Central amygdala metabotropic glutamate receptor 5 in the modulation of visceral pain

Painful bladder syndrome is a debilitating condition that affects 3–6% of women in the United States. Multiple lines of evidence suggest that changes in central nervous system processing are key to the development of chronic bladder pain conditions, but little is known regarding the underlying cellular, molecular, and neuronal mechanisms. Using a mouse model of distension-induced bladder pain, we found that the central nucleus of the amygdala (CeA) is a critical site of neuromodulation for processing of bladder nociception. Furthermore, we demonstrate that metabotropic glutamate receptor 5 (mGluR5) activation in the CeA induces bladder pain sensitization by increasing CeA output. Thus, pharmacological activation of mGluR5 in the CeA is sufficient to increase the response to bladder distension. Additionally, pharmacological blockade or virally-mediated conditional deletion of mGluR5 in the CeA reduced responses to bladder distention suggesting that mGluR5 in the CeA is also necessary for these responses. Finally, we used optogenetic activation of the CeA and demonstrated that this caused a robust increase in the visceral pain response. The CeA localized effects on responses to bladder distention are associated with changes in extracellular signal regulated kinases 1/2 phosphorylation in the spinal cord. Overall, these data demonstrate that mGluR5 activation leads to increased CeA output that drives bladder pain sensitization

ERK2 alone drives inflammatory pain but cooperates with ERK1 in sensory neuron survival

Extracellular signal-regulated kinases 1 and 2 (ERK1/2) are highly homologous yet distinct components of signal transduction pathways known to regulate cell survival and function. Recent evidence indicates an isoform-specific role for ERK2 in pain processing and peripheral sensitization. However, the function of ERK2 in primary sensory neurons has not been directly tested. To dissect the isoform-specific function of ERK2 in sensory neurons, we used mice with Cre-loxP-mediated deletion of ERK2 in Na(v)1.8(+) sensory neurons that are predominantly nociceptors. We find that ERK2, unlike ERK1, is required for peripheral sensitization and cold sensation. We also demonstrate that ERK2, but not ERK1, is required to preserve epidermal innervation in a subset of peptidergic neurons. Additionally, deletion of both ERK isoforms in Na(v)1.8(+) sensory neurons leads to neuron loss not observed with deletion of either isoform alone, demonstrating functional redundancy in the maintenance of sensory neuron survival. Thus, ERK1 and ERK2 exhibit both functionally distinct and redundant roles in sensory neurons. SIGNIFICANCE STATEMENT ERK1/2 signaling affects sensory neuron function and survival. However, it was not clear whether ERK isoform-specific roles exist in these processes postnatally. Previous work from our laboratory suggested either functional redundancy of ERK isoforms or a predominant role for ERK2 in pain; however, the tools to discriminate between these possibilities were not available at the time. In the present study, we use new genetic knock-out lines to demonstrate that ERK2 in sensory neurons is necessary for development of inflammatory pain and for postnatal maintenance of peptidergic epidermal innervation. Interestingly, postnatal loss of both ERK isoforms leads to a profound loss of sensory neurons. Therefore, ERK1 and ERK2 display both functionally distinct and redundant roles in sensory neurons

Stepping across the line: Information sharing, truth-telling and the role of the personal carer in the Australian Nursing Home

The author draws on an Australian study using multiple qualitative methods to investigate truth telling in aged care. Thematic analysis of data from five nursing homes involving 23 personal care assistants revealed participants’ role understanding as influencing their perceptions about truth telling in practice. Five themes emerged: role as the happy comfort carer, division of labor, division of disclosure, role tension and frustration, and managing the division of disclosure. Role emphasis on comfort and happiness and a dominant perception that telling the truth can cause harm mean that disclosure will be withheld, edited, or partial. Participants’ role understanding divides labor and disclosure responsibility between the personal carer and registered nurse. Personal carers’ strategies for managing the division of disclosure include game playing, obfuscation, lying (denial), and the use of nonverbals. These perceptions about personal carer role, information sharing, and truth telling are paramount for understanding and improving nursing home eldercare

Constraints on lithosphere net rotation and asthenospheric viscosity from global mantle flow models and seismic anisotropy

Author Posting. © American Geophysical Union, 2010. This article is posted here by permission of American Geophysical Union for personal use, not for redistribution. The definitive version was published in Geochemistry Geophysics Geosystems 11 (2010): Q05W05, doi:10.1029/2009GC002970.Although an average westward rotation of the Earth's lithosphere is indicated by global analyses of surface features tied to the deep mantle (e.g., hot spot tracks), the rate of lithospheric drift is uncertain despite its importance to global geodynamics. We use a global viscous flow model to predict asthenospheric anisotropy computed from linear combinations of mantle flow fields driven by relative plate motions, mantle density heterogeneity, and westward lithosphere rotation. By comparing predictions of lattice preferred orientation to asthenospheric anisotropy in oceanic regions inferred from SKS splitting observations and surface wave tomography, we constrain absolute upper mantle viscosity (to 0.5–1.0 × 1021 Pa s, consistent with other constraints) simultaneously with net rotation rate and the decrease in the viscosity of the asthenosphere relative to that of the upper mantle. For an asthenosphere 10 times less viscous than the upper mantle, we find that global net rotation must be <0.26°/Myr (<60% of net rotation in the HS3 (Pacific hot spot) reference frame); larger viscosity drops amplify asthenospheric shear associated with net rotation and thus require slower net rotation to fit observed anisotropy. The magnitude of westward net rotation is consistent with lithospheric drift relative to Indo-Atlantic hot spots but is slower than drift in the Pacific hot spot frame (HS3 ≈ 0.44°/Myr). The latter may instead express net rotation relative to the deep mantle beneath the Pacific plate, which is moving rapidly eastward in our models.This research was supported by NSF grants EAR‐0855546 (C.P.C.) and EAR‐0854673 (M.D.B.)

Big Data: Managing the Future\u27s Agriculture and Natural Resource Systems

Big Data: Managing the Future\u27s Agriculture and Natural Resource Systems Big data is the incredible flow of information that surrounds each of us, every day. Big data tools identify patterns and habits, not only in research, but in manufacturing, logistics–even ordering items online

Rare coding variants in PLCG2, ABI3, and TREM2 implicate microglial-mediated innate immunity in Alzheimer's disease

We identified rare coding variants associated with Alzheimer’s disease (AD) in a 3-stage case-control study of 85,133 subjects. In stage 1, 34,174 samples were genotyped using a whole-exome microarray. In stage 2, we tested associated variants (P<1×10-4) in 35,962 independent samples using de novo genotyping and imputed genotypes. In stage 3, an additional 14,997 samples were used to test the most significant stage 2 associations (P<5×10-8) using imputed genotypes. We observed 3 novel genome-wide significant (GWS) AD associated non-synonymous variants; a protective variant in PLCG2 (rs72824905/p.P522R, P=5.38×10-10, OR=0.68, MAFcases=0.0059, MAFcontrols=0.0093), a risk variant in ABI3 (rs616338/p.S209F, P=4.56×10-10, OR=1.43, MAFcases=0.011, MAFcontrols=0.008), and a novel GWS variant in TREM2 (rs143332484/p.R62H, P=1.55×10-14, OR=1.67, MAFcases=0.0143, MAFcontrols=0.0089), a known AD susceptibility gene. These protein-coding changes are in genes highly expressed in microglia and highlight an immune-related protein-protein interaction network enriched for previously identified AD risk genes. These genetic findings provide additional evidence that the microglia-mediated innate immune response contributes directly to AD development

AusTraits, a curated plant trait database for the Australian flora

We introduce the AusTraits database - a compilation of values of plant traits for taxa in the Australian flora (hereafter AusTraits). AusTraits synthesises data on 448 traits across 28,640 taxa from field campaigns, published literature, taxonomic monographs, and individual taxon descriptions. Traits vary in scope from physiological measures of performance (e.g. photosynthetic gas exchange, water-use efficiency) to morphological attributes (e.g. leaf area, seed mass, plant height) which link to aspects of ecological variation. AusTraits contains curated and harmonised individual- and species-level measurements coupled to, where available, contextual information on site properties and experimental conditions. This article provides information on version 3.0.2 of AusTraits which contains data for 997,808 trait-by-taxon combinations. We envision AusTraits as an ongoing collaborative initiative for easily archiving and sharing trait data, which also provides a template for other national or regional initiatives globally to fill persistent gaps in trait knowledge