Genomic analysis of 48 paenibacillus larvae bacteriophages

Indexación: Scopus.Funding: Research at UNLV was funded by National Institute of General Medical Sciences grant GM103440 (NV INBRE), the UNLV School of Life Sciences, and the UNLV College of Sciences. E.C.-N. was funded by CONICYT-FONDECYT de iniciación en la investigación 11160905. Research at BYU was funded by the BYU Microbiology & Molecular Biology Department, and private donations through LDS Philanthropies.The antibiotic-resistant bacterium Paenibacillus larvae is the causative agent of American foulbrood (AFB), currently the most destructive bacterial disease in honeybees. Phages that infect P. larvae were isolated as early as the 1950s, but it is only in recent years that P. larvae phage genomes have been sequenced and annotated. In this study we analyze the genomes of all 48 currently sequenced P. larvae phage genomes and classify them into four clusters and a singleton. The majority of P. larvae phage genomes are in the 38–45 kbp range and use the cohesive ends (cos) DNA-packaging strategy, while a minority have genomes in the 50–55 kbp range that use the direct terminal repeat (DTR) DNA-packaging strategy. The DTR phages form a distinct cluster, while the cos phages form three clusters and a singleton. Putative functions were identified for about half of all phage proteins. Structural and assembly proteins are located at the front of the genome and tend to be conserved within clusters, whereas regulatory and replication proteins are located in the middle and rear of the genome and are not conserved, even within clusters. All P. larvae phage genomes contain a conserved N-acetylmuramoyl-L-alanine amidase that serves as an endolysin. © 2018 by the authors. Licensee MDPI, Basel, Switzerland.https://www.mdpi.com/1999-4915/10/7/37

Quantum superchemistry: Role of trapping profile and quantum statistics

The process of Raman photoassociation of a trapped atomic condensate to form condensed molecules has been labeled superchemistry because it can occur at 0 K and experiences coherent bosonic stimulation. We show here that the differences from ordinary chemical processes go even deeper, with the conversion rates depending on the quantum state of the reactants, as expressed by the Wigner function. We consider different initial quantum states of the trapped atomic condensate and different forms of the confining potentials, demonstrating the importance of the quantum statistics and the extra degrees of freedom which massive particles and trapping potentials make available over the analogous optical process of second-harmonic generation. We show that both mean-field analyses and quantum calculations using an inappropriate initial condition can make inaccurate predictions for a given system. This is possible whether using a spatially dependent analysis or a zero-dimensional approach as commonly used in quantum optics

Length of carotid stenosis predicts peri-procedural stroke or death and restenosis in patients randomized to endovascular treatment or endarterectomy.

BACKGROUND: The anatomy of carotid stenosis may influence the outcome of endovascular treatment or carotid endarterectomy. Whether anatomy favors one treatment over the other in terms of safety or efficacy has not been investigated in randomized trials. METHODS: In 414 patients with mostly symptomatic carotid stenosis randomized to endovascular treatment (angioplasty or stenting; n = 213) or carotid endarterectomy (n = 211) in the Carotid and Vertebral Artery Transluminal Angioplasty Study (CAVATAS), the degree and length of stenosis and plaque surface irregularity were assessed on baseline intraarterial angiography. Outcome measures were stroke or death occurring between randomization and 30 days after treatment, and ipsilateral stroke and restenosis ≥50% during follow-up. RESULTS: Carotid stenosis longer than 0.65 times the common carotid artery diameter was associated with increased risk of peri-procedural stroke or death after both endovascular treatment [odds ratio 2.79 (1.17-6.65), P = 0.02] and carotid endarterectomy [2.43 (1.03-5.73), P = 0.04], and with increased long-term risk of restenosis in endovascular treatment [hazard ratio 1.68 (1.12-2.53), P = 0.01]. The excess in restenosis after endovascular treatment compared with carotid endarterectomy was significantly greater in patients with long stenosis than with short stenosis at baseline (interaction P = 0.003). Results remained significant after multivariate adjustment. No associations were found for degree of stenosis and plaque surface. CONCLUSIONS: Increasing stenosis length is an independent risk factor for peri-procedural stroke or death in endovascular treatment and carotid endarterectomy, without favoring one treatment over the other. However, the excess restenosis rate after endovascular treatment compared with carotid endarterectomy increases with longer stenosis at baseline. Stenosis length merits further investigation in carotid revascularisation trials

Current- and Wave-Generated Bedforms on Mixed Sand–Clay Intertidal Flats: A New Bedform Phase Diagram and Implications for Bed Roughness and Preservation Potential

The effect of bedforms on frictional roughness felt by the overlying flow is crucial to the regional modelling of estuaries and coastal seas. Bedforms are also a key marker of palaeoenvironments. Experiments have shown that even modest biotic and abiotic cohesion in sand inhibits bedform formation, modifies bedform size, and slows bedform development, but this has rarely been tested in nature. The present study used a comprehensive dataset recorded over a complete spring–neap cycle on an intertidal flat to investigate bedform dynamics controlled by a wide range of wave and current conditions, including the effects of wave–current angle and bed cohesion. A detailed picture of different bedform types and their relationship to the flow, be they equilibrium, non-equilibrium, or relict, was produced, and captured in a phase diagram that integrates wave-dominated, current-dominated, and combined wave–current bedforms. This bedform phase diagram incorporates a substantially wider range of flow conditions than previous phase diagrams, including bedforms related to near-orthogonal wave–current angles, such as ladderback ripples. Comparison with laboratory-derived bedform phase diagrams indicates that washed-out ripples, lunate interference ripples and upper-stage plane beds replace the subaqueous dune field; such bedform distributions may be a key characteristic of intertidal flats. The field data also provide a means of predicting the dimensions of these bedforms, which can be transferred to other areas and grain sizes. We show that an equation for the prediction of equilibrium bedform size is sufficient to predict the roughness, even though the bedforms are highly variable in character and only in equilibrium with the flow for approximately half the time. Whilst the effect of cohesive clay is limited under more active spring conditions, clay does play a role in reducing the bedform dimensions under more quiescent neap conditions. We also investigated which combinations of waves, currents, and bed clay contents in the intertidal zone have the highest potential for bedform preservation in the geological record. This shows that combined wave–current bedforms have the lowest preservation potential and equilibrium current ripples have the highest preservation potential, even in the presence of moderate and storm waves. Hence, the absence of wave ripples and combined-flow bedforms and their primary stratification in sedimentary successions cannot be taken as evidence that waves were absent at the time of deposition

SJS/TEN 2019: From Science to Translation

Stevens-Johnson syndrome and toxic epidermal necrolysis (SJS/TEN) are potentially life-threatening, immune-mediated adverse reactions characterized by widespread erythema, epidermal necrosis, and detachment of skin and mucosa. Efforts to grow and develop functional international collaborations and a multidisciplinary interactive network focusing on SJS/TEN as an uncommon but high burden disease will be necessary to improve efforts in prevention, early diagnosis and improved acute and long-term management. SJS/TEN 2019: From Science to Translation was a 1.5-day scientific program held April 26-27, 2019, in Vancouver, Canada. The meeting successfully engaged clinicians, researchers, and patients and conducted many productive discussions on research and patient care needs

Rapid in vitro generation of bona fide exhausted CD8+ T cells is accompanied by Tcf7 promotor methylation

Exhaustion is a dysfunctional state of cytotoxic CD8+ T cells (CTL) observed in chronic infection and cancer. Current in vivo models of CTL exhaustion using chronic viral infections or cancer yield very few exhausted CTL, limiting the analysis that can be done on these cells. Establishing an in vitro system that rapidly induces CTL exhaustion would therefore greatly facilitate the study of this phenotype, identify the truly exhaustion-associated changes and allow the testing of novel approaches to reverse or prevent exhaustion. Here we show that repeat stimulation of purified TCR transgenic OT-I CTL with their specific peptide induces all the functional (reduced cytokine production and polyfunctionality, decreased in vivo expansion capacity) and phenotypic (increased inhibitory receptors expression and transcription factor changes) characteristics of exhaustion. Importantly, in vitro exhausted cells shared the transcriptomic characteristics of the gold standard of exhaustion, CTL from LCMV cl13 infections. Gene expression of both in vitro and in vivo exhausted CTL was distinct from T cells anergy. Using this system, we show that Tcf7 promoter DNA methylation contributes to TCF1 downregulation in exhausted CTL. Thus this novel in vitro system can be used to identify genes and signaling pathways involved in exhaustion and will facilitate the screening of reagents that prevent/reverse CTL exhaustion

Identification of common genetic risk variants for autism spectrum disorder

Autism spectrum disorder (ASD) is a highly heritable and heterogeneous group of neurodevelopmental phenotypes diagnosed in more than 1% of children. Common genetic variants contribute substantially to ASD susceptibility, but to date no individual variants have been robustly associated with ASD. With a marked sample-size increase from a unique Danish population resource, we report a genome-wide association meta-analysis of 18,381 individuals with ASD and 27,969 controls that identified five genome-wide-significant loci. Leveraging GWAS results from three phenotypes with significantly overlapping genetic architectures (schizophrenia, major depression, and educational attainment), we identified seven additional loci shared with other traits at equally strict significance levels. Dissecting the polygenic architecture, we found both quantitative and qualitative polygenic heterogeneity across ASD subtypes. These results highlight biological insights, particularly relating to neuronal function and corticogenesis, and establish that GWAS performed at scale will be much more productive in the near term in ASD.Peer reviewe

Track A Basic Science

Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/138319/1/jia218438.pd

Reduction of dynamics for optimal control of stochastic and deterministic systems

The optimal estimation theory of the Wiener-Kalman filter is extended to cover the situation in which the number of memory elements in the estimator is restricted. A method, based on the simultaneous diagonalisation of two symmetric positive definite matrices, is given which allows the weighted least square estimation error to be minimised. A control system design method is developed utilising this estimator, and this allows the dynamic controller in the feedback path to have a low order. A 12-order once-through boiler model is constructed and the performance of controllers of various orders generated by the design method is investigated. Little cost penalty is found even for the one-order controller when compared with the optimal Kalman filter system. Whereas in the Kalman filter all information from past observations is stored, the given method results in an estimate of the state variables which is a weighted sum of the selected information held in the storage elements. For the once-through boiler these weighting coefficients are found to be smooth functions of position, their form illustrating the implicit model reduction properties of the design method. Minimal-order estimators of the Luenberger type also generate low order controllers and the relation between the two design methods is examined. It is concluded that the design method developed in this thesis gives better plant estimates than the Luenberger system and, more fundamentally, allows a lower order control system to be constructed. Finally some possible extensions of the theory are indicated. An immediate application is to multivariable control systems, while the existence of a plant state estimate even in control systems of very low order allows a certain adaptive structure to be considered for systems with time-varying parameters