Evaluation of Drug Concentrations Delivered by Microiontophoresis

Microiontophoresis uses an electric current to eject a drug solution from a glass capillary and is often utilized for targeted delivery in neurochemical investigations. The amount of drug ejected, and its effective concentration at the tip, has historically been difficult to determine, which has precluded its use in quantitative studies. To address this, a method called controlled iontophoresis was developed which employs a carbon-fiber microelectrode incorporated into a multibarreled iontophoretic probe to detect the ejection of electroactive species. Here, we evaluate the accuracy of this method. To do this, we eject different concentrations of quinpirole, a D2 receptor agonist, into a brain slice containing the dorsal striatum, a brain region with a high density of dopamine terminals. Local electrical stimulation was used to evoke dopamine release, and inhibitory actions of quinpirole on this release were examined. The amount of drug ejected was estimated by detection of a coejected electrochemical mar..

Characterization of Solute Distribution Following Iontophoresis from a Micropipet

Iontophoresis uses a current to eject solution from the tip of a barrel formed from a pulled glass capillary and has been employed as a method of drug delivery for neurochemical investigations. Much attention has been devoted to resolving perhaps the greatest limitation of iontophoresis, the inability to determine the concentration of substances delivered by ejections. To further address this issue, we evaluate the properties of typical ejections such as barrel solution velocity and its relation to the ejection current using an amperometric and liquid chromatographic approach. These properties were used to predict the concentration distribution of ejected solute that was then confirmed by fluorescence microscopy. Additionally, incorporation of oppositely charged fluorophores into the barrel investigated the role of migration on the mass transport of an ejected species. Results indicate that location relative to the barrel tip is the primary influence on the distribution of ejected species. At short distances (100 μm), even solute ejected using high currents exhibits diffusion-limited behavior. Lastly a time-dependent theoretical model was constructed and is used with experimental fluorescent profiles to demonstrate how iontophoresis can generate near-uniform concentration distributions near the ejection source

Medullary Norepinephrine Neurons Modulate Local Oxygen Concentrations in the Bed Nucleus of the Stria Terminalis

Neurovascular coupling is understood to be the underlying mechanism of functional hyperemia, but the actions of the neurotransmitters involved are not well characterized. Here we investigate the local role of the neurotransmitter norepinephrine in the ventral bed nucleus of the stria terminalis (vBNST) of the anesthetized rat by measuring O2, which is delivered during functional hyperemia. Extracellular changes in norepinephrine and O2 were simultaneously monitored using fast-scan cyclic voltammetry. Introduction of norepinephrine by electrical stimulation of the ventral noradrenergic bundle or by iontophoretic ejection induced an initial increase in O2 levels followed by a brief dip below baseline. Supporting the role of a hyperemic response, the O2 increases were absent in a brain slice containing the vBNST. Administration of selective pharmacological agents demonstrated that both phases of this response involve β-adrenoceptor activation, where the delayed decrease in O2 is sensitive to both α- and β-receptor subtypes. Selective lesioning of the locus coeruleus with the neurotoxin DSP-4 confirmed that these responses are caused by the noradrenergic cells originating in the nucleus of the solitary tract and A1 cell groups. Overall, these results support that non-coerulean norepinephrine release can mediate activity-induced O2 influx in a deep brain region

Microbial activity in the marine deep biosphere: progress and prospects

The vast marine deep biosphere consists of microbial habitats within sediment, pore waters, upper basaltic crust and the fluids that circulate throughout it. A wide range of temperature, pressure, pH, and electron donor and acceptor conditions exists—all of which can combine to affect carbon and nutrient cycling and result in gradients on spatial scales ranging from millimeters to kilometers. Diverse and mostly uncharacterized microorganisms live in these habitats, and potentially play a role in mediating global scale biogeochemical processes. Quantifying the rates at which microbial activity in the subsurface occurs is a challenging endeavor, yet developing an understanding of these rates is essential to determine the impact of subsurface life on Earth\u27s global biogeochemical cycles, and for understanding how microorganisms in these “extreme” environments survive (or even thrive). Here, we synthesize recent advances and discoveries pertaining to microbial activity in the marine deep subsurface, and we highlight topics about which there is still little understanding and suggest potential paths forward to address them. This publication is the result of a workshop held in August 2012 by the NSF-funded Center for Dark Energy Biosphere Investigations (C-DEBI) “theme team” on microbial activity (www.darkenergybiosphere.org)

Measuring the impact and costs of a universal group based parenting programme : protocol and implementation of a trial

Background Sub-optimal parenting is a common risk factor for a wide range of negative health, social and educational outcomes. Most parenting programmes have been developed in the USA in the context of delinquency prevention for targeted or indicated groups and the main theoretical underpinning for these programmes is behaviour management. The Family Links Nurturing Programme (FLNP) focuses on family relationships as well as behaviour management and is offered on a universal basis. As a result it may be better placed to improve health and educational outcomes. Developed in the UK voluntary sector, FLNP is popular with practitioners, has impressed policy makers throughout the UK, has been found to be effective in before/after and qualitative studies, but lacks a randomised controlled trial (RCT) evidence base. Methods/Design A multi-centre, investigator blind, randomised controlled trial of the FLNP with a target sample of 288 south Wales families who have a child aged 2-4 yrs living in or near to Flying Start/Sure Start areas. Changes in parenting, parent child relations and parent and child wellbeing are assessed with validated measures immediately and at 6 months post intervention. Economic components include cost consequences and cost utility analyses based on parental ranking of states of quality of life. Attendance and completion rates and fidelity to the FLNP course delivery are assessed. A nested qualitative study will assess reasons for participation and non-participation and the perceived value of the programme to families. By the end of May 2010, 287 families have been recruited into the trial across four areas of south Wales. Recruitment has not met the planned timescales with barriers including professional anxiety about families entering the control arm of the trial, family concern about video and audio recording, programme facilitator concern about the recording of FLNP sessions for fidelity purposes and delays due to the new UK research governance procedures. Discussion Whilst there are strong theoretical arguments to support universal provision of parenting programmes, few universal programmes have been subjected to randomised controlled trials. In this paper we describe a RCT protocol with quantitative and qualitative outcome measures and an economic evaluation designed to provide clear evidence with regard to effectiveness and costs. We describe challenges implementing the protocol and how we are addressing these

The substellar mass function in sigma Orionis. II. Optical, near-infrared and IRAC/Spitzer photometry of young cluster brown dwarfs and planetary-mass objects

We investigate the mass function in the substellar domain down to a few Jupiter masses in the young sigma Orionis open cluster (3+/-2 Ma, d = 360^+70_-60 pc). We have performed a deep IJ-band search, covering an area of 790 arcmin^2 close to the cluster centre. This survey was complemented with an infrared follow-up in the HKs- and Spitzer 3.6-8.0 mum-bands. Using colour-magnitude diagrams, we have selected 49 candidate cluster members in the magnitude interval 16.1 mag < I < 23.0 mag. Accounting for flux excesses at 8.0 mum and previously known spectral features of youth, 30 objects are bona fide cluster members. Four are first identified from our optical-near infrared data. Eleven have most probable masses below the deuterium burning limit and are classified as planetary-mass object candidates. The slope of the substellar mass spectrum (Delta N / Delta M = a M^-alpha) in the mass interval 0.11 Msol M < 0.006 Msol is alpha = +0.6+/-0.2. Any opacity mass-limit, if these objects form via fragmentation, may lie below 0.006 Msol. The frequency of sigma Orionis brown dwarfs with circumsubstellar discs is 47+/-15 %. The continuity in the mass function and in the frequency of discs suggests that very low-mass stars and substellar objects, even below the deuterium-burning mass limit, may share the same formation mechanism.Comment: Accepted for publication in A&A (12/04/2007). It has not been edited for language ye

Science Impacts of the SPHEREx All-Sky Optical to Near-Infrared Spectral Survey: Report of a Community Workshop Examining Extragalactic, Galactic, Stellar and Planetary Science

SPHEREx is a proposed SMEX mission selected for Phase A. SPHEREx will carry out the first all-sky spectral survey and provide for every 6.2" pixel a spectra between 0.75 and 4.18 $\mu$m [with R$\sim$41.4] and 4.18 and 5.00 $\mu$m [with R$\sim$135]. The SPHEREx team has proposed three specific science investigations to be carried out with this unique data set: cosmic inflation, interstellar and circumstellar ices, and the extra-galactic background light. It is readily apparent, however, that many other questions in astrophysics and planetary sciences could be addressed with the SPHEREx data. The SPHEREx team convened a community workshop in February 2016, with the intent of enlisting the aid of a larger group of scientists in defining these questions. This paper summarizes the rich and varied menu of investigations that was laid out. It includes studies of the composition of main belt and Trojan/Greek asteroids; mapping the zodiacal light with unprecedented spatial and spectral resolution; identifying and studying very low-metallicity stars; improving stellar parameters in order to better characterize transiting exoplanets; studying aliphatic and aromatic carbon-bearing molecules in the interstellar medium; mapping star formation rates in nearby galaxies; determining the redshift of clusters of galaxies; identifying high redshift quasars over the full sky; and providing a NIR spectrum for most eROSITA X-ray sources. All of these investigations, and others not listed here, can be carried out with the nominal all-sky spectra to be produced by SPHEREx. In addition, the workshop defined enhanced data products and user tools which would facilitate some of these scientific studies. Finally, the workshop noted the high degrees of synergy between SPHEREx and a number of other current or forthcoming programs, including JWST, WFIRST, Euclid, GAIA, K2/Kepler, TESS, eROSITA and LSST.Comment: Report of the First SPHEREx Community Workshop, http://spherex.caltech.edu/Workshop.html , 84 pages, 28 figure

Microbial activity in the marine deep biosphere: progress and prospects

The vast marine deep biosphere consists of microbial habitats within sediment, pore waters, upper basaltic crust and the fluids that circulate throughout it. A wide range of temperature, pressure, pH, and electron donor and acceptor conditions exists—all of which can combine to affect carbon and nutrient cycling and result in gradients on spatial scales ranging from millimeters to kilometers. Diverse and mostly uncharacterized microorganisms live in these habitats, and potentially play a role in mediating global scale biogeochemical processes. Quantifying the rates at which microbial activity in the subsurface occurs is a challenging endeavor, yet developing an understanding of these rates is essential to determine the impact of subsurface life on Earth's global biogeochemical cycles, and for understanding how microorganisms in these “extreme” environments survive (or even thrive). Here, we synthesize recent advances and discoveries pertaining to microbial activity in the marine deep subsurface, and we highlight topics about which there is still little understanding and suggest potential paths forward to address them.This is the publisher’s final pdf. The published article is copyrighted by the author(s) and published by Frontiers Research Foundation. The published article can be found at: http://www.frontiersin.org/Microbiology.Keywords: Subsurface microbiology, Biogeochemistry, C-DEBI, Deep biosphere, IODP, Sediment, Oceanic crustKeywords: Subsurface microbiology, Biogeochemistry, C-DEBI, Deep biosphere, IODP, Sediment, Oceanic crus