Intrinsic and Extrinsic Regulation of Type III Secretion Gene Expression in Pseudomonas Aeruginosa

Pseudomonas aeruginosa is an opportunistic pathogen that is particularly problematic in the healthcare setting where it is a frequent cause of pneumonia, bloodstream, and urinary tract infections. An important determinant of P. aeruginosa virulence is a type III secretion system (T3SS). T3SS-dependent intoxication is a complex process that minimally requires binding of P. aeruginosa to host cells, injection of the cytotoxic effector proteins through the host cell plasma membrane, and induction of T3SS gene expression. The latter process, referred to as contact-dependent expression, involves a well-characterized regulatory cascade that activates T3SS gene expression in response to host cell contact. Although host cell contact is a primary activating signal for T3SS gene expression, the involvement of multiple membrane-bound regulatory systems indicates that additional environmental signals also play a role in controlling expression of the T3SS. These regulatory systems coordinate T3SS gene expression with many other cellular activities including motility, mucoidy, polysaccharide production, and biofilm formation. The signals to which the organism responds are poorly understood but many seem to be coupled to the metabolic state of the cell and integrated within a master circuit that assimilates informational signals from endogenous and exogenous sources. Herein we review progress toward unraveling this complex circuitry, provide analysis of the current knowledge gaps, and highlight potential areas for future studies. Complete understanding of the regulatory networks that control T3SS gene expression will maximize opportunities for the development of strategies to treat P. aeruginosa infections

The C-Band All-Sky Survey: Instrument design, status, and first-look data

The C-Band All-Sky Survey (C-BASS) aims to produce sensitive, all-sky maps of diffuse Galactic emission at 5 GHz in total intensity and linear polarization. These maps will be used (with other surveys) to separate the several astrophysical components contributing to microwave emission, and in particular will allow an accurate map of synchrotron emission to be produced for the subtraction of foregrounds from measurements of the polarized Cosmic Microwave Background. We describe the design of the analog instrument, the optics of our 6.1 m dish at the Owens Valley Radio Observatory, the status of observations, and first-look data.Comment: 10 pages, 11 figures, published in Proceedings of SPIE MIllimeter, Submillimeter, and Far-Infrared Detectors and Instrumentation for Astronomy V (2010), Vol. 7741, 77411I-1 - 77411I-1

Impact of real-time antimicrobial stewardship team intervention versus conventional microbiology reporting on time to appropriate antimicrobial therapy in patients with Enterobacterales bacteremia

Scott C. King Alyssa B. Christensen, Brent W. Footer, Timothy G. Shan, Kim Health, Ivor Thomas, and Margret Oethinger Impact of real-time antimicrobial stewardship team intervention versus conventional microbiology reporting on time to appropriate antimicrobial therapy in patients with Enterobacterales bacteremia. Introduction: The benefit of rapid laboratory speciation combined with real time antimicrobial stewardship team (AMT) interventions has been shown to improve patient outcomes and decrease hospital costs. The Providence Oregon region conducts direct from blood culture matrix-assisted laser desorption/ionization time of flight (MALDI-TOF) identification, which results in decreased time to organism identification. The MALDI-TOF identification has allowed the AMT to intervene earlier than a health system using standard MALDI identification or comparable methods. The purpose of this study is to assess the impact of real time notification plus AMT intervention on clinical outcomes in patients with Enterobacterales blood stream infections (BSI). Methods: This was an IRB approved, retrospective, multi-center, pre- and post- quasi-experimental study conducted at eight acute care hospitals in the Providence Health & Services Oregon region. Adult patients (\u3e18 years old) with a diagnosed BSI caused by an Enterobacterales species were included. The control group was from August 2018 to January 2019 and the intervention group was from February 2019 to June 2019. Patients were matched based on age, gender, and admission to the ICU. Exclusion criteria included polymicrobial infection, Pitt bacteremia score \u3e1, unable to take PO therapy, and patients discharged to hospice care. During the intervention period the AMT members received real-time alerts for all blood culture speciation via a paging system. These cases where then reviewed and recommendations were made to the primary care team based off an approved protocol. The primary outcome for the study was time to de-escalation of therapy. Secondary outcomes include hospital length of stay and total duration of therapy. Results: A total of 60 patients were include in this study: 30 patients in the pre-intervention group and 30 patients in the post-intervention group. The most common age group was patients 60-69 years of age (43% vs 43%). The most common causative organism for the BSI was found to be Escherichia coli (76.7% vs 50%). During the intervention period a decrease was noted in median time to de-escalation of therapy (2.7 days vs 1.8 days, p=0.0061) and length of stay (5.3 days vs 4.3 days, p=0.0475). There was no statistical difference in the total length of therapy (combined inpatient and outpatient duration) noted between the two groups (9 days vs 9.5 days, p=1). Conclusion: The results show a statistically significant decrease in both time to de-escalation and length of stay within the intervention group due to AMT recommendations. This is in line with previous studies and also highlights the benefit de-escalation could have on length of stay in the hospital. Studies with larger samples sizes should be considered to further explore these results. IRB Status: Approvedhttps://digitalcommons.psjhealth.org/pharmacy_PGY1/1009/thumbnail.jp

The N- or C-terminal domains of DSH-2 can activate the C. elegans Wnt/β-catenin asymmetry pathway

AbstractDishevelleds are modular proteins that lie at the crossroads of divergent Wnt signaling pathways. The DIX domain of dishevelleds modulates a β-catenin destruction complex, and thereby mediates cell fate decisions through differential activation of Tcf transcription factors. The DEP domain of dishevelleds mediates planar polarity of cells within a sheet through regulation of actin modulators. In Caenorhabditis elegans asymmetric cell fate decisions are regulated by asymmetric localization of signaling components in a pathway termed the Wnt/β-catenin asymmetry pathway. Which domain(s) of Disheveled regulate this pathway is unknown. We show that C. elegans embryos from dsh-2(or302) mutant mothers fail to successfully undergo morphogenesis, but transgenes containing either the DIX or the DEP domain of DSH-2 are sufficient to rescue the mutant phenotype. Embryos lacking zygotic function of SYS-1/β-catenin, WRM-1/β-catenin, or POP-1/Tcf show defects similar to dsh-2 mutants, including a loss of asymmetry in some cell fate decisions. Removal of two dishevelleds (dsh-2 and mig-5) leads to a global loss of POP-1 asymmetry, which can be rescued by addition of transgenes containing either the DIX or DEP domain of DSH-2. These results indicate that either the DIX or DEP domain of DSH-2 is capable of activating the Wnt/β-catenin asymmetry pathway and regulating anterior–posterior fate decisions required for proper morphogenesis

Age Reflects on the Occurrence of Bovine Periodontal Lesions

No abstract available

Genetic mixed stock analysis of an interceptory Atlantic salmonfishery in the Northwest Atlantic

Interceptory fisheries represent an ongoing threat to migratory fish stocks particularly when managed in the absence of stock specific catch and exploitation information. Atlantic salmon from the southern portion of the North American range may be subject to exploitation in the commercial and recreational salmon fisheries occurring in the French territorial waters surrounding St. Pierre and Miquelon off southern Newfoundland. We evaluated stock composition of Atlantic salmon harvested in the St. Pierreand Miquelon Atlantic salmon fishery using genetic mixture analysis and individual assignment with a microsatellite baseline (15 loci, 12,409 individuals, 12 regional groups) encompassing the species western Atlantic range. Individual salmon were sampled from the St. Pierre and Miquelon fishery over four years (2004, 2011, 2013, and 2014). Biological characteristics indicate significant variation among years in the size and age distribution. Nonetheless, estimates of stock composition of the samples showed consistent dominance of three regions (i.e., Southern Gulf of St. Lawrence, Gaspe Peninsula, and New-foundland). Together salmon from these regions accounted for more than 70% of annual harvest over the decade examined. Comparison of individual assignments and biological characteristics revealed a trend of declining fresh water age with latitude of assigned region. Moreover, locally harvested Newfoundland salmon were ten times more likely to be small or one sea winter individuals whereas Quebec and Gaspe Peninsula salmon were two-three times more likely to be harvested as large or two sea winter salmon.Estimates of region specific catch were highest for salmon from the southern Gulf of St. Lawrence region ranging from 242 to 887 individuals annually. This work illustrates how genetic analysis of interceptory marine fisheries can directly inform assessment and management efforts in highly migratory marines pecies

Moving boundary problems for quasi-steady conduction limited melting

The problem of melting a crystal dendrite is modelled as a quasi-steady Stefan 5 problem. By employing the Baiocchi transform, asymptotic results are derived in the limit that 6 the crystal melts completely, extending previous results that hold for a special class of initial and 7 boundary conditions. These new results, together with predictions for whether the crystal pinches off 8 and breaks into two, are supported by numerical calculations using the level set method. The effects of 9 surface tension are subsequently considered, leading to a canonical problem for near-complete-melting 10 which is studied in linear stability terms and then solved numerically. Our study is motivated in 11 part by experiments undertaken as part of the Isothermal Dendritic Growth Experiment, in which 12 dendritic crystals of pivalic acid were melted in a microgravity environment: these crystals were 13 found to be prolate spheroidal in shape, with an aspect ratio initially increasing with time then 14 rather abruptly decreasing to unity. By including a kinetic undercooling-type boundary condition in 15 addition to surface tension, our model suggests the aspect ratio of a melting crystal can reproduce 16 the same non-monotonic behaviour as that which was observed experimentally. 1

Resonance line-profile calculations based on hydrodynamical models of cataclysmic variable winds

We present synthetic line profiles as predicted by the models of 2-D line- driven disk winds due to Proga, Stone & Drew. We compare the model line profiles with HST observations of the cataclysmic variable IX Vel. The model wind consists of a slow outflow that is bounded on the polar side by a fast stream. We find that these two components of the wind produce distinct spectral features. The fast stream produces profiles which show features consistent with observations. These include the appearance of the P-Cygni shape for a range of inclinations, the location of the maximum depth of the absorption component at velocities less than the terminal velocity, and the transition from absorption to emission with increasing inclination. However the model profiles have too little absorption or emission equivalent width. This quantitative difference between our models and observations is not a surprise because the line-driven wind models predict a mass loss rate that is lower than the rate required by the observations. We note that the model profiles exhibit a double-humped structure near the line center which is not echoed in observations. We identify this structure with a non-negligible redshifted absorption which is formed in the slow component of the wind where the rotational velocity dominates over expansion velocity. We conclude that the next generation of disk wind models, developed for application to CVs, needs to yield stronger wind driving out to larger disk radii than do the present models.Comment: LaTeX, 19 pages, to appear in Ap