Notes

Influence associated with bodyweight about the result of pregnancy: A potential cohort study.
tant to multiple drugs, making the development of alternative therapies a priority. Although Mycobacterium tuberculosis is naturally resistant to β-lactam drugs, previous studies have shown sensitivity in strains resistant to classical drug treatment, but we currently lack understanding of the molecular underpinnings behind this phenomenon. We found that genes involved in β-lactam susceptibility are activated after classical drug treatment resulting from tight regulatory links with genes involved in drug resistance. Our study supports the hypothesis that β-lactam susceptibility observed in drug-resistant strains results from the underlying regulatory network of M. tuberculosis, supporting further exploration of the use of β-lactams for tuberculosis treatment.Metaphors are ubiquitous in science and have important implications for how we frame our research objectives as well as how we communicate to the public. This piece focuses on the power of metaphors to shape our attitude and actions toward antimicrobial-resistant bacteria. It begins by emphasizing the pervasiveness of war metaphors to describe bacteria. Then it highlights that, with this type of framing, the solutions follow a similar suit. Ultimately, this metaphorical framing can imply dangerously incorrect solutions to the problem of antibiotic resistance. I propose that we need metaphors that represent the problem of antimicrobial resistance as an ecological and evolutionary issue rather than a single bacterial enemy. I end by offering a new metaphor that does not downplay the healthy fear we should have for antimicrobial-resistant bacteria but acknowledges that living things evolve and self-preserve. This piece is a call to action to use metaphors that express microbes' exceptional resilience rather than our brute strength in combat against them.Maria del Pilar Quintana works on immunology and pathogenesis of severe malaria. In this mSphere of Influence article, she reflects on how the papers "Structural basis for placental malaria mediated by Plasmodium falciparum VAR2CSA" (R. Ma, T. Lian, R. Huang, J. P. Renn, J. D. Petersen, J. Zimmerberg, P. E. Duffy, N. click here H. Tolia, Nat Microbiol 6380-391, 2021, https//doi.org/10.1038/s41564-020-00858-9) and "Cryo-EM reveals the architecture of placental malaria VAR2CSA and provides molecular insight into chondroitin sulfate binding" (K. Wang, R. Dagil, T. Lavsten, S. K. Misra, C. B. Spliid, Y. Wang, T. Gustavsson, D. R. Sandoval, E. E. Vidal-Calvo, S. Choudary, M. O. Agerback, K. Lindorff-Larsen, M. A. Nielsen, T. G. Theander, J. S. Sharp, T. M. Clausen, P. Gourdon, A. Salanti, A. Salanti, Nat Commun 122956, 2021, https//doi.org/10.1038/s41467-021-23254-1) shed light on the precise structural details behind Plasmodium falciparum VAR2CSA binding to chondroitin sulfate A (CSA) in the placenta and how these novel insights have changed the way she will approach her work toward the discovery of new broadly cross-reactive/inhibitory antibodies targeting VAR2CSA.Annie Mayer Bridwell works in the field of tuberculosis pathogenesis from the host perspective. She is fascinated by comorbidities, and in this paper, she reflects on three publications that shaped her model of neutrophil-centric pathology in tuberculosis and type 2 diabetes comorbidity. She explains that "Systems immunology of diabetes-tuberculosis comorbidity reveals signatures of disease complications" (C. A. Prada-Medina, K. F. Fukutani, N. Pavan Kumar, L. Gil-Santana, et al., Sci Rep 71999, 2017, https//doi.org/10.1038/s41598-017-01767-4) led her to consider neutrophils as a central immunological player in comorbid patients. "Type I IFN exacerbates disease in tuberculosis-susceptible mice by inducing neutrophil-mediated lung inflammation and NETosis" (L. Moreira-Teixeira, P. J. Stimpson, E. Stavropoulos, S. Hadebe, et al., Nat Commun 115566, 2020, https//doi.org/10.1038/s41467-020-19412-6) and "Diabetes primes neutrophils to undergo NETosis, which impairs wound healing" (S. L. Wong, M. Demers, K. Martinod, M. Gallant, et al., Nat Med 21815-819, 2015, https//doi.org/10.1038/nm.3887) then shed light on neutrophil extracellular trap (NET) formation as a common pathological feature of dysregulated neutrophils in tuberculosis and diabetes, respectively. Together, these works laid the foundation for Dr. Mayer Bridwell's interest in metabolic regulation of NETosis during TB infection and diabetes comorbidity.The PorX/PorY two-component system in the periodontal pathogen Porphyromonas gingivalis controls the expression of the por genes, encoding a type IX secretion system, and the sigP gene, encoding sigma factor σP. Previous results implied that PorX/PorY and σP formed a regulatory cascade because the PorX/PorY-activated σP enhanced the por genes, including porT, via binding to their promoters. We recently showed that PorX also binds to the por promoters, thus suggesting that an alternative mechanism is required for the PorX/PorY- and σP-governed expression. Here, our in vitro assays show the PorX response regulator binds to the sigP promoter at a sequence shared with the porT promoter and enhances its transcription, mediated by a reconstituted P. gingivalis RNA polymerase holoenzyme. Merely producing σP in trans fails to reverse the porT transcription in a porX mutant, which further argues against the action of the proposed regulatory cascade. An in vitro transcription assay using a reconstituted RNA polymerase- and sigma factor σP build a specific regulatory network to coordinately control transcription of the genes encoding the type IX secretion system, and perhaps also other virulence factors. Results in this study verify that the response regulator PorX stimulates the expression of the genes encoding both σP and the type IX secretion system by binding to their promoters. This study also provides evidence that σP, like the PorX/PorY system, contributes to P. gingivalis virulence in a mouse model.Rediscovered as a potential epigenetic mark, N6-methyladenine DNA modification (6mA) was recently reported to be sensitive to environmental stressors in several multicellular eukaryotes. As 6mA distribution and function differ significantly in multicellular and unicellular organisms, whether and how 6mA in unicellular eukaryotes responds to environmental stress remains elusive. Here, we characterized the dynamic changes of 6mA under starvation in the unicellular model organism Tetrahymena thermophila. Single-molecule, real-time (SMRT) sequencing reveals that DNA 6mA levels in starved cells are significantly reduced, especially symmetric 6mA, compared to those in vegetatively growing cells. Despite a global 6mA reduction, the fraction of asymmetric 6mA with a high methylation level was increased, which might be the driving force for stronger nucleosome positioning in starved cells. Starvation affects expression of many metabolism-related genes, the expression level change of which is associated with the amount of 6mA change, thereby linking 6mA with global transcription and starvation adaptation.
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