Cyclophilin D links programmed cell death and organismal aging in Podospora anserina

This is the final version of the article. Available from Wiley via the DOI in this record.Cyclophilin D (CYPD) is a mitochondrial peptidyl prolyl-cis,trans-isomerase involved in opening of the mitochondrial permeability transition pore (mPTP). CYPD abundance increases during aging in mammalian tissues and in the aging model organism Podospora anserina. Here, we show that treatment of the P. anserina wild-type with low concentrations of the cyclophilin inhibitor cyclosporin A (CSA) extends lifespan. Transgenic strains overexpressing PaCypD are characterized by reduced stress tolerance, suffer from pronounced mitochondrial dysfunction and are characterized by accelerated aging and induction of cell death. Treatment with CSA leads to correction of mitochondrial function and lifespan to that of the wild-type. In contrast, PaCypD deletion strains are not affected by CSA within the investigated concentration range and show increased resistance against inducers of oxidative stress and cell death. Our data provide a mechanistic link between programmed cell death (PCD) and organismal aging and bear implications for the potential use of CSA to intervene into biologic aging.The research was supported by grants of the Deutsche Forschungsgemeinschaft (Os75/12-1) and by the European Commission via the Integrated Project with the acronym MiMage; (LSHM-CT-2004-512020)

SUSY Stops at a Bump

We discuss collider signatures of the "natural supersymmetry" scenario with baryon-number violating R-parity violation. We argue that this is one of the few remaining viable incarnations of weak scale supersymmetry consistent with full electroweak naturalness. We show that this intriguing and challenging scenario contains distinctive LHC signals, resonances of hard jets in conjunction with relatively soft leptons and missing energy, which are easily overlooked by existing LHC searches. We propose novel strategies for distinguishing these signals above background, and estimate their potential reach at the 8 TeV LHC. We show that other multi-lepton signals of this scenario can be seen by currently existing searches with increased statistics, but these opportunities are more spectrum-dependent.Comment: 23 pages, 7 figures, 3 tables. V2: spectrum discussion corrected, most of the changes are in Sec. 2. Benchmarks, analysis and conclusions unchanged. References adde

BLUF Domain Function Does Not Require a Metastable Radical Intermediate State

BLUF (blue light using flavin) domain proteins are an important family of blue light-sensing proteins which control a wide variety of functions in cells. The primary light-activated step in the BLUF domain is not yet established. A number of experimental and theoretical studies points to a role for photoinduced electron transfer (PET) between a highly conserved tyrosine and the flavin chromophore to form a radical intermediate state. Here we investigate the role of PET in three different BLUF proteins, using ultrafast broadband transient infrared spectroscopy. We characterize and identify infrared active marker modes for excited and ground state species and use them to record photochemical dynamics in the proteins. We also generate mutants which unambiguously show PET and, through isotope labeling of the protein and the chromophore, are able to assign modes characteristic of both flavin and protein radical states. We find that these radical intermediates are not observed in two of the three BLUF domains studied, casting doubt on the importance of the formation of a population of radical intermediates in the BLUF photocycle. Further, unnatural amino acid mutagenesis is used to replace the conserved tyrosine with fluorotyrosines, thus modifying the driving force for the proposed electron transfer reaction; the rate changes observed are also not consistent with a PET mechanism. Thus, while intermediates of PET reactions can be observed in BLUF proteins they are not correlated with photoactivity, suggesting that radical intermediates are not central to their operation. Alternative nonradical pathways including a keto–enol tautomerization induced by electronic excitation of the flavin ring are considered

Top quark forward-backward asymmetry in R-parity violating supersymmetry

The interaction of bottom squark-mediated top quark pair production, occurring in the R-parity violating minimal supersymmetric standard model (MSSM), is proposed as an explanation of the anomalously large $t\bar{t}$ forward-backward asymmetry (FBA) observed at the Tevatron. We find that this model can give a good fit to top quark data, both the inclusive and invariant mass-dependent asymmetries, while remaining consistent (at the 2-$\sigma$ level) with the total and differential production cross-sections. The scenario is challenged by strong constraints from atomic parity violation (APV), but we point out an extra diagram for the effective down quark-Z vertex, involving the same coupling constant as required for the FBA, which tends to weaken the APV constraint, and which can nullify it for reasonable values of the top squark masses and mixing angle. Large contributions to flavor-changing neutral currents can be avoided if only the third generation of sparticles is light.Comment: 24 pages, 7 figures. v3: included LHC top production cross section data; model still consistent at 2 sigma leve

Supersymmetry in the shadow of photini

Additional neutral gauge fermions -- "photini" -- arise in string compactifications as superpartners of U(1) gauge fields. Unlike their vector counterparts, the photini can acquire weak-scale masses from soft SUSY breaking and lead to observable signatures at the LHC through mass mixing with the bino. In this work we investigate the collider consequences of adding photini to the neutralino sector of the MSSM. Relatively large mixing of one or more photini with the bino can lead to prompt decays of the lightest ordinary supersymmetric particle; these extra cascades transfer most of the energy of SUSY decay chains into Standard Model particles, diminishing the power of missing energy as an experimental handle for signal discrimination. We demonstrate that the missing energy in SUSY events with photini is reduced dramatically for supersymmetric spectra with MSSM neutralinos near the weak scale, and study the effects on limits set by the leading hadronic SUSY searches at ATLAS and CMS. We find that in the presence of even one light photino the limits on squark masses from hadronic searches can be reduced by 400 GeV, with comparable (though more modest) reduction of gluino mass limits. We also consider potential discovery channels such as dilepton and multilepton searches, which remain sensitive to SUSY spectra with photini and can provide an unexpected route to the discovery of supersymmetry. Although presented in the context of photini, our results apply in general to theories in which additional light neutral fermions mix with MSSM gauginos.Comment: 23 pages, 8 figures, references adde

Consequences of local gauge symmetry in empirical tight-binding theory

A method for incorporating electromagnetic fields into empirical tight-binding theory is derived from the principle of local gauge symmetry. Gauge invariance is shown to be incompatible with empirical tight-binding theory unless a representation exists in which the coordinate operator is diagonal. The present approach takes this basis as fundamental and uses group theory to construct symmetrized linear combinations of discrete coordinate eigenkets. This produces orthogonal atomic-like "orbitals" that may be used as a tight-binding basis. The coordinate matrix in the latter basis includes intra-atomic matrix elements between different orbitals on the same atom. Lattice gauge theory is then used to define discrete electromagnetic fields and their interaction with electrons. Local gauge symmetry is shown to impose strong restrictions limiting the range of the Hamiltonian in the coordinate basis. The theory is applied to the semiconductors Ge and Si, for which it is shown that a basis of 15 orbitals per atom provides a satisfactory description of the valence bands and the lowest conduction bands. Calculations of the dielectric function demonstrate that this model yields an accurate joint density of states, but underestimates the oscillator strength by about 20% in comparison to a nonlocal empirical pseudopotential calculation.Comment: 23 pages, 7 figures, RevTeX4; submitted to Phys. Rev.

A Stealth Supersymmetry Sampler

The LHC has strongly constrained models of supersymmetry with traditional missing energy signatures. We present a variety of models that realize the concept of Stealth Supersymmetry, i.e. models with R-parity in which one or more nearly-supersymmetric particles (a "stealth sector") lead to collider signatures with only a small amount of missing energy. The simplest realization involves low-scale supersymmetry breaking, with an R-odd particle decaying to its superpartner and a soft gravitino. We clarify the stealth mechanism and its differences from compressed supersymmetry and explain the requirements for stealth models with high-scale supersymmetry breaking, in which the soft invisible particle is not a gravitino. We also discuss new and distinctive classes of stealth models that couple through a baryon portal or Z' gauge interactions. Finally, we present updated limits on stealth supersymmetry in light of current LHC searches.Comment: 45 pages, 16 figure

Constraints on supersymmetry with light third family from LHC data

We present a re-interpretation of the recent ATLAS limits on supersymmetry in channels with jets (with and without b-tags) and missing energy, in the context of light third family squarks, while the first two squark families are inaccessible at the 7 TeV run of the Large Hadron Collider (LHC). In contrast to interpretations in terms of the high-scale based constrained minimal supersymmetric standard model (CMSSM), we primarily use the low-scale parametrisation of the phenomenological MSSM (pMSSM), and translate the limits in terms of physical masses of the third family squarks. Side by side, we also investigate the limits in terms of high-scale scalar non-universality, both with and without low-mass sleptons. Our conclusion is that the limits based on 0-lepton channels are not altered by the mass-scale of sleptons, and can be considered more or less model-independent.Comment: 20 pages, 8 figures, 2 tables. Version published in JHE

Constraining compressed supersymmetry using leptonic signatures

We study the impact of the multi-lepton searches at the LHC on supersymmetric models with compressed mass spectra. For such models the acceptances of the usual search strategies are significantly reduced due to requirement of large effective mass and missing E_T. On the other hand, lepton searches do have much lower thresholds for missing E_T and p_T of the final state objects. Therefore, if a model with a compressed mass spectrum allows for multi-lepton final states, one could derive constraints using multi-lepton searches. For a class of simplified models we study the exclusion limits using ATLAS multi-lepton search analyses for the final states containing 2-4 electrons or muons with a total integrated luminosity of 1-2/fb at \sqrt{s}=7 TeV. We also modify those analyses by imposing additional cuts, so that their sensitivity to compressed supersymmetric models increase. Using the original and modified analyses, we show that the exclusion limits can be competitive with jet plus missing E_T searches, providing exclusion limits up to gluino masses of 1 TeV. We also analyse the efficiencies for several classes of events coming from different intermediate state particles. This allows us to assess exclusion limits in similar class of models with different cross sections and branching ratios without requiring a Monte Carlo simulation.Comment: 18 pages, 5 figure