Construction of a DNA Chip for Screening of Genetic Hearing Loss

ObjectivesHearing loss is the most common sensory disorder in humans and genetic causes are estimated to cause more than 50% of all incidents of congenital hearing loss. To develop an efficient method for a genetic diagnosis of hearing loss, we have developed and validated a genetic hearing loss DNA chip that allows the simultaneous analysis of 7 different mutations in the GJB2, SLC26A4, and the mtDNA 12S rRNA genes in Koreans.MethodsA genotyping microarray, based on the allele-specific primer extension (ASPE) method, was used and preliminary validation was examined from the five patients and five controls that were already known their genotypes by DNA sequencing analysis.ResultsThe cutoff Genotyping index (GI) of genotyping for each mutation was set up and validated to discriminate among the genotypes. The result of the DNA chip assay was identical to those of previous results.ConclusionWe successfully designed the genetic hearing loss DNA chip for the first time in Korea and it would be useful for a clinical genetic diagnosis of hearing loss. Further consideration will be needed in order to examine the accuracy of this DNA chip with much larger patient sample numbers

Unique features of bovine lymphocytes exposed to a staphylococcal enterotoxin

We previously demonstrated that stimulation of bovine peripheral blood mononuclear cells (PBMCs) with staphylococcal enterotoxin C (SEC), led to an inversion of the CD4+:CD8+ T cell ratio and generation of an atypical CD8+ T cell subpopulation expressing CD26. In the present study, we examined T cell apoptosis and proliferation profiles of PBMC subpopulations in cultures stimulated with SEC. Unlike when stimulated with concanavalin A, nucleic acid synthesis in bovine PBMC cultures stimulated with SEC was low during the first four days but increased greatly on day 5. In contrast, nucleic acid synthesis in human PBMC cultures stimulated with SEC increased continuously. To investigate the mechanism of delayed bovine T cell proliferation, various cell phenotypes were monitored. The inversion of the bovine CD4+:CD8+ T cell ratio in PBMC cultures stimulated by SEC was associated with higher proliferation and lower apoptosis of CD8+ T cells compared to CD4+ T cells. The mRNA levels for interleukin (IL)-4 and IL-13 were sustained over 4 days but IL-12 mRNA levels dropped to background on day 2. These data suggest that SEC induces a prolonged Th-2- biased microenvironment, and together with the inversion of the bovine CD4+:CD8+ T cell ratios in bovine PBMC cultures with SEC, may in part explain the inability of the mammary immune system to establish an effective response to Staphylococcus aureus infections.This work was supported by USDA NRICGP Grants 99- 35201-8581 (G.A.B) and 99-3504-8556 (W.C.D), USDA WNV Grants 00144-0182085 (W.C.D.) and 9902050- 0183734 (W.C.D.), PHS Grants U54AI57141 (G.A.B.), P20 RR016454 and P20-RR15587 (G.A.B), and the Idaho Agricultural Experiment Station (G.A.B), USA. This work was also funded by BK21 Program for Veterinary Science, and Korea Research Foundation Grant (KRF-005-E00076)

Measurement of quarkonium production at forward rapidity in pp collisions at √s=7 TeV

The inclusive production cross sections at forward rapidity of J/ψ , ψ(2S) , Υ (1S) and Υ (2S) are measured in pp collisions at s√=7 TeV with the ALICE detector at the LHC. The analysis is based on a data sample corresponding to an integrated luminosity of 1.35 pb‾¹ . Quarkonia are reconstructed in the dimuon-decay channel and the signal yields are evaluated by fitting the μ+μ− invariant mass distributions. The differential production cross sections are measured as a function of the transverse momentum pT and rapidity y , over the ranges 0<pT<20 GeV/c for J/ψ , 0<pT<12 GeV/c for all other resonances and for \(2.5 . The measured cross sections integrated over pT and y , and assuming unpolarized quarkonia, are: σJ/ψ=6.69±0.04±0.63 μ b, σψ(2S)=1.13±0.07±0.19 μ b, σΥ(1S)=54.2±5.0±6.7 nb and σΥ(2S)=18.4±3.7±2.9 nb, where the first uncertainty is statistical and the second one is systematic. The results are compared to measurements performed by other LHC experiments and to theoretical models

Event-by-event mean pT fluctuations in pp and Pb–Pb collisions at the LHC

Event-by-event fluctuations of the mean transverse momentum of charged particles produced in pp collisions at TeX TeX 0.9, 2.76 and 7 TeV, and Pb–Pb collisions at TeX TeX 2.76 TeV are studied as a function of the charged-particle multiplicity using the ALICE detector at the LHC. Dynamical fluctuations indicative of correlated particle emission are observed in all systems. The results in pp collisions show little dependence on collision energy. The Monte Carlo event generators PYTHIA and PHOJET are in qualitative agreement with the data. Peripheral Pb–Pb data exhibit a similar multiplicity dependence as that observed in pp. In central Pb–Pb, the results deviate from this trend, featuring a significant reduction of the fluctuation strength. The results in Pb–Pb are in qualitative agreement with previous measurements in Au–Au at lower collision energies and with expectations from models that incorporate collective phenomena

Suppression of ψ(2S) production in p-Pb collisions at √sNN=5.02 TeV .

The ALICE Collaboration has studied the inclusive production of the charmonium state ψ(2S) in proton-lead (p-Pb) collisions at the nucleon-nucleon centre of mass energy √sNN = 5.02TeV at the CERN LHC. The measurement was performed at forward (2.03 < ycms < 3.53) and backward (−4.46 < ycms < −2.96) centre of mass rapidities, studying the decays into muon pairs. In this paper, we present the inclusive production cross sections σ (2S), both integrated and as a function of the transverse momentum pT, for the two ycms domains. The results are compared to those obtained for the 1S vector state (J/ψ), by showing the ratios between the production cross sections, as well as the double ratios [σ (2S)/σJ/ ]pPb/[σ (2S)/σJ/ ]pp between p-Pb and proton-proton collisions. Finally, the nuclear modification factor for inclusive ψ(2S) is evaluated and compared to the measurement of the same quantity for J/ψ and to theoretical models including parton shadowing and coherent energy loss mechanisms. The results show a significantly larger suppression of the ψ(2S) compared to that measured for J/ψ and to models. These observations represent a clear indication for sizeable final state effects on ψ(2S) production

Production of charged pions, kaons and protons at large transverse momenta in pp and Pb-Pb collisions at sNN\sqrt{s_{NN}} = 2.76 TeV

Transverse momentum spectra of $\pi^{\pm}, K^{\pm}$ and $p(\bar{p})$ up to $p_T$ = 20 GeV/c at mid-rapidity, |y| $\le$ 0.8, in pp and Pb-Pb collisions at $\sqrt{s_{NN}}$ = 2.76 TeV have been measured using the ALICE detector at the LHC. At intermediate $p_T$ (2-8 GeV/c) an enhancement of the proton-to-proton ratio, (p + \bar{p})/(\pi^+ + \pi^-\(), with respect to pp collisions is observed and the ratio reaches 0.80 in central Pb-Pb collisions. The measurement of the nuclear modification factors for \(\pi^{\pm}, K^{\pm} and $p(\bar{p})$ indicates that within the systematic and statistical uncertainties they are the same at high $p_T$ (> 10 GeV/c), suggesting that the chemical composition of leading particles from jets in the medium is similar to that of vacuum jets.publishedVersio

Transverse momentum dependence of inclusive primary charged-particle production in p–Pb collisions at √sNN=5.02 TeV

The transverse momentum ( pT ) distribution of primary charged particles is measured at midrapidity in minimum-bias p–Pb collisions at sNN−−−√=5.02 TeV with the ALICE detector at the LHC in the range \(0.15 GeV/ c . The spectra are compared to the expectation based on binary collision scaling of particle production in pp collisions, leading to a nuclear modification factor consistent with unity for pT larger than 2 GeV/ c , with a weak indication of a Cronin-like enhancement for pT around 4 GeV/c . The measurement is compared to theoretical calculations and to data in Pb–Pb collisions at sNN−−−√=2.76 TeV

The Behavior, onḂ0,11, of an Oscillatory Integral with Polynomial Phase Function

AbstractWe study the convolution oscillatory singular integral operatorTf=p.v.Ω∗f, with Ω(x)=eiq(x)K(x), whereqis a real-valued polynomial of a real variable, of degreed≥2, andKis a Calderón–Zygmund-type kernel. We prove that this operator extends to an operator that maps the Besov spaceḂ0,11into the Hardy-type spaceH10

Dehydroepiandrosterone sulfate mediates activation of transcription factors CREB and ATF-1 via a Gα11-coupled receptor in the spermatogenic cell line GC-2

AbstractDehydroepiandrosterone sulfate (DHEAS) is a circulating steroid produced in the adrenal cortex, brain, and gonads. Whereas a series of investigations attest to neuroprotective effects of the steroid in the brain, surprisingly little is known about the physiological effects of DHEAS on cells of the reproductive system. Here we demonstrate that DHEAS acting on the spermatogenic cell line GC-2 induces a time- and concentration-dependent phosphorylation of c-Src and Erk1/2 and activates the transcription factors activating transforming factor-1 (ATF-1) and cyclic AMP-responsive element binding protein (CREB). These actions are consistent with the non-classical signaling pathway of testosterone and suggest that DHEAS is a pro-androgen that is converted into testosterone in order to exert its biological activity. The fact, however, that steroid sulfatase mRNA was not detected in the GC-2 cells and the clear demonstration of DHEAS-induced activation of Erk1/2, ATF-1 and CREB after silencing the androgen receptor by small interfering RNA (siRNA) clearly contradict this assumption and make it appear unlikely that DHEAS has to be converted in the cytosol into a different steroid in order to activate the kinases and transcription factors mentioned. Instead, it is likely that the DHEAS-induced signaling is mediated through the interaction of the steroid with a membrane-bound G-protein-coupled receptor, since silencing of Guanine nucleotide-binding protein subunit alpha-11 (Gnα11) leads to the abolition of the DHEAS-induced stimulation of Erk1/2, ATF-1, and CREB. The investigation presented here shows a hormone-like activity of DHEAS on a spermatogenic cell line. Since DHEAS is produced in male and female reproductive organs, these findings could help to define new roles for DHEAS in the physiology of reproduction

Multiplicity dependence of the average transverse momentum in pp, p-Pb, and Pb-Pb collisions at the LHC

The average transverse momentum versus the charged-particle multiplicity $N_{ch}$ was measured in p-Pb collisions at a collision energy per nucleon-nucleon pair $\sqrt{s_{NN}}$ = 5.02 TeV and in pp collisions at collision energies of $\sqrt{s}$ = 0.9, 2.76, and 7 Tev in the kinematic range 0.15 with $N_{ch}$ is observed, which is much stronger than that measured in Pb-Pb collisions. For pp collisions, this could be attributed, within a model of hadronizing strings, to multiple-parton interactions and to a final-state color reconnection mechanism. The data in p-Pb and Pb-Pb collisions cannot be described by an incoherent superposition of nucleon-nucleon collisions and pose a challenge to most of the event generators.publishedVersio