Modulation of neurosteroid potentiation by protein kinases at synaptic- and extrasynaptic-type GABAA receptors.

GABAA receptors are important for inhibition in the CNS where neurosteroids and protein kinases are potent endogenous modulators. Acting individually, these can either enhance or depress receptor function, dependent upon the type of neurosteroid or kinase and the receptor subunit combination. However, in vivo, these modulators probably act in concert to fine-tune GABAA receptor activity and thus inhibition, although how this is achieved remains unclear. Therefore, we investigated the relationship between these modulators at synaptic-type α1β3γ2L and extrasynaptic-type α4β3δ GABAA receptors using electrophysiology. For α1β3γ2L, potentiation of GABA responses by tetrahydro-deoxycorticosterone was reduced after inhibiting protein kinase C, and enhanced following its activation, suggesting this kinase regulates neurosteroid modulation. In comparison, neurosteroid potentiation was reduced at α1β3(S408A,S409A)γ2L receptors, and unaltered by PKC inhibitors or activators, indicating that phosphorylation of β3 subunits is important for regulating neurosteroid activity. To determine whether extrasynaptic-type GABAA receptors were similarly modulated, α4β3δ and α4β3(S408A,S409A)δ receptors were investigated. Neurosteroid potentiation was reduced at both receptors by the kinase inhibitor staurosporine. By contrast, neurosteroid-mediated potentiation at α4(S443A)β3(S408A,S409A)δ receptors was unaffected by protein kinase inhibition, strongly suggesting that phosphorylation of α4 and β3 subunits is required for regulating neurosteroid activity at extrasynaptic receptors. Western blot analyses revealed that neurosteroids increased phosphorylation of β3(S408,S409) implying that a reciprocal pathway exists for neurosteroids to modulate phosphorylation of GABAA receptors. Overall, these findings provide important insight into the regulation of GABAA receptors in vivo, and into the mechanisms by which GABAergic inhibitory transmission may be simultaneously tuned by two endogenous neuromodulators

Sonority distance and similarity avoidance effects in Moroccan Judeo-Spanish

This article investigates consonant gemination in late Nineteenth-and early Twentieth-century haketía, a now moribund, regional dialect of Judeo-Spanish spoken in northern Morocco since the late fifteenth century. Some, but not all, consonant clusters arising across a word boundary undergo regressive total assimilation, e.g. [n.n] siudad ninguna 'no city' but [z.n] laz niñas 'the girls'. We present novel descriptive generalizations to show that regressive gemination is sensitive to the degree of sonority distance between the coda and the onset. Evidence of parasitic harmony comes from lateral+consonant clusters, which undergo gemination only if the target and trigger consonants are already similar in some respect. In the framework of Optimality Theory, we formalize syllable contact as a relational hierarchy of ∗Distance constraints and capture parasitic harmony effects by similarity avoidance, or Obligatory Contour Principle, constraints against adjacent consonants with identical manner and/or place features. These markedness constraints interact with other universal faithfulness and markedness constraints in a language-specific ranking that predicts the attested patterns of regressive gemination. This study lends further support to sonority distance effects and gradient syllable contact in phonological theory and shows that similarity avoidance is also necessary to give a full account of regressive gemination in Moroccan Judeo-Spanish

Closely Related Tree Species Differentially Influence the Transfer of Carbon and Nitrogen from Leaf Litter Up the Aquatic Food Web

Decomposing leaf litter in streams provides habitat and nutrition for aquatic insects. Despite large differences in the nutritional qualities of litter among different plant species, their effects on aquatic insects are often difficult to detect. We evaluated how leaf litter of two dominant riparian species (Populus fremontii and P. angustifolia) influenced carbon and nitrogen assimilation by aquatic insect communities, quantifying assimilation rates using stable isotope tracers (13C, 15N). We tested the hypothesis that element fluxes from litter of different plant species better define aquatic insect community structure than insect relative abundances, which often fail. We found that (1) functional communities (defined by fluxes of carbon and nitrogen from leaf litter to insects) were different between leaf litter species, whereas more traditional insect communities (defined by relativized taxa abundances) were not different between leaf litter species, (2) insects assimilated N, but not C, at a higher rate from P. angustifolia litter compared to P. fremontii, even though P. angustifolia decomposes more slowly, and (3) the C:N ratio of material assimilated by aquatic insects was lower for P. angustifolia compared to P. fremontii, indicating higher nutritional quality, despite similar initial litter C:N ratios. These findings provide new evidence for the effects of terrestrial plant species on aquatic ecosystems via their direct influence on the transfer of elements up the food web. We demonstrate how isotopically labeled leaf litter can be used to assess the functioning of insect communities, uncovering patterns undetected by traditional approaches and improving our understanding of the association between food web structure and element cycling

Optimal search strategies for identifying sound clinical prediction studies in EMBASE

BACKGROUND: Clinical prediction guides assist clinicians by pointing to specific elements of the patient's clinical presentation that should be considered when forming a diagnosis, prognosis or judgment regarding treatment outcome. The numbers of validated clinical prediction guides are growing in the medical literature, but their retrieval from large biomedical databases remains problematic and this presents a barrier to their uptake in medical practice. We undertook the systematic development of search strategies ("hedges") for retrieval of empirically tested clinical prediction guides from EMBASE. METHODS: An analytic survey was conducted, testing the retrieval performance of search strategies run in EMBASE against the gold standard of hand searching, using a sample of all 27,769 articles identified in 55 journals for the 2000 publishing year. All articles were categorized as original studies, review articles, general papers, or case reports. The original and review articles were then tagged as 'pass' or 'fail' for methodologic rigor in the areas of clinical prediction guides and other clinical topics. Search terms that depicted clinical prediction guides were selected from a pool of index terms and text words gathered in house and through request to clinicians, librarians and professional searchers. A total of 36,232 search strategies composed of single and multiple term phrases were trialed for retrieval of clinical prediction studies. The sensitivity, specificity, precision, and accuracy of search strategies were calculated to identify which were the best. RESULTS: 163 clinical prediction studies were identified, of which 69 (42.3%) passed criteria for scientific merit. A 3-term strategy optimized sensitivity at 91.3% and specificity at 90.2%. Higher sensitivity (97.1%) was reached with a different 3-term strategy, but with a 16% drop in specificity. The best measure of specificity (98.8%) was found in a 2-term strategy, but with a considerable fall in sensitivity to 60.9%. All single term strategies performed less well than 2- and 3-term strategies. CONCLUSION: The retrieval of sound clinical prediction studies from EMBASE is supported by several search strategies

Management Impacts on Forest Floor and Soil Organic Carbon in Northern Temperate Forests of the US

<p>Abstract</p> <p>Background</p> <p>The role of forests in the global carbon cycle has been the subject of a great deal of research recently, but the impact of management practices on forest soil dynamics at the stand level has received less attention. This study used six forest management experimental sites in five northern states of the US to investigate the effects of silvicultural treatments (light thinning, heavy thinning, and clearcutting) on forest floor and soil carbon pools.</p> <p>Results</p> <p>No overall trend was found between forest floor carbon stocks in stands subjected to partial or complete harvest treatments. A few sites had larger stocks in control plots, although estimates were often highly variable. Forest floor carbon pools did show a trend of increasing values from southern to northern sites. Surface soil (0-5 cm) organic carbon content and concentration were similar between treated and untreated plots. Overall soil carbon (0-20 cm) pool size was not significantly different from control values in sites treated with partial or complete harvests. No geographic trends were evident for any of the soil properties examined.</p> <p>Conclusions</p> <p>Results indicate that it is unlikely that mineral soil carbon stocks are adversely affected by typical management practices as applied in northern hardwood forests in the US; however, the findings suggest that the forest floor carbon pool may be susceptible to loss.</p

Measurements of the transverse-momentum-dependent cross sections of J /ψ production at mid-rapidity in proton+proton collisions at s =510 and 500 GeV with the STAR detector

We present measurements of the differential cross sections of inclusive J/ψ meson production as a function of transverse momentum (pTJ/ψ) using the μ+μ- and e+e- decay channels in proton+proton collisions at center-of-mass energies of 510 and 500 GeV, respectively, recorded by the STAR detector at the Relativistic Heavy Ion Collider. The measurement from the μ+μ- channel is for

Bulk properties of the system formed in Au+Au collisions at sNN =14.5 GeV at the BNL STAR detector

We report systematic measurements of bulk properties of the system created in Au+Au collisions at sNN=14.5 GeV recorded by the STAR detector at the Relativistic Heavy Ion Collider (RHIC). The transverse momentum spectra of π±, K±, and p(p) are studied at midrapidity (|y|&lt;0.1) for nine centrality intervals. The centrality, transverse momentum (pT), and pseudorapidity (η) dependence of inclusive charged particle elliptic flow (v2), and rapidity-odd charged particles directed flow (v1) results near midrapidity are also presented. These measurements are compared with the published results from Au+Au collisions at other energies, and from Pb+Pb collisions at sNN=2.76 TeV. The results at sNN=14.5 GeV show similar behavior as established at other energies and fit well in the energy dependence trend. These results are important as the 14.5-GeV energy fills the gap in μB, which is of the order of 100 MeV, between sNN=11.5 and 19.6 GeV. Comparisons of the data with UrQMD and AMPT models show poor agreement in general

Charge-dependent pair correlations relative to a third particle in p + Au and d + Au collisions at RHIC

Quark interactions with topological gluon configurations can induce chirality imbalance and local parity violation in quantum chromodynamics. This can lead to electric charge separation along the strong magnetic field in relativistic heavy-ion collisions – the chiral magnetic effect (CME). We report measurements by the STAR collaboration of a CME-sensitive observable in p+Au and d+Au collisions at 200 GeV, where the CME is not expected, using charge-dependent pair correlations relative to a third particle. We observe strong charge-dependent correlations similar to those measured in heavy-ion collisions. This bears important implications for the interpretation of the heavy-ion data