Isocitrate Dehydrogenase Mutation in \u3ci\u3eVibrio anguillarum\u3c/i\u3e Results in Virulence Attenuation and Immunoprotection in Rainbow Trout (\u3ci\u3eOncorhynchus mykiss\u3c/i\u3e)

Background Vibrio anguillarum is an extracellular bacterial pathogen that is a causative agent of vibriosis in finfish and crustaceans with mortality rates ranging from 30% to 100%. Mutations in central metabolism (glycolysis and the TCA cycle) of intracellular pathogens often result in attenuated virulence due to depletion of required metabolic intermediates; however, it was not known whether mutations in central metabolism would affect virulence in an extracellular pathogen such as V. anguillarum. Results Seven central metabolism mutants were created and characterized with regard to growth in minimal and complex media, expression of virulence genes, and virulence in juvenile rainbow trout (Oncorhynchus mykiss). Only the isocitrate dehydrogenase (icd) mutant was attenuated in virulence against rainbow trout challenged by either intraperitoneal injection or immersion. Further, the icd mutant was shown to be immunoprotective against wild type V. anguillarum infection. There was no significant decrease in the expression of the three hemolysin genes detected by qRT-PCR. Additionally, only the icd mutant exhibited a significantly decreased growth yield in complex media. Growth yield was directly related to the abundance of glutamate. A strain with a restored wild type icd gene was created and shown to restore growth to a wild type cell density in complex media and pathogenicity in rainbow trout. Conclusions The data strongly suggest that a decreased growth yield, resulting from the inability to synthesize α-ketoglutarate, caused the attenuation despite normal levels of expression of virulence genes. Therefore, the ability of an extracellular pathogen to cause disease is dependent upon the availability of host-supplied nutrients for growth. Additionally, a live vaccine strain could be created from an icd deletion strain

Effects of Classroom-Based Resistance Training With and Without Cognitive Training on Adolescents’ Cognitive Function, On-task Behavior, and Muscular Fitness

Aim: Participation in classroom physical activity breaks may improve children’s cognition, but few studies have involved adolescents. The primary aim of this study was to examine the effects of classroom-based resistance training with and without cognitive training on adolescents’ cognitive function. Methods: Participants were 97 secondary school students (45.4% females, mean age 15.78 ± 0.44). Four-year 10 classes from one school were included in this four-arm cluster randomized controlled trial. Classes were randomly assigned to the following groups: sedentary control with no cognitive training, sedentary with cognitive training, resistance training without cognitive training, and resistance training with cognitive training. Sessions varied in levels of both cognitive demand and resistance training (i.e., high vs. low) and were administered three times per week for 4 weeks (12 sessions). Inhibition, cognitive flexibility, episodic memory, on-task behavior, and muscular fitness were assessed at baseline and post-test. Linear mixed models were used to examine changes within and between groups. Results: In comparison with the control group, episodic memory improved significantly in the resistance training without cognitive training group (−9.87 units, 95% CI: −17.71 to −2.03, p = 0.014, d = 0.72). There were no group-by-time effects for inhibition or cognitive flexibility. Classroom activity breaks both with and without cognitive demand improved participants’ on-task behavior in comparison with the control and sedentary group. The resistance training programs did not lead to improvements in muscular fitness. Conclusion: Participation in body weight resistance training without cognitive training led to selective improvements in episodic memory. No training effects were found for inhibition or cognitive flexibility. A longer study period may be necessary to induce improvements in muscular fitness and associated changes in inhibition and cognitive flexibilit

Placenta-specific Slc38a2/SNAT2 knockdown causes fetal growth restriction in mice

Fetal growth restriction (FGR) is a complication of pregnancy that reduces birth weight, markedly increases infant mortality and morbidity and is associated with later-life cardiometabolic disease. No specific treatment is available for FGR. Placentas of human FGR infants have low abundance of sodium-coupled neutral amino acid transporter 2 (Slc38a2/SNAT2), which supplies the fetus with amino acids required for growth. We determined the mechanistic role of placental Slc38a2/SNAT2 deficiency in the development of restricted fetal growth, hypothesizing that placenta-specific Slc38a2 knockdown causes FGR in mice. Using lentiviral transduction of blastocysts with a small hairpin RNA (shRNA), we achieved 59% knockdown of placental Slc38a2, without altering fetal Slc38a2 expression. Placenta-specific Slc38a2 knockdown reduced near-term fetal and placental weight, fetal viability, trophoblast plasma membrane (TPM) SNAT2 protein abundance, and both absolute and weight-specific placental uptake of the amino acid transport System A tracer, 14C-methylaminoisobutyric acid (MeAIB). We also measured human placental SLC38A2 gene expression in a well-defined term clinical cohort and found that SLC38A2 expression was decreased in late-onset, but not early-onset FGR, compared with appropriate for gestational age (AGA) control placentas. The results demonstrate that low placental Slc38a2/SNAT2 causes FGR and could be a target for clinical therapies for late-onset FGR

Neuronal birthdate reveals topography in a vestibular brainstem circuit for gaze stabilization

Across the nervous system, neurons with similar attributes are topographically organized. This topography reflects developmental pressures. Oddly, vestibular (balance) nuclei are thought to be disorganized. By measuring activity in birthdated neurons, we revealed a functional map within the central vestibular projection nucleus that stabilizes gaze in the larval zebrafish. We first discovered that both somatic position and stimulus selectivity follow projection neuron birthdate. Next, with electron microscopy and loss-of-function assays, we found that patterns of peripheral innervation to projection neurons were similarly organized by birthdate. Finally, birthdate revealed spatial patterns of axonal arborization and synapse formation to projection neuron outputs. Collectively, we find that development reveals previously hidden organization to the input, processing, and output layers of a highly conserved vertebrate sensorimotor circuit. The spatial and temporal attributes we uncover constrain the developmental mechanisms that may specify the fate, function, and organization of vestibulo-ocular reflex neurons. More broadly, our data suggest that, like invertebrates, temporal mechanisms may assemble vertebrate sensorimotor architecture

Neuronal Birthdate Reveals Topography in a Vestibular Brainstem Circuit for Gaze Stabilization

Across the nervous system, neurons with similar attributes are topographically organized. This topography reflects developmental pressures. Oddly, vestibular (balance) nuclei are thought to be disorganized. By measuring activity in birthdated neurons, we revealed a functional map within the central vestibular projection nucleus that stabilizes gaze in the larval zebrafish. We first discovered that both somatic position and stimulus selectivity follow projection neuron birthdate. Next, with electron microscopy and loss-of-function assays, we found that patterns of peripheral innervation to projection neurons were similarly organized by birthdate. Finally, birthdate revealed spatial patterns of axonal arborization and synapse formation to projection neuron outputs. Collectively, we find that development reveals previously hidden organization to the input, processing, and output layers of a highly conserved vertebrate sensorimotor circuit. The spatial and temporal attributes we uncover constrain the developmental mechanisms that may specify the fate, function, and organization of vestibulo-ocular reflex neurons. More broadly, our data suggest that, like invertebrates, temporal mechanisms may assemble vertebrate sensorimotor architecture

High-intensity interval training on cognitive and mental health in adolescents

PURPOSE: Emerging literature suggests that physical activity and fitness may have a positive impact on cognitive and mental health for adolescents. The purpose of the current study was to evaluate the efficacy of two high intensity interval training (HIIT) protocols for improving cognitive and mental health outcomes (executive function, psychological wellbeing, psychological distress and physical self-concept) in adolescents. METHODS: Participants (n=65; mean age=15.8±0.6) were randomized to three conditions: aerobic exercise program (AEP; n=21), resistance and aerobic exercise program (RAP; n=22) and control (n=22). HIIT sessions (8-10min/session) were delivered during physical education lessons or at lunchtime three times/week for 8-weeks. Assessments were conducted at baseline and immediate post-intervention to detect changes in executive function (Trail Making Test, TMT), psychological wellbeing, psychological distress and physical self-description, by researchers blinded to treatment allocation. Intervention effects were examined using linear mixed models. Cohen\u27s d effect sizes and clinical inference were also calculated. RESULTS: Small improvements in executive function (d=-0.32, 95%CI -9.12 to 9.77; p=0.386) and psychological wellbeing (d=0.34, 95%CI -1.73 to 2.37; p=0.252) were evident in the AEP group. Moderate improvements in executive function (d=-0.51, 95% CI -8.92 to 9.73; p=0.171), and small improvements in wellbeing (d=0.35, 95%CI -1.46 to 2.53; p=0.219) and perceived appearance (d=0.35, 95%CI -0.74 to 0.41; p=0.249), were observed for the RAP group. Mean feelings state scores improved from pre-workout to post-post workout in both HIIT conditions, with significant results for the AEP (p=0.001). CONCLUSIONS: This study highlights the potential of embedding HIIT within the school day for improving cognitive and mental health among adolescents

Process evaluation of a school-based high-intensity interval training program for older adolescents : the Burn 2 Learn cluster randomised controlled trial

Process evaluations can help to optimise the implementation of school-based physical activity interventions. The purpose of this paper is to describe the process evaluation of a school-based high-intensity interval training (HIIT) program for older adolescent students, known as Burn 2 Learn (B2L). B2L was evaluated via a cluster randomised controlled trial in 20 secondary schools (10 intervention, 10 control) in New South Wales, Australia. Teachers (n = 22 (55% female)) from the 10 intervention schools, delivered the program over three phases (Phases 1 and 2, 6 months; Phase 3, 6 months) to older adolescent students (n = 337 (50% female); mean ± standard deviation (SD) age = 16.0 ± 0.4 years). Process evaluation data were collected across the 12-month study period. Teachers delivered 2.0 ± 0.8 and 1.7 ± 0.6 sessions/week in Phases 1 and 2 respectively (mean total 25.9 ± 5.2), but only 0.6 ± 0.7 sessions/week in Phase 3. Observational data showed that session quality was high, however heart rate (HR) data indicated that only half of the students reached the prescribed threshold of ≥85% predicted HRmax during sessions. Over 80% of teachers reported they intended to deliver the B2L program to future student cohorts. Almost 70% of students indicated they intended to participate in HIIT in the future. Teachers considered the program to be adaptable, and both students and teachers were satisfied with the intervention. B2L was implemented with moderate-to-high fidelity in Phases 1 and 2, but low in Phase 3. Our findings add to the relatively scant process evaluation literature focused on the delivery of school-based physical activity programs

Dynamic Bayesian belief network to model the development of walking and cycling schemes

This paper aims to describe a model which represents the formulation of decision-making processes (over a number of years) affecting the step-changes of walking and cycling (WaC) schemes. These processes can be seen as being driven by a number of causal factors, many of which are associated with the attitudes of a variety of factors, in terms of both determining whether any scheme will be implemented and, if it is implemented, the extent to which it is used. The outputs of the model are pathways as to how the future might unfold (in terms of a number of future time steps) with respect to specific pedestrian and cyclist schemes. The transitions of the decision making processes are formulated using a qualitative simulation method, which describes the step-changes of the WaC scheme development. In this article a Bayesian belief network (BBN) theory is extended to model the influence between and within factors in the dynamic decision making process

Comparative Transcriptomic Analysis of Primary and Recurrent Ovarian Granulosa Cell Tumors

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