Consider the Source: Adolescents and Adults Similarly Follow Older Adult Advice More than Peer Advice

Individuals learn which of their actions are likely to be rewarded through trial and error. This form of learning is critical for adapting to new situations, which adolescents frequently encounter. Adolescents are also greatly influenced by their peers. The current study tested the extent to which adolescents rely on peer advice to guide their actions. Adolescent and young adult participants completed a probabilistic learning task in which they chose between four pairs of stimuli with different reinforcement probabilities, with one stimulus in each pair more frequently rewarded. Participants received advice about two of these pairs, once from a similarly aged peer and once from an older adult. Crucially, this advice was inaccurate, enabling the dissociation between experience-based and instruction-based learning. Adolescents and adults learned equally well from experience and no age group difference was evident in the overall influence of advice on choices. Surprisingly, when considering the source of advice, there was no evident influence of peer advice on adolescent choices. However, both adolescents and adults were biased toward choosing the stimulus recommended by the older adult. Contrary to conventional wisdom, these data suggest that adolescents may prioritize the advice of older adults over that of peers in certain decision-making contexts.     

Abacavir-Reactive Memory T Cells Are Present in Drug Na?ve Individuals

BackgroundFifty-five percent of individuals with HLA-B*57:01 exposed to the antiretroviral drug abacavir develop a hypersensitivity reaction (HSR) that has been attributed to naïve T-cell responses to neo-antigen generated by the drug. Immunologically confirmed abacavir HSR can manifest clinically in less than 48 hours following first exposure suggesting that, at least in some cases, abacavir HSR is due to re-stimulation of a pre-existing memory T-cell population rather than priming of a high frequency naïve T-cell population.MethodsTo determine whether a pre-existing abacavir reactive memory T-cell population contributes to early abacavir HSR symptoms, we studied the abacavir specific naïve or memory T-cell response using HLA-B*57:01 positive HSR patients or healthy controls using ELISpot assay, intra-cellular cytokine staining and tetramer labelling.ResultsAbacavir reactive CD8+ T-cell responses were detected in vitro in one hundred percent of abacavir unexposed HLA-B*57:01 positive healthy donors. Abacavir-specific CD8+ T cells from such donors can be expanded from sorted memory, and sorted naïve, CD8+ T cells without need for autologous CD4+ T cells.ConclusionsWe propose that these pre-existing abacavir-reactive memory CD8+ T-cell responses must have been primed by earlier exposure to another foreign antigen and that these T cells cross-react with an abacavir-HLA-B*57:01-endogenous peptide ligand complex, in keeping with the model of heterologous immunity proposed in transplant rejection.     

A Four-Compartment Metabolomics Analysis of the Liver,Muscle, Serum,and Urine Response to Polytrauma with Hemorrhagic Shock following Carbohydrate Prefeed

Objective

Hemorrhagic shock accompanied by injury represents a major physiologic stress. Fasted animals are often used to study hemorrhagic shock (with injury). A fasted state is not guaranteed in the general human population. The objective of this study was to determine if fed animals would exhibit a different metabolic profile in response to hemorrhagic shock with trauma when compared to fasted animals.

Methods

Proton (1H) NMR spectroscopy was used to determine concentrations of metabolites from four different compartments (liver, muscle, serum, urine) taken at defined time points throughout shock/injury and resuscitation. PLS-DA was performed and VIP lists established for baseline, shock and resuscitation (10 metabolites for each compartment at each time interval) on metabolomics data from surviving animals.

Results

Fed status prior to the occurrence of hemorrhagic shock with injury alters the metabolic course of this trauma and potentially affects mortality. The death rate for CPF animals is higher than FS animals (47 vs 28%). The majority of deaths occur post-resuscitation suggesting reperfusion injury. The metabolomics response to shock reflects priorities evident at baseline. FS animals raise the baseline degree of proteolysis to provide additional amino acids for energy production while CPF animals rely on both glucose and, to a lesser extent, amino acids. During early resuscitation levels of metabolites associated with energy production drop, suggesting diminished demand.

Conclusions

Feeding status prior to the occurrence of hemorrhagic shock with injury alters the metabolic course of this trauma and potentially affects mortality. The response to shock reflects metabolic priorities at baseline.     

The Highly Conserved Codon following the Slippery Sequence Supports ?1 Frameshift Efficiency at the HIV-1 Frameshift Site

HIV-1 utilises −1 programmed ribosomal frameshifting to translate structural and enzymatic domains in a defined proportion required for replication. A slippery sequence, U UUU UUA, and a stem-loop are well-defined RNA features modulating −1 frameshifting in HIV-1. The GGG glycine codon immediately following the slippery sequence (the ‘intercodon’) contributes structurally to the start of the stem-loop but has no defined role in current models of the frameshift mechanism, as slippage is inferred to occur before the intercodon has reached the ribosomal decoding site. This GGG codon is highly conserved in natural isolates of HIV. When the natural intercodon was replaced with a stop codon two different decoding molecules—eRF1 protein or a cognate suppressor tRNA—were able to access and decode the intercodon prior to −1 frameshifting. This implies significant slippage occurs when the intercodon is in the (perhaps distorted) ribosomal A site. We accommodate the influence of the intercodon in a model of frame maintenance versus frameshifting in HIV-1.     

Individuals with higher metabolic rates have lower levels of reactive oxygen species in vivo

There is increasing interest in the effect of energy metabolism on oxidative stress, but much ambiguity over the relationship between the rate of oxygen consumption and the generation of reactive oxygen species (ROS). Production of ROS (such as hydrogen peroxide, H₂O₂) in the mitochondria is primarily inferred indirectly from measurements in vitro, which may not reflect actual ROS production in living animals. Here, we measured in vivo H₂O₂ content using the recently developed MitoB probe that becomes concentrated in the mitochondria of living organisms, where it is converted by H₂O₂ into an alternative form termed MitoP; the ratio of MitoP/MitoB indicates the level of mitochondrial H₂O₂ in vivo. Using the brown trout Salmo trutta, we tested whether this measurement of in vivo H₂O₂ content over a 24 h-period was related to interindividual variation in standard metabolic rate (SMR). We showed that the H₂O₂ content varied up to 26-fold among fish of the same age and under identical environmental conditions and nutritional states. Interindividual variation in H₂O₂ content was unrelated to mitochondrial density but was significantly associated with SMR: fish with a higher mass-independent SMR had a lower level of H₂O₂. The mechanism underlying this observed relationship between SMR and in vivo H₂O₂ content requires further investigation, but may implicate mitochondrial uncoupling which can simultaneously increase SMR but reduce ROS production. To our knowledge, this is the first study in living organisms to show that individuals with higher oxygen consumption rates can actually have lower levels of H₂O₂.     

Validated predictive modelling of the environmental resistome

Multi-drug-resistant bacteria pose a significant threat to public health. The role of the environment in the overall rise in antibiotic-resistant infections and risk to humans is largely unknown. This study aimed to evaluate drivers of antibiotic-resistance levels across the River Thames catchment, model key biotic, spatial and chemical variables and produce predictive models for future risk assessment. Sediment samples from 13 sites across the River Thames basin were taken at four time points across 2011 and 2012. Samples were analysed for class 1 integron prevalence and enumeration of third-generation cephalosporin-resistant bacteria. Class 1 integron prevalence was validated as a molecular marker of antibiotic resistance; levels of resistance showed significant geospatial and temporal variation. The main explanatory variables of resistance levels at each sample site were the number, proximity, size and type of surrounding wastewater-treatment plants. Model 1 revealed treatment plants accounted for 49.5% of the variance in resistance levels. Other contributing factors were extent of different surrounding land cover types (for example, Neutral Grassland), temporal patterns and prior rainfall; when modelling all variables the resulting model (Model 2) could explain 82.9% of variations in resistance levels in the whole catchment. Chemical analyses correlated with key indicators of treatment plant effluent and a model (Model 3) was generated based on water quality parameters (contaminant and macro- and micro-nutrient levels). Model 2 was beta tested on independent sites and explained over 78% of the variation in integron prevalence showing a significant predictive ability. We believe all models in this study are highly useful tools for informing and prioritising mitigation strategies to reduce the environmental resistome.     

Nitrogen and harvest effects on soil properties under rainfed switchgrass and no‐till corn over 9 years: implications for soil quality

Nitrogen fertilizer and harvest management will alter soils under bioenergy crop production and the long‐term effects of harvest timing and residue removal remain relatively unknown. Compared to no‐tilled corn (NT‐C, Zea mays L.), switchgrass (Panicum virgatum L.) is predicted to improve soil properties [i.e. soil organic C (SOC), soil microbial biomass (SMB‐C), and soil aggregation] due to its perennial nature and deep‐rooted growth form, but few explicit field comparisons exist. We assessed soil properties over 9 years for a rainfed study of N fertilizer rate (0, 60, 120, and 180 kg N ha^?1) and harvest management on switchgrass (harvested in August and postfrost) and NT‐C (with and without 50% stover removal) in eastern NE. We measured SOC, aggregate stability, SMB‐C, bulk density (BD), pH, P and K in the top 0–30 cm. Both NT‐C and switchgrass increased SMB‐C, SOC content, and aggregate stability over the 9 years, reflecting improvement from previous conventional management. However, the soils under switchgrass had double the percent aggregate stability, 1.3 times more microbial biomass, and a 5–8% decrease in bulk density in the 0–5 and 5–10 cm depths compared to NT‐C. After 9 years, cumulative decrease in available P was significantly greater beneath NT‐C (?24.0 kg P ha^?1) compared to switchgrass (?5.4 kg P ha^?1). When all measured soil parameters were included in the Soil Management Assessment Framework (SMAF), switchgrass improved soil quality index over time (ΔSQI) in all depths. NT‐C without residue removal did not affect ΔSQI, but 50% residue removal decreased ΔSQI (0–30 cm) due to reduced aggregate stability and SMB‐C. Even with best‐management practices such as NT, corn stover removal will have to be carefully managed to prevent soil degradation. Long‐term N and harvest management studies that include biological, chemical, and physical soil measurements are necessary to accurately assess bioenergy impacts on soils.