Genetic and pharmacological intervention of the p75NTR pathway alters morphological and behavioural recovery following traumatic brain injury in mice.

PRIMARY OBJECTIVE: Neurotrophin levels are elevated after TBI, yet there is minimal regeneration. It was hypothesized that the pro-neurotrophin/p75NTR pathway is induced more than the mature neurotrophin/Trk pathway and that interfering with p75 signalling improves recovery following TBI. RESEARCH DESIGN: Lateral Fluid Percussion (LFP) injury was performed on wildtype and p75 mutant mice. In addition, TrkB agonist 7,8 Dihydroxyflavone or p75 antagonist TAT-Pep5 were tested. Western blot and immunohistochemistry revealed biochemical and cellular changes. Morris Water Maze and Rotarod tests demonstrated cognitive and vestibulomotor function. MAIN OUTCOMES AND RESULTS: p75 was up-regulated and TrkB was down-regulated 1 day post-LFP. p75 mutant mice as well as mice treated with the p75 antagonist or the TrkB agonist exhibited reduced neuronal death and degeneration and less astrocytosis. The cells undergoing apoptosis appear to be neurons rather than glia. There was improved motor function and spatial learning in p75 mutant mice and mice treated with the p75 antagonist. CONCLUSIONS: Many of the pathological and behavioural consequences of TBI might be due to activation of the pro-neurotrophin/p75 toxic pathway overriding the protective mechanisms of the mature neurotrophin/Trk pathway. Targeting p75 can be a novel strategy to counteract the damaging effects of TBI.

Rhodium-Catalyzed Allylic C-H Functionalization of Unactivated Alkenes with α-Diazocarbonyl Compounds.

A redox-neutral mild methodology for the allylic C-H alkylation of unactivated alkenes with diazo compounds is demonstrated. The developed protocol is able to bypass the possibility of the cyclopropanation of an alkene upon its reaction with the acceptor-acceptor diazo compounds. The protocol is highly accomplished due to its compatibility with various unactivated alkenes functionalized with different sensitive functional groups. A rhodacycle π-allyl intermediate has been synthesized and proved to be the active intermediate. Additional mechanistic investigations aided the elucidation of the plausible reaction mechanism.

Effects of acute and repeated administration of Staphylococcal enterotoxin A on Morris water maze learning, corticosterone and hippocampal IL-1ß and TNFα.

Staphylococcal enterotoxin A (SEA) is a bacterial superantigen that induces pronounced T cell expansion and cytokine production. In addition, SEA activates the HPA axis and forebrain regions relevant to cognitive functions. Since learning-related cognitive changes have not been assessed in response to SEA, spatial learning in the Morris water maze (MWM) was determined in male C57BL/6J mice subjected to acute or repeated injections of 5µg SEA or Saline. Injections were given 2h prior to 4-5days of hidden platform sessions. Animals were then rested for 1month and given retraining without further injections. In addition, splenic IL-1ß, IL-2 and TNFα, plasma corticosterone, and hippocampal IL-1ß and TNFα were measured after the regimen of treatment used in the behavioral experiments. The results showed no learning impairment following acute or repeated SEA challenge. Moreover, when retested 1month later, and without further injections, the SEA group showed more rapid relearning of the MWM. This suggested that coincidental superantigenic T cell activation and training served to promote long-term improvement in recovery of learning. Furthermore, repeated SEA challenge continued to drive increases in plasma corticosterone, but with a compensatory reduction in hippocampal IL-1ß. However, while hippocampal TNFα was reduced after acute and repeated SEA treatment, this was not statistically significant. In view of the importance of modest glucocorticoid elevations and hippocampal IL-1ß in promoting contextual learning, the data point to the hypothesis that SEA promotes long-term plasticity by restraining disruptive increases in hippocampal IL-1ß, and possibly TNFα, during learning.

Stanene-hexagonal boron nitride heterobilayer: Structure and characterization of electronic property.

The structural and electronic properties of stanene/hexagonal boron nitride (Sn/h-BN) heterobilayer with different stacking patterns are studied using first principle calculations within the framework of density functional theory. The electronic band structure of different stacking patterns shows a direct band gap of ~30 meV at Dirac point and at the Fermi energy level with a Fermi velocity of ~0.53 × 106 ms-1. Linear Dirac dispersion relation is nearly preserved and the calculated small effective mass in the order of 0.05mo suggests high carrier mobility. Density of states and space charge distribution of the considered heterobilayer structure near the conduction and the valence bands show unsaturated π orbitals of stanene. This indicates that electronic carriers are expected to transport only through the stanene layer, thereby leaving the h-BN layer to be a good choice as a substrate for the heterostructure. We have also explored the modulation of the obtained band gap by changing the interlayer spacing between h-BN and Sn layer and by applying tensile biaxial strain to the heterostructure. A small increase in the band gap is observed with the increasing percentage of strain. Our results suggest that, Sn/h-BN heterostructure can be a potential candidate for Sn-based nanoelectronics and spintronic applications.

The smell of fear: innate threat of 2,5-dihydro-2,4,5-trimethylthiazoline, a single molecule component of a predator odor.

In the last several years, the importance of understanding what innate threat and fear is, in addition to learning of threat and fear, has become evident. Odors from predators are ecologically relevant stimuli used by prey animals as warnings for the presence of danger. Of importance, these odors are not necessarily noxious or painful, but they have innate threat-like properties. This review summarizes the progress made on the behavioral and neuroanatomical fundamentals of innate fear of the predator odor, 2,5-dihydro-2,4,5-trimethylthiazoline (TMT), a component of fox feces. TMT is one of several single molecule components of predator odors that have been isolated in the last several years. Isolation of these single molecules has allowed for rapid advances in delineating the behavioral constraints and selective neuroanatomical pathways of predator odor induced fear. In naïve mice and rats, TMT induces a number of fear and defensive behaviors, including robust freezing, indicating it is an innate threat stimulus. However, there are a number of behavioral constraints that we do not yet understand. Similarly, while some of the early olfactory sensory pathways for TMT-induced fear are being delineated, the pathways from olfactory systems to emotional and motor output regions are less well understood. This review will focus on what we know and what we still need to learn about the behavior and neuroanatomy of TMT-induced fear.