Ultrafast Structural Dynamics of BlsA, a Photoreceptor from the Pathogenic Bacterium Acinetobacter baumannii

Acinetobacter baumannii is an important human pathogen that can form biofilms and persist under harsh environmental conditions. Biofilm formation and virulence are modulated by blue light, which is thought to be regulated by a BLUF protein, BlsA. To understand the molecular mechanism of light sensing, we have used steady-state and ultrafast vibrational spectroscopy to compare the photoactivation mechanism of BlsA to the BLUF photosensor AppA from Rhodobacter sphaeroides. Although similar photocycles are observed, vibrational data together with homology modeling identify significant differences in the β5 strand in BlsA caused by photoactivation, which are proposed to be directly linked to downstream signaling

T-cell derived acetylcholine aids host defenses during enteric bacterial infection with Citrobacter rodentium.

The regulation of mucosal immune function is critical to host protection from enteric pathogens but is incompletely understood. The nervous system and the neurotransmitter acetylcholine play an integral part in host defense against enteric bacterial pathogens. Here we report that acetylcholine producing-T-cells, as a non-neuronal source of ACh, were recruited to the colon during infection with the mouse pathogen Citrobacter rodentium. These ChAT+ T-cells did not exclusively belong to one Th subset and were able to produce IFNγ, IL-17A and IL-22. To interrogate the possible protective effect of acetylcholine released from these cells during enteric infection, T-cells were rendered deficient in their ability to produce acetylcholine through a conditional gene knockout approach. Significantly increased C. rodentium burden was observed in the colon from conditional KO (cKO) compared to WT mice at 10 days post-infection. This increased bacterial burden in cKO mice was associated with increased expression of the cytokines IL-1β, IL-6, and TNFα, but without significant changes in T-cell and ILC associated IL-17A, IL-22, and IFNγ, or epithelial expression of antimicrobial peptides, compared to WT mice. Despite the increased expression of pro-inflammatory cytokines during C. rodentium infection, inducible nitric oxide synthase (Nos2) expression was significantly reduced in intestinal epithelial cells of ChAT T-cell cKO mice 10 days post-infection. Additionally, a cholinergic agonist enhanced IFNγ-induced Nos2 expression in intestinal epithelial cell in vitro. These findings demonstrated that acetylcholine, produced by specialized T-cells that are recruited during C. rodentium infection, are a key mediator in host-microbe interactions and mucosal defenses

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

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

Supersymmetry with Light Stops

Recent LHC data, together with the electroweak naturalness argument, suggest that the top squarks may be significantly lighter than the other sfermions. We present supersymmetric models in which such a split spectrum is obtained through "geometries": being "close to" electroweak symmetry breaking implies being "away from" supersymmetry breaking, and vice versa. In particular, we present models in 5D warped spacetime, in which supersymmetry breaking and Higgs fields are located on the ultraviolet and infrared branes, respectively, and the top multiplets are localized to the infrared brane. The hierarchy of the Yukawa matrices can be obtained while keeping near flavor degeneracy between the first two generation sfermions, avoiding stringent constraints from flavor and CP violation. Through the AdS/CFT correspondence, the models can be interpreted as purely 4D theories in which the top and Higgs multiplets are composites of some strongly interacting sector exhibiting nontrivial dynamics at a low energy. Because of the compositeness of the Higgs and top multiplets, Landau pole constraints for the Higgs and top couplings apply only up to the dynamical scale, allowing for a relatively heavy Higgs boson, including m_h = 125 GeV as suggested by the recent LHC data. We analyze electroweak symmetry breaking for a well-motivated subset of these models, and find that fine-tuning in electroweak symmetry breaking is indeed ameliorated. We also discuss a flat space realization of the scenario in which supersymmetry is broken by boundary conditions, with the top multiplets localized to a brane while other matter multiplets delocalized in the bulk.Comment: 27 pages, 7 figure

Infarction in the territory of the anterior cerebral artery: clinical study of 51 patients

<p>Abstract</p> <p>Background</p> <p>Little is known about clinical features and prognosis of patients with ischaemic stroke caused by infarction in the territory of the anterior cerebral artery (ACA). This single centre, retrospective study was conducted with the following objectives: a) to describe the clinical characteristics and short-term outcome of stroke patients with ACA infarction as compared with that of patients with ischaemic stroke due to middle cerebral artery (MCA) and posterior cerebral artery (PCA) infarctions, and b) to identify predictors of ACA stroke.</p> <p>Methods</p> <p>Fifty-one patients with ACA stroke were included in the "Sagrat Cor Hospital of Barcelona Stroke Registry" during a period of 19 years (1986–2004). Data from stroke patients are entered in the stroke registry following a standardized protocol with 161 items regarding demographics, risk factors, clinical features, laboratory and neuroimaging data, complications and outcome. The characteristics of these 51 patients with ACA stroke were compared with those of the 1355 patients with MCA infarctions and 232 patients with PCA infarctions included in the registry.</p> <p>Results</p> <p>Infarctions of the ACA accounted for 1.3% of all cases of stroke (<it>n </it>= 3808) and 1.8% of cerebral infarctions (<it>n </it>= 2704). Stroke subtypes included cardioembolic infarction in 45.1% of patients, atherothrombotic infarction in 29.4%, lacunar infarct in 11.8%, infarct of unknown cause in 11.8% and infarction of unusual aetiology in 2%. In-hospital mortality was 7.8% (<it>n </it>= 4). Only 5 (9.8%) patients were symptom-free at hospital discharge. Speech disturbances (odds ratio [OR] = 0.48) and altered consciousness (OR = 0.31) were independent variables of ACA stroke in comparison with MCA infarction, whereas limb weakness (OR = 9.11), cardioembolism as stroke mechanism (OR = 2.49) and sensory deficit (OR = 0.35) were independent variables associated with ACA stroke in comparison with PCA infarction.</p> <p>Conclusion</p> <p>Cardioembolism is the main cause of brain infarction in the territory of the ACA. Several clinical features are more frequent in stroke patients with ACA infarction than in patients with ischaemic stroke due to infarction in the MCA and PCA territories.</p

Fitting Neutrino Physics with a U(1)_R Lepton Number

We study neutrino physics in the context of a supersymmetric model where a continuous R-symmetry is identified with the total Lepton Number and one sneutrino can thus play the role of the down type Higgs. We show that R-breaking effects communicated to the visible sector by Anomaly Mediation can reproduce neutrino masses and mixing solely via radiative contributions, without requiring any additional degree of freedom. In particular, a relatively large reactor angle (as recently observed by the Daya Bay collaboration) can be accommodated in ample regions of the parameter space. On the contrary, if the R-breaking is communicated to the visible sector by gravitational effects at the Planck scale, additional particles are necessary to accommodate neutrino data.Comment: 19 pages, 3 figures; v2: references added, constraints updated, overall conclusions unchange

Flavor Mediation Delivers Natural SUSY

If supersymmetry (SUSY) solves the hierarchy problem, then naturalness considerations coupled with recent LHC bounds require non-trivial superpartner flavor structures. Such "Natural SUSY" models exhibit a large mass hierarchy between scalars of the third and first two generations as well as degeneracy (or alignment) among the first two generations. In this work, we show how this specific beyond the standard model (SM) flavor structure can be tied directly to SM flavor via "Flavor Mediation". The SM contains an anomaly-free SU(3) flavor symmetry, broken only by Yukawa couplings. By gauging this flavor symmetry in addition to SM gauge symmetries, we can mediate SUSY breaking via (Higgsed) gauge mediation. This automatically delivers a natural SUSY spectrum. Third-generation scalar masses are suppressed due to the dominant breaking of the flavor gauge symmetry in the top direction. More subtly, the first-two-generation scalars remain highly degenerate due to a custodial U(2) symmetry, where the SU(2) factor arises because SU(3) is rank two. This custodial symmetry is broken only at order (m_c/m_t)^2. SUSY gauge coupling unification predictions are preserved, since no new charged matter is introduced, the SM gauge structure is unaltered, and the flavor symmetry treats all matter multiplets equally. Moreover, the uniqueness of the anomaly-free SU(3) flavor group makes possible a number of concrete predictions for the superpartner spectrum.Comment: 17 pages, 7 figures, 2 tables. v2 references added, minor changes to flavor constraints and a little discussion adde

Calculations of collisions between cold alkaline earth atoms in a weak laser field

We calculate the light-induced collisional loss of laser-cooled and trapped magnesium atoms for detunings up to 50 atomic linewidths to the red of the ^1S_0-^1P_1 cooling transition. We evaluate loss rate coefficients due to both radiative and nonradiative state-changing mechanisms for temperatures at and below the Doppler cooling temperature. We solve the Schrodinger equation with a complex potential to represent spontaneous decay, but also give analytic models for various limits. Vibrational structure due to molecular photoassociation is present in the trap loss spectrum. Relatively broad structure due to absorption to the Mg_2 ^1Sigma_u state occurs for detunings larger than about 10 atomic linewidths. Much sharper structure, especially evident at low temperature, occurs even at smaller detunings due to of Mg_2 ^1Pi_g absorption, which is weakly allowed due to relativistic retardation corrections to the forbidden dipole transition strength. We also perform model studies for the other alkaline earth species Ca, Sr, and Ba and for Yb, and find similar qualitative behavior as for Mg.Comment: 20 pages, RevTex, 13 eps figures embedde