The aggregation of cytochrome C may be linked to its flexibility during refolding

Large-scale expression of biopharmaceutical proteins in cellular hosts results in production of large insoluble mass aggregates. In order to generate functional product, these aggregates require further processing through refolding with denaturant, a process in itself that can result in aggregation. Using a model folding protein, cytochrome C, we show how an increase in final denaturant concentration decreases the propensity of the protein to aggregate during refolding. Using polarised fluorescence anisotropy, we show how reduced levels of aggregation can be achieved by increasing the period of time the protein remains flexible during refolding, mediated through dilution ratios. This highlights the relationship between the flexibility of a protein and its propensity to aggregate. We attribute this behaviour to the preferential urea-residue interaction, over self-association between molecules

Freeze-In Production of FIMP Dark Matter

We propose an alternate, calculable mechanism of dark matter genesis, "thermal freeze-in," involving a Feebly Interacting Massive Particle (FIMP) interacting so feebly with the thermal bath that it never attains thermal equilibrium. As with the conventional "thermal freeze-out" production mechanism, the relic abundance reflects a combination of initial thermal distributions together with particle masses and couplings that can be measured in the laboratory or astrophysically. The freeze-in yield is IR dominated by low temperatures near the FIMP mass and is independent of unknown UV physics, such as the reheat temperature after inflation. Moduli and modulinos of string theory compactifications that receive mass from weak-scale supersymmetry breaking provide implementations of the freeze-in mechanism, as do models that employ Dirac neutrino masses or GUT-scale-suppressed interactions. Experimental signals of freeze-in and FIMPs can be spectacular, including the production of new metastable coloured or charged particles at the LHC as well as the alteration of big bang nucleosynthesis.Comment: 30 pages, 7 figures, PDFLaTex. References adde

Decaying Dark Matter in Supersymmetric Model and Cosmic-Ray Observations

We study cosmic-rays in decaying dark matter scenario, assuming that the dark matter is the lightest superparticle and it decays through a R-parity violating operator. We calculate the fluxes of cosmic-rays from the decay of the dark matter and those from the standard astrophysical phenomena in the same propagation model using the GALPROP package. We reevaluate the preferred parameters characterizing standard astrophysical cosmic-ray sources with taking account of the effects of dark matter decay. We show that, if energetic leptons are produced by the decay of the dark matter, the fluxes of cosmic-ray positron and electron can be in good agreements with both PAMELA and Fermi-LAT data in wide parameter region. It is also discussed that, in the case where sizable number of hadrons are also produced by the decay of the dark matter, the mass of the dark matter is constrained to be less than 200-300 GeV in order to avoid the overproduction of anti-proton. We also show that the cosmic gamma-ray flux can be consistent with the results of Fermi-LAT observation if the mass of the dark matter is smaller than nearly 4 TeV.Comment: 24 pages, 5 figure

Slepton mass-splittings as a signal of LFV at the LHC

Precise measurements of slepton mass-splittings might represent a powerful tool to probe supersymmetric (SUSY) lepton flavour violation (LFV) at the LHC. We point out that mass-splittings of the first two generations of sleptons are especially sensitive to LFV effects involving $\tau-\mu$ transitions. If these mass-splittings are LFV induced, high-energy LFV processes like the neutralino decay {\nt}_2\to\nt_1\tau^{\pm}\mu^{\mp} as well as low-energy LFV processes like $\tau\to\mu\gamma$ are unavoidable. We show that precise slepton mass-splitting measurements and LFV processes both at the high- and low-energy scales are highly complementary in the attempt to (partially) reconstruct the flavour sector of the SUSY model at work. The present study represents another proof of the synergy and interplay existing between the LHC, i.e. the {\em high-energy frontier}, and high-precision low-energy experiments, i.e. the {\em high-intensity frontier}.Comment: 11 pages, 5 figures. v2: added discussion on backgrounds, added references, version to be published on JHE

Understanding p300-transcription factor interactions using sequence variation and hybridization

The hypoxic response is central to cell function and plays a significant role in the growth and survival of solid tumours. HIF-1 regulates the hypoxic response by activating over 100 genes responsible for adaptation to hypoxia, making it a potential target for anticancer drug discovery. Although there is significant structural and mechanistic understanding of the interaction between HIF-1α and p300 alongside negative regulators of HIF-1α such as CITED2, there remains a need to further understand the sequence determinants of binding. In this work we use a combination of protein expression, chemical synthesis, fluorescence anisotropy and isothermal titration calorimetry for HIF-1α sequence variants and a HIF-1α-CITED hybrid sequence which we term CITIF. We show the HIF-1α sequence is highly tolerant to sequence variation through reduced enthalpic and less unfavourable entropic contributions, These data imply backbone as opposed to side chain interactions and ligand folding control the binding interaction and that sequence variations are tolerated as a result of adopting a more disordered bound interaction or “fuzzy” complex

Decaying Dark Matter in the Supersymmetric Standard Model with Freeze-in and Seesaw mechanims

Inspired by the decaying dark matter (DM) which can explain cosmic ray anomalies naturally, we consider the supersymmetric Standard Model with three right-handed neutrinos (RHNs) and R-parity, and introduce a TeV-scale DM sector with two fields \phi_{1,2} and a $Z_3$ discrete symmetry. The DM sector only interacts with the RHNs via a very heavy field exchange and then we can explain the cosmic ray anomalies. With the second right-handed neutrino N_2 dominant seesaw mechanism at the low scale around 10^4 GeV, we show that \phi_{1,2} can obtain the vacuum expectation values around the TeV scale, and then the lightest state from \phi_{1,2} is the decay DM with lifetime around \sim 10^{26}s. In particular, the DM very long lifetime is related to the tiny neutrino masses, and the dominant DM decay channels to \mu and \tau are related to the approximate \mu-\tau symmetry. Furthermore, the correct DM relic density can be obtained via the freeze-in mechanism, the small-scale problem for power spectrum can be solved due to the decays of the R-parity odd meta-stable states in the DM sector, and the baryon asymmetry can be generated via the soft leptogensis.Comment: 24 pages,3 figure

MSSM in view of PAMELA and Fermi-LAT

We take the MSSM as a complete theory of low energy phenomena, including neutrino masses and mixings. This immediately implies that the gravitino is the only possible dark matter candidate. We study the implications of the astrophysical experiments such as PAMELA and Fermi-LAT, on this scenario. The theory can account for both the realistic neutrino masses and mixings, and the PAMELA data as long as the slepton masses lie in the $500-10^6$TeV range. The squarks can be either light or heavy, depending on their contribution to radiative neutrino masses. On the other hand, the Fermi-LAT data imply heavy superpartners, all out of LHC reach, simply on the grounds of the energy scale involved, for the gravitino must weigh more than 2 TeV. The perturbativity of the theory also implies an upper bound on its mass, approximately $6-7$TeV.Comment: Published version, figures update

Global analyses of TetR family transcriptional regulators in mycobacteria indicates conservation across species and diversity in regulated functions

BACKGROUND: Mycobacteria inhabit diverse niches and display high metabolic versatility. They can colonise both humans and animals and are also able to survive in the environment. In order to succeed, response to environmental cues via transcriptional regulation is required. In this study we focused on the TetR family of transcriptional regulators (TFTRs) in mycobacteria. RESULTS: We used InterPro to classify the entire complement of transcriptional regulators in 10 mycobacterial species and these analyses showed that TFTRs are the most abundant family of regulators in all species. We identified those TFTRs that are conserved across all species analysed and those that are unique to the pathogens included in the analysis. We examined genomic contexts of 663 of the conserved TFTRs and observed that the majority of TFTRs are separated by 200 bp or less from divergently oriented genes. Analyses of divergent genes indicated that the TFTRs control diverse biochemical functions not limited to efflux pumps. TFTRs typically bind to palindromic motifs and we identified 11 highly significant novel motifs in the upstream regions of divergently oriented TFTRs. The C-terminal ligand binding domain from the TFTR complement in M. tuberculosis showed great diversity in amino acid sequence but with an overall architecture common to other TFTRs. CONCLUSION: This study suggests that mycobacteria depend on TFTRs for the transcriptional control of a number of metabolic functions yet the physiological role of the majority of these regulators remain unknown. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12864-015-1696-9) contains supplementary material, which is available to authorized users

Atmospheric Evolution

Earth's atmosphere has evolved as volatile species cycle between the atmosphere, ocean, biomass and the solid Earth. The geochemical, biological and astrophysical processes that control atmospheric evolution are reviewed from an "Earth Systems" perspective, with a view not only to understanding the history of Earth, but also to generalizing to other solar system planets and exoplanets.Comment: 34 pages, 3 figures, 2 tables. Accepted as a chapter in "Encyclopaedia of Geochemistry", Editor Bill White, Springer-Nature, 201