Environmental exposure to manganese in air: Tremor, motor and cognitive symptom profiles.

Background: Excessive exposure to manganese (Mn) may cause parkinsonian-like motor and tremor symptoms and adverse cognitive effects, including problems with executive functioning (EF), resembling those found in later-stage Parkinson's disease (PD). Studies seeking to differentiate PD patients into subgroups with associated cognitive and functional outcomes using motor and tremor symptoms identified tremor-dominant (TD) and non-tremor dominant (NTD) subtypes. It is unclear whether differing patterns of pathophysiology and symptoms exist in Mn neurotoxicity, as they do in PD.

Validity of self-reported concentration and memory problems: Relationship with neuropsychological assessment and depression.

Background: This study investigated the validity of self-reported concentration and memory problems (CMP) in residents environmentally exposed to manganese (Mn).

Method: Self-report of CMP from a health questionnaire (HQ) and the Symptom Checklist-90-Revised (SCL-90-R) was compared to neuropsychological assessment (Trails A&B; Digit Span; Digit Symbol; Similarities; Auditory Consonant Trigrams, ACT; NAB Memory; Rey-Osterrieth, Rey-O, Delayed). Participants included 146 residents from Ohio exposed to air-Mn, with a modeled average concentration of 0.

AnglerFish: a webserver for defining the geometry of α-helices in membrane proteins.

Summary: Integral membrane proteins that form helical pores and bundles constitute major drug targets, and many of their structures have been defined by crystallography and cryo-electron microscopy. The gating of channels and ligand binding of transporters generally involve changes in orientation of one or more the constituent helices in the structures. At present there is no standard easily accessible means for defining the orientation of a helix in a membrane protein structure.

Medication use associated with exposure to manganese in two Ohio towns.

This report describes the use of medications as a proxy when medical record reviews are unavailable, to study the health effects of residents environmentally exposed to air-manganese (n = 185) compared to unexposed residents (n = 90). Participants' current medication lists and medication questionnaire responses were collected in clinical interviews and categorized into 13 domains. Exposed participants reported fewer hours of sleep than controls (6.

Environmental exposure to manganese in air: Associations with tremor and motor function.

Background: Manganese (Mn) inhalation has been associated with neuropsychological and neurological sequelae in exposed workers. Few environmental epidemiologic studies have examined the potentially neurotoxic effects of Mn exposure in ambient air on motor function and hand tremor in adult community residents. Mn exposed residents were recruited in two Ohio towns: Marietta, a town near a ferro-manganese smelter, and East Liverpool, a town adjacent to a facility processing, crushing, screening, and packaging Mn products.

Characterization of air manganese exposure estimates for residents in two Ohio towns.

This study was conducted to derive receptor-specific outdoor exposure concentrations of total suspended particulate (TSP) and respirable (dae ≤ 10 µm) air manganese (air-Mn) for East Liverpool and Marietta (Ohio) in the absence of facility emissions data, but where long-term air measurements were available. Our "site-surface area emissions method" used U.S.

Environmental exposure to manganese in air: Associations with cognitive functions.

Manganese (Mn), an essential element, can be neurotoxic in high doses. This cross-sectional study explored the cognitive function of adults residing in two towns (Marietta and East Liverpool, Ohio, USA) identified as having high levels of environmental airborne Mn from industrial sources. Air-Mn site surface emissions method modeling for total suspended particulate (TSP) ranged from 0.

A-kinase Anchoring Protein 79/150 Recruits Protein Kinase C to Phosphorylate Roundabout Receptors.

Anchoring proteins direct protein kinases and phosphoprotein phosphatases toward selected substrates to control the efficacy, context, and duration of neuronal phosphorylation events. The A-kinase anchoring protein AKAP79/150 interacts with protein kinase A (PKA), protein kinase C (PKC), and protein phosphatase 2B (calcineurin) to modulate second messenger signaling events. In a mass spectrometry-based screen for additional AKAP79/150 binding partners, we have identified the Roundabout axonal guidance receptor Robo2 and its ligands Slit2 and Slit3.

Dimerization of complement factor H-related proteins modulates complement activation in vivo.

The complement system is a key component regulation influences susceptibility to age-related macular degeneration, meningitis, and kidney disease. Variation includes genomic rearrangements within the complement factor H-related (CFHR) locus. Elucidating the mechanism underlying these associations has been hindered by the lack of understanding of the biological role of CFHR proteins.

The implementation of electronic services: planned or organic growth?

The literature on innovation suggests that projects are successful when rigorous project management is mixed judiciously with 'organic' development. This paper argues that organic growth can play a substantial role in the implementation of electronic services in healthcare settings. Evidence for organic growth is presented, based on a study of email use.

Role for A kinase-anchoring proteins (AKAPS) in glutamate receptor trafficking and long term synaptic depression.

Expression of N-methyl d-aspartate (NMDA) receptor-dependent homosynaptic long term depression at synapses in the hippocampus and neocortex requires the persistent dephosphorylation of postsynaptic protein kinase A substrates. An attractive mechanism for expression of long term depression is the loss of surface AMPA (alpha-amino-3-hydroxy-5-methylisoxazale-4-propionate) receptors at synapses. Here we show that a threshold level of NMDA receptor activation must be exceeded to trigger a stable loss of AMPA receptors from the surface of cultured hippocampal neurons.

Ubiquitination regulates PSD-95 degradation and AMPA receptor surface expression.

PSD-95 is a major scaffolding protein of the postsynaptic density, tethering NMDA- and AMPA-type glutamate receptors to signaling proteins and the neuronal cytoskeleton. Here we show that PSD-95 is regulated by the ubiquitin-proteasome pathway. PSD-95 interacts with and is ubiquitinated by the E3 ligase Mdm2.

A-kinase anchoring protein 79/150 facilitates the phosphorylation of GABA(A) receptors by cAMP-dependent protein kinase via selective interaction with receptor beta subunits.

GABA(A) receptors, the key mediators of fast synaptic inhibition in the brain, are predominantly constructed from alpha(1-6), beta(1-3), gamma(1-3), and delta subunit classes. Phosphorylation by cAMP-dependent protein kinase (PKA) differentially regulates receptor function dependent upon beta subunit identity, but how this kinase is selectively targeted to GABA(A) receptor subtypes remains unresolved. Here we establish that the A-kinase anchoring protein 150 (AKAP150), directly binds to the receptor beta1 and beta3, but not to alpha1, alpha2, alpha3, alpha6, beta2, gamma2, or delta subunits.

Regulation of GluR1 by the A-kinase anchoring protein 79 (AKAP79) signaling complex shares properties with long-term depression.

Second messengers regulate synaptic plasticity by influencing the balance between kinase and phosphatase activity. One target of this balance is the phosphorylation state of the AMPA receptor glutamate receptor 1 (GluR1) subunit. Hippocampal long-term depression (LTD) is a calcium-dependent downregulation of synaptic AMPA receptor currents associated with dephosphorylation of Ser845, a cAMP-dependent protein kinase (PKA) site on GluR1.

Missed appointments in general practice: retrospective data analysis from four practices.

Little is known about which patients miss appointments or why they do so. Using routinely collected data from four practices, we aimed to determine whether patients who missed appointments differed in terms of their age, sex, and deprivation scores from those who did not, and to examine differences between the practices with respect to missed appointments. The likelihood of someone missing at least one appointment was independently associated with being female, living in a deprived area, and being a young adult.

The effect of the full moon on general practice consultation rates.

Background: The effect of the full moon on human behaviour, the so-called 'Transylvania hypothesis', has fascinated the public and occupied the mind of researchers for centuries.

Objective: The aim of the present study was to determine whether or not there was any change in general practice consultation patterns around the time of the full moon.

Method: We analysed data from the fourth national morbidity study of general practice.

Targeting of PKA to glutamate receptors through a MAGUK-AKAP complex.

Compartmentalization of glutamate receptors with the signaling enzymes that regulate their activity supports synaptic transmission. Two classes of binding proteins organize these complexes: the MAGUK proteins that cluster glutamate receptors and AKAPs that anchor kinases and phosphatases. In this report, we demonstrate that glutamate receptors and PKA are recruited into a macromolecular signaling complex through direct interaction between the MAGUK proteins, PSD-95 and SAP97, and AKAP79/150.

Neuregulin-increased expression of acetylcholine receptor epsilon-subunit gene requires ErbB interaction with Shc.

Selective transcription of acetylcholine receptor (AChR) subunit genes by neuregulin is one of the mechanisms involved in the synaptic localization of AChRs to the neuromuscular junction. Neuregulin stimulates ErbB receptor tyrosine kinases and subsequently activates the Ras/ERK pathway, which is required for neuregulin-mediated induction of AChR subunit genes in muscle cells and synapse-specific expression in vivo. Here we investigated the neuregulin transduction mechanism that leads to ERK activation after ErbB receptor tyrosine phosphorylation.

AKAPs: from structure to function.

Compartmentalization of signalling molecules through association with anchoring proteins ensures specificity in signal transduction by placing enzymes close to their appropriate effectors and substrates. For example, 'A-kinase anchoring proteins' (AKAPs) bind to the regulatory subunit of cAMP-dependent protein kinase (PKA) to direct the kinase to discrete intracellular locations. Recently, functional studies aimed at disrupting AKAP-PKA complexes have demonstrated a role for anchored PKA in various cellular processes, including gene transcription, hormone-mediated insulin secretion and ion-channel modulation.

Good health care: patient and professional perspectives.

Many health needs assessment exercises are professionally led, employing complex epidemiological methods. An alternative method that gives valuable information about patient preferences is a forced-choice questionnaire, which this study used in five practices in the West of Scotland. In each practice, patient-centred care was the most highly valued attribute of service provision.