421 research outputs found

    'The world is full of big bad wolves': investigating the experimental therapeutic spaces of R.D. Laing and Aaron Esterson

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    In conjunction with the recent critical assessments of the life and work of R.D. Laing, this paper seeks to demonstrate what is revealed when Laing’s work on families and created spaces of mental health care are examined through a geographical lens. The paper begins with an exploration of Laing’s time at the Tavistock Clinic in London during the 1960s, and of the co-authored text with Aaron Esterson entitled, Sanity, Madness and the Family (1964). The study then seeks to demonstrate the importance Laing and his colleague placed on the time-space situatedness of patients and their worlds. Finally, an account is provided of Laing’s and Esterson’s spatial thinking in relation to their creation of both real and imagined spaces of therapeutic care

    TetR-Based Gene Regulation Systems for Francisella tularensis

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    ABSTRACT There are a number of genetic tools available for studying Francisella tularensis , the etiological agent of tularemia; however, there is no effective inducible or repressible gene expression system. Here, we describe inducible and repressible gene expression systems for F. tularensis based on the Tet repressor, TetR. For the inducible system, a tet operator sequence was cloned into a modified F. tularensis groESL promoter sequence and carried in a plasmid that constitutively expressed TetR. To monitor regulation the luminescence operon, luxCDABE , was cloned under the hybrid Francisella tetracycline-regulated promoter ( FTRp ), and transcription was initiated with addition of anhydrotetracycline (ATc), which binds TetR and alleviates TetR association with tetO. Expression levels measured by luminescence correlated with ATc inducer concentrations ranging from 20 to 250 ng ml −1 . In the absence of ATc, luminescence was below the level of detection. The inducible system was also functional during the infection of J774A.1 macrophages, as determined by both luminescence and rescue of a mutant strain with an intracellular growth defect. The repressible system consists of FTRp regulated by a reverse TetR mutant (revTetR), TetR r1.7. Using this system with the lux reporter, the addition of ATc resulted in decreased luminescence, while in the absence of ATc the level of luminescence was not significantly different from that of a construct lacking TetR r1.7. Utilizing both systems, the essentiality of SecA, the protein translocase ATPase, was confirmed, establishing that they can effectively regulate gene expression. These two systems will be invaluable in exploring F. tularensis protein function

    Extragenic suppressor mutations in ΔripA disrupt stability and function of LpxA

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    Abstract Background Francisella tularensis is a Gram-negative bacterium that infects hundreds of species including humans, and has evolved to grow efficiently within a plethora of cell types. RipA is a conserved membrane protein of F. tularensis, which is required for growth inside host cells. As a means to determine RipA function we isolated and mapped independent extragenic suppressor mutants in ∆ripA that restored growth in host cells. Each suppressor mutation mapped to one of two essential genes, lpxA or glmU, which are involved in lipid A synthesis. We repaired the suppressor mutation in lpxA (S102, LpxA T36N) and the mutation in glmU (S103, GlmU E57D), and demonstrated that each mutation was responsible for the suppressor phenotype in their respective strains. We hypothesize that the mutation in S102 altered the stability of LpxA, which can provide a clue to RipA function. LpxA is an UDP-N-acetylglucosamine acyltransferase that catalyzes the transfer of an acyl chain from acyl carrier protein (ACP) to UDP-N-acetylglucosamine (UDP-GlcNAc) to begin lipid A synthesis. Results LpxA was more abundant in the presence of RipA. Induced expression of lpxA in the ΔripA strain stopped bacterial division. The LpxA T36N S102 protein was less stable and therefore less abundant than wild type LpxA protein. Conclusion These data suggest RipA functions to modulate lipid A synthesis in F. tularensis as a way to adapt to the host cell environment by interacting with LpxA.http://deepblue.lib.umich.edu/bitstream/2027.42/110509/1/12866_2014_Article_336.pd

    Examining the Role of Marine Mammals and Seabirds in Southeast Alaska’s Marine Ecosystem Dynamics

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    Primary producers are the foundation of marine food webs and require reliable nutrient sources to maintain their important role with ecosystems. While marine mammals and seabirds can play critical roles in marine nutrient cycling, their contributions are often overlooked. The fjord systems of Southeast Alaska support a high diversity of marine mammals and seabirds in addition to some of the most valuable fisheries in the US. Nonetheless, there is still relatively little known about nutrient sources and fluxes in this region which is a critical component of fisheries management. The goal of our study was to advance knowledge of the role of mammals and seabirds in marine nutrient cycling and to understand how changing marine mammal and seabird populations may alter ecosystem dynamics. We analyzed nutrient levels in marine mammal scat, seabird guano, and seawater samples collected in Berners Bay, Southeast Alaska, to determine the influence of marine mammals and seabirds on nearshore nutrient concentrations. Utilizing qualitative network models (QNMs), we then examined how a simulated Berners Bay ecosystem would respond to an increase in marine mammals, seabirds, and nutrients. Researchers are increasingly utilizing QNMs as a first step in the development of ecosystem-based fisheries management plans as their adaptable nature is well suited to address rapidly changing climatic conditions. Our direct nutrient measurements and QNM results indicate that marine mammals and seabirds have the potential to provide substantial contributions to marine nutrient concentrations in the region and that these valuable ecosystem services should not be overlooked.We sincerely thank the reviewers for their suggestions and feedbackYe

    The Circadian Rhythm of Blood Pressure During Pregnancy

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    To review the literature on the circadian rhythm of blood pressure during pregnancy. Data Sources : Computerized searches on MEDLINE, CINAHL, and MIRLYN. Study Selection : Selected studies from 1969 to 1997 were evaluated. Data Extraction : Data were extracted and information was organized under the following areas: definition of and the interconnection between circadian rhythm and blood pressure; the circadian variability of blood pressure throughout the trimesters; the patterns of the circadian rhythm of blood pressure in pregnancies defined as normal and those complicated by chronic hypertension and preeclampsia; and clinical implications. Data Synthesis : The circadian rhythm of blood pressure in pregnancy is the same as in the nonpregnant state, with a nocturnal decrease, especially during sleep. In patients with chronic hypertension, the nocturnal fall in blood pressure may be steeper. Patients with mild preeclampsia may experience a less pronounced nocturnal decrease in blood pressure. Patients with severe preeclampsia may display a reversed circadian rhythm, with no decrease and/or an increase in nocturnal blood pressure. Conclusions : The patterns of the circadian rhythm of blood pressure during normal pregnancy and pregnancies complicated by chronic hypertension and preeclampsia warrant consideration when monitoring patients and implementing management plans.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/71412/1/j.1552-6909.2000.tb02771.x.pd

    When to update COVID-19 vaccine composition

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    Vaccines against different SARS-CoV-2 variants have been approved, but continued surveillance is needed to determine when the antigen composition of vaccines should be updated, together with clinical studies to assess vaccine efficacy
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