434 research outputs found
Homology of 54K protein of signal-recognition particle, docking protein and two E. coli proteins with putative GTP-binding domains
Revisiting unexploited antibiotics in search of new antibacterial drug candidates: the case of MSD-819 (6-chloro-2-quinoxalinecarboxylic acid 1,4-dioxide)
When Anomaly Mediation is UV Sensitive
Despite its successes---such as solving the supersymmetric flavor
problem---anomaly mediated supersymmetry breaking is untenable because of its
prediction of tachyonic sleptons. An appealing solution to this problem was
proposed by Pomarol and Rattazzi where a threshold controlled by a light field
deflects the anomaly mediated supersymmetry breaking trajectory, thus evading
tachyonic sleptons. In this paper we examine an alternate class of deflection
models where the non-supersymmetric threshold is accompanied by a heavy,
instead of light, singlet. The low energy form of this model is the so-called
extended anomaly mediation proposed by Nelson and Weiner, but with potential
for a much higher deflection threshold. The existence of this high deflection
threshold implies that the space of anomaly mediated supersymmetry breaking
deflecting models is larger than previously thought.Comment: 14 pages, 1 figure (version to appear in JHEP
Soft branes in supersymmetry-breaking backgrounds
We revisit the analysis of effective field theories resulting from
non-supersymmetric perturbations to supersymmetric flux compactifications of
the type-IIB superstring with an eye towards those resulting from the
backreaction of a small number of anti-D3-branes. Independently of the
background, we show that the low-energy Lagrangian describing the fluctuations
of a stack of probe D3-branes exhibits soft supersymmetry breaking, despite
perturbations to marginal operators that were not fully considered in some
previous treatments. We take this as an indication that the breaking of
supersymmetry by anti-D3-branes or other sources may be spontaneous rather than
explicit. In support of this, we consider the action of an anti-D3-brane
probing an otherwise supersymmetric configuration and identify a candidate for
the corresponding goldstino.Comment: 36+5 pages. References added, minor typos correcte
Phenomenological Implications of Deflected Mirage Mediation: Comparison with Mirage Mediation
We compare the collider phenomenology of mirage mediation and deflected
mirage mediation, which are two recently proposed "mixed" supersymmetry
breaking scenarios motivated from string compactifications. The scenarios
differ in that deflected mirage mediation includes contributions from gauge
mediation in addition to the contributions from gravity mediation and anomaly
mediation also present in mirage mediation. The threshold effects from gauge
mediation can drastically alter the low energy spectrum from that of pure
mirage mediation models, resulting in some cases in a squeezed gaugino spectrum
and a gluino that is much lighter than other colored superpartners. We provide
several benchmark deflected mirage mediation models and construct model lines
as a function of the gauge mediation contributions, and discuss their discovery
potential at the LHC.Comment: 29 pages, 9 figure
Why do women invest in pre-pregnancy health and care? A qualitative investigation with women attending maternity services
Background Despite the importance attributed to good pre-pregnancy care and its potential to improve pregnancy and child health outcomes, relatively little is known about why women invest in pre-pregnancy health and care. We sought to gain insight into why women invested in pre-pregnancy health and care. Methods We carried out 20 qualitative in-depth interviews with pregnant or recently pregnant women who were drawn from a survey of antenatal clinic attendees in London, UK. Interviewees were purposively sampled to include high and low investors in pre-pregnancy health and care, with variation in age, partnership status, ethnicity and pre-existing medical conditions. Data analysis was conducted using the Framework method. Results We identified three groups in relation to pre-pregnancy health and care: 1) The “prepared” group, who had high levels of pregnancy planning and mostly positive attitudes to micronutrient supplementation outside of pregnancy, carried out pre-pregnancy activities such as taking folic acid and making changes to diet and lifestyle. 2) The “poor knowledge” group, who also had high levels of pregnancy planning, did not carry out pre-pregnancy activities and described themselves as having poor knowledge. Elsewhere in their interviews they expressed a strong dislike of micronutrient supplementation. 3) The “absent pre-pregnancy period” group, had the lowest levels of pregnancy planning and also expressed anti-supplement views. Even discussing the pre-pregnancy period with this group was difficult as responses to questions quickly shifted to focus on pregnancy itself. Knowledge of folic acid was poor in all groups. Conclusion Different pre-pregnancy care approaches are likely to be needed for each of the groups. Among the “prepared” group, who were proactive and receptive to health messages, greater availability of information and better response from health professionals could improve the range of pre-pregnancy activities carried out. Among the “poor knowledge” group, better response from health professionals might yield greater uptake of pre-pregnancy information. A different, general health strategy might be more appropriate for the “absent pre-pregnancy period” group. The fact that general attitudes to micronutrient supplementation were closely related to whether or not women invested in pre-pregnancy health and care was an unanticipated finding and warrants further investigation.This report is independent research commissioned and funded by the Department of Health Policy Research Programme Pre-Pregnancy Health and Care in England: Exploring Implementation and Public Health Impact, 006/0068
Mixed Mediation of Supersymmetry Breaking with Anomalous U(1) Gauge Symmetry
Models with anomalous U(1) gauge symmetry contain various superfields which
can have nonzero supersymmetry breaking auxiliary components providing the
origin of soft terms in the visible sector, e.g. the U(1) vector superfield,
the modulus or dilaton superfield implementing the Green-Schwarz anomaly
cancellation mechanism, U(1)-charged but standard model singlet matter
superfield required to cancel the Fayet-Iliopoulos term, and finally the
supergravity multiplet. We examine the relative strength between these
supersymmetry breaking components in a simple class of models, and find that
various different mixed mediations of supersymmetry breaking, involving the
modulus, gauge, anomaly and D-term mediations, can be realized depending upon
the characteristics of D-flat directions and how those D-flat directions are
stabilized with a vanishing cosmological constant. We identify two parameters
which represent such properties and thus characterize how the various
mediations are mixed. We also discuss the moduli stabilization and soft terms
in a variant of KKLT scenario, in which the visible sector K\"ahler modulus is
stabilized by the D-term potential of anomalous U(1) gauge symmetry.Comment: 30 pages, 5 figure
Dimeric SecA Couples the Preprotein Translocation in an Asymmetric Manner
The Sec translocase mediates the post-translational translocation of a number of preproteins through the inner membrane in bacteria. In the initiatory translocation step, SecB targets the preprotein to the translocase by specific interaction with its receptor SecA. The latter is the ATPase of Sec translocase which mediates the post-translational translocation of preprotein through the protein-conducting channel SecYEG in the bacterial inner membrane. We examined the structures of Escherichia coli Sec intermediates in solution as visualized by negatively stained electron microscopy in order to probe the oligomeric states of SecA during this process. The symmetric interaction pattern between the SecA dimer and SecB becomes asymmetric in the presence of proOmpA, and one of the SecA protomers predominantly binds to SecB/proOmpA. Our results suggest that during preprotein translocation, the two SecA protomers are different in structure and may play different roles
Site-directed mutations in the C-terminal extension of human aB-Crystalline affect chaperone function and block amyloid fibril formation
Copyright: 2007 Treweek et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.Background. Alzheimer’s, Parkinson’s and Creutzfeldt-Jakob disease are associated with inappropriate protein deposition and ordered amyloid fibril assembly. Molecular chaperones, including aB-crystallin, play a role in the prevention of protein deposition. Methodology/Principal Findings. A series of site-directed mutants of the human molecular chaperone, aBcrystallin, were constructed which focused on the flexible C-terminal extension of the protein. We investigated the structural role of this region as well as its role in the chaperone function of aB-crystallin under different types of protein aggregation, i.e. disordered amorphous aggregation and ordered amyloid fibril assembly. It was found that mutation of lysine and glutamic acid residues in the C-terminal extension of aB-crystallin resulted in proteins that had improved chaperone activity against amyloid fibril forming target proteins compared to the wild-type protein. Conclusions/Significance. Together, our results highlight the important role of the C-terminal region of aB-crystallin in regulating its secondary, tertiary and quaternary structure and conferring thermostability to the protein. The capacity to genetically modify aB-crystallin for improved ability to block amyloid fibril formation provides a platform for the future use of such engineered molecules in treatment of diseases caused by amyloid fibril formation
Elucidation of the Mode of Action of a New Antibacterial Compound Active against Staphylococcus aureus and Pseudomonas aeruginosa.
Nosocomial and community-acquired infections caused by multidrug resistant bacteria represent a major human health problem. Thus, there is an urgent need for the development of antibiotics with new modes of action. In this study, we investigated the antibacterial characteristics and mode of action of a new antimicrobial compound, SPI031 (N-alkylated 3, 6-dihalogenocarbazol 1-(sec-butylamino)-3-(3,6-dichloro-9H-carbazol-9-yl)propan-2-ol), which was previously identified in our group. This compound exhibits broad-spectrum antibacterial activity, including activity against the human pathogens Staphylococcus aureus and Pseudomonas aeruginosa. We found that SPI031 has rapid bactericidal activity (7-log reduction within 30 min at 4x MIC) and that the frequency of resistance development against SPI031 is low. To elucidate the mode of action of SPI031, we performed a macromolecular synthesis assay, which showed that SPI031 causes non-specific inhibition of macromolecular biosynthesis pathways. Liposome leakage and membrane permeability studies revealed that SPI031 rapidly exerts membrane damage, which is likely the primary cause of its antibacterial activity. These findings were supported by a mutational analysis of SPI031-resistant mutants, a transcriptome analysis and the identification of transposon mutants with altered sensitivity to the compound. In conclusion, our results show that SPI031 exerts its antimicrobial activity by causing membrane damage, making it an interesting starting point for the development of new antibacterial therapies
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