Anatomical heterogeneity of tendon: Fascicular and interfascicular tendon compartments have distinct proteomic composition

This study was funded by the BBSRC (BB/K008412/1)

Analytical profile, in vitro metabolism and behavioral properties of the lysergamide 1P-AL-LAD

Lysergic acid diethylamide (LSD) is known to induce powerful psychoactive effects in humans, which cemented its status as an important tool for clinical research. A range of analogues and derivatives has been investigated over the years, including those classified as new psychoactive substances. This study presents the characterization of the novel lysergamide N,N-diethyl-1-propanoyl-6-(prop-2-en-1-yl)-9,10-didehydroergoline-8β-carboxamide (1P-AL-LAD) using various mass spectrometric, gas- and liquid chromatographic and spectroscopic methods. In vitro metabolism studies using pooled human liver microsomes (pHLM) confirmed that 1P-AL-LAD converted to AL-LAD as the most abundant metabolite consistent with the hypothesis that 1P-AL-LAD may act as a prodrug. Fourteen metabolites were detected in total; metabolic reactions included hydroxylation of the core lysergamide ring structure or the N6-allyl group, formation of dihydrodiol metabolites, N-dealkylation, N1-deacylation, dehydrogenation, and combinations thereof. The in vivo behavioral activity of 1P-AL-LAD was evaluated using the mouse head twitch response (HTR), a 5-HT2A-mediated head movement that serves as a behavioral proxy in rodents for human hallucinogenic effects. 1P-AL-LAD induced a dose-dependent increase in HTR counts with an inverted U-shaped dose-response function, similar to lysergic acid diethylamide (LSD), psilocybin, and other psychedelics. Following intraperitoneal injection, the median effective dose (ED50) for 1P-AL-LAD was 491 nmol/kg, making it almost three times less potent than AL-LAD (174.9 nmol/kg). Previous studies have shown that N1-substitution disrupts the ability of lysergamides to activate the 5-HT2A receptor; based on the in vitro metabolism data, 1P-AL-LAD may induce the HTR because it acts as a prodrug and is metabolized to AL-LAD after administration to mice

The impact of big data on world-class sustainable manufacturing

Big data (BD) has attracted increasing attention from both academics and practitioners. This paper aims at illustrating the role of big data analytics in supporting world-class sustainable manufacturing (WCSM). Using an extensive literature review to identify different factors that enable the achievement of WCSM through BD and 405 usable responses from senior managers gathered through social networking sites (SNS), we propose a conceptual framework using constructs obtained using reduction of gathered data that summarizes this role; test this framework using data which is heterogeneous, diverse, voluminous, and possess high velocity; and highlight the importance for academia and practice. Finally, we conclude our research findings and further outlined future research directions

Dust and molecular formation in supernovae

Up to 1987, supernovae (SNe) and supernova remnants (SNRs) had been thought to be hostile environments for molecules and dust grains. Fast-moving electrons in young SNe can destroy molecules, and strong X-ray radiation and shocks can destroy molecules and dust grains in SNRs. That concept was broken by detection of CO, SiO, and dust thermal emission in Supernova 1987A. Since 1987, the number of studies which have found molecules and dust in SNe and SNRs is slowly increasing. Detecting molecules can be a powerful tool to investigate dynamical motion, density, temperature, and chemistry. Dust formation can affect the thermal balance in SNe and SNRs, and radiation from dust grains can be about as high as 50 % of the cooling of the expanding ejecta. Isotopologues are molecules that differ only in respect to the isotopes of some of the constituent elements. Isotopologues found in SNe and SNR probe isotopes that can be compared with predictions of explosive nucleosynthesis. Because SNe are a major source of heavy elements, if a significant fraction of refractory elements condense into dust grains, SNe can be an important source of the dust in the interstellar medium of galaxies. In this review, the discovery of molecules and dust in SNe and SNRs and their implications are summarised