not to the actual erroneous trials. Thus, designing explainable AI systems can also come with inadequate behavioral adaptations, as explainability was associated with benefits (i.e., more adequate behavior in non-error-prone trials), but also costs (stronger changes to the AI recommendations in correct error-prone trials).

The role of cAMP-dependent protein kinase A in the formation of long-term memory in Bactrocera dorsalis

The cAMP-dependent protein kinase A (PKA) signaling pathway has long been considered critical for long-term memory (LTM) formation. Previous studies have mostly focused on the role of PKA signaling in LTM induction by multiple spaced conditioning with less attention to LTM induction by a single conditioning. Here, we conducted behavioral-pharmacology, enzyme immunoassay and RNA interference experiments to study the role of the PKA signaling pathway in LTM formation in the agricultural pest Bactrocera dorsalis, which has a strong memory capacity allowing it to form a two-day memory even from a single conditioning trial. We found that either blocking or activating PKA prior to conditioning pretreatment affected multiple spaced LTM, and conversely, they did not affect LTM formed by single conditioning. This was further confirmed by enzyme-linked immunosorbent assay (ELISA) and silencing of the protein kinase regulatory subunit 2 and catalytic subunit 1. Taken together, these results suggest that activating PKA during memory acquisition helps to induce the LTM formed by multiple spaced conditioning but not by a single conditioning. Our findings challenge the conserved role of PKA signaling in LTM, which provides a basis for the greater diversity of molecular mechanisms underlying LTM formation across species, as well as possible functional and evolutionary implications.

The Rescorla-Wagner model, prediction error, and fear learning

The Rescorla-Wagner model remains one of the most important and influential theoretical accounts of the conditions under which Pavlovian learning occurs. Moreover, the experimental approaches that inspired the model continue to provide powerful behavioral tools to advance mechanistic understanding of how we and other animals learn to fear and learn to reduce fear. Here we consider key features of the Rescorla-Wagner model as applied to study of fear learning. We review evidence for key insights of the model. First, learning to fear and learning to reduce fear are governed by a common, signed prediction error. Second, this error drives variations in effectiveness of the shock US that are causal to whether and how much fear is learned or lost during a conditioning trial. We also consider behavioral and neural findings inconsistent with the model and which will be essential to understand and advance understanding of fear learning.

Plant Growth Promoting and Colonization of Endophytic Streptomyces albus CINv1 against Strawberry Anthracnose

Strawberry anthracnose is a serious disease, and fungicides are currently widely used by farmers. Thus, biological control is a good alternative. This study aims to identify the species of endophytic Streptomyces CINv1 that was previously isolated from Cinnamomum verum J. Presl. and to evaluate its properties as a biocontrol agent, plant growth promoter, and plant colonizing endophyte. This strain was identified by analysis of its 16S rRNA gene sequences, and the result shows 100% similarity to Streptomyces albus CINv1. The CINv1 strain displayed high resistance (81.83%) against Colletotrichum sp. isolate CA0110, as tested by the dual culture technique. Additionally, inhibited pathogen growth on IMA-2 agar was observed under a compound microscope. The results demonstrated swelling, bulbousness, and cytoplasmic aggregation of abnormal hyphal, which were confirmed by SEM as well. Furthermore, the functional media used to evaluate plant growth-promoting properties, including nitrogen fixation, phosphate solubilization, and siderophore production, yielded positive results. Analyses of plant hormones by HPLC found their ability to produce indole-3-acetic acid (IAA). Thus, a biological control trial in greenhouse conditions was conducted by spraying a spore suspension of the strain onto strawberry seedlings once a week, which showed a significant reduction in disease severity. After the seventh spraying, the assessment of the number of leaves and canopy height of the seedling showed significant promotion. In addition, the CINv1 strain established a mutualistic interaction with the plant cells through colonization inter-and intracellularly in strawberry roots, leaves, and petioles. Moreover, using LC-MS/MS to analyze the secondary metabolites of this strain, various groups of compounds were found that could potentially benefit pharmaceutical and agricultural uses.

Genetic and environmental influences on one-trial conditioned context aversion in mice.

Anticipatory nausea (AN) is caused by an association between contextual cues and the experience of nausea (the side effects of chemotherapy or radiation treatment) and it develops predominantly in female patients undergoing chemotherapy. Preclinical studies in rodents show that the administration of an illness-inducing agent in the presence of novel contextual cues can cause conditioned context aversion (CCA) and this has been proposed to model AN. The literature also suggests that brief pre-exposure to a novel context prior to shock delivery is critical in the development of contextual fear conditioning in rodents (a phenomenon known as Immediate Shock Deficit), but this has not been assessed in CCA. The aim of present study was to develop a CCA paradigm to assess this in outbred (CD1) and inbred (C57BL/6J) mice and evaluate potential sex differences. The results revealed that a single conditioning trial in which a distinctive context was paired with LiCl-induced illness was sufficient to elicit a conditioned response in both female and male CD1 outbred mice, but not in C57BL/6J inbred mice. In addition, CCA was facilitated when animals had prior experience with the context. Finally, outbred female mice showed longer and more robust retention of CCA than male mice, which parallels clinical findings. The results indicate the importance of using CD1 outbred mice as an animal model of AN as well as examining sex differences in the CCA paradigm. Similar findings in humans encourage the future use of this novel CCA preclinical mouse model.