219 research outputs found

    The S-layer Associated Serine Protease Homolog PrtX Impacts Cell Surface-Mediated Microbe-Host Interactions of Lactobacillus acidophilus NCFM

    Get PDF
    Health-promoting aspects attributed to probiotic microorganisms, including adhesion to intestinal epithelia and modulation of the host mucosal immune system, are mediated by proteins found on the bacterial cell surface. Notably, certain probiotic and commensal bacteria contain a surface (S-) layer as the outermost stratum of the cell wall. S-layers are non-covalently bound semi-porous, crystalline arrays of self-assembling, proteinaceous subunits called S-layer proteins (SLPs). Recent evidence has shown that multiple proteins are non-covalently co-localized within the S-layer, designated S-layer associated proteins (SLAPs). In Lactobacillus acidophilus NCFM, SLP and SLAPs have been implicated in both mucosal immunomodulation and adhesion to the host intestinal epithelium. In this study, a S-layer associated serine protease homolog, PrtX (prtX, lba1578), was deleted from the chromosome of L. acidophilus NCFM. Compared to the parent strain, the PrtX-deficient strain (ΔprtX) demonstrated increased autoaggregation, an altered cellular morphology, and pleiotropic increases in adhesion to mucin and fibronectin, in vitro. Furthermore, ΔprtX demonstrated increased in vitro immune stimulation of IL-6, IL-12, and IL-10 compared to wild-type, when exposed to mouse dendritic cells. Finally, in vivo colonization of germ-free mice with ΔprtX led to an increase in epithelial barrier integrity. The absence of PrtX within the exoproteome of a ΔprtX strain caused morphological changes, resulting in a pleiotropic increase of the organisms’ immunomodulatory properties and interactions with some intestinal epithelial cell components

    Structured Decision-Making and Rapid Prototyping to Plan a Management Response to an Invasive Species

    Get PDF
    We developed components of a decision structure that could be used in an adaptive management framework for responding to invasion of hemlock woolly adelgid Adeleges tsugae on the Cumberland Plateau of northern Tennessee. Hemlock woolly adelgid, an invasive forest pest, was first detected in this area in 2007. We used a structured decision-making process to identify and refine the management problem, objectives, and alternative management actions, and to assess consequences and tradeoffs among selected management alternatives. We identified four fundamental objectives: 1) conserve the aquatic and terrestrial riparian conservation targets, 2) protect and preserve hemlock, 3) develop and maintain adequate budget, and 4) address public concerns. We designed two prototype responses using an iterative process. By rapidly prototyping a first solution, insights were gained and shortcomings were identified, and some of these shortcomings were incorporated and corrected in the second prototype. We found that objectives were best met when management focused on early treatment of lightly to moderately infested but relatively healthy hemlock stands with biological control agent predator beetles and insect-killing fungi. Also, depending on the cost constraint, early treatment should be coupled with silvicultural management of moderately to severely infested and declining hemlock stands to accelerate conversion to nonhemlock mature forest cover. The two most valuable contributions of the structured decision-making process were 1) clarification and expansion of our objectives, and 2) application of tools to assess tradeoffs and predict consequences of alternative actions. Predicting consequences allowed us to evaluate the influence of uncertainty on the decision. For example, we found that the expected number of mature forest stands over 30 y would be increased by 4% by resolving the uncertainty regarding predator beetle effectiveness. The adaptive management framework requires further development including identifying and evaluating uncertainty, formalizing other competing predictive models, designing a monitoring program to update the predictive models, developing a process for re-evaluating the predictive models and incorporating new management technologies, and generating support for planning and implementation

    Chemical cues and pheromones in the sea lamprey (Petromyzon marinus)

    Get PDF
    Chemical cues and pheromones guide decisions in organisms throughout the animal kingdom. The neurobiology, function, and evolution of olfaction are particularly well described in insects, and resulting concepts have driven novel approaches to pest control. However, aside from several exceptions, the olfactory biology of vertebrates remains poorly understood. One exception is the sea lamprey (Petromyzon marinus), which relies heavily upon olfaction during reproduction. Here, we provide a broad review of the chemical cues and pheromones used by the sea lamprey during reproduction, including overviews of the sea lamprey olfactory system, chemical cues and pheromones, and potential applications to population management. The critical role of olfaction in mediating the sea lamprey life cycle is evident by a well-developed olfactory system. Sea lamprey use chemical cues and pheromones to identify productive spawning habitat, coordinate spawning behaviors, and avoid risk. Manipulation of olfactory biology offers opportunities for management of populations in the Laurentian Great Lakes, where the sea lamprey is a destructive invader. We suggest that the sea lamprey is a broadly useful organism with which to study vertebrate olfaction because of its simple but well-developed olfactory organ, the dominant role of olfaction in guiding behaviors during reproduction, and the direct implications for vertebrate pest management

    The impact of training and working conditions on junior doctors' intention to leave clinical practice

    Get PDF
    Background: The shortage of physicians is an evolving problem throughout the world. In this study we aimed to identify to what extent junior doctors' training and working conditions determine their intention to leave clinical practice after residency training. Methods: A prospective cohort study was conducted in 557 junior doctors undergoing residency training in German hospitals. Self-reported specialty training conditions, working conditions and intention to leave clinical practice were measured over three time points. Scales covering training conditions were assessed by structured residency training, professional support, and dealing with lack of knowledge; working conditions were evaluated by work overload, job autonomy and social support, based on the Demand-Control-Support model. Multivariate ordinal logistic regression analyses with random intercept for longitudinal data were applied to determine the odds ratio of having a higher level of intention to leave clinical practice. Results: In the models that considered training and working conditions separately to predict intention to leave clinical practice we found significant baseline effects and change effects. After modelling training and working conditions simultaneously, we found evidence that the change effect of job autonomy (OR 0.77, p = .005) was associated with intention to leave clinical practice, whereas for the training conditions, only the baseline effects of structured residency training (OR 0.74, p = .017) and dealing with lack of knowledge (OR 0.74, p = .026) predicted intention to leave clinical practice. Conclusions: Junior doctors undergoing specialty training experience high workload in hospital practice and intense requirements in terms of specialty training. Our study indicates that simultaneously improving working conditions over time and establishing a high standard of specialty training conditions may prevent junior doctors from considering leaving clinical practice after residency training

    Collective and broken pair states of 65,67Ga

    Get PDF
    Excited states of 65Ga and 67Ga nuclei were populated through the 12C(58Ni,αp) and 12C(58Ni,3p) reactions, respectively, and investigated by in-beam γ-ray spectroscopic methods. The NORDBALL array equipped with a charged particle ball and 11 neutron detectors was used to detect the evaporated particles and γ rays. The level schemes of 65,67Ga were constructed on the basis of γγ-coincidence relations up to 8.6 and 10 MeV excitation energy, and Iπ=27/2 and 33/2+ spin and parity, respectively. The structure of 65,67Ga nuclei was described in the interacting boson-fermion plus broken pair model, including quasiproton, quasiproton-two-quasineutron, and three-quasiproton fermion configurations in the boson-fermion basis states. Most of the states were assigned to quasiparticle + phonon and three quasiparticle configurations on the basis of their electromagnetic decay properties

    The JWST Advanced Deep Extragalactic Survey: Discovery of an Extreme Galaxy Overdensity at z = 5.4 with JWST/NIRCam in GOODS-S

    Get PDF
    © 2024 The Author(s). Published by the American Astronomical Society. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY), https://creativecommons.org/licenses/by/4.0/We report the discovery of an extreme galaxy overdensity at z=5.4z = 5.4 in the GOODS-S field using JWST/NIRCam imaging from JADES and JEMS alongside JWST/NIRCam wide field slitless spectroscopy from FRESCO. We identified potential members of the overdensity using HST+JWST photometry spanning λ=0.45.0 μm\lambda = 0.4-5.0\ \mu\mathrm{m}. These data provide accurate and well-constrained photometric redshifts down to m2930magm \approx 29-30\,\mathrm{mag}. We subsequently confirmed N=81N = 81 galaxies at 5.2<z<5.55.2 < z < 5.5 using JWST slitless spectroscopy over λ=3.95.0 μm\lambda = 3.9-5.0\ \mu\mathrm{m} through a targeted line search for Hα\mathrm{H} \alpha around the best-fit photometric redshift. We verified that N=42N = 42 of these galaxies reside in the field while N=39N = 39 galaxies reside in a density around 10\sim 10 times that of a random volume. Stellar populations for these galaxies were inferred from the photometry and used to construct the star-forming main sequence, where protocluster members appeared more massive and exhibited earlier star formation (and thus older stellar populations) when compared to their field galaxy counterparts. We estimate the total halo mass of this large-scale structure to be 12.6log10(Mhalo/M)12.812.6 \lesssim \mathrm{log}_{10} \left( M_{\mathrm{halo}}/M_{\odot} \right) \lesssim 12.8 using an empirical stellar mass to halo mass relation, which is likely an underestimate as a result of incompleteness. Our discovery demonstrates the power of JWST at constraining dark matter halo assembly and galaxy formation at very early cosmic times.Peer reviewe

    The JWST Advanced Deep Extragalactic Survey: Discovery of an Extreme Galaxy Overdensity at z=5.4z = 5.4 with JWST/NIRCam in GOODS-S

    Full text link
    We report the discovery of an extreme galaxy overdensity at z=5.4z = 5.4 in the GOODS-S field using JWST/NIRCam imaging from JADES and JEMS alongside JWST/NIRCam wide field slitless spectroscopy from FRESCO. We identified potential members of the overdensity using HST+JWST photometry spanning λ=0.45.0 μm\lambda = 0.4-5.0\ \mu\mathrm{m}. These data provide accurate and well-constrained photometric redshifts down to m2930magm \approx 29-30\,\mathrm{mag}. We subsequently confirmed N=81N = 81 galaxies at 5.2<z<5.55.2 < z < 5.5 using JWST slitless spectroscopy over λ=3.95.0 μm\lambda = 3.9-5.0\ \mu\mathrm{m} through a targeted line search for Hα\mathrm{H} \alpha around the best-fit photometric redshift. We verified that N=42N = 42 of these galaxies reside in the field while N=39N = 39 galaxies reside in a density around 10\sim 10 times that of a random volume. Stellar populations for these galaxies were inferred from the photometry and used to construct the star-forming main sequence, where protocluster members appeared more massive and exhibited earlier star formation (and thus older stellar populations) when compared to their field galaxy counterparts. We estimate the total halo mass of this large-scale structure to be 12.6log10(Mhalo/M)12.812.6 \lesssim \mathrm{log}_{10} \left( M_{\mathrm{halo}}/M_{\odot} \right) \lesssim 12.8 using an empirical stellar mass to halo mass relation, which is likely an underestimate as a result of incompleteness. Our discovery demonstrates the power of JWST at constraining dark matter halo assembly and galaxy formation at very early cosmic times.Comment: Resubmitted to ApJ based on reviewer report; main text has 15 pages, 6 figures and 1 table; appendix has 1 page, 2 figure sets, and 2 table

    Occupancy maps of 208 chromatin-associated proteins in one human cell type

    Get PDF
    Transcription factors are DNA-binding proteins that have key roles in gene regulation. Genome-wide occupancy maps of transcriptional regulators are important for understanding gene regulation and its effects on diverse biological processes. However, only a minority of the more than 1,600 transcription factors encoded in the human genome has been assayed. Here we present, as part of the ENCODE (Encyclopedia of DNA Elements) project, data and analyses from chromatin immunoprecipitation followed by high-throughput sequencing (ChIP–seq) experiments using the human HepG2 cell line for 208 chromatin-associated proteins (CAPs). These comprise 171 transcription factors and 37 transcriptional cofactors and chromatin regulator proteins, and represent nearly one-quarter of CAPs expressed in HepG2 cells. The binding profiles of these CAPs form major groups associated predominantly with promoters or enhancers, or with both. We confirm and expand the current catalogue of DNA sequence motifs for transcription factors, and describe motifs that correspond to other transcription factors that are co-enriched with the primary ChIP target. For example, FOX family motifs are enriched in ChIP–seq peaks of 37 other CAPs. We show that motif content and occupancy patterns can distinguish between promoters and enhancers. This catalogue reveals high-occupancy target regions at which many CAPs associate, although each contains motifs for only a minority of the numerous associated transcription factors. These analyses provide a more complete overview of the gene regulatory networks that define this cell type, and demonstrate the usefulness of the large-scale production efforts of the ENCODE Consortium
    corecore