IMPACT OF PROPHYLACTIC INTRANASAL OXYTOCIN ADMINISTRATION ON SYMPTOMS OF POST-TRAUMATIC STRESS

Post-traumatic stress disorder (PTSD) is a mental health condition that affects people after instances of severe emotional trauma. Research suggests that oxytocin treatment decreases PTSD symptoms. This study served to evaluate the efficacy of intranasal oxytocin pre-treatment on symptoms related to PTSD. The hypotheses are that oxytocin will decrease fear and anxiety, and increase reward-seeking behaviors. Sprague Dawley rats were assigned to three groups (Control, Stress, Oxytocin, and Oxytocin+Stress; n=6 per group) to conduct this experiment. Prior to foot shock treatment, rats were trained to expect a food reward (Kellogg’s Froot Loops) in an open field enclosure. Subsequently, the Oxytocin and the Oxytocin+Stress groups were pre-treated with intranasal oxytocin and then the Stress and Oxytocin+Stress groups were exposed to an inescapable foot shock (a model PTSD inducing stressor). After oxytocin and shock treatments, rats underwent various behavioral tests: re-exposure to the shock chamber to assess fear, elevated O-maze to assess anxiety, and food reward trials in the open field enclosure to assess reward-seeking behavior. The oxytocin treatment decreased fear related symptoms upon re-exposure to the fear conditioning chamber; both colonic motility and freezing time were lower in the Oxytocin+Stress group compared to the Stress group. The foot shock model failed to produce significant behavioral changes related to anxiety and reward-seeking behavior between the Control and Stress groups

Do Cross-National Differences in the Costs of Children Generate Cross-National Differences in Fertility Rates?

Parity-specific probabilities of having a next birth are estimated from national fertility data and are compared with nation-specific costs of having children as measured by time-budget data, by attitude data from the International Social Survey Program, and by panel data on labor earnings and standard of living changes following a birth. We focus on five countries (the US, West Germany, Denmark, Italy, and the United Kingdom), whose fertility rates span the observed fertility range in the contemporary industrialized world and whose social welfare and family policies span the conceptual space of standard welfare-state typologies. Definitive conclusions are difficult because of the multiple dimensions on which child costs can be measured, the possibility that child costs affect both the quantum and the tempo of fertility, the relatively small fertility differences across industrialized nations, and the inherent small-N problem resulting from nation-level comparisons. Empirical analysis, however, supports the assertion that institutionally driven child costs affect the fertility patterns of industrialized nations.

Development of a high-throughput in vitro assay to identify selective inhibitors for human ALDH1A1

The human aldehyde dehydrogenase (ALDH) superfamily consists of at least 19 enzymes that metabolize endogenous and exogenous aldehydes. Currently, there are no commercially available inhibitors that target ALDH1A1 but have little to no effect on the structurally and functionally similar ALDH2. Here we present the first human ALDH1A1 structure, as the apo-enzyme and in complex with its cofactor NADH to a resolution of 1.75 and 2.1Å, respectfully. Structural comparisons of the cofactor binding sites in ALDH1A1 with other closely related ALDH enzymes illustrate a high degree of similarity. In order to minimize discovery of compounds that inhibit both isoenzymes by interfering with their conserved cofactor binding sites, this study reports the use of an in vitro, NAD(+)-independent, esterase-based high-throughput screen (HTS) of 64,000 compounds to discover novel, selective inhibitors of ALDH1A1. We describe 256 hits that alter the esterase activity of ALDH1A1. The effects on aldehyde oxidation of 67 compounds were further analyzed, with 30 selectively inhibiting ALDH1A1 compared to ALDH2 and ALDH3A1. One compound inhibited ALDH1A1 and ALDH2, while another inhibited ALDH1A1, ALDH2, and the more distantly related ALDH3A1. The results presented here indicate that this in vitro enzyme activity screening protocol successfully identified ALDH1A1 inhibitors with a high degree of isoenzyme selectivity. The compounds identified via this screen plus the screening methodology itself represent a starting point for the development of highly potent and selective inhibitors of ALDH1A1 that may be utilized to better understand the role of this enzyme in both normal and disease states

Characterization of Two Distinct Structural Classes of Selective Aldehyde Dehydrogenase 1A1 Inhibitors.

Aldehyde dehydrogenases (ALDH) catalyze the irreversible oxidation of aldehydes to their corresponding carboxylic acid. Alterations in ALDH1A1 activity are associated with such diverse diseases as cancer, Parkinson?s disease, obesity, and cataracts. Inhibitors of ALDH1A1 could aid in illuminating the role of this enzyme in disease processes. However, there are no commercially available selective inhibitors for ALDH1A1. Here we characterize two distinct chemical classes of inhibitors that are selective for human ALDH1A1 compared to eight other ALDH isoenzymes. The prototypical members of each structural class, CM026 and CM037, exhibit submicromolar inhibition constants but have different mechanisms of inhibition. The crystal structures of these compounds bound to ALDH1A1 demonstrate that they bind within the aldehyde binding pocket of ALDH1A1 and exploit the presence of a unique glycine residue to achieve their selectivity. These two novel and selective ALDH1A1 inhibitors may serve as chemical tools to better understand the contributions of ALDH1A1 to normal biology and to disease states

Communicating moral legitimacy in controversial industries: the trade in human tissue

Globally active companies are involved in the discursive construction of moral legitimacy. Establishing normative conformance is problematic given the plurality of norms and values worldwide, and is particularly difficult for companies operating in morally controversial industries. In this paper, we investigate how organizations publicly legitimize the trade of human tissue for private profit when this practice runs counter to deep-seated and widespread moral beliefs. To do so, we use inductive, qualitative methods to analyze the website discourse of three types of organizations that trade in human tissue and are associated with different degrees of moral controversy with respect to tissue procurement and use. Our analysis reveals an object-oriented approach to moral legitimizing centered on the human tissue as a morally disputed good. We find that the website discourse translates human tissue into technology, constructs normative meaning around a dominant instrumental value associated with human-tissue-as-technology, and reproduces and stabilizes this meaning by six discursive mechanisms that amplify and anchor it. Moreover, the use of amplifying and anchoring discourse was greater in organizations associated with greater controversy. The results are consistent with an object-oriented sociality

Effect of reactor irradiation on Santowax WR : irradiations from 425° F to 800° F at 40% fast neutron fraction

"MIT-334-34."Includes bibliographical referencesM.I.T. DSR Project no. 9819Contract AT(38-1)-33

Superconducting Diamond on Silicon Nitride for Device Applications

Chemical vapour deposition (CVD) grown nanocrystalline diamond is an attractive material for the fabrication of devices. For some device architectures, optimisation of its growth on silicon nitride is essential. Here, the effects of three pre-growth surface treatments, often employed as cleaning methods of silicon nitride, were investigated. Such treatments provide control over the surface charge of the substrate through modification of the surface functionality, allowing for the optimisation of electrostatic diamond seeding densities. Zeta potential measurements and X-ray photoelectron spectroscopy (XPS) were used to analyse the silicon nitride surface following each treatment. Exposing silicon nitride to an oxygen plasma offered optimal surface conditions for the electrostatic self-assembly of a hydrogen-terminated diamond nanoparticle monolayer. The subsequent growth of boron-doped nanocrystalline diamond thin films on modified silicon nitride substrates under CVD conditions produced coalesced films for oxygen plasma and solvent treatments, whilst pin-holing of the diamond film was observed following RCA-1 treatment. The sharpest superconducting transition was observed for diamond grown on oxygen plasma treated silicon nitride, demonstrating it to be of the least structural disorder. Modifications to the substrate surface optimise the seeding and growth processes for the fabrication of diamond on silicon nitride devices

Continuous Diffraction of Molecules and Disordered Molecular Crystals

The diffraction pattern of a single non-periodic compact object, such as a molecule, is continuous and is proportional to the square modulus of the Fourier transform of that object. When arrayed in a crystal, the coherent sum of the continuous diffracted wave-fields from all objects gives rise to strong Bragg peaks that modulate the single-object transform. Wilson statistics describe the distribution of continuous diffraction intensities to the same extent that they apply to Bragg diffraction. The continuous diffraction obtained from translationally-disordered molecular crystals consists of the incoherent sum of the wave-fields from the individual rigid units (such as molecules) in the crystal, which is proportional to the incoherent sum of the diffraction from the rigid units in each of their crystallographic orientations. This sum over orientations modifies the statistics in a similar way that crystal twinning modifies the distribution of Bragg intensities. These statistics are applied to determine parameters of continuous diffraction such as its scaling, the beam coherence, and the number of independent wave-fields or object orientations contributing. Continuous diffraction is generally much weaker than Bragg diffraction and may be accompanied by a background that far exceeds the strength of the signal. Instead of just relying upon the smallest measured intensities to guide the subtraction of the background it is shown how all measured values can be utilised to estimate the background, noise, and signal, by employing a modified "noisy Wilson" distribution that explicitly includes the background. Parameters relating to the background and signal quantities can be estimated from the moments of the measured intensities. The analysis method is demonstrated on previously-published continuous diffraction data measured from imperfect crystals of photosystem II.Comment: 34 pages, 11 figures, 2 appendice