A novel compartment, the 'subqpical stem' of the aerial hyphae, is the location of a sigN-dependent, developmentally distinct transcription in Streptomyces coelicolor.

Streptomyces coelicolor has nine SigB-like RNA polymerase sigma factors, several of them implicated in morphological differentiation and/or responses to different stresses. One of the nine, SigN, is the focus of this article. A constructed sigN null mutant was delayed in development and exhibited a bald phenotype when grown on minimal medium containing glucose as carbon source. One of two distinct sigN promoters, sigNP1, was active only during growth on solid medium, when its activation coincided with aerial hyphae formation. Transcription from sigNP1 was readily detected in several whi mutants (interrupted in morphogenesis of aerial mycelium into spores), but was absent from all bld mutants tested, suggesting that sigNP1 activity was restricted to the aerial hyphae. It also depended on sigN, thus sigN was autoregulated. Mutational and transcription studies revealed no functional significance to the location of sigN next to sigF, encoding another SigB-like sigma factor. We identified another potential SigN target, nepA, encoding a putative small secreted protein. Transcription of nepA originated from a single, aerial hyphae-specific and sigN-dependent promoter. While in vitro run-off transcription using purified SigN on the Bacillus subtilis ctc promoter confirmed that SigN is an RNA polymerase sigma factor, SigN failed to initiate transcription from sigNP1 and from the nepA promoter in vitro. Additional in vivo data indicated that further nepA upstream sequences, which are likely to bind a potential activator, are required for successful transcription. Using a nepA–egfp transcriptional fusion we located nepA transcription to a novel compartment, the ‘subapical stem’ of the aerial hyphae. We suggest that this newly recognized compartment defines an interface between the aerial and vegetative parts of the Streptomyces colony and might also be involved in communication between these two compartments

A connection between stress and development in the multicelular prokaryote Streptomyces coelicolor

Morphological changes leading to aerial mycelium formation and sporulation in the mycelial bacterium Streptomyces coelicolor rely on establishing distinct patterns of gene expression in separate regions of the colony. sH was identified previously as one of three paralogous sigma factors associated with stress responses in S. coelicolor. Here, we show that sigH and the upstream gene prsH (encoding a putative antisigma factor of sH) form an operon transcribed from two developmentally regulated promoters, sigHp1 and sigHp2. While sigHp1 activity is confined to the early phase of growth, transcription of sigHp2 is dramatically induced at the time of aerial hyphae formation. Localization of sigHp2 activity using a transcriptional fusion to the green fluorescent protein reporter gene (sigHp2–egfp) showed that sigHp2 transcription is spatially restricted to sporulating aerial hyphae in wild-type S. coelicolor. However, analysis of mutants unable to form aerial hyphae (bld mutants) showed that sigHp2 transcription and sH protein levels are dramatically upregulated in a bldD mutant, and that the sigHp2–egfp fusion was expressed ectopically in the substrate mycelium in the bldD background. Finally, a protein possessing sigHp2 promoter-binding activity was purified to homogeneity from crude mycelial extracts of S. coelicolor and shown to be BldD. The BldD binding site in the sigHp2 promoter was defined by DNase I footprinting. These data show that expression of sH is subject to temporal and spatial regulation during colony development, that this tissue-specific regulation is mediated directly by the developmental transcription factor BldD and suggest that stress and developmental programmes may be intimately connected in Streptomyces morphogenesis

Computing gravitational waves from slightly nonspherical stellar collapse to black hole: Odd-parity perturbation

Nonspherical stellar collapse to a black hole is one of the most promising gravitational wave sources for gravitational wave detectors. We numerically study gravitational waves from a slightly nonspherical stellar collapse to a black hole in linearized Einstein theory. We adopt a spherically collapsing star as the zeroth-order solution and gravitational waves are computed using perturbation theory on the spherical background. In this paper we focus on the perturbation of odd-parity modes. Using the polytropic equations of state with polytropic indices $n_p=1$ and 3, we qualitatively study gravitational waves emitted during the collapse of neutron stars and supermassive stars to black holes from a marginally stable equilibrium configuration. Since the matter perturbation profiles can be chosen arbitrarily, we provide a few types for them. For $n_p=1$, the gravitational waveforms are mainly characterized by a black hole quasinormal mode ringing, irrespective of perturbation profiles given initially. However, for $n_p=3$, the waveforms depend strongly on the initial perturbation profiles. In other words, the gravitational waveforms strongly depend on the stellar configuration and, in turn, on the ad hoc choice of the functional form of the perturbation in the case of supermassive stars.Comment: 31 pages, accepted for publication in Phys. Rev. D, typos and minor errors correcte

Genetic Variation among Temporally and Geographically Distinct West Nile Virus Isolates, United States, 2001, 2002

Analysis of partial nucleotide sequences of 22 West Nile virus (WNV) isolates collected during the summer and fall of 2001 and 2002 indicated genetic variation among strains circulating in geographically distinct regions of the United States and continued divergence from isolates collected in the northeastern United States during 1999 and 2000. Sequence analysis of a 2,004-nucleotide region showed that 14 isolates shared two nucleotide mutations and one amino acid substitution when they were compared with the prototype WN-NY99 strain, with 10 of these isolates sharing an additional nucleotide mutation. In comparison, isolates collected from coastal regions of southeast Texas shared the following differences from WN-NY99: five nucleotide mutations and one amino acid substitution. The maximum nucleotide divergence of the 22 isolates from WN-NY99 was 0.35% (mean = 0.18%). These results show the geographic clustering of genetically similar WNV isolates and the possible emergence of a dominant variant circulating across much of the United States during 2002

Minibeam radiation therapy enhanced tumor delivery of PEGylated liposomal doxorubicin in a triple-negative breast cancer mouse model

Background: Minibeam radiation therapy is an experimental radiation therapy utilizing an array of parallel submillimeter planar X-ray beams. In preclinical studies, minibeam radiation therapy has been shown to eradicate tumors and cause significantly less damage to normal tissue compared to equivalent radiation doses delivered by conventional broadbeam radiation therapy, where radiation dose is uniformly distributed. Methods: Expanding on prior studies that suggested minibeam radiation therapy increased perfusion in tumors, we compared a single fraction of minibeam radiation therapy (peak dose:valley dose of 28 Gy:2.1 Gy and 100 Gy:7.5 Gy) and broadbeam radiation therapy (7 Gy) in their ability to enhance tumor delivery of PEGylated liposomal doxorubicin and alter the tumor microenvironment in a murine tumor model. Plasma and tumor pharmacokinetic studies of PEGylated liposomal doxorubicin and tumor microenvironment profiling were performed in a genetically engineered mouse model of claudin-low triple-negative breast cancer (T11). Results: Minibeam radiation therapy (28 Gy) and broadbeam radiation therapy (7 Gy) increased PEGylated liposomal doxorubicin tumor delivery by 7.1-fold and 2.7-fold, respectively, compared to PEGylated liposomal doxorubicin alone, without altering the plasma disposition. The enhanced tumor delivery of PEGylated liposomal doxorubicin by minibeam radiation therapy is consistent after repeated dosing, is associated with changes in tumor macrophages but not collagen or angiogenesis, and nontoxic to local tissues. Our study indicated that the minibeam radiation therapy’s ability to enhance the drug delivery decreases from 28 to 100 Gy peak dose. Discussion: Our studies suggest that low-dose minibeam radiation therapy is a safe and effective method to significantly enhance the tumor delivery of nanoparticle agents

Carbon cycle uncertainty in the Alaskan Arctic

Climate change is leading to a disproportionately large warming in the high northern latitudes, but the magnitude and sign of the future carbon balance of the Arctic are highly uncertain. Using 40 terrestrial biosphere models for the Alaskan Arctic from four recent model intercomparison projects – NACP (North American Carbon Program) site and regional syntheses, TRENDY (Trends in net land atmosphere carbon exchanges), and WETCHIMP (Wetland and Wetland CH4 Inter-comparison of Models Project) – we provide a baseline of terrestrial carbon cycle uncertainty, defined as the multi-model standard deviation (o) for each quantity that follows. Mean annual absolute uncertainty was largest for soil carbon (14.0±9.2 kgCm−2), then gross primary production (GPP) (0.22±0.50 kgCm−2 yr−1), ecosystem respiration (Re) (0.23±0.38 kgCm−2 yr−1), net primary production (NPP) (0.14±0.33 kgCm−2 yr−1), autotrophic respiration (Ra) (0.09±0.20 kgCm−2 yr−1), heterotrophic respiration (Rh) (0.14±0.20 kgCm−2 yr−1), net ecosystem exchange (NEE) (−0.01±0.19 kgCm−2 yr−1), and CH4 flux (2.52±4.02 g CH4 m−2 yr−1). There were no consistent spatial patterns in the larger Alaskan Arctic and boreal regional carbon stocks and fluxes, with some models showing NEE for Alaska as a strong carbon sink, others as a strong carbon source, while still others as carbon neutral. Finally, AmeriFlux data are used at two sites in the Alaskan Arctic to evaluate the regional patterns; observed seasonal NEE was captured within multi-model uncertainty. This assessment of carbon cycle uncertainties may be used as a baseline for the improvement of experimental and modeling activities, as well as a reference for future trajectories in carbon cycling with climate change in the Alaskan Arctic and larger boreal region

The Intentional Use of Service Recovery Strategies to Influence Consumer Emotion, Cognition and Behaviour

Service recovery strategies have been identified as a critical factor in the success of. service organizations. This study develops a conceptual frame work to investigate how specific service recovery strategies influence the emotional, cognitive and negative behavioural responses of . consumers., as well as how emotion and cognition influence negative behavior. Understanding the impact of specific service recovery strategies will allow service providers' to more deliberately and intentionally engage in strategies that result in positive organizational outcomes. This study was conducted using a 2 x 2 between-subjects quasi-experimental design. The results suggest that service recovery has a significant impact on emotion, cognition and negative behavior. Similarly, satisfaction, negative emotion and positive emotion all influence negative behavior but distributive justice has no effect

Search for direct production of charginos and neutralinos in events with three leptons and missing transverse momentum in √s = 7 TeV pp collisions with the ATLAS detector

A search for the direct production of charginos and neutralinos in final states with three electrons or muons and missing transverse momentum is presented. The analysis is based on 4.7 fb−1 of proton–proton collision data delivered by the Large Hadron Collider and recorded with the ATLAS detector. Observations are consistent with Standard Model expectations in three signal regions that are either depleted or enriched in Z-boson decays. Upper limits at 95% confidence level are set in R-parity conserving phenomenological minimal supersymmetric models and in simplified models, significantly extending previous results

Jet size dependence of single jet suppression in lead-lead collisions at sqrt(s(NN)) = 2.76 TeV with the ATLAS detector at the LHC

Measurements of inclusive jet suppression in heavy ion collisions at the LHC provide direct sensitivity to the physics of jet quenching. In a sample of lead-lead collisions at sqrt(s) = 2.76 TeV corresponding to an integrated luminosity of approximately 7 inverse microbarns, ATLAS has measured jets with a calorimeter over the pseudorapidity interval |eta| < 2.1 and over the transverse momentum range 38 < pT < 210 GeV. Jets were reconstructed using the anti-kt algorithm with values for the distance parameter that determines the nominal jet radius of R = 0.2, 0.3, 0.4 and 0.5. The centrality dependence of the jet yield is characterized by the jet "central-to-peripheral ratio," Rcp. Jet production is found to be suppressed by approximately a factor of two in the 10% most central collisions relative to peripheral collisions. Rcp varies smoothly with centrality as characterized by the number of participating nucleons. The observed suppression is only weakly dependent on jet radius and transverse momentum. These results provide the first direct measurement of inclusive jet suppression in heavy ion collisions and complement previous measurements of dijet transverse energy imbalance at the LHC.Comment: 15 pages plus author list (30 pages total), 8 figures, 2 tables, submitted to Physics Letters B. All figures including auxiliary figures are available at http://atlas.web.cern.ch/Atlas/GROUPS/PHYSICS/PAPERS/HION-2011-02

Indications of Linkage and Association of Gilles de la Tourette Syndrome in Two Independent Family Samples: 17q25 Is a Putative Susceptibility Region

Gilles de la Tourette syndrome (GTS) is characterized by multiple motor and phonic tics and high comorbidity rates with other neurobehavioral disorders. It is hypothesized that frontal-subcortical pathways and a complex genetic background are involved in the etiopathogenesis of the disorder. The genetic basis of GTS remains elusive. However, several genomic regions have been implicated. Among them, 17q25 appears to be of special interest, as suggested by various independent investigators. In the present study, we explored the possibility that 17q25 contributes to the genetic component of GTS. The initial scan of chromosome 17 performed on two large pedigrees provided a nonparametric LOD score of 2.41 near D17S928. Fine mapping with 17 additional microsatellite markers increased the peak to 2.61 (P=.002). The original families, as well as two additional pedigrees, were genotyped for 25 single-nucleotide polymorphisms (SNPs), with a focus on three genes in the indicated region that could play a role in the development of GTS, on the basis of their function and expression profile. Multiple three-marker haplotypes spanning all three genes studied provided highly significant association results (P<.001). An independent sample of 96 small families with one or two children affected with GTS was also studied. Of the 25 SNPs, 3 were associated with GTS at a statistically significant level. The transmission/disequilibrium test for a three-site haplotype moving window again provided multiple positive results. The background linkage disequilibrium (LD) of the region was studied in eight populations of European origin. A complicated pattern was revealed, with the pairwise tests producing unexpectedly high LD values at the telomeric TBCD gene. In conclusion, our findings warrant the further investigation of 17q25 as a candidate susceptibility region for GTS