Photoelectrochemical fabrication of spectroscopic diffraction gratings, phase 2

This program was directed toward the production of Echelle diffraction gratings by a light-driven, electrochemical etching technique (photoelectrochemical etching). Etching is carried out in single crystal materials, and the differential rate of etching of the different crystallographic planes used to define the groove profiles. Etching of V-groove profiles was first discovered by us during the first phase of this project, which was initially conceived as a general exploration of photoelectrochemical etching techniques for grating fabrication. This highly controllable V-groove etching process was considered to be of high significance for producing low pitch Echelles, and provided the basis for a more extensive Phase 2 investigation

Identification of Dimethyldioctadecylammonium Ion (m/z 550.6) and Related Species (m/z 522.6, 494.6) as a Source of Contamination in Mass Spectrometry

Chemical contamination can be one of the more common problems encountered when performing trace-level analysis regardless of the analytical technique. Minimizing or eliminating background interferences can be a difficult task, so knowledge of the chemical composition of these contaminants can prove invaluable when it comes to identifying the source. Once the source is identified, proper steps may be taken to reduce or eliminate it. In this study, we report the identity of some commonly seen contaminants (m/z 550.6, 522.6, and 494.6) in electrospray ionization (ESI) mass spectrometry (MS). Through MS, tandem MS, accurate-mass, and high-resolution measurements we have identified these background contaminants as being quaternary ammonium species that contain long-chain hydrocarbon groups, where m/z 550.6 is a dimethyldioctadecylammonium ion (C18, C18) and m/z 522.6 and 494.6 are similar in nature but have shorter alkyl-chain groups. The lipophilic nature of these compounds and the fact that they have molecular weights similar to lysophospholipids make them a frequent contaminant in lipidomic studies. The likely sources of these compounds are commonly used personal and household products

Mice with altered serotonin 2C receptor RNA editing display characteristics of Prader–Willi syndrome

RNA transcripts encoding the 2C-subtype of serotonin (5HT2C) receptor undergo up to five adenosine-to-inosine editing events to encode twenty-four protein isoforms. To examine the effects of altered 5HT2C editing in vivo, we generated mutant mice solely expressing the fully-edited (VGV) isoform of the receptor. Mutant animals present phenotypic characteristics of Prader-Willi Syndrome (PWS) including a failure to thrive, decreased somatic growth, neonatal muscular hypotonia, and reduced food consumption followed by post-weaning hyperphagia. Though previous studies have identified alterations in both 5HT2C receptor expression and 5HT2C-mediated behaviors in both PWS patients and mouse models of this disorder, to our knowledge the 5HT2C gene is the first locus outside the PWS imprinted region in which mutations can phenocopy numerous aspects of this syndrome. These results not only strengthen the link between the molecular etiology of PWS and altered 5HT2C expression, but also demonstrate the importance of normal patterns of 5HT2C RNA editing in vivo

Obesity and altered glucose metabolism impact HDL composition in CETP transgenic mice: a role for ovarian hormones

Mechanisms underlying changes in HDL composition caused by obesity are poorly defined, partly because mice lack expression of cholesteryl ester transfer protein (CETP), which shuttles triglyceride and cholesteryl ester between lipoproteins. Because menopause is associated with weight gain, altered glucose metabolism, and changes in HDL, we tested the effect of feeding a high-fat diet (HFD) and ovariectomy (OVX) on glucose metabolism and HDL composition in CETP transgenic mice. After OVX, female CETP-expressing mice had accelerated weight gain with HFD-feeding and impaired glucose tolerance by hyperglycemic clamp techniques, compared with OVX mice fed a low-fat diet (LFD). Sham-operated mice (SHAM) did not show HFD-induced weight gain and had less glucose intolerance than OVX mice. Using shotgun HDL proteomics, HFD-feeding in OVX mice had a large effect on HDL composition, including increased levels of apoA2, apoA4, apoC2, and apoC3, proteins involved in TG metabolism. These changes were associated with decreased hepatic expression of SR-B1, ABCA1, and LDL receptor, proteins involved in modulating the lipid content of HDL. In SHAM mice, there were minimal changes in HDL composition with HFD feeding. These studies suggest that the absence of ovarian hormones negatively influences the response to high-fat feeding in terms of glucose tolerance and HDL composition. CETP-expressing mice may represent a useful model to define how metabolic changes affect HDL composition and function

Melatonin in Children with Autism Spectrum Disorders: Endogenous and Pharmacokinetic Profiles in Relation to Sleep

Supplemental melatonin has been used to treat sleep onset insomnia in children with autism spectrum disorders (ASD), although the mechanism of action is uncertain. We assessed endogenous and supplemental melatonin profiles in relation to sleep in nine children with ASD. In endogenous samples, maximal melatonin concentration ( C max ) and time to peak concentration ( T max ) were comparable to those previously published in the literature for typically developing children, and dim light melatonin onsets were captured in the majority of children. In treatment samples (supplemental melatonin), melatonin parameters were also comparable to those previously published for typically developing children. Our findings support that children with ASD and insomnia responsive to low dose melatonin treatment have relatively normal profiles of endogenous and supplemental melatonin