Distinct forms of synaptic inhibition and neuromodulation regulate calretinin positive neuron excitability in the spinal cord dorsal horn

The dorsal horn (DH) of the spinal cord contains a heterogenous population of neurons that process incoming sensory signals before information ascends to the brain. We have recently characterized calretinin-expressing (CR+) neurons in the DH and shown that they can be divided into excitatory and inhibitory subpopulations. The excitatory population receives high-frequency excitatory synaptic input and expresses delayed firing action potential discharge, whereas the inhibitory population receives weak excitatory drive and exhibits tonic or initial bursting discharge. Here, we characterize inhibitory synaptic input and neuromodulation in the two CR+ populations, in order to determine how each is regulated. We show that excitatory CR+ neurons receive mixed inhibition from GABAergic and glycinergic sources, whereas inhibitory CR+ neurons receive inhibition, which is dominated by glycine. Noradrenaline and serotonin produced robust outward currents in excitatory CR+ neurons, predicting an inhibitory action on these neurons, but neither neuromodulator produced a response in CR+ inhibitory neurons. In contrast, enkephalin (along with selective mu and delta opioid receptor agonists) produced outward currents in inhibitory CR+ neurons, consistent with an inhibitory action but did not affect the excitatory CR+ population. Our findings show that the pharmacology of inhibitory inputs and neuromodulator actions on CR+ cells, along with their excitatory inputs can define these two subpopulations further, and this could be exploited to modulate discrete aspects of sensory processing selectively in the DH

The 2dF QSO Redshift Survey - XII. The spectroscopic catalogue and luminosity function

We present the final catalogue of the 2dF QSO Redshift Survey (2QZ), based on Anglo-Australian Telescope 2dF spectroscopic observations of 44 576 colour-selected (ubJr) objects with 18.2

The 2dF QSO Redshift Survey - IV. The QSO power spectrum from the 10k catalogue

We present a power spectrum analysis of the 10k catalogue from the 2dF QSO Redshift Survey. Although the Survey currently has a patchy angular selection function, we use the Virgo Consortium's Hubble Volume simulation to demonstrate that we are able to make a useful first measurement of the power spectrum over a wide range of scales. We compare the redshift-space power spectra of QSOs with those measured for galaxies and Abell clusters at low redshift and find that they show similar shapes in their overlap range, , with . The amplitude of the QSO power spectrum at is almost comparable to that of galaxies at the present day if and (the Λ cosmology), and a factor of ≈ 3 lower if (the EdS cosmology) is assumed. The amplitude of the QSO power spectrum is a factor of ≈ 10 lower than that measured for Abell clusters at the present day. At larger scales, the QSO power spectra continue to rise robustly to ≈ 400 h1 Mpc, implying more power at large scales than in the APM galaxy power spectrum measured by Baugh & Efstathiou. We split the QSO sample into two redshift bins and find little evolution in the amplitude of the power spectrum, consistent with the result for the QSO correlation function. In models with this represents evidence for a QSO-mass bias that evolves as a function of time. We compare the QSO power spectra with cold dark matter (CDM) models to obtain a constraint on the shape parameter, Γ. For two choices of cosmology , and , , we find that the best-fitting model has . In addition, we have shown that a power spectrum analysis of the Hubble Volume ΛCDM mock QSO catalogues with as input produces a result that is statistically consistent with the data. The analysis of the mock catalogues also indicates that the above results for Γ are unlikely to be dominated by systematic effects, owing to the current catalogue window. We conclude that the form of the QSO power spectrum shows large-scale power significantly in excess of the standard CDM prediction, similar to that seen in local galaxy surveys at intermediate scales

Microbial flora of commercially produced vacuum packaged, cooked beef roast

Commercially produced vacuum packaged, fully cooked, microwaveable beef roasts from four producers were purchased from local retail markets. Salt concentration, pH, water activity (aw), and percent moisture, fat and protein were determined. Samples of both package juice and homogenized beef plus juice were analyzed for the presence of aerobic, anaerobic and lactic acid bacteria and clostridia-type organisms. The cooked beef products had pH values from 5.82 to 6.19, water activity of 0.992 to 0.997, and contained 0.34 to 1.07% salt, 61.89 to 72.39% moisture, 4.29 to 18.21% fat and 15.92 to 20.62% protein. No growth was detected in juice for aerobic, anaerobic or lactic acid bacteria or clostridia-type organisms. Combined beef and juice had less than 2 CFU/g for aerobic, anaerobic or lactic acid bacteria or clostridia-type organisms. Cooking and chilling schedules used in the manufacture of the four products we evaluated in this study limited survival and outgrowth of microorganisms

The 2dF QSO Redshift Survey - XIV. Structure and evolution from the two-point correlation function

In this paper we present a clustering analysis of quasi-stellar objects (QSOs) using over 20000 objects from the final catalogue of the 2dF QSO Redshift Survey (2QZ), measuring the redshift-space two-point correlation function, ξ(s). When averaged over the redshift range 0.3 < z < 2.2 we find that ξ(s) is flat on small scales, steepening on scales above ~25h-1 Mpc. In a WMAP/2dF cosmology (Ωm= 0.27, ΩΛ= 0.73) we find a best-fitting power law with s0= 5.48+0.42-0.48h-1 Mpc and γ= 1.20 +/- 0.10 on scales s= 1 to 25h-1 Mpc. We demonstrate that non-linear redshift-space distortions have a significant effect on the QSO ξ(s) at scales less than ~10h-1 Mpc. A cold dark matter model assuming WMAP/2dF cosmological parameters is a good description of the QSO ξ(s) after accounting for non-linear clustering and redshift-space distortions, and allowing for a linear bias at the mean redshift of bQ(z= 1.35) = 2.02 +/- 0.07. We subdivide the 2QZ into 10 redshift intervals with effective redshifts from z= 0.53 to 2.48. We find a significant increase in clustering amplitude at high redshift in the WMAP/2dF cosmology. The QSO clustering amplitude increases with redshift such that the integrated correlation function, , within 20h-1 Mpc is and . We derive the QSO bias and find it to be a strong function of redshift with bQ(z= 0.53) = 1.13 +/- 0.18 and bQ(z= 2.48) = 4.24 +/- 0.53. We use these bias values to derive the mean dark matter halo (DMH) mass occupied by the QSOs. At all redshifts 2QZ QSOs inhabit approximately the same mass DMHs with MDH= (3.0 +/- 1.6) × 1012h-1 Msolar, which is close to the characteristic mass in the Press-Schechter mass function, M*, at z= 0. These results imply that L*Q QSOs at z~ 0 should be largely unbiased. If the relation between black hole (BH) mass and MDH or host velocity dispersion does not evolve, then we find that the accretion efficiency (L/LEdd) for L*Q QSOs is approximately constant with redshift. Thus the fading of the QSO population from z~ 2 to ~0 appears to be due to less massive BHs being active at low redshift. We apply different methods to estimate, tQ, the active lifetime of QSOs and constrain tQ to be in the range 4 × 106-6 × 108 yr at z~ 2. We test for any luminosity dependence of QSO clustering by measuring ξ(s) as a function of apparent magnitude (equivalent to luminosity relative to L*Q). However, we find no significant evidence of luminosity-dependent clustering from this data set

Functional and molecular analysis of proprioceptive sensory neuron excitability in mice

Neurons located in dorsal root ganglia (DRG) are crucial for transmitting peripheral sensations such as proprioception, touch, temperature, and nociception to the spinal cord before propagating these signals to higher brain structures. To date, difficulty in identifying modality-specific DRG neurons has limited our ability to study specific populations in detail. As the calcium-binding protein parvalbumin (PV) is a neurochemical marker for proprioceptive DRG cells we used a transgenic mouse line expressing green fluorescent protein (GFP) in PV positive DRGs, to study the functional and molecular properties of putative proprioceptive neurons. Immunolabeled DRGs showed a 100% overlap between GFP positive (GFP+) and PV positive cells, confirming the PVeGFP mouse accurately labeled PV neurons. Targeted patch-clamp recording from isolated GFP+ and GFP negative (GFP−) neurons showed the passive membrane properties of the two groups were similar, however, their active properties differed markedly. All GFP+ neurons fired a single spike in response to sustained current injection and their action potentials (APs) had faster rise times, lower thresholds and shorter half widths. A hyperpolarization-activated current (Ih) was observed in all GFP+ neurons but was infrequently noted in the GFP− population (100% vs. 11%). For GFP+ neurons, Ih activation rates varied markedly, suggesting differences in the underlying hyperpolarization-activated cyclic nucleotide-gated channel (HCN) subunit expression responsible for the current kinetics. Furthermore, quantitative polymerase chain reaction (qPCR) showed the HCN subunits 2, 1, and 4 mRNA (in that order) was more abundant in GFP+ neurons, while HCN 3 was more highly expressed in GFP− neurons. Likewise, immunolabeling confirmed HCN 1, 2, and 4 protein expression in GFP+ neurons. In summary, certain functional properties of GFP+ and GFP− cells differ markedly, providing evidence for modality-specific signaling between the two groups. However, the GFP+ DRG population demonstrates considerable internal heterogeneity when hyperpolarization-activated cyclic nucleotide-gated channel (HCN channel) properties and subunit expression are considered. We propose this heterogeneity reflects the existence of different peripheral receptors such as tendon organs, muscle spindles or mechanoreceptors in the putative proprioceptive neuron population

Effectiveness and cost-effectiveness of daily all-over-body application of emollient during the first year of life for preventing atopic eczema in high-risk children (The BEEP trial): protocol for a randomised controlled trial.

BACKGROUND: Atopic eczema (AE) is a common skin problem that impairs quality of life and is associated with the development of other atopic diseases including asthma, food allergy and allergic rhinitis. AE treatment is a significant cost burden for health care providers. The purpose of the trial is to investigate whether daily application of emollients for the first year of life can prevent AE developing in high-risk infants (first-degree relative with asthma, AE or allergic rhinitis). METHODS: This is a protocol for a pragmatic, two-arm, randomised controlled, multicentre trial. Up to 1400 term infants at high risk of developing AE will be recruited through the community, primary and secondary care in England. Participating families will be randomised in a 1:1 ratio to receive general infant skin-care advice, or general skin-care advice plus emollients with advice to apply daily to the infant for the first year of life. Families will not be blinded to treatment allocation. The primary outcome will be a blinded assessment of AE at 24 months of age using the UK Working Party Diagnostic Criteria for Atopic Eczema. Secondary outcomes are other definitions of AE, time to AE onset, severity of AE (EASI and POEM), presence of other allergic diseases including food allergy, asthma and hay fever, allergic sensitisation, quality of life, cost-effectiveness and safety of the emollients. Subgroup analyses are planned for the primary outcome according to filaggrin genotype and the number of first-degree relatives with AE and other atopic diseases. Families will be followed up by online and postal questionnaire at 3, 6, 12 and 18 months with a face-to-face visit at 24 months. Long-term follow-up until 60 months will be via annual questionnaires. DISCUSSION: This trial will demonstrate whether skin-barrier enhancement through daily emollient for the first year of life can prevent AE from developing in high-risk infants. If effective, this simple and cheap intervention has the potential to result in significant cost savings for health care providers throughout the world by preventing AE and possibly other associated allergic diseases. TRIAL REGISTRATION: ISRCTN registry; ID: ISRCTN21528841 . Registered on 25 July 2014

The 2dF QSO Redshift Survey - V. The 10k catalogue

We present a catalogue comprising over 10 000 QSOs covering an effective area of 289.6 deg2, based on spectroscopic observations with the 2-degree Field (2dF) instrument at the Anglo-Australian Telescope. This catalogue forms the first release of the 2dF QSO Redshift Survey. QSO candidates with 18.2

Ultra-High Energy Neutrino Fluxes and Their Constraints

Applying our recently developed propagation code we review extragalactic neutrino fluxes above 10^{14} eV in various scenarios and how they are constrained by current data. We specifically identify scenarios in which the cosmogenic neutrino flux, produced by pion production of ultra high energy cosmic rays outside their sources, is considerably higher than the "Waxman-Bahcall bound". This is easy to achieve for sources with hard injection spectra and luminosities that were higher in the past. Such fluxes would significantly increase the chances to detect ultra-high energy neutrinos with experiments currently under construction or in the proposal stage.Comment: 11 pages, 15 figures, version published in Phys.Rev.

The obscured growth of massive black holes

The mass density of massive black holes observed locally is consistent with the hard X-ray Background provided that most of the radiation produced during their growth was absorbed by surrounding gas. A simple model is proposed here for the formation of galaxy bulges and central black holes in which young spheroidal galaxies have a significant distributed component of cold dusty clouds which accounts for the absorption. The central accreting black hole is assumed to emit both a quasar-like spectrum, which is absorbed by the surrounding gas, and a slow wind. The power in both is less than the Eddington limit for the black hole. The wind however exerts the most force on the gas and, as earlier suggested by Silk & Rees, when the black hole reaches a critical mass, it is powerful enough to eject the cold gas from the galaxy, so terminating the growth of both black hole and galaxy. In the present model this point occurs when the Thomson depth in the surrounding gas has dropped to about unity and results in the mass of the black hole being proportional to the mass of the spheroid, with the normalization agreeing with that found for local galaxies by Magorrian et al. for reasonable wind parameters. The model predicts a new population of hard X-ray and sub-mm sources at redshifts above one which are powered by black holes in their main growth phase.Comment: 5 pages, no figures, MN LATEX style, accepted for publication in the MNRA