Action ability modulates time‑to‑collision judgments

Time-to-collision (TTC) underestimation has been interpreted as an adaptive response that allows observers to have more time to engage in a defensive behaviour. This bias seems, therefore, strongly linked to action preparation. There is evidence that the observer’s physical fitness modulates the underestimation effect so that people who need more time to react (i.e. those with less physical fitness) show a stronger underestimation effect. Here we investigated whether this bias is influenced by the momentary action capability of the observers. In the first experiment, participants estimated the time-to-collision of threatening or non-threatening stimuli while being mildly immobilized (with a chin rest) or while standing freely. Having reduced the possibility of movement led participants to show more underestimation of the approaching stimuli. However, this effect was not stronger for threatening relative to non-threatening stimuli. The effect of the action capability found in the first experiment could be interpreted as an expansion of peripersonal space (PPS). In the second experiment, we thus investigated the generality of this effect using an established paradigm to measure the size of peripersonal space. Participants bisected lines from different distances while in the chin rest or standing freely. The results replicated the classic left-to-right gradient in lateral spatial attention with increasing viewing distance, but no effect of immobilization was found. The manipulation of the momentary action capability of the observers influenced the participants’ performance in the TTC task but not in the line bisection task. These results are discussed in relation to the different functions of PPS

Altering APP Proteolysis: Increasing sAPPalpha Production by Targeting Dimerization of the APP Ectodomain

One of the events associated with Alzheimer's disease is the dysregulation of α- versus β-cleavage of the amyloid precursor protein (APP). The product of α-cleavage (sAPPα) has neuroprotective properties, while Aβ1-42 peptide, a product of β-cleavage, is neurotoxic. Dimerization of APP has been shown to influence the relative rate of α- and β- cleavage of APP. Thus finding compounds that interfere with dimerization of the APP ectodomain and increase the α-cleavage of APP could lead to the development of new therapies for Alzheimer's disease. Examining the intrinsic fluorescence of a fragment of the ectodomain of APP, which dimerizes through the E2 and Aβ-cognate domains, revealed significant changes in the fluorescence of the fragment upon binding of Aβ oligomers—which bind to dimers of the ectodomain— and Aβ fragments—which destabilize dimers of the ectodomain. This technique was extended to show that RERMS-containing peptides (APP695 328–332), disulfiram, and sulfiram also inhibit dimerization of the ectodomain fragment. This activity was confirmed with small angle x-ray scattering. Analysis of the activity of disulfiram and sulfiram in an AlphaLISA assay indicated that both compounds significantly enhance the production of sAPPα by 7W-CHO and B103 neuroblastoma cells. These observations demonstrate that there is a class of compounds that modulates the conformation of the APP ectodomain and influences the ratio of α- to β-cleavage of APP. These compounds provide a rationale for the development of a new class of therapeutics for Alzheimer's disease

Testicular Steroidogenesis

Testosterone is the major androgen in circulation in male humans, produced primarily in the Leydig cells of the testis. Biosynthesis of testosterone from cholesteroloccursviaaseriesofenzymaticreactions.Testosteronemaybefurther metabolized into a more potent androgen, dihydrotestosterone. In recent years an alternate pathway of dihydrotestosterone biosynthesis without using testosterone as a precursor has emerged. Majority of classically studied effects of androgens are thought to be mediated via nuclear receptor-dependent long-term transcriptional effects, but there also exist membrane receptor-based effects of androgens which are being uncovered from recent studies that may explain rapid effects of androgens in many cases. In this chapter we are describing the biosynthesis, mechanism of action, and therapeutic effects of testosterone and related androgens