Distribution and characterisation of Glucagon-like peptide-1 receptor expressing cells in the mouse brain.

© 2015 The Authors.Objective: Although Glucagon-like peptide 1 is a key regulator of energy metabolism and food intake, the precise location of GLP-1 receptors and the physiological relevance of certain populations is debatable. This study investigated the novel GLP-1R-Cre mouse as a functional tool to address this question. Methods: Mice expressing Cre-recombinase under the Glp1r promoter were crossed with either a ROSA26 eYFP or tdRFP reporter strain to identify GLP-1R expressing cells. Patch-clamp recordings were performed on tdRFP-positive neurons in acute coronal brain slices from adult mice and selective targeting of GLP-1R cells in vivo was achieved using viral gene delivery. Results: Large numbers of eYFP or tdRFP immunoreactive cells were found in the circumventricular organs, amygdala, hypothalamic nuclei and the ventrolateral medulla. Smaller numbers were observed in the nucleus of the solitary tract and the thalamic paraventricular nucleus. However, tdRFP positive neurons were also found in areas without preproglucagon-neuronal projections like hippocampus and cortex. GLP-1R cells were not immunoreactive for GFAP or parvalbumin although some were catecholaminergic. GLP-1R expression was confirmed in whole-cell recordings from BNST, hippocampus and PVN, where 100 nM GLP-1 elicited a reversible inward current or depolarisation. Additionally, a unilateral stereotaxic injection of a cre-dependent AAV into the PVN demonstrated that tdRFP-positive cells express cre-recombinase facilitating virally-mediated eYFP expression. Conclusions: This study is a comprehensive description and phenotypic analysis of GLP-1R expression in the mouse CNS. We demonstrate the power of combining the GLP-1R-CRE mouse with a virus to generate a selective molecular handle enabling future in vivo investigation as to their physiological importance

Discovery of the Cadmium Isotopes

Thirty-seven cadmium isotopes have so far been observed; the discovery of these isotopes is discussed. For each isotope a brief summary of the first refereed publication, including the production and identification method, is presented.Comment: to be published in Atomic Data and Nuclear Data Table

Overview and status of the 0.5NA EUV microfield exposure tool at Berkeley Lab

A 0.5-NA extreme ultraviolet micro-field exposure tool has been installed and commissioned at beamline 12.0.1.4 of the Advanced Light Source synchrotron facility at Lawrence Berkeley National Laboratory. Commissioning has demonstrated a patterning resolution of 13 nm half-pitch with annular 0.35-0.55 illumination; a patterning resolution of 8 nm half-pitch with annular 0.1-0.2 illumination; critical dimension (CD) uniformity of 0.7 nm 1σ on 16 nm nominal CD across 80% of the 200 um x 30 um aberration corrected field of view; aerial image vibration relative to the wafer of 0.75 nn RMS and focus control and focus stepping better than 15 nm

Achieving diffraction-limited performance on the Berkeley MET5

The Berkeley MET5, funded by EUREKA, is a 0.5-NA EUV projection lithography tool located at the Advanced Light Source at Berkeley National Lab. Wavefront measurements of the MET5 optic have been performed using a custom in-situ lateral shearing interferometer suitable for high-NA interferometry. In this paper, we report on the most recent characterization of the MET5 optic demonstrating an RMS wavefront 0.31 nm, and discuss the specialized mask patterns, gratings, and illumination geometries that were employed to accommodate the many challenges associated with high-NA EUV interferometry

PPG neurons of the lower brain stem and their role in brain GLP-1 receptor activation

Within the brain, glucagon-like peptide-1 (GLP-1) affects central autonomic neurons, including those controlling the cardiovascular system, thermogenesis, and energy balance. Additionally, GLP-1 influences the mesolimbic reward system to modulate the rewarding properties of palatable food. GLP-1 is produced in the gut and by hindbrain preproglucagon (PPG) neurons, located mainly in the nucleus tractus solitarii (NTS) and medullary intermediate reticular nucleus. Transgenic mice expressing glucagon promoter-driven yellow fluorescent protein revealed that PPG neurons not only project to central autonomic control regions and mesolimbic reward centers, but also strongly innervate spinal autonomic neurons. Therefore, these brain stem PPG neurons could directly modulate sympathetic outflow through their spinal inputs to sympathetic preganglionic neurons. Electrical recordings from PPG neurons in vitro have revealed that they receive synaptic inputs from vagal afferents entering via the solitary tract. Vagal afferents convey satiation to the brain from signals like postprandial gastric distention or activation of peripheral GLP-1 receptors. CCK and leptin, short- and long-term satiety peptides, respectively, increased the electrical activity of PPG neurons, while ghrelin, an orexigenic peptide, had no effect. These findings indicate that satiation is a main driver of PPG neuronal activation. They also show that PPG neurons are in a prime position to respond to both immediate and long-term indicators of energy and feeding status, enabling regulation of both energy balance and general autonomic homeostasis. This review discusses the question of whether PPG neurons, rather than gut-derived GLP-1, are providing the physiological substrate for the effects elicited by central nervous system GLP-1 receptor activation

Exploring community pharmacists' use of health literacy interventions in their everyday practice.

BACKGROUND: Limited health literacy often results in people inadequately understanding medicines-related information and subsequently not taking medicines as prescribed. Using health literacy interventions is important for community pharmacists, as they are increasingly managing long-term conditions. However, there appear to be no previous studies of community pharmacists' everyday use of health literacy interventions in the UK. OBJECTIVES: To explore UK community pharmacists' perspectives on the usability of health literacy interventions in their everyday practice. METHODS: Semi-structured interviews were conducted with participants, following attendance at health literacy training that included practicing the use of four health literacy interventions (Teach-Back, Chunk and Check, Simple Language and visual aids) and two months experience of attempting to use them in their everyday practice. Participants were pharmacists from community pharmacies in Staffordshire, England who were invited to participate by an email sent to the pharmacy. Interviews were audio-recorded, transcribed verbatim and analysed using the Framework Analysis technique. RESULTS: Four themes emerged from 11 interviews undertaken: intervention appeal, limitations, adaptations and continued use. Participants reported using all four health literacy interventions in their everyday practice but Teach-Back appeared to be favoured most. Most participants talked about practicing Teach-Back before using it with patients but described it as useable with patients of all ages, without being prohibitively time consuming. Chunk and Check seemed to be viewed as a type of Teach-Back, whilst visual aids were reported as being used in conjunction with Teach Back rather than as a standalone intervention. Participants reported that Simple Language was an easy concept but easily 'slipped back' into medical jargon and were challenged to use simple enough words. All participants said they would continue to use all four health literacy interventions. CONCLUSIONS: The findings suggest that with training, community pharmacists can successfully incorporate these four health literacy interventions into their everyday practice

Changes in Habitat Use of Montezuma Quail in Response to Tree Canopy Reduction in the Capitan Mountains of New Mexico

Montezuma quail (Cyrtonyx montezumae) are unique among quail with respect to clutch size, diet, covey dynamics, and habitat use. With the exception of a few notable early studies, there is relatively little information on the ecology of Montezuma quail. Pervious research has indicated that one of the primary habitats utilized by Montezuma quail is pinyon–juniper (Pinus spp.–Juniperus spp.) woodlands. Throughout many areas of the southwestern United States, pinyon–juniper woodlands are often targeted for thinning projects. Many studies have been conducted on the amount of canopy cover needed by other quail species. However, data on characteristics of their preferred habitat in many of the mountains they inhabit is limited in the literature and no data are currently published on their response to thinning projects. Therefore, studies are warranted to fill in these missing data, which will increase our knowledge about the habitat requirements of Montezuma quail and allow us to make informed decisions about thinning projects in areas occupied by Montezuma quail. The goal of this research was to evaluate Montezuma quail responses to common silvicultural practices, specifically pinyon–juniper thinning in the Capitan Mountains of New Mexico. Results of our project indicated that Montezuma quail selected for sites that had been thinned to reduce canopy cover to a 30–40% mosaic. Selection for this habitat was much higher than selection for the surrounding area, which consisted of ≥70% canopy cover (Manly–Chesson Selectivity Index = 1.68). Overall, this study yields vital information for managers considering implanting thinning projects in Montezuma quail habitat

W-Curve Alignments for HIV-1 Genomic Comparisons

The W-curve was originally developed as a graphical visualization technique for viewing DNA and RNA sequences. Its ability to render features of DNA also makes it suitable for computational studies. Its main advantage in this area is utilizing a single-pass algorithm for comparing the sequences. Avoiding recursion during sequence alignments offers advantages for speed and in-process resources. The graphical technique also allows for multiple models of comparison to be used depending on the nucleotide patterns embedded in similar whole genomic sequences. The W-curve approach allows us to compare large numbers of samples quickly.We are currently tuning the algorithm to accommodate quirks specific to HIV-1 genomic sequences so that it can be used to aid in diagnostic and vaccine efforts. Tracking the molecular evolution of the virus has been greatly hampered by gap associated problems predominantly embedded within the envelope gene of the virus. Gaps and hypermutation of the virus slow conventional string based alignments of the whole genome. This paper describes the W-curve algorithm itself, and how we have adapted it for comparison of similar HIV-1 genomes. A treebuilding method is developed with the W-curve that utilizes a novel Cylindrical Coordinate distance method and gap analysis method. HIV-1 C2-V5 env sequence regions from a Mother/Infant cohort study are used in the comparison.The output distance matrix and neighbor results produced by the W-curve are functionally equivalent to those from Clustal for C2-V5 sequences in the mother/infant pairs infected with CRF01_AE.Significant potential exists for utilizing this method in place of conventional string based alignment of HIV-1 genomes, such as Clustal X. With W-curve heuristic alignment, it may be possible to obtain clinically useful results in a short time-short enough to affect clinical choices for acute treatment. A description of the W-curve generation process, including a comparison technique of aligning extremes of the curves to effectively phase-shift them past the HIV-1 gap problem, is presented. Besides yielding similar neighbor-joining phenogram topologies, most Mother and Infant C2-V5 sequences in the cohort pairs geometrically map closest to each other, indicating that W-curve heuristics overcame any gap problem