Entering adolescence: resistance to peer influence, risky behavior, and neural changes in emotion reactivity

Adolescence is often described as a period of heightened reactivity to emotions paired with reduced regulatory capacities, a combination suggested to contribute to risk-taking and susceptibility to peer influence during puberty. However, no longitudinal research has definitively linked these behavioral changes to underlying neural development. Here, 38 neurotypical participants underwent two fMRI sessions across the transition from late childhood (10 years) to early adolescence (13 years). Responses to affective facial displays exhibited a combination of general and emotion-specific changes in ventral striatum (VS), ventromedial PFC, amygdala, and temporal pole. Furthermore, VS activity increases correlated with decreases in susceptibility to peer influence and risky behavior. VS and amygdala responses were also significantly more negatively coupled in early adolescence than in late childhood while processing sad and happy versus neutral faces. Together, these results suggest that VS responses to viewing emotions may play a regulatory role that is critical to adolescent interpersonal functioning.     

Binding of phencyclidine to the detergent solubilized acetylcholine receptor from Torpedo marmorata

The binding of phencyclidine to the acetylcholine receptor from Torpedo marmorata electroplaque was measured following solubilization of the receptor in sodium cholate followed by the exchange of cholate for Tween 80. In both the membrane-bound and solubilized AChR, the addition of cholinergic agonists simultaneously with the addition of PCP results in a 100 to 1000 fold increase in the PCP association rate and a 5 to 10 fold increase in the dissociation rate as compared to the unliganded AChR or AChR equilibrated with agonist prior to PCP addition. In addition, the number of binding sites and the pharmacological properties of the binding are not markedly changed in the soluble receptor. These results suggest that the acetylcholine receptor can undergo similar conformational transitions in the membrane-bound and the Tween 80 solubilized form and that phencyclidine can monitor these transitions in both cases.     

MAPK signaling in H9c2 cardiomyoblasts exposed to cholesterol secoaldehyde – Role of hydrogen peroxide

3β-Hydroxy-5,6-secocholestan-6-al (cholesterol secoaldehyde or ChSeco), an oxysterol known to be formed in ozone- and singlet oxygen-mediated oxidations of cholesterol, has been detected in the atherosclerotic plaque and in the brain of patients suffering from Alzheimer’s disease and Lewy body dementia. Previously, we have shown that, in H9c2 cardiomyoblasts, ChSeco induces oxidative stress followed by apoptosis involving both intrinsic and extrinsic signaling pathways. In the present study, we investigated the nature of reactive oxygen species (ROS) and its associated redox signaling in H9c2 cells upon treatment with ChSeco. Both catalase and deferoxamine, which lowered intracellular ROS, were found to alleviate the ChSeco-induced cytotoxicity. ChSeco-treated H9c2 cells showed a significant decrease in the intracellular catalase activity, suggesting the involvement of H₂O₂ in the associated cytotoxicity. Additionally, in ChSeco-exposed cells, there was a marked increase in lipid peroxidation and pre-treatment with SB 203580 (p38 MAPK inhibitor) and MEK1/2 inhibitor (ERK1/2 and JNK inhibitor) rendered protection against the cytotoxicity. An early increase in the expression of p-SAPK/JNK or delayed p38 MAPK did not alter ATF-2 but decreased c-Jun expression in these cells. Overall, these findings are consistent with MAPK signaling resulting from increased cellular H₂O₂ in ChSeco-induced cytotoxicity in cardiomyoblasts.     

From interesting details to dynamical relevance: toward more effective use of empirical insights in theory construction

A perennial challenge in ecology is to develop dynamical systems models that appropriately abstract and characterize the dynamics of natural systems. Deriving an appropriate model of system dynamics can be a long and iterative process whose outcome depends critically on the quality of empirical data describing the long‐term behavior of a natural system. Most ecological time series are insufficient to offer insight into the way organizational hierarchies and spatial scales are causally linked to natural system dynamics. Moreover, the classic tradition of hypothesis testing in ecology is not likely to lead to those key insights. This because empirical research is geared almost exclusively toward testing model predictions based on underlying causal relationships assumed by theorists. So, empirical research relies heavily on theory for guidance on what is or is not dynamically relevant. I argue here that it is entirely possible to reduce much of this guesswork involved with deciding on causal structure by giving empirical research a new role in theory development. In this role, natural history and field observations are used to develop stochastic, individual‐based and spatially explicit computational models or IBMs that can explore the range of contingency and complexity inherent in real‐world systems.
IBMs can be used to run simulations allowing deductions to be made about the causal linkages between organizational hierarchies, spatial scales, and dynamics. These deductions can be tested under field conditions using experiments that manipulate the putative causal structure and evaluate the dynamical consequences. The emerging insights from this stage can then be used to inspire an analytical construct that embodies the dynamically relevant scales and mechanisms. In essence, computational modeling serves as an intermediate step in theory development in that a wide range of possibly important biological details are considered and then reduced to a subset that is dynamically relevant.