Environmental stress alters genetic regulation of novelty seeking in vervet monkeys.

Considerable attention has been paid to identifying genetic influences and gene-environment interactions that increase vulnerability to environmental stressors, with promising but inconsistent results. A nonhuman primate model is presented here that allows assessment of genetic influences in response to a stressful life event for a behavioural trait with relevance for psychopathology. Genetic and environmental influences on free-choice novelty seeking behaviour were assessed in a pedigreed colony of vervet monkeys before and after relocation from a low stress to a higher stress environment. Heritability of novelty seeking scores, and genetic correlations within and between environments were conducted using variance components analysis. The results showed that novelty seeking was markedly inhibited in the higher stress environment, with effects persisting across a 2-year period for adults but not for juveniles. There were significant genetic contributions to novelty seeking scores in each year (h(2) = 0.35-0.43), with high genetic correlations within each environment (rhoG > 0.80) and a lower genetic correlation (rhoG = 0.35, non-significant) between environments. There were also significant genetic contributions to individual change scores from before to after the move (h(2) = 0.48). These results indicate that genetic regulation of novelty seeking was modified by the level of environmental stress, and they support a role for gene-environment interactions in a behavioural trait with relevance for mental health

Ctk1 promotes dissociation of basal transcription factors from elongating RNA polymerase II

As RNA polymerase II (RNApII) transitions from initiation to elongation, Mediator and the basal transcription factors TFIID, TFIIA, TFIIH, and TFIIE remain at the promoter as part of a scaffold complex, whereas TFIIB and TFIIF dissociate. The yeast Ctk1 kinase associates with elongation complexes and phosphorylates serine 2 in the YSPTSPS repeats of the Rpb1 C-terminal domain, a modification that couples transcription to mRNA 3′-end processing. The higher eukaryotic kinase Cdk9 not only performs a similar function, but also functions at the 5′-end of genes in the transition from initiation to elongation. In strains lacking Ctk1, many basal transcription factors cross-link throughout transcribed regions, apparently remaining associated with RNApII until it terminates. Consistent with this observation, preinitiation complexes formed on immobilized templates with transcription extracts lacking Ctk1 leave lower levels of the scaffold complex behind after escape. Taken together, these results suggest that Ctk1 is necessary for the release of RNApII from basal transcription factors. Interestingly, this function of Ctk1 is independent of its kinase activity, suggesting a structural function of the protein

Discovering the composite Higgs through the decay of a heavy fermion

A possible composite nature of the Higgs could be revealed at the early stage of the LHC, by analyzing the channels where the Higgs is produced from the decay of a heavy fermion. The Higgs production from a singly-produced heavy bottom, in particular, proves to be a promising channel. For a value \lambda=3 of the Higgs coupling to a heavy bottom, for example, we find that, considering a 125 GeV Higgs which decays into a pair of b-quarks, a discovery is possible at the 8 TeV LHC with 30 fb^{-1} if the heavy bottom is lighter than roughly 530 GeV (while an observation is possible for heavy bottom masses up to 650 GeV). Such a relatively light heavy bottom is realistic in composite Higgs models of the type considered and, up to now, experimentally allowed. At \sqrt{s}=14 TeV the LHC sensitivity on the channel increases significantly. With \lambda=3 a discovery can occur, with 100 fb^{-1}, for heavy bottom masses up to 1040 GeV. In the case the heavy bottom was as light as 500 GeV, the 14 TeV LHC would be sensitive to the measure of the \lambda\ coupling in basically the full range \lambda>1 predicted by the theory.Comment: 25 pp. v2: Minor changes. v3: Version accepted for publication in JHEP. v4: typos fixe

The Maximal U(1)LU(1)_L Inverse Seesaw from d=5d=5 Operator and Oscillating Asymmetric Sneutrino Dark Matter

The maximal $U(1)_L$ supersymmetric inverse seesaw mechanism (M$L$SIS) provides a natural way to relate asymmetric dark matter (ADM) with neutrino physics. In this paper we point out that, M$L$SIS is a natural outcome if one dynamically realizes the inverse seesaw mechanism in the next-to minimal supersymmetric standard model (NMSSM) via the dimension-five operator $(N)^2S^2/M_*$, with $S$ the NMSSM singlet developing TeV scale VEV; it slightly violates lepton number due to the suppression by the fundamental scale $M_*$, thus preserving $U(1)_L$ maximally. The resulting sneutrino is a distinguishable ADM candidate, oscillating and favored to have weak scale mass. A fairly large annihilating cross section of such a heavy ADM is available due to the presence of singlet.Comment: journal versio

Challenges to the development of antigen-specific breast cancer vaccines

Continued progress in the development of antigen-specific breast cancer vaccines depends on the identification of appropriate target antigens, the establishment of effective immunization strategies, and the ability to circumvent immune escape mechanisms. Methods such as T cell epitope cloning and serological expression cloning (SEREX) have led to the identification of a number target antigens expressed in breast cancer. Improved immunization strategies, such as using dendritic cells to present tumor-associated antigens to T lymphocytes, have been shown to induce antigen-specific T cell responses in vivo and, in some cases, objective clinical responses. An outcome of successful tumor immunity is the evolution of antigen-loss tumor variants. The development of a polyvalent breast cancer vaccine, directed against a panel of tumor-associated antigens, may counteract this form of immune escape

Search for the Elusive Higgs Boson Using Jet Structure at LHC

We consider the production of a light non-standard model Higgs boson of order 100~\GEV with an associated $W$ boson at CERN Large Hadron Collider. We focus on an interesting scenario that, the Higgs boson decays predominately into two light scalars $\chi$ with mass of few GeV which sequently decay into four gluons, i.e. $h\to 2\chi \to 4g$. Since $\chi$ is much lighter than the Higgs boson, it will be highly boosted and its decay products, the two gluons, will move close to each other, resulting in a single jet for $\chi$ decay in the detector. By using electromagnetic calorimeter-based and jet substructure analyses, we show in two cases of different $\chi$ masses that it is quite promising to extract the signal of Higgs boson out of large QCD background.Comment: 20 pages, 7 figure

Flavor in Minimal Conformal Technicolor

We construct a complete, realistic, and natural UV completion of minimal conformal technicolor that explains the origin of quark and lepton masses and mixing angles. As in "bosonic technicolor", we embed conformal technicolor in a supersymmetric theory, with supersymmetry broken at a high scale. The exchange of heavy scalar doublets generates higher-dimension interactions between technifermions and quarks and leptons that give rise to quark and lepton masses at the TeV scale. Obtaining a sufficiently large top quark mass requires strong dynamics at the supersymmetry breaking scale in both the top and technicolor sectors. This is natural if the theory above the supersymmetry breaking also has strong conformal dynamics. We present two models in which the strong top dynamics is realized in different ways. In both models, constraints from flavor-changing effects can be easily satisfied. The effective theory below the supersymmetry breaking scale is minimal conformal technicolor with an additional light technicolor gaugino. We argue that this light gaugino is a general consequence of conformal technicolor embedded into a supersymmetric theory. If the gaugino has mass below the TeV scale it will give rise to an additional pseudo Nambu-Goldstone boson that is observable at the LHC.Comment: 37 pages; references adde

Dual conformal constraints and infrared equations from global residue theorems in N=4 SYM theory

Infrared equations and dual conformal constraints arise as consistency conditions on loop amplitudes in N=4 super Yang-Mills theory. These conditions are linear relations between leading singularities, which can be computed in the Grassmannian formulation of N=4 super Yang-Mills theory proposed recently. Examples for infrared equations have been shown to be implied by global residue theorems in the Grassmannian picture. Both dual conformal constraints and infrared equations are mapped explicitly to global residue theorems for one-loop next-to-maximally-helicity-violating amplitudes. In addition, the identity relating the BCFW and its parity-conjugated form of tree-level amplitudes, is shown to emerge from a particular combination of global residue theorems.Comment: 21 page

Sphingosine 1-phosphate modulates antigen capture by murine langerhans cells via the S1P2 receptor subtype

Dendritic cells (DCs) play a pivotal role in the development of cutaneous contact hypersensitivity (CHS) and atopic dermatitis as they capture and process antigen and present it to T lymphocytes in the lymphoid organs. Recently, it has been indicated that a topical application of the sphingolipid sphingosine 1-phosphate (S1P) prevents the inflammatory response in CHS, but the molecular mechanism is not fully elucidated. Here we indicate that treatment of mice with S1P is connected with an impaired antigen uptake by Langerhans cells (LCs), the initial step of CHS. Most of the known actions of S1P are mediated by a family of five specific G protein-coupled receptors. Our results indicate that S1P inhibits macropinocytosis of the murine LC line XS52 via S1P2 receptor stimulation followed by a reduced phosphatidylinositol 3-kinase (PI3K) activity. As down-regulation of S1P2 not only diminished S1P-mediated action but also enhanced the basal activity of LCs on antigen capture, an autocrine action of S1P has been assumed. Actually, S1P is continuously produced by LCs and secreted via the ATP binding cassette transporter ABCC1 to the extracellular environment. Consequently, inhibition of ABCC1, which decreased extracellular S1P levels, markedly increased the antigen uptake by LCs. Moreover, stimulation of sphingosine kinase activity, the crucial enzyme for S1P formation, is connected not only with enhanced S1P levels but also with diminished antigen capture. These results indicate that S1P is essential in LC homeostasis and influences skin immunity. This is of importance as previous reports suggested an alteration of S1P levels in atopic skin lesions

New Higgs Production Mechanism in Composite Higgs Models

Composite Higgs models are only now starting to be probed at the Large Hadron Collider by Higgs searches. We point out that new resonances, abundant in these models, can mediate new production mechanisms for the composite Higgs. The new channels involve the exchange of a massive color octet and single production of new fermion resonances with subsequent decays into the Higgs and a Standard Model quark. The sizable cross section and very distinctive kinematics allow for a very clean extraction of the signal over the background with high statistical significance. Heavy gluon masses up to 2.8 TeV can be probed with data collected during 2012 and up to 5 TeV after the energy upgrade to $\sqrt{s}=14$ TeV.Comment: 27 pages, 22 figures. V2: typos corrected, matches published versio