Altered protein expression and protein nitration pattern during d-galactosamine-induced cell death in human hepatocytes: a proteomic analysis

BACKGROUND/AIMS: Hepatic injury by d-galactosamine (d-GalN) is a suitable experimental model of hepatocellular injury. The induction of oxidative and nitrosative stress participates during d-GalN-induced cell death in cultured rat hepatocytes. This study aimed to identify protein expression changes during the induction of apoptosis and necrosis by d-GalN in cultured human hepatocytes. METHODS: A proteomic approach was used to identify the proteins involved and those altered by tyrosine nitration. A high dose of d-GalN (40 mM) was used to induce apoptosis and necrosis in primary culture of human hepatocytes. Cellular lysates prepared at different times after addition of d-GalN were separated by two-dimensional electrophoresis. Gel spots with an altered expression and those matching nitrotyrosine-immunopositive proteins were excised and analyzed by mass spectrometry. RESULTS: d-GalN treatment upregulated microsomal cytochrome b5, fatty acid binding protein and manganese superoxide dismutase, and enhanced annexin degradation. d-GalN increased tyrosine nitration of four cytosolic (Hsc70, Hsp70, annexin A4 and carbonyl reductase) and three mitochondrial (glycine amidinotransferase, ATP synthase beta chain, and thiosulfate sulfurtransferase) proteins in human hepatocytes. CONCLUSIONS: The results provide evidences that oxidative stress and nitric oxide-derived reactive oxygen intermediates induce specific alterations in protein expression that may be critical for the induction of apoptosis and necrosis by d-GalN in cultured human hepatocytes

Responses of a native and a recent invader snail to warming and dry conditions: the case of the lower Ebro River

Aquatic habitats have been highly modified by human actions that reduce their native diversity and create conditions suitable for tolerant alien species. Pomacea maculata was detected in 2009 in both the alluvial plain and the final stretch of the Ebro River. Since then, a permanent population has stabilized in the littoral area of the river where the water level fluctuates according to the river discharge. Melanopsis tricarinata is an endemic snail species highly affected by the reduction in its natural habitat. Currently, the two species do not share the same reaches in the river, but the possibility exists, as the distribution of the P. maculata is constantly increasing. This study aims to analyse the diets and to assess the responses of both snails to global change. The diet of both species was analysed in the field and their responses to water warming and dryness compared under laboratory conditions. This study includes the calculation of future river water temperatures based on air temperature projections. In addition, based on water discharge management scenarios, the study estimated the increase in dry river bed area. The diet of both snail species was similar and based on Cladophora. P. maculata better resisted high temperatures and dry conditions than M. tricarinata. The projections of water temperatures showed an increase in daily temperatures, especially in summer. The hydraulic model suggested that a relevant increase in dry river bed areas will occur. Overall, these results provide insight into the global change factors that could favour P. maculata spread in the river and the reduction in suitable habitat for M. tricarinata and will be useful for future decisions of water discharge management

First Experience with the LHC Cryogenic Instrumentation

The LHC under commissioning at CERN will be the world's largest superconducting accelerator and therefore makes extensive use of cryogenic instruments. These instruments are installed in the tunnel and therefore have to withstand the LHC environment that imposes radiation-tolerant design and construction. Most of the instruments require individual calibration; some of them exhibit several variants as concerns measuring span; all relevant data are therefore stored in an Oracle® database. Those data are used for the various quality assurance procedures defined for installation and commissioning, as well as for generating tables used by the control system to configure automatically the input/output channels. This paper describes the commissioning of the sensors and the corresponding electronics, the first measurement results during the cool-down of one machine sector; it discusses the different encountered problems and their corresponding solutions

Experimental aspects of SU(5)xU(1) supergravity

We study various aspects of $SU(5)\times U(1)$ supergravity as they relate to the experimental verification or falsification of this model. We consider two string-inspired, universal, one-parameter, no-scale soft-supersymmetry-breaking scenarios, driven by the $F$-terms of the moduli and dilaton fields. The model is described in terms of the supersymmetry mass scale (\ie, the chargino mass $m_{\chi^\pm_1}$), $\tan\beta$, and the top-quark mass. We first determine the combined effect on the parameter space of all presently available direct and indirect experimental constraints, including the LEP lower bounds on sparticle and Higgs-boson masses, the $b\to s\gamma$ rate, the anomalous magnetic moment of the muon, the high-precision electroweak parameters $\epsilon_1,\epsilon_b$ (which imply m_t\lsim180\GeV), and the muon fluxes in underground detectors (neutrino telescopes). For the still-allowed points in $(m_{\chi^\pm_1},\tan\beta)$ parameter space, we re-evaluate the experimental situation at the Tevatron, LEPII, and HERA. In the 1994 run, the Tevatron could probe chargino masses as high as 100 GeV. At LEPII the parameter space could be explored with probes of different resolutions: Higgs boson searches, selectron searches, and chargino searches. Moreover, for m_t\lsim150\GeV, these Higgs-boson searches could explore all of the allowed parameter space with \sqrt{s}\lsim210\GeV.Comment: latex, 36 pages, 25 figures (not included). Figures are available via anonymous ftp from hplaa02.cern.ch (/pub/lopez) as either 33 ps files (Easpects*.ps, 8.1MB) or one uuencoded file (AllFigures.uu, 3.7MB

A Classification of 3-Family Grand Unification in String Theory I. The SO(10) and E_6 Models

We give a classification of 3-family SO(10) and E_6 grand unification in string theory within the framework of conformal field theory and asymmetric orbifolds. We argue that the construction of such models in the heterotic string theory requires certain Z_6 asymmetric orbifolds that include a Z_3 outer-automorphism, the latter yielding a level-3 current algebra for the grand unification gauge group SO(10) or E_6. We then classify all such Z_6 asymmetric orbifolds that result in models with a non-abelian hidden sector. All models classified in this paper have only one adjoint (but no other higher representation) Higgs field in the grand unified gauge group. In addition, all of them are completely anomaly free. There are two types of such 3-family models. The first type consists of the unique SO(10) model with SU(2) X SU(2) X SU(2) as its hidden sector (which is not asymptotically-free at the string scale). This SO(10) model has 4 left-handed and 1 right-handed 16s. The second type is described by a moduli space containing 17 models (distinguished by their massless spectra). All these models have an SU(2) hidden sector, and 5 left-handed and 2 right-handed families in the grand unified gauge group. One of these models is the unique E_6 model with an asymptotically-free SU(2) hidden sector. The others are SO(10) models, 8 of them with an asymptotically free hidden sector at the string scale.Comment: 35 pages, Revtex 3.0, one eps figure (to appear in Phys. Rev. D

Higgs Mass Bounds Separate Models of Electroweak Symmetry Breaking

Vacuum stability implies a lower limit on the mass of the higgs boson in the Standard Model (SM). In contrast, an upper limit on the lightest higgs mass can be calculated in supersymmetric (susy) models. The main uncertainty in each limit is the value of the top mass, which may now be fixed by the recent CDF result. We study the possibility that these bounds do not overlap, and find that (i) a mass gap emerges at $m_t\sim 160$ GeV between the SM and the Minimal Susy Standard Model (MSSM); and between the SM and the Minimal plus Singlet Susy Model [(M+1)SSM] if the independent scalar self--coupling of the latter is perturbatively small or if the $\tan\beta$ parameter is large; this gap widens with increasing $m_t$; (ii) there is no overlap between the SM and the MSSM bounds at even smaller values of $m_t$ for the $\tan\beta$ value ($\sim 1$--2) preferred in Supersymmetric Grand Unified Theories. Thus, if the new top mass measurement remains valid, a measurement of the first higgs mass will serve to exclude either the SM or MSSM/(M+1)SSM higgs sectors. In addition, we discuss the upper bound on the lightest higgs mass in susy models with an extended higgs sector, and in models with a strongly interacting higgs sector. Finally, we comment on the discovery potential for the lightest higgses in these models.Comment: 18 pages, 5 figures, VAND-TH-94-1

Measuring the cosmological lepton asymmetry through the CMB anisotropy

A large lepton asymmetry in the Universe is still a viable possibility and leads to many interesting phenomena such as gauge symmetry nonrestoration at high temperature. We show that a large lepton asymmetry changes the predicted cosmic microwave background (CMB) anisotropy and that any degeneracy in the relic neutrino sea will be measured to a precision of 1% or better when the CMB anisotropy is measured at the accuracy expected to result from the planned satellite missions MAP and Planck. In fact, the current measurements already put an upper limit on the lepton asymmetry of the Universe which is stronger than the one coming from considerations of primordial nucleosynthesis and structure formation.Comment: 4 pagex LaTex, 1 color postscript figure, uses epsf. Version submitted to PRL. (Bug in code fixed, new figure, conclusions unchanged

QCD Improved b→sγb\to s\gamma Constraints on the Minimal Supergravity Model

Recent advances in the QCD corrections to $b\to s\gamma$ decay in the MSSM include i.) evaluation of the relevant operators, Wilson coefficients and anomalous dimension matrix elements for the various MSSM effective theories valid at scales beyond $Q =M_W$, ii.) calculations of most of the needed anomalous dimension matrix elements to next-to-leading order for scales m_b\alt Q , and iii.) calculations of ${\cal O}(\alpha_s)$ virtual and bremsstrahlung corrections to the $b\to s\gamma$ decay operators at scale $Q\sim m_b$. We assemble all these known results to gain an estimate of $B(b\to s\gamma )$ for the parameter space of the minimal supergravity model (mSUGRA). We find a much reduced scale dependence of our result compared to usual leading-log evaluations. Comparison with the latest CLEO results yields stringent constraints on parameter space. Much of mSUGRA parameter space is ruled out for $\mu <0$, especially for large $tan\beta$. We compare these results with other constraints from cosmology and non-standard vacua. Also, we compare with expectations for discovering mSUGRA at LEP2, the Tevatron and the CERN LHC.Comment: 14 pages REVTEX plus 7 PS figures; this version contains revised figures and text due to discovery of a bug in the program used to generate results for the previous version of this manuscrip

Left-Right Symmetric Heterotic-String Derived Models

Recently it was demonstrated that free fermionic heterotic-strings can produce models with solely the Minimal Supersymmetric Standard Model states in the low energy spectrum. This unprecedented result provides further strong evidence for the possibility that the true string vacuum shares some of the properties of the free fermionic models. Past free fermionic models have focused on several possible unbroken observable SO(10) subgroups at the string scale, which include the flipped SU(5) (FSU5), the Pati-Salam (PS) string models, and the string Standard-like Models (SLM). We extend this study to include the case in which the SO(10) symmetry is broken to the Left-Right Symmetric (LRS) gauge group, SO(10) -> SU(3)_C X U(1)_{B-L} X SU(2)_L X SU(2)_R. We present several models of this type and discuss their phenomenological features. The most striking new outcome of the LRS string models, in contrast to the case of the FSU5, the PS, and the SLM string models, is that they can produce effective field theories that are free of Abelian anomalies. We discuss the distinction between the two types of free fermionic models which result in the presence, or absence, of an anomalous U(1). As a counter example we also present a LRS model that does contain an anomalous U(1). Additionally, we discuss how in string models the Standard Model spectrum may arise from the three \mbf 16 representations of SO(10), while the weak-hypercharge does not have the canonical SO(10) embedding.Comment: 39 pages. Standard Latex. Version to appear in PR