182 research outputs found

    A viable axion from gauged flavor symmetries

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    We consider a string inspired non-supersymmetric extension of the standard model with gauged anomalous U(1) flavor symmetries. Consistency requires the Green-Schwarz mechanism to cancel mixed anomalies. The additional required scalars provide Stuckelberg masses for the ZZ' particles associated to the gauged flavor symmetry, so they decouple at low energies. Our models also include a complex scalar field ϕ\phi to generate Froggatt-Nielsen mass terms for light particles giving a partial solution to the fermion mass problem. A residual approximate (anomalous) global symmetry survives at low energies. The associated pseudo-Goldstone mode is the phase of the ϕ\phi scalar field, and it becomes the dominant contribution to the physical axion. An effective field theory analysis that includes neutrino masses gives a prediction for the axion decay constant. We find a simple modeI where the axion decay constant is in the center of the allowed window.Comment: 4 pages, 1 figure. v2: Couplings of axions to matter revised, other minor revision

    Feasibility of upright patient positioning and intubation success rates at two academic emergency departments

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    Objectives Endotracheal intubation is most commonly taught and performed in the supine position. Recent literature suggests that elevating the patient's head to a more upright position may decrease peri-intubation complications. However, there is little data on the feasibility of upright intubation in the emergency department. The goal of this study was to measure the success rate of emergency medicine residents performing intubation in supine and non-supine, including upright positions. Methods This was a prospective observational study. Residents performing intubation recorded the angle of the head of the bed. The number of attempts required for successful intubation was recorded by faculty and espiratory therapists. The primary outcome of first past success was calculated with respect to three groups: 0–10° (supine), 11–44° (inclined), and ≥ 45° (upright); first past success was also analyzed in 5 degree angle increments. Results A total of 231 intubations performed by 58 residents were analyzed. First pass success was 65.8% for the supine group, 77.9% for the inclined group, and 85.6% for the upright group (p = 0.024). For every 5 degree increase in angle, there was increased likelihood of first pass success (AOR = 1.11; 95% CI = 1.01–1.22, p = 0.043). Conclusions In our study emergency medicine residents had a high rate of success intubating in the upright position. While this does not demonstrate causation, it correlates with recent literature challenging the traditional supine approach to intubation and indicates that further investigation into optimal positioning during emergency department intubations is warranted

    A DNA Sequence Directed Mutual Transcription Regulation of HSF1 and NFIX Involves Novel Heat Sensitive Protein Interactions

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    BACKGROUND: Though the Nuclear factor 1 family member NFIX has been strongly implicated in PDGFB-induced glioblastoma, its molecular mechanisms of action remain unknown. HSF1, a heat shock-related transcription factor is also a powerful modifier of carcinogenesis by several factors, including PDGFB. How HSF1 transcription is controlled has remained largely elusive. METHODOLOGY/PRINCIPAL FINDINGS: By combining microarray expression profiling and a yeast-two-hybrid screen, we identified that NFIX and its interactions with CGGBP1 and HMGN1 regulate expression of HSF1. We found that CGGBP1 organizes a bifunctional transcriptional complex at small CGG repeats in the HSF1 promoter. Under chronic heat shock, NFIX uses CGGBP1 and HMGN1 to get recruited to this promoter and in turn affects their binding to DNA. Results show that the interactions of NFIX with CGGBP1 and HMGN1 in the soluble fraction are heat shock sensitive due to preferential localization of CGGBP1 to heterochromatin after heat shock. HSF1 in turn was found to bind to the NFIX promoter and repress its expression in a heat shock sensitive manner. CONCLUSIONS/SIGNIFICANCE: NFIX and HSF1 exert a mutual transcriptional repressive effect on each other which requires CGG repeat in HSF1 promoter and HSF1 binding site in NFIX promoter. We unravel a unique mechanism of heat shock sensitive DNA sequence-directed reciprocal transcriptional regulation between NFIX and HSF1. Our findings provide new insights into mechanisms of transcription regulation under stress

    Trade-Offs and Constraints in Allosteric Sensing

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    Sensing extracellular changes initiates signal transduction and is the first stage of cellular decision-making. Yet relatively little is known about why one form of sensing biochemistry has been selected over another. To gain insight into this question, we studied the sensing characteristics of one of the biochemically simplest of sensors: the allosteric transcription factor. Such proteins, common in microbes, directly transduce the detection of a sensed molecule to changes in gene regulation. Using the Monod-Wyman-Changeux model, we determined six sensing characteristics – the dynamic range, the Hill number, the intrinsic noise, the information transfer capacity, the static gain, and the mean response time – as a function of the biochemical parameters of individual sensors and of the number of sensors. We found that specifying one characteristic strongly constrains others. For example, a high dynamic range implies a high Hill number and a high capacity, and vice versa. Perhaps surprisingly, these constraints are so strong that most of the space of characteristics is inaccessible given biophysically plausible ranges of parameter values. Within our approximations, we can calculate the probability distribution of the numbers of input molecules that maximizes information transfer and show that a population of one hundred allosteric transcription factors can in principle distinguish between more than four bands of input concentrations. Our results imply that allosteric sensors are unlikely to have been selected for high performance in one sensing characteristic but for a compromise in the performance of many

    Bacterial Leaf Symbiosis in Angiosperms: Host Specificity without Co-Speciation

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    Bacterial leaf symbiosis is a unique and intimate interaction between bacteria and flowering plants, in which endosymbionts are organized in specialized leaf structures. Previously, bacterial leaf symbiosis has been described as a cyclic and obligate interaction in which the endosymbionts are vertically transmitted between plant generations and lack autonomous growth. Theoretically this allows for co-speciation between leaf nodulated plants and their endosymbionts. We sequenced the nodulated Burkholderia endosymbionts of 54 plant species from known leaf nodulated angiosperm genera, i.e. Ardisia, Pavetta, Psychotria and Sericanthe. Phylogenetic reconstruction of bacterial leaf symbionts and closely related free-living bacteria indicates the occurrence of multiple horizontal transfers of bacteria from the environment to leaf nodulated plant species. This rejects the hypothesis of a long co-speciation process between the bacterial endosymbionts and their host plants. Our results indicate a recent evolutionary process towards a stable and host specific interaction confirming the proposed maternal transmission mode of the endosymbionts through the seeds. Divergence estimates provide evidence for a relatively recent origin of bacterial leaf symbiosis, dating back to the Miocene (5–23 Mya). This geological epoch was characterized by cool and arid conditions, which may have triggered the origin of bacterial leaf symbiosis

    Effect of remote ischaemic conditioning on infarct size and remodelling in ST-segment elevation myocardial infarction patients: the CONDI-2/ERIC-PPCI CMR substudy.

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    The effect of limb remote ischaemic conditioning (RIC) on myocardial infarct (MI) size and left ventricular ejection fraction (LVEF) was investigated in a pre-planned cardiovascular magnetic resonance (CMR) substudy of the CONDI-2/ERIC-PPCI trial. This single-blind multi-centre trial (7 sites in UK and Denmark) included 169 ST-segment elevation myocardial infarction (STEMI) patients who were already randomised to either control (n = 89) or limb RIC (n = 80) (4 × 5 min cycles of arm cuff inflations/deflations) prior to primary percutaneous coronary intervention. CMR was performed acutely and at 6 months. The primary endpoint was MI size on the 6 month CMR scan, expressed as median and interquartile range. In 110 patients with 6-month CMR data, limb RIC did not reduce MI size [RIC: 13.0 (5.1-17.1)% of LV mass; control: 11.1 (7.0-17.8)% of LV mass, P = 0.39], or LVEF, when compared to control. In 162 patients with acute CMR data, limb RIC had no effect on acute MI size, microvascular obstruction and LVEF when compared to control. In a subgroup of anterior STEMI patients, RIC was associated with lower incidence of microvascular obstruction and higher LVEF on the acute scan when compared with control, but this was not associated with an improvement in LVEF at 6 months. In summary, in this pre-planned CMR substudy of the CONDI-2/ERIC-PPCI trial, there was no evidence that limb RIC reduced MI size or improved LVEF at 6 months by CMR, findings which are consistent with the neutral effects of limb RIC on clinical outcomes reported in the main CONDI-2/ERIC-PPCI trial
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