60 research outputs found

    Identification of Chromosomal Genes in Yersinia pestis that Influence Type III Secretion and Delivery of Yops into Target Cells

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    Pathogenic Yersinia species possess a type III secretion system, which is required for the delivery of effector Yop proteins into target cells during infection. Genes encoding the type III secretion machinery, its substrates, and several regulatory proteins all reside on a 70-Kb virulence plasmid. Genes encoded in the chromosome of yersiniae are thought to play important roles in bacterial perception of host environments and in the coordinated activation of the type III secretion pathway. Here, we investigate the contribution of chromosomal genes to the complex regulatory process controlling type III secretion in Yersinia pestis. Using transposon mutagenesis, we identified five chromosomal genes required for expression or secretion of Yops in laboratory media. Four out of the five chromosomal mutants were defective to various extents at injecting Yops into tissue culture cells. Interestingly, we found one mutant that was not able to secrete in vitro but was fully competent for injecting Yops into host cells, suggesting independent mechanisms for activation of the secretion apparatus. When tested in a mouse model of plague disease, three mutants were avirulent, whereas two strains were severely attenuated. Together these results demonstrate the importance of Y. pestis chromosomal genes in the proper function of type III secretion and in the pathogenesis of plague

    Planning for precarity? Experiencing the carceral continuum of imprisonment and reentry

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    Drawing on qualitative interviews with formerly imprisoned people in Canada, we show that most prisoners experience reentry into communities with little to no pre-release planning, and must rely upon their own resourcefulness to navigate fragmented social services and often informal supports. In this respect, our research findings contrast with U.S. punishment and society scholarship that highlights a complex shadow carceral state that extends the reach of incarceration into communities. Our participants expressed a critical analysis of the failure of the prison to address the needs of prisoners for release planning and supports in the community. Our findings concur with other empirical studies that demonstrate the enduring effects of the continuum of carceral violence witnessed and experienced by prisoners after release. Thus, reentry must be understood in relation to the conditions of confinement and the experience of incarceration itself. We conclude that punishment and society scholarship needs to attend to a nuanced understanding of prisoner reentry and connect reentry studies to a wider critique of the prison industrial complex, offering more empirical evidence of the failure of prisons

    Variable-wavelength frequency-domain terahertz ellipsometry

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    We report an experimental setup for wavelength-tunable frequency-domain ellipsometric measurements in the terahertz spectral range from 0.2 to 1.5 THz employing a desktop-based backward wave oscillator source. The instrument allows for variable angles of incidence between 30Β° and 90Β° and operates in a polarizer-sample-rotating analyzer scheme. The backward wave oscillator source has a tunable base frequency of 107–177 GHz and is augmented with a set of Schottky diode frequency multipliers in order to extend the spectral range to 1.5 THz. We use an odd-bounce image rotation system in combination with a wire grid polarizer to prepare the input polarization state. A highly phosphorous-doped Si substrate serves as a first sample model system. We show that the ellipsometric data obtained with our novel terahertz ellipsometer can be well described within the classical Drude model, which at the same time is in perfect agreement with midinfrared ellipsometry data obtained from the same sample for comparison. The analysis of the terahertz ellipsometric data of a low phosphorous-doped n-type Si substrate demonstrates that ellipsometry in the terahertz spectral range allows the determination of free charge-carrier properties for electron concentrations as low as 8x1014 cmβˆ’3

    Effect of the Family-Centered Advance Care Planning for Teens with Cancer Intervention on Sustainability of Congruence About End-of-Life Treatment Preferences: A Randomized Clinical Trial

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    Importance: The effect of pediatric advance care planning (pACP) on the sustainability of end-of-life treatment preference congruence between adolescents with cancer and their families has not been examined. Objective: To evaluate the longitudinal efficacy of the Family-Centered Advance Care Planning for Teens with Cancer (FACE-TC) intervention to sustain adolescent-family congruence about end-of-life treatment preferences. Design, Setting, and Participants: This multisite, assessor-blinded, randomized clinical trial enrolled adolescents with cancer (aged 14-21 years) and their family members from 4 pediatric hospitals between July 16, 2016, and April 30, 2019. Participants were randomized 2:1 to FACE-TC (intervention group) or treatment as usual (control group) and underwent 5 follow-up visits over an 18-month postintervention period. Intention-to-treat analyses were conducted from March 9, 2021, to April 14, 2022. Exposures: Adolescent-family dyads randomized to the FACE-TC group received 3 weekly 60-minute sessions consisting of the discussion and/or completion of the Lyon Family-Centered Advance Care Planning Survey (session 1), Respecting Choices Next Steps pACP conversation (session 2), and Five Wishes advance directive (session 3). Dyads in the control group received treatment as usual. Both groups received pACP information. Main Outcomes and Measures: Congruence was measured by completion of the Statement of Treatment Preferences (a document that discusses 4 hypothetical clinical situations and treatment choices for each scenario: continue all treatments, stop all efforts to keep me alive, or unsure) after session 2 (time 1) and at 3 months (time 2), 6 months (time 3), 12 months (time 4), and 18 months (time 5) after intervention. The influence of FACE-TC on the trajectory of congruence over time was measured by longitudinal latent class analysis. Results: A total of 252 participants (126 adolescent-family dyads) were randomized. Adolescents (mean [SD] age, 17 [1.9] years) and family members (mean [SD] age, 46 [8.3] years) were predominantly female (72 [57%] and 104 [83%]) and White individuals (100 [79%] and 103 [82%]). There was an 83% (104 of 126) retention at the 18-month assessment. Two latent classes of congruence over time were identified: high-congruence latent class (69 of 116 [60%]) and low-congruence latent class (47 of 116 [41%]). The dyads in the FACE-TC group had a 3-fold odds of being in the high-congruence latent class (odds ratio [OR], 3.22; 95% CI, 1.09-9.57) compared with the control group. Statistically significant differences existed at 12 months (Ξ² [SE] = 1.17 [0.55]; P = .03]) but not at 18 months (OR, 2.08; 95% CI, 0.92-4.69). In the high-congruence latent class, good agreement (agreement on 2 or 3 of 4 situations) increased over 12 months. White adolescents and families had significantly greater odds of congruence than a small population of American Indian or Alaska Native, Asian, Black or African American, Hispanic or Latino, or multiracial adolescents and families (OR, 3.97; 95% CI, 1.07-14.69). Conclusions and Relevance: Results of this trial showed that, for those who received the FACE-TC intervention, the families\u27 knowledge of their adolescents\u27 end-of-life treatment preferences was sustained for 1 year, suggesting yearly follow-up sessions. Race and ethnicity-based differences in the sustainability of this knowledge reflect a difference in the effect of the intervention and require further study. Trial Registration: ClinicalTrials.gov Identifier: NCT02693665
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