Building a Sustainable Comprehensive Women's Health Program: The Michigan Model

The Women's Health Program at the University of Michigan was established in 1993 and has developed into a successful, federally supported program that links clinical research and education activities across the University. It has focused on human resource capacity building, sustainable financial support and infrastructure, and adaptability to change and opportunities. Widely accepted standards, demonstrated value, committed leaders/champions, and participatory culture have contributed to its success and are important to its future.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/63102/1/jwh.2006.0192.pd

Expression of ZIC genes in the development of the chick inner ear and nervous system

ZIC genes, vertebrate homologues of the Drosophila pair-rule gene odd-paired ( opa ), function in embryonic pattern formation, in the early stages of central nervous system neurogenesis and in cerebellar maturation. Mouse Zic genes are expressed in restricted, and in some cases overlapping, patterns during development, particularly in the central and peripheral nervous systems. We identified chick ZIC2 in a differential display analysis of the auditory system designed to find genes up-regulated after noise trauma. In this study, we examined the expression of chick ZIC1 , ZIC2 , and ZIC3 by in situ hybridization in normal inner ear development and in the tissues that influence its development, including the hindbrain, the neural crest, and the periotic mesenchyme. Between Hamburger and Hamilton stages 13 and 24, all three ZIC genes were found in the dorsal periotic mesenchyme adjacent to the developing inner ear. ZIC1 mRNA was expressed in the otocyst epithelium between stages 12 and 24, in some sensory tissue, as well as in a striped pattern in the floorplate of the hindbrain that appears to be complementary to that of Chordin, a gene known to regulate ZIC expression in frogs. Chick ZIC genes are also expressed in the neuroectoderm, paraxial mesenchyme, brain, spinal cord, neural crest, and/or the overlying ectoderm as well as the limb buds. In general, ZIC1 and ZIC2 expression patterns overlapped, although ZIC2 expression was less robust; ZIC3 expression was minimal. These observations suggest that ZIC genes, in addition to their known roles in brain development, may play an important role in the development of the chick inner ear. Developmental Dynamics 702–712, 2003. © 2003 Wiley-Liss, Inc.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/35173/1/10262_ftp.pd

The collapse of intermediate structures?

How can we explain the rise of President Trump and the attraction of his campaign behavior before and since he took office? We argue here that the collapse of ‘intermediate structures’ has been a key factor; that the associations and groups which are building blocks of pluralistic politics have been eroded to such an extent that Trump’s personality politics have been able to take over the political stage

Structural basis for receptor activity-modifying protein-dependent selective peptide recognition by a G protein-coupled receptor

Association of receptor activity-modifying proteins (RAMP1-3) with the G protein-coupled receptor (GPCR) calcitonin receptor-like receptor (CLR) enables selective recognition of the peptides calcitonin gene-related peptide (CGRP) and adrenomedullin (AM) that have diverse functions in the cardiovascular and lymphatic systems. How peptides selectively bind GPCR:RAMP complexes is unknown. We report crystal structures of CGRP analog-bound CLR:RAMP1 and AM-bound CLR:RAMP2 extracellular domain heterodimers at 2.5 and 1.8 Å resolutions, respectively. The peptides similarly occupy a shared binding site on CLR with conformations characterized by a β-turn structure near their C termini rather than the α-helical structure common to peptides that bind related GPCRs. The RAMPs augment the binding site with distinct contacts to the variable C-terminal peptide residues and elicit subtly different CLR conformations. The structures and accompanying pharmacology data reveal how a class of accessory membrane proteins modulate ligand binding of a GPCR and may inform drug development targeting CLR:RAMP complexes

Identifying work related injuries: comparison of methods for interrogating text fields

Background: Work-related injuries in Australia are estimated to cost around $57.5 billion annually, however there are currently insufficient surveillance data available to support an evidence-based public health response. Emergency departments (ED) in Australia are a potential source of information on work-related injuries though most ED’s do not have an ‘Activity Code’ to identify work-related cases with information about the presenting problem recorded in a short free text field. This study compared methods for interrogating text fields for identifying work-related injuries presenting at emergency departments to inform approaches to surveillance of work-related injury.---------- Methods: Three approaches were used to interrogate an injury description text field to classify cases as work-related: keyword search, index search, and content analytic text mining. Sensitivity and specificity were examined by comparing cases flagged by each approach to cases coded with an Activity code during triage. Methods to improve the sensitivity and/or specificity of each approach were explored by adjusting the classification techniques within each broad approach.---------- Results: The basic keyword search detected 58% of cases (Specificity 0.99), an index search detected 62% of cases (Specificity 0.87), and the content analytic text mining (using adjusted probabilities) approach detected 77% of cases (Specificity 0.95).---------- Conclusions The findings of this study provide strong support for continued development of text searching methods to obtain information from routine emergency department data, to improve the capacity for comprehensive injury surveillance

Taqman Real-Time PCR Detects Avipoxvirus DNA in Blood of Hawaìi `Amakihi (Hemignathus virens)

Margaret E. M. Farias et al...Background Avipoxvirus sp. is a significant threat to endemic bird populations on several groups of islands worldwide, including Hawaìi, the Galapagos Islands, and the Canary Islands. Accurate identification and genotyping of Avipoxvirus is critical to the study of this disease and how it interacts with other pathogens, but currently available methods rely on invasive sampling of pox-like lesions and may be especially harmful in smaller birds. Methodology/Principal Findings Here, we present a nested TaqMan Real-Time PCR for the detection of the Avipoxvirus 4b core protein gene in archived blood samples from Hawaiian birds. The method was successful in amplifying Avipoxvirus DNA from packed blood cells of one of seven Hawaiian honeycreepers with confirmed Avipoxvirus infections and 13 of 28 Hawaìi `amakihi (Hemignathus virens) with suspected Avipoxvirus infections based on the presence of pox-like lesions. Mixed genotype infections have not previously been documented in Hawaìi but were observed in two individuals in this study. Conclusions/Significance We anticipate that this method will be applicable to other closely related strains of Avipoxvirus and will become an important and useful tool in global studies of the epidemiology of Avipoxvirus.Funding for this study was provided by: U.S. Geological Survey, Pacific Island Ecosystems Research Center (biology.usgs.gov/pierc/); U.S. Geological Survey Wildlife (biology.usgs.gov/wter/) and Invasive Species (biology.usgs.gov/invasive/) Programs; National Science Foundation (DEB0083944, www.nsf.gov); NIH/NCRR IDeA Networks of Biomedical Research Excellence (INBRE), P20RR016467 (http://www.ncrr.nih.gov/research_infrast​ructure/institutional_development_award/​idea_networks_of_biomedical_research_exc​ellence/). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.Peer reviewe

LSST: from Science Drivers to Reference Design and Anticipated Data Products

(Abridged) We describe here the most ambitious survey currently planned in the optical, the Large Synoptic Survey Telescope (LSST). A vast array of science will be enabled by a single wide-deep-fast sky survey, and LSST will have unique survey capability in the faint time domain. The LSST design is driven by four main science themes: probing dark energy and dark matter, taking an inventory of the Solar System, exploring the transient optical sky, and mapping the Milky Way. LSST will be a wide-field ground-based system sited at Cerro Pach\'{o}n in northern Chile. The telescope will have an 8.4 m (6.5 m effective) primary mirror, a 9.6 deg$^2$ field of view, and a 3.2 Gigapixel camera. The standard observing sequence will consist of pairs of 15-second exposures in a given field, with two such visits in each pointing in a given night. With these repeats, the LSST system is capable of imaging about 10,000 square degrees of sky in a single filter in three nights. The typical 5$\sigma$ point-source depth in a single visit in $r$ will be $\sim 24.5$ (AB). The project is in the construction phase and will begin regular survey operations by 2022. The survey area will be contained within 30,000 deg$^2$ with $\delta<+34.5^\circ$, and will be imaged multiple times in six bands, $ugrizy$, covering the wavelength range 320--1050 nm. About 90\% of the observing time will be devoted to a deep-wide-fast survey mode which will uniformly observe a 18,000 deg$^2$ region about 800 times (summed over all six bands) during the anticipated 10 years of operations, and yield a coadded map to $r\sim27.5$. The remaining 10\% of the observing time will be allocated to projects such as a Very Deep and Fast time domain survey. The goal is to make LSST data products, including a relational database of about 32 trillion observations of 40 billion objects, available to the public and scientists around the world.Comment: 57 pages, 32 color figures, version with high-resolution figures available from https://www.lsst.org/overvie

Calcitonin receptor N-glycosylation enhances peptide hormone affinity by controlling receptor dynamics

The class B G protein-coupled receptor (GPCR) calcitonin receptor (CTR) is a drug target for osteoporosis and diabetes. N-glycosylation of asparagine 130 in its extracellular domain (ECD) enhances calcitonin hormone affinity with the proximal GlcNAc residue mediating this effect through an unknown mechanism. Here, we present two crystal structures of salmon calcitonin-bound, GlcNAc-bearing CTR ECD at 1.78 and 2.85 Å resolutions and analyze the mechanism of the glycan effect. The N130 GlcNAc does not contact the hormone. Surprisingly, the structures are nearly identical to a structure of hormone-bound, N-glycan-free ECD, which suggested that the GlcNAc might affect CTR dynamics not observed in the static crystallographic snapshots. Hydrogen-deuterium exchange mass spectrometry and molecular dynamics simulations revealed that glycosylation stabilized a β-sheet adjacent to the N130 GlcNAc and the N-terminal α-helix near the peptide-binding site, while increasing flexibility of the peptide-binding site turret loop. These changes due to N-glycosylation increased the ligand on-rate and decreased its off rate. The glycan effect extended to RAMP-CTR amylin receptor complexes and was also conserved in the related CGRP receptor. These results reveal that N-glycosylation can modulate GPCR function by altering receptor dynamics

Is healthy neuroticism associated with longevity? A coordinated integrative data analysis

Early investigations of the neuroticism by conscientiousness interaction with regards to health have been promising, but to date, there have been no systematic investigations of this interaction that account for the various personality measurement instruments, varying populations, or aspects of health. The current study - the second of three - uses a coordinated analysis approach to test the impact of the neuroticism by conscientiousness interaction on the prevalence and incidence of chronic conditions. Using 15 pre-existing longitudinal studies (N > 49,375), we found that conscientiousness did not moderate the relationship between neuroticism and having hypertension (OR = 1.00,95%CI[0.98,1.02]), diabetes (OR = 1.02[0.99,1.04]), or heart disease (OR = 0.99[0.97,1.01]). Similarly, we found that conscientiousness did not moderate the prospective relationship between neuroticism and onset of hypertension (OR = 0.98,[0.95,1.01]), diabetes (OR = 0.99[0.94,1.05]), or heart disease (OR = 0.98[0.94,1.03]). Heterogeneity of effect sizes was largely nonsignificant, with one exception, indicating that the effects are consistent between datasets. Overall, we conclude that there is no evidence that healthy neuroticism, operationalized as the conscientiousness by neuroticism interaction, buffers against chronic conditions