Sigma 54-Regulated Transcription Is Associated with Membrane Reorganization and Type III Secretion Effectors during Conversion to Infectious Forms of Chlamydia trachomatis

This work is licensed under a Creative Commons Attribution 4.0 International License.Chlamydia bacteria are obligate intracellular organisms with a phylum-defining biphasic developmental cycle that is intrinsically linked to its ability to cause disease. The progression of the chlamydial developmental cycle is regulated by the temporal expression of genes predominantly controlled by RNA polymerase sigma (σ) factors. Sigma 54 (σ54) is one of three sigma factors encoded by Chlamydia for which the role and regulon are unknown. CtcC is part of a two-component signal transduction system that is requisite for σ54 transcriptional activation. CtcC activation of σ54 requires phosphorylation, which relieves inhibition by the CtcC regulatory domain and enables ATP hydrolysis by the ATPase domain. Prior studies with CtcC homologs in other organisms have shown that expression of the ATPase domain alone can activate σ54 transcription. Biochemical analysis of CtcC ATPase domain supported the idea of ATP hydrolysis occurring in the absence of the regulatory domain, as well as the presence of an active-site residue essential for ATPase activity (E242). Using recently developed genetic approaches in Chlamydia to induce expression of the CtcC ATPase domain, a transcriptional profile was determined that is expected to reflect the σ54 regulon. Computational evaluation revealed that the majority of the differentially expressed genes were preceded by highly conserved σ54 promoter elements. Reporter gene analyses using these putative σ54 promoters reinforced the accuracy of the model of the proposed regulon. Investigation of the gene products included in this regulon supports the idea that σ54 controls expression of genes that are critical for conversion of Chlamydia from replicative reticulate bodies into infectious elementary bodies.NIH T32 GM008545AI126785NIH (AI126785)P20GM113117P20GM10363

Densification and residual stress induced by CO2 laserbased mitigation of SiO2 surfaces

ABSTRACT Knowing the ultimate surface morphology resulting from CO 2 laser mitigation of induced laser damage is important both for determining adequate treatment protocols, and for preventing deleterious intensification upon subsequent illumination of downstream optics. Physical effects such as evaporation, viscous flow and densification can strongly affect the final morphology of the treated site. Evaporation is a strong function of temperature and will play a leading role in determining pit shapes when the evaporation rate is large, both because of material loss and redeposition. Viscous motion of the hot molten material during heating and cooling can redistribute material due to surface tension gradients (Marangoni effect) and vapor recoil pressure effects. Less well known, perhaps, is that silica can densify as a result of structural relaxation, to a degree depending on the local thermal history. The specific volume shrinkage due to structural relaxation can be mistaken for material loss due to evaporation. Unlike evaporation, however, local density change can be reversed by post annealing. All of these effects must be taken into account to adequately describe the final morphology and optical properties of single and multiple-pass mitigation protocols. We have investigated, experimentally and theoretically, the significance of such densification on residual stress and under what circumstances it can compete with evaporation in determining the ultimate post treatment surface shape. In general, understanding final surface configurations requires taking all these factors including local structural relaxation densification, and therefore the thermal history, into account. We find that surface depressions due to densification can dominate surface morphology in the non-evaporative regime when peak temperatures are below 2100K

Structural and ligand binding analyses of the periplasmic sensor domain of RsbU in Chlamydia trachomatis support a role in TCA cycle regulation

Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/154297/1/mmi14401-sup-0001-Supinfo.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/154297/2/mmi14401_am.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/154297/3/mmi14401.pd

An Assessment of Molecular Dynamic Force Fields for Silica for Use in Simulating Laser Damage Mitigation

We compare force fields (FF's) that have been used in molecular dynamic (MD) simulations of silica in order to assess their applicability for use in simulating IR-laser damage mitigation. Although pairwise FF?s obtained by fitting quantum mechanical calculations such as the BKS and CHIK potentials have been shown to reproduce many of the properties of silica including the stability of silica polymorphs and the densification of the liquid, we show that melting temperatures and fictive temperatures are much too high. Softer empirical force fields give liquid and glass properties at experimental temperatures but may not predict all properties important to laser mitigation experiments

Wikipedia as informal self-education for clinical decision-making in medical practice

Background For almost any topic, a Wikipedia page will appear among the first ten items of a search online. Wikipedia is also a site whose quality and reliability has been called into question. Methods In this paper, we aim to discuss medical practitioners’ use of Wikipedia, what this consists of and what it might be. We consider the context and history of Wikipedia before discussing the relationship between Wikipedia and the medical profession. In so doing, we will consider Wikipedia as a means of informal self-education and the extent to which it might inform clinical decision-making. We compare with the existing literature results from our two small-scale empirical studies of Wikipedia and clinical decision-making. Results Notwithstanding issues over quality and reliability, Wikipedia’s rules on verifiability are such that its articles are very heavily referenced, and this is just as true of health-related articles. The Cochrane/Wikipedia Initiative in improving the quality and reliability of medical and health pages in Wikipedia is significant in increasing reliability. Our respondents largely concurred with the results from earlier studies on the use of Wikipedia by medical practitioners. Conclusion Perhaps the very doubt over Wikipedia’s accuracy is its greatest strength as a means of informal education of doctors. That medical and health articles on Wikipedia can be so fully referenced and still be doubted is arguably a good thing and one whose effects may be spread into other, more trusted, publications. Hence, one might envisage a future where no one source is taken automatically on trust. Keywords Wikipedia, informal education, continued professional development, medical education

Antidepressants during and after Menopausal Transition: A Systematic Review and Meta-Analysis

To assess the therapeutic benefits of antidepressants in depressive women during and after menopausal transition, PubMed, Cochrane Library, EMBASE and Science Direct were systematically searched from inception to February 1, 2020 for randomized controlled trials examining antidepressants compared to placebo. Primary outcome was change in depressive symptom severity, while secondary outcomes were rates of response/remission rates and dropout/discontinuation due to adverse events. Seven trials involving 1,676 participants (mean age = 52.6 years) showed significant improvement in depressive symptoms (k = 7, Hedges’ g = 0.44, 95% confidence interval (CI) = 0.32 to 0.57, p < 0.001) relative to that in controls. Furthermore, response (k = 3, odds ratio (OR) = 2.53, 95% CI = 1.24 to 5.15, p = 0.01) and remission (k = 3, OR = 1.84, 95% CI = 1.32 to 2.57, p < 0.001) rates were significantly higher in antidepressant-treated groups compared to those with controls. Although dropout rates did not differ between antidepressant and control groups (k = 6, OR = 0.93, 95% CI = 0.70 to 1.26, p = 0.68), the rate of discontinuation due to adverse events was significantly higher in antidepressant-treated groups (k = 6, OR = 0.55, 95% CI = 0.35 to 0.86, p = 0.01). Subgroup analysis indicated that antidepressants were also efficacious for depressive symptoms in those without diagnosis of MDD. The results demonstrated that antidepressants were efficacious for women with depressive syndromes during and after menopausal transition but associated with a higher risk of discontinuation due to adverse events

Mutations in Zebrafish lrp2 Result in Adult-Onset Ocular Pathogenesis That Models Myopia and Other Risk Factors for Glaucoma

The glaucomas comprise a genetically complex group of retinal neuropathies that typically occur late in life and are characterized by progressive pathology of the optic nerve head and degeneration of retinal ganglion cells. In addition to age and family history, other significant risk factors for glaucoma include elevated intraocular pressure (IOP) and myopia. The complexity of glaucoma has made it difficult to model in animals, but also challenging to identify responsible genes. We have used zebrafish to identify a genetically complex, recessive mutant that shows risk factors for glaucoma including adult onset severe myopia, elevated IOP, and progressive retinal ganglion cell pathology. Positional cloning and analysis of a non-complementing allele indicated that non-sense mutations in low density lipoprotein receptor-related protein 2 (lrp2) underlie the mutant phenotype. Lrp2, previously named Megalin, functions as an endocytic receptor for a wide-variety of bioactive molecules including Sonic hedgehog, Bone morphogenic protein 4, retinol-binding protein, vitamin D-binding protein, and apolipoprotein E, among others. Detailed phenotype analyses indicated that as lrp2 mutant fish age, many individuals—but not all—develop high IOP and severe myopia with obviously enlarged eye globes. This results in retinal stretch and prolonged stress to retinal ganglion cells, which ultimately show signs of pathogenesis. Our studies implicate altered Lrp2-mediated homeostasis as important for myopia and other risk factors for glaucoma in humans and establish a new genetic model for further study of phenotypes associated with this disease