TOWARDS MODELS FOR IMPROVEMENT OF THE PLANNING PROCESS IN DETRIOT AND EDINBURGH

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The Discovery and Analysis of PFAS (‘Forever Chemicals’) in Human Blood and Biological Materials

This paper reviews the development of analytical techniques used prior to the early 1980s in the identification of organofluorine compounds in human blood. The compounds of interest are industrial products, the so-called Forever Chemicals, which are stable long-chain per- and polyfluoroalkyl substances (PFAS) that are highly resistant to breakdown. Because of their special properties they have been used since the 1950s in a wide range of commercial and domestic products. Academic research in the 1960s and 1970s that originally focused on fluoride in dentistry and human health led to the finding that PFAS were present in the blood of residents of several cities in the United States. This, and concerns over their toxic properties, encouraged industrial research into analytical methods for their detection. Notably, and because long-chain PFAS are nonvolatile, special techniques were developed for analysis by gas chromatography

Neuroendocrine and neurotrophic signaling in Huntington\u27s disease: Implications for pathogenic mechanisms and treatment strategies

Huntington\u27s disease (HD) is a fatal neurodegenerative disease caused by an extended polyglutamine tract in the huntingtin protein. Circadian, sleep and hypothalamic-pituitary-adrenal (HPA) axis disturbances are observed in HD as early as 15 years before clinical disease onset. Disturbances in these key processes result in increased cortisol and altered melatonin release which may negatively impact on brain-derived neurotrophic factor (BDNF) expression and contribute to documented neuropathological and clinical disease features. This review describes the normal interactions between neurotrophic factors, the HPA-axis and circadian rhythm, as indicated by levels of BDNF, cortisol and melatonin, and the alterations in these intricately balanced networks in HD. We also discuss the implications of these alterations on the neurobiology of HD and the potential to result in hypothalamic, circadian, and sleep pathologies. Measurable alterations in these pathways provide targets that, if treated early, may reduce degeneration of brain structures. We therefore focus here on the means by which multidisciplinary therapy could be utilised as a non-pharmaceutical approach to restore the balance of these pathways

Rate of torque development and striatal shape in individuals with prodromal Huntington\u27s disease

The aim of the present study was to quantify explosive joint torque or the ability to develop joint torque rapidly, typically measured as the rate of torque development, in individuals with prodromal Huntington’s disease and healthy controls and its associations with measures of disease burden and striatal pathology. Twenty prodromal Huntington’s disease and 19 healthy control individuals volunteered for this study. Plantar flexor isometric rate of torque development values were evaluated using isokinetic dynamometry. Pathological changes in striatal shape were evaluated using magnetic resonance imaging. Disease burden was evaluated using the disease burden score and cytosine-adenine-guanine age product score. No statistical differences in the rate of torque development were observed between individuals with prodromal Huntington’s disease and healthy controls. However, significant associations were observed between the rate of torque development values and measures of disease burden (r = −0.42 to −0.69) and striatal pathology (r = 0.71–0.60) in individuals with prodromal Huntington’s disease. We found significant associations between lower rate of torque development values and greater striatal shape deflation and disease burden and striatal pathology in individuals with prodromal Huntington’s disease. While no significant differences in the rate of torque development were found between prodromal Huntington’s disease and healthy controls, the noted associations suggest that differences may emerge as the disease advances, which should be investigated longitudinally in future studies

Effects of Cyclic Chronic Heat Stress on the Expression of Nutrient Transporters in the Jejunum of Modern Broilers and Their Ancestor Wild Jungle Fowl

snibaThe mechanisms associated between growth rate, gut integrity and heat stress (HS) responses are not known. The current study aimed to evaluate the effect of chronic HS on jejunal nutrient transport in slow- (ACRB from 1950), moderate- (95RAN from 1995), rapid-(modern broilers, MRB) growing birds, and their ancestor wild jungle fowl (JF). One-day male chicks (n=150/line) were placed by line in environmentally controlled chambers and kept under the same environmental conditions until d28. On d29, an 8-h daily cyclic HS (36ºC) was applied to half of the chambers, which lasts until d55, while keeping the rest under thermal neutral conditions (TN, 24°C). Jejunum tissues were collected for morphology assessment and molecular analysis of carbohydrate-, amino acid- and fatty acid- transporters. MRB exhibited the highest BW followed by 95RAN under both conditions. HS decreased FI in MRB and 95RAN, which results in lower BW compared to their TN counterparts, however no effect was observed in ACRB and JF. MRB showed greater villus height to crypt depth ratio under both environmental conditions. Molecular analyses showed that GLUT2, 5, 10, and 11 were upregulated in MRB compared to some of the other populations under TN conditions. HS down regulated GLUT2, 10, 11, and 12 in MRB while it increased the expression of GLUT1, 5, 10, and 11 in JF. GLUT2 protein expression was higher in JF compared to ACRB and MRB under TN conditions. It also showed an increase in ACRB but no effect on 95RAN and MRB under HS conditions. ACRB exhibited greater expression of EAAT3 gene as compared to the rest of populations maintained under TN conditions. HS exposure did not alter the gene expression of amino acid transporters in MRB. Gene expression of CD36 and FABP2 was up-regulated in HS JF birds. Protein expression of CD36 was down-regulated in HS JF while no effect was observed in ACRB, 95RAN and MRB. Taken together, these data are the first to show the effect of HS on jejunal expression of nutrient transporters in three broiler populations known to represent 70 years of genetic progress in the poultry industr

A microRNA negative feedback loop downregulates vesicle transport and inhibits fear memory

The SNARE-mediated vesicular transport pathway plays major roles in synaptic remodeling associated with formation of long-term memories, but the mechanisms that regulate this pathway during memory acquisition are not fully understood. Here we identify miRNAs that are up-regulated in the rodent hippocampus upon contextual fear-conditioning and identify the vesicular transport and synaptogenesis pathways as the major targets of the fear-induced miRNAs. We demonstrate that miR-153, a member of this group, inhibits the expression of key components of the vesicular transport machinery, and down-regulates Glutamate receptor A1 trafficking and neurotransmitter release. MiR-153 expression is specifically induced during LTP induction in hippocampal slices and its knockdown in the hippocampus of adult mice results in enhanced fear memory. Our results suggest that miR-153, and possibly other fear-induced miRNAs, act as components of a negative feedback loop that blocks neuronal hyperactivity at least partly through the inhibition of the vesicular transport pathway.Brain & Behavior Research Foundation (Young Investigator Award)JPB Foundatio

Performance of the Gemini Planet Imager Non-Redundant Mask and spectroscopy of two close-separation binaries HR 2690 and HD 142527

The Gemini Planet Imager (GPI) contains a 10-hole non-redundant mask (NRM), enabling interferometric resolution in complement to its coronagraphic capabilities. The NRM operates both in spectroscopic (integral field spectrograph, henceforth IFS) and polarimetric configurations. NRM observations were taken between 2013 and 2016 to characterize its performance. Most observations were taken in spectroscopic mode with the goal of obtaining precise astrometry and spectroscopy of faint companions to bright stars. We find a clear correlation between residual wavefront error measured by the AO system and the contrast sensitivity by comparing phase errors in observations of the same source, taken on different dates. We find a typical 5-$\sigma$ contrast sensitivity of $2-3~\times~10^{-3}$ at $\sim\lambda/D$. We explore the accuracy of spectral extraction of secondary components of binary systems by recovering the signal from a simulated source injected into several datasets. We outline data reduction procedures unique to GPI's IFS and describe a newly public data pipeline used for the presented analyses. We demonstrate recovery of astrometry and spectroscopy of two known companions to HR 2690 and HD 142527. NRM+polarimetry observations achieve differential visibility precision of $\sigma\sim0.4\%$ in the best case. We discuss its limitations on Gemini-S/GPI for resolving inner regions of protoplanetary disks and prospects for future upgrades. We summarize lessons learned in observing with NRM in spectroscopic and polarimetric modes.Comment: Accepted to AJ, 22 pages, 14 figure

Performance of the Gemini Planet Imager Non-Redundant Mask and Spectroscopy of Two Close-Separation Binaries: HR 2690 and HD 142527

The Gemini Planet Imager (GPI) contains a 10-hole non-redundant mask (NRM), enabling interferometric resolution in complement to its coronagraphic capabilities. The NRM operates both in spectroscopic (integral field spectrograph, henceforth IFS) and polarimetric configurations. NRM observations were taken between 2013 and 2016 to characterize its performance. Most observations were taken in spectroscopic mode, with the goal of obtaining precise astrometry and spectroscopy of faint companions to bright stars. We find a clear correlation between residual wavefront error measured by the adaptive optic system and the contrast sensitivity by comparing phase errors in observations of the same source, taken on different dates. We find a typical 5σ contrast sensitivity of (2-3) × 10-3 at ∼λ/D. We explore the accuracy of spectral extraction of secondary components of binary systems by recovering the signal from a simulated source injected into several data sets. We outline data reduction procedures unique to GPI\u27s IFS and describe a newly public data pipeline used for the presented analyses. We demonstrate recovery of astrometry and spectroscopy of two known companions to HR 2690 and HD 142527. NRM+polarimetry observations achieve differential visibility precision of σ ∼ 0.4% in the best case. We discuss its limitations on Gemini-S/GPI for resolving inner regions of protoplanetary disks and prospects for future upgrades. We summarize lessons learned in observing with NRM in spectroscopic and polarimetric modes