mGluR control of interneuron output regulates feedforward tonic GABAA inhibition in the visual thalamus

Metabotropic glutamate receptors (mGluRs) play a crucial role in regulation of phasic inhibition within the visual thalamus. Here we demonstrate that mGluR-dependent modulation of interneuron GABA release results in dynamic changes in extrasynaptic GABAA receptor (eGABAAR)-dependent tonic inhibition in thalamocortical (TC) neurons of the rat dorsal lateral geniculate nucleus (dLGN). Application of the group I selective mGluR agonist dihydroxyphenylglycine produces a concentration-dependent enhancement of both IPSC frequency and tonic GABAA current (IGABAtonic) that is due to activation of both mGluR1a and mGluR5 subtypes. In contrast, group II/III mGluR activation decreases both IPSC frequency and IGABAtonic amplitude. Using knock-out mice, we show that the mGluR-dependent modulation of IGABAtonic is dependent upon expression of δ-subunit containing eGABAARs. Furthermore, unlike the dLGN, no mGluR-dependent modulation of IGABAtonic is present in TC neurons of the somatosensory ventrobasal thalamus, which lacks GABAergic interneurons. In the dLGN, enhancement of IPSC frequency and IGABAtonic by group I mGluRs is not action potential dependent, being insensitive to TTX, but is abolished by the L-type Ca2+ channel blocker nimodipine. These results indicate selective mGluR-dependent modulation of dendrodendritic GABA release from F2-type terminals on interneuron dendrites and demonstrate for the first time the presence of eGABAARs on TC neuron dendritic elements that participate in “triadic” circuitry within the dLGN. These findings present a plausible novel mechanism for visual contrast gain at the thalamic level and shed new light upon the potential role of glial ensheathment of synaptic triads within the dLGN.peer-reviewe

Weak Interaction Studies with 6He

The 6He nucleus is an ideal candidate to study the weak interaction. To this end we have built a high-intensity source of 6He delivering ~10^10 atoms/s to experiments. Taking full advantage of that available intensity we have performed a high-precision measurement of the 6He half-life that directly probes the axial part of the nuclear Hamiltonian. Currently, we are preparing a measurement of the beta-neutrino angular correlation in 6He beta decay that will allow to search for new physics beyond the Standard Model in the form of tensor currents.Comment: 5 pages, 4 figures, proceedings for the Eleventh Conference on the Intersections of Particle and Nuclear Physics (CIPANP 2012

GABAB receptors regulate extrasynaptic GABAA receptors

Tonic inhibitory GABAA receptor-mediated currents are observed in numerous cell types in the CNS, including thalamocortical neurons of the ventrobasal thalamus, dentate gyrus granule cells, and cerebellar granule cells. Here we show that in rat brain slices, activation of postsynaptic GABAB receptors enhances the magnitude of the tonic GABAA current recorded in these cell types via a pathway involving Gi/o G proteins, adenylate cyclase, and cAMP-dependent protein kinase. Using a combination of pharmacology and knockout mice, we show that this pathway is independent of potassium channels or GABA transporters. Furthermore, the enhancement in tonic current is sufficient to significantly alter the excitability of thalamocortical neurons. These results demonstrate for the first time a postsynaptic crosstalk between GABAB and GABAA receptors.peer-reviewe

Observations and comparisons of cloud microphysical properties in spring and summertime Arctic stratocumulus clouds during the ACCACIA campaign

Measurements from four case studies in spring and summer-time Arctic stratocumulus clouds during the Aerosol-Cloud Coupling And Climate Interactions in the Arctic (ACCACIA) campaign are presented. We compare microphysics observations between cases and with previous measurements made in the Arctic and Antarctic. During ACCACIA, stratocumulus clouds were observed to consist of liquid at cloud tops, often at distinct temperature inversions. The cloud top regions precipitated low concentrations of ice into the cloud below. During the spring cases median ice number concentrations (~ 0.5 L−1) were found to be lower by about a factor of 5 than observations from the summer campaign (~ 3 L−1). Cloud layers in the summer spanned a warmer temperature regime than in the spring and enhancement of ice concentrations in these cases was found to be due to secondary ice production through the Hallett–Mossop (H–M) process. Aerosol concentrations during spring ranged from ~ 300–400 cm−3 in one case to lower values of ~ 50–100 cm−3 in the other. The concentration of aerosol with sizes Dp > 0.5 μm was used in a primary ice nucleus (IN) prediction scheme (DeMott et al., 2010). Predicted IN values varied depending on aerosol measurement periods but were generally greater than maximum observed median values of ice crystal concentrations in the spring cases, and less than the observed ice concentrations in the summer due to the influence of secondary ice production. Comparison with recent cloud observations in the Antarctic summer (Grosvenor et al., 2012), reveals lower ice concentrations in Antarctic clouds in comparable seasons. An enhancement of ice crystal number concentrations (when compared with predicted IN numbers) was also found in Antarctic stratocumulus clouds spanning the H–M temperature zone; however, concentrations were about an order of magnitude lower than those observed in the Arctic summer cases but were similar to the peak values observed in the colder Arctic spring cases, where the H–M mechanism did not operate

Further evidence for the involvement of EFL1 in a Shwachman-Diamond-like syndrome and expansion of the phenotypic features.

Recent evidence has implicated EFL1 in a phenotype overlapping Shwachman-Diamond syndrome (SDS), with the functional interplay between EFL1 and the previously known causative gene SBDS accounting for the similarity in clinical features. Relatively little is known about the phenotypes associated with pathogenic variants in the EFL1 gene, but the initial indication was that phenotypes may be more severe, when compared with SDS. We report a pediatric patient who presented with a metaphyseal dysplasia and was found to have biallelic variants in EFL1 on reanalysis of trio whole-exome sequencing data. The variant had not been initially reported because of the research laboratory's focus on de novo variants. Subsequent phenotyping revealed variability in her manifestations. Although her metaphyseal abnormalities were more severe than in the original reported cohort with EFL1 variants, the bone marrow abnormalities were generally mild, and there was equivocal evidence for pancreatic insufficiency. Despite the limited number of reported patients, variants in EFL1 appear to cause a broader spectrum of symptoms that overlap with those seen in SDS. Our report adds to the evidence of EFL1 being associated with an SDS-like phenotype and provides information adding to our understanding of the phenotypic variability of this disorder. Our report also highlights the value of exome data reanalysis when a diagnosis is not initially apparent

The impact of a chief planning officer on the administrative environment for planning

Institution-wide planning, to be effective, must have the support of key administrators. Presidents, vice-presidents, deans, and directors must feel that sufficient consensus can be reached on explicit goals to make comprehensive planning possible and worthwhile. While much has been written about the importance of CEO leadership in gaining broad support for planning, little has been said about the role of the chief planning officer in this regard. This paper, based on a national survey of administrators' views of planning, studies the relationship between having a chief planning officer and administrators' perceptions of campus planning. Its intended audience includes all those interested in institutional planning.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/43608/1/11162_2004_Article_BF00991968.pd

Eine verbesserte fluorimetrische Cortisolbestimmung im Serum

Die fluorimetrische Methode zur Bestimmung von Serumcortisol wurde durch blasenfreie Füllung einer Spezialküvette mittels Pumpvorrichtung, durch Benützung eines Spectralfluorimeters, sowie Verlegung des Meßzeitpunktes (80 min) und durch optimale Anregung (464 nm) und Emissionsmessung (522 nm) verbessert. Empfindlichkeit (<1 µg Cortisol/100 ml), Richtigkeit, Genauigkeit, Reproduzierbarkeit von Tag zu Tag (VK=6–7%) und Störfaktoren der Methode werden angegeben. Mit dieser Methode wurden Normalberciche für die 9 Uhr-Nüchterncortisolwerte und die i.v. ACTH-Belastung ermittelt. Bei NNR-insuffizienten Patienten (M. Addison; Zustand nach Operation eines Hypophysentumors; total Adrenalektomierte) wurden i.v. ACTH-Belastungen durchgeführt, wobei sich bereits beim 9 Uhr-Nüchterncortisolwert eine diagnostisch gut brauchbare Trennung gegenüber dem Normalbereich ergab. Unter Dexamethasonsubstitution wurden bei NNR-Insuffizienz sehr niedrige Cortisolspiegel gemessen, was für die Spezifität der Methode spricht. Dic Bestimmung des 24 Std-Rhythmus der Cortisolwerte bei NNR-Insuffizienten zeigte, daß besonders in den frühen Morgenstunden im Vergleich zu Normalpersonen erniedrigte Cortisolspiegel bestehen. Daraus wird ein besserer Verteilungsvorschlag für die Cortisol-substitution abgeleitet.The fluorimetric determination of serum cortisol was improved 1. using a pumpdevice to fill a special microcuvette avoiding the development of small bubbles, 2. using a recording spectrofluorometer with optimal absorption (464 nm) and emission (522 nm), and 3. allowing for maximal fluorescence of cortisol (80 min). Sensitivity (<1 µg cortisol/100 ml), accuracy, precision and specificity of the method are reported. Normal values of 9.00 a.m. serum cortisol (9.7–32.0 µg/100 ml) and of values before and after ACTH infusion tests were determined. For adrenal insufficiency (Addisons disease, total adrenalectomy, or after hypophysectomy) the 9.00 a.m. values of serum cortisol were generally satisfactory for diagnosis. In partial adrenal insufficiency ACTH infusion tests had to be performed. Very low levels of serum cortisol (2–4 µg/100 ml) were obtained, when patients with adrenal insufficiency were substituted with dexamethasone for three days, proving the specificity of the method. Determination of circadian rhythms of serum cortisol in patients with adrenal insufficiency on cortisol substitutive therapy in divided doses demonstrated cortisol levels far below the normal values during the carly morning hours. This situation should be improved by dividing the cortisol dose as follows: 6 a.m.: 10 mg, 10 a.m.: 5 mg, 2 p.m.: 5 mg and 8 p.m. or later: 10 mg cortisol

Changing attitudes about concurrency among young African Americans: Results of a radio campaign

We created and evaluated an 8-month campaign of provocative radio ads to change attitudes about concurrent (overlapping) sexual partnerships among young African Americans. We created a concurrency attitude scale and compared its score distributions in independent samples of African Americans, ages 18–34 years, interviewed by telephone before (n = 678) and after (n = 479) the campaign. Pre- and post-campaign samples reflected similar response rates (pre: 32.6%; post: 31.8%) and distributions of personal characteristics. Reported exposure to concurrency messages was greater after the campaign (pre: 6.3%, post: 30.9%), and mean scores indicated less acceptance of concurrency (pre: 3.40 [95% CI 3.23, 3.57]; post: 2.62 [2.46, 2.78]). Score differences were not a function of differences in composition of the samples (adjusted means: pre: 3.37 [3.21, 3.53]; post: 2.62 [2.47, 2.76]). Findings demonstrate that a carefully targeted, intensive mass media campaign can change attitudes about concurrency, which should facilitate behavior change

U–Pb zircon-rutile dating of the Llangynog Inlier, Wales: constraints on an Ediacaran shallow marine fossil assemblage from East Avalonia

The Llangynog Inlier of south Wales contains an assemblage of Ediacaran macrofossils from a shallow-marine environment, including discoidal morphs of Aspidella and rare examples of Hiemalora, Palaeopascichnus and Yelovichnus. These are taxa found in other sites in the Avalonian microcontinent (e.g. Charnwood Forest and eastern Newfoundland) and in the younger White Sea Ediacaran assemblages. As the Charnwood fossils reflect a deep-water environment, and no macrofossils have been found in the Ediacaran rocks of the Long Mynd, the fossils of the Llangynog Inlier represent a unique glimpse of shallow marine life in southern Britain (East Avalonia). However, the lack of absolute age constraints has hampered direct comparison with other assemblages. Here, we report in-situ zircon and rutile U–Pb dates from a rhyolitic ash-flow layer of the Coed Cochion Volcaniclastic Member, Llangynog Inlier, which constrains the age of the fossiliferous strata. A weighted mean single grain zircon ID-TIMS U–Pb age of 564.09 ± 0.70 Ma is interpreted as the rhyolite's crystallisation age. This age is consistent with in-situ LA-ICPMS zircon and rutile U–Pb dating. The Llangynog age temporally correlates these fossils to dated horizons within East Avalonia at the Beacon Hill Formation, Charnwood (565.22 ± 0.89 Ma), and the Stretton Shale Formation, Long Mynd (566.6 ± 2.9 Ma). Correlations to West Avalonia include the time-equivalent Fermeuse Formation, St John’s Group, eastern Newfoundland (564.13 ± 0.65 Ma). The data presented here establish the biota of the Llangynog Inlier as a lateral equivalent to the similarly shallow marine, tidally influenced ecosystem of the upper Fermeuse Formation. Intra-terrane depositional environmental variability also affects what is preserved in Avalonian fossil sites. Further, time-constrained geochemical data reinforce the Llangynog Inlier's classification within the Wrekin Terrane