Glycine receptor in rat hippocampal and spinal cord neurons as a molecular target for rapid actions of 17-β-estradiol

Glycine receptors (GlyRs) play important roles in regulating hippocampal neural network activity and spinal nociception. Here we show that, in cultured rat hippocampal (HIP) and spinal dorsal horn (SDH) neurons, 17-β-estradiol (E2) rapidly and reversibly reduced the peak amplitude of whole-cell glycine-activated currents (IGly). In outside-out membrane patches from HIP neurons devoid of nuclei, E2 similarly inhibited IGly, suggesting a non-genomic characteristic. Moreover, the E2 effect on IGly persisted in the presence of the calcium chelator BAPTA, the protein kinase inhibitor staurosporine, the classical ER (i.e. ERα and ERβ) antagonist tamoxifen, or the G-protein modulators, favoring a direct action of E2 on GlyRs. In HEK293 cells expressing various combinations of GlyR subunits, E2 only affected the IGly in cells expressing α2, α2β or α3β subunits, suggesting that either α2-containing or α3β-GlyRs mediate the E2 effect observed in neurons. Furthermore, E2 inhibited the GlyR-mediated tonic current in pyramidal neurons of HIP CA1 region, where abundant GlyR α2 subunit is expressed. We suggest that the neuronal GlyR is a novel molecular target of E2 which directly inhibits the function of GlyRs in the HIP and SDH regions. This finding may shed new light on premenstrual dysphoric disorder and the gender differences in pain sensation at the CNS level

Bilinear R-parity violation with flavor symmetry

Bilinear R-parity violation (BRPV) provides the simplest intrinsically supersymmetric neutrino mass generation scheme. While neutrino mixing parameters can be probed in high energy accelerators, they are unfortunately not predicted by the theory. Here we propose a model based on the discrete flavor symmetry $A_4$ with a single R-parity violating parameter, leading to (i) correct Cabbibo mixing given by the Gatto-Sartori-Tonin formula, and a successful unification-like b-tau mass relation, and (ii) a correlation between the lepton mixing angles $\theta_{13}$ and $\theta_{23}$ in agreement with recent neutrino oscillation data, as well as a (nearly) massless neutrino, leading to absence of neutrinoless double beta decay.Comment: 16 pages, 3 figures. Extended version, as published in JHE

New Constraints (and Motivations) for Abelian Gauge Bosons in the MeV-TeV Mass Range

We survey the phenomenological constraints on abelian gauge bosons having masses in the MeV to multi-GeV mass range (using precision electroweak measurements, neutrino-electron and neutrino-nucleon scattering, electron and muon anomalous magnetic moments, upsilon decay, beam dump experiments, atomic parity violation, low-energy neutron scattering and primordial nucleosynthesis). We compute their implications for the three parameters that in general describe the low-energy properties of such bosons: their mass and their two possible types of dimensionless couplings (direct couplings to ordinary fermions and kinetic mixing with Standard Model hypercharge). We argue that gauge bosons with very small couplings to ordinary fermions in this mass range are natural in string compactifications and are likely to be generic in theories for which the gravity scale is systematically smaller than the Planck mass - such as in extra-dimensional models - because of the necessity to suppress proton decay. Furthermore, because its couplings are weak, in the low-energy theory relevant to experiments at and below TeV scales the charge gauged by the new boson can appear to be broken, both by classical effects and by anomalies. In particular, if the new gauge charge appears to be anomalous, anomaly cancellation does not also require the introduction of new light fermions in the low-energy theory. Furthermore, the charge can appear to be conserved in the low-energy theory, despite the corresponding gauge boson having a mass. Our results reduce to those of other authors in the special cases where there is no kinetic mixing or there is no direct coupling to ordinary fermions, such as for recently proposed dark-matter scenarios.Comment: 49 pages + appendix, 21 figures. This is the final version which appears in JHE

The e-Index, Complementing the h-Index for Excess Citations

BACKGROUND: The h-index has already been used by major citation databases to evaluate the academic performance of individual scientists. Although effective and simple, the h-index suffers from some drawbacks that limit its use in accurately and fairly comparing the scientific output of different researchers. These drawbacks include information loss and low resolution: the former refers to the fact that in addition to h(2) citations for papers in the h-core, excess citations are completely ignored, whereas the latter means that it is common for a group of researchers to have an identical h-index. METHODOLOGY/PRINCIPAL FINDINGS: To solve these problems, I here propose the e-index, where e(2) represents the ignored excess citations, in addition to the h(2) citations for h-core papers. Citation information can be completely depicted by using the h-index together with the e-index, which are independent of each other. Some other h-type indices, such as a and R, are h-dependent, have information redundancy with h, and therefore, when used together with h, mask the real differences in excess citations of different researchers. CONCLUSIONS/SIGNIFICANCE: Although simple, the e-index is a necessary h-index complement, especially for evaluating highly cited scientists or for precisely comparing the scientific output of a group of scientists having an identical h-index

Night-sky brightness monitoring in Hong Kong - a city-wide light pollution assessment

Results of the first comprehensive light pollution survey in Hong Kong are presented. The night-sky brightness was measured and monitored around the city using a portable light sensing device called the Sky Quality Meter over a 15-month period beginning in March 2008. A total of 1,957 data sets were taken at 199 distinct locations, including urban and rural sites covering all 18 Administrative Districts of Hong Kong. The survey shows that the environmental light pollution problem in Hong Kong is severe - the urban night-skies (sky brightness at 15.0 mag per arcsec square) are on average ~100 times brighter than at the darkest rural sites (20.1 mag per arcsec square), indicating that the high lighting densities in the densely populated residential and commercial areas lead to light pollution. In the worst polluted urban location studied, the night-sky at 13.2 mag per arcsec square can be over 500 times brighter than the darkest sites in Hong Kong. The observed night-sky brightness is found to be affected by human factors such as land utilization and population density of the observation sites, together with meteorological and/or environmental factors. Moreover, earlier night-skies (at 9:30pm local time) are generally brighter than later time (at 11:30pm), which can be attributed to some public and commercial lightings being turned off later at night. On the other hand, no concrete relationship between the observed sky brightness and air pollutant concentrations could be established with the limited survey sampling. Results from this survey will serve as an important database for the public to assess whether new rules and regulations are necessary to control the use of outdoor lightings in Hong Kong.Comment: 33 pages, 13 figures, Environmental Monitoring and Assessment, in pres

Mixed Mediation of Supersymmetry Breaking with Anomalous U(1) Gauge Symmetry

Models with anomalous U(1) gauge symmetry contain various superfields which can have nonzero supersymmetry breaking auxiliary components providing the origin of soft terms in the visible sector, e.g. the U(1) vector superfield, the modulus or dilaton superfield implementing the Green-Schwarz anomaly cancellation mechanism, U(1)-charged but standard model singlet matter superfield required to cancel the Fayet-Iliopoulos term, and finally the supergravity multiplet. We examine the relative strength between these supersymmetry breaking components in a simple class of models, and find that various different mixed mediations of supersymmetry breaking, involving the modulus, gauge, anomaly and D-term mediations, can be realized depending upon the characteristics of D-flat directions and how those D-flat directions are stabilized with a vanishing cosmological constant. We identify two parameters which represent such properties and thus characterize how the various mediations are mixed. We also discuss the moduli stabilization and soft terms in a variant of KKLT scenario, in which the visible sector K\"ahler modulus is stabilized by the D-term potential of anomalous U(1) gauge symmetry.Comment: 30 pages, 5 figure

Longitudinal seroepidemiologic study of the 2009 pandemic influenza A (H1N1) infection among health care workers in a children's hospital

<p>Abstract</p> <p>Background</p> <p>To probe seroepidemiology of the 2009 pandemic influenza A (H1N1) among health care workers (HCWs) in a children's hospital.</p> <p>Methods</p> <p>From August 2009 to March 2010, serum samples were drawn from 150 HCWs in a children's hospital in Taipei before the 2009 influenza A (H1N1) pandemic, before H1N1 vaccination, and after the pandemic. HCWs who had come into direct contact with 2009 influenza A (H1N1) patients or their clinical respiratory samples during their daily work were designated as a high-risk group. Antibody levels were determined by hemagglutination inhibition (HAI) assay. A four-fold or greater increase in HAI titers between any successive paired sera was defined as seroconversion, and factors associated with seroconversion were analyzed.</p> <p>Results</p> <p>Among the 150 HCWs, 18 (12.0%) showed either virological or serological evidence of 2009 pandemic influenza A (H1N1) infection. Of the 90 unvaccinated HCWs, baseline and post-pandemic seroprotective rates were 5.6% and 20.0%. Seroconversion rates among unvaccinated HCWs were 14.4% (13/90), 22.5% (9/40), and 8.0% (4/50) for total, high-risk group, and low-risk group, respectively. Multivariate analysis revealed being in the high-risk group is an independent risk factor associated with seroconversion.</p> <p>Conclusion</p> <p>The infection rate of 2009 pandemic influenza A (H1N1) in HCWs was moderate and not higher than that for the general population. The majority of unvaccinated HCWs remained susceptible. Direct contact of influenza patients and their respiratory samples increased the risk of infection.</p

Ctr2 Links Copper Homeostasis to Polysaccharide Capsule Formation and Phagocytosis Inhibition in the Human Fungal Pathogen Cryptococcus neoformans

Cryptococcus neoformans is a human opportunistic fungal pathogen responsible for ∼1/3 of HIV/AIDS deaths worldwide. This budding yeast expresses a polysaccharide capsule necessary for virulence. Capsule production inhibits phagocytosis by macrophages. Here we describe results that link copper homeostasis to capsule production and the inhibition of phagocytosis. Specifically, using Agrobacterium-mediated insertional mutagenesis, we identified an insertion in the promoter region of the putative copper transporter-encoding gene CTR2 that results in reduced expression of CTR2 and increased phagocytosis by murine RAW264.7 macrophages. The mutant also displayed sensitivity to copper starvation and defects in polysaccharide capsule production and melanization. These defects were all reversed by genetic correction of the promoter insertion by homologous targeting. Several melanization-defective mutants identified previously, those in the RIM20, RIM101, and VPS25 genes, also display sensitivity to copper starvation, reduced capsule production and increased phagocytosis. Together these results indicate a previously undescribed link between copper homeostasis to polysaccharide capsule production and phagocytosis inhibition in Cryptococcus neoformans

Ranking insertion, deletion and nonsense mutations based on their effect on genetic information

<p>Abstract</p> <p>Background</p> <p>Genetic variations contribute to normal phenotypic differences as well as diseases, and new sequencing technologies are greatly increasing the capacity to identify these variations. Given the large number of variations now being discovered, computational methods to prioritize the functional importance of genetic variations are of growing interest. Thus far, the focus of computational tools has been mainly on the prediction of the effects of amino acid changing single nucleotide polymorphisms (SNPs) and little attention has been paid to indels or nonsense SNPs that result in premature stop codons.</p> <p>Results</p> <p>We propose computational methods to rank insertion-deletion mutations in the coding as well as non-coding regions and nonsense mutations. We rank these variations by measuring the extent of their effect on biological function, based on the assumption that evolutionary conservation reflects function. Using sequence data from budding yeast and human, we show that variations which that we predict to have larger effects segregate at significantly lower allele frequencies, and occur less frequently than expected by chance, indicating stronger purifying selection. Furthermore, we find that insertions, deletions and premature stop codons associated with disease in the human have significantly larger predicted effects than those not associated with disease. Interestingly, the large-effect mutations associated with disease show a similar distribution of predicted effects to that expected for completely random mutations.</p> <p>Conclusions</p> <p>This demonstrates that the evolutionary conservation context of the sequences that harbour insertions, deletions and nonsense mutations can be used to predict and rank the effects of the mutations.</p