ABSTRACT
[This corrects the article DOI: 10.3389/fcimb.2023.1289359.].
ABSTRACT
Cytolethal distending toxins (CDTs) are intracellular-acting bacterial genotoxins generated by a diverse group of mucocutaneous human pathogens. CDTs must successfully bind to the plasma membrane of host cells in order to exert their modulatory effects. Maximal toxin activity requires all three toxin subunits, CdtA, CdtB, and CdtC, which, based primarily on high-resolution structural data, are believed to preassemble into a tripartite complex necessary for toxin activity. However, biologically active toxin has not been experimentally demonstrated to require assembly of the three subunits into a heterotrimer. Here, we experimentally compared concentration-dependent subunit interactions and toxin cellular activity of the Campylobacter jejuni CDT (Cj-CDT). Co-immunoprecipitation and dialysis retention experiments provided evidence for the presence of heterotrimeric toxin complexes, but only at concentrations of Cj-CdtA, Cj-CdtB, and Cj-CdtC several logs higher than required for Cj-CDT-mediated arrest of the host cell cycle at the G2/M interface, which is triggered by the endonuclease activity associated with the catalytic Cj-CdtB subunit. Microscale thermophoresis confirmed that Cj-CDT subunit interactions occur with low affinity. Collectively, our data suggest that at the lowest concentrations of toxin sufficient for arrest of cell cycle progression, mixtures of Cj-CdtA, Cj-CdtB, and Cj-CdtC consist primarily of non-interacting, subunit monomers. The lack of congruence between toxin tripartite structure and cellular activity suggests that the widely accepted model that CDTs principally intoxicate host cells as preassembled heterotrimeric structures should be revisited.
Subject(s)
Bacterial Toxins , Campylobacter jejuni , Humans , Bacterial Toxins/metabolism , Campylobacter jejuni/metabolism , Cell CycleABSTRACT
The uterine lining (endometrium) regenerates repeatedly over the life span as part of its normal physiology. Substantial portions of the endometrium are shed during childbirth (parturition) and, in some species, menstruation, but the tissue is rapidly rebuilt without scarring, rendering it a powerful model of regeneration in mammals. Nonetheless, following some assaults, including medical procedures and infections, the endometrium fails to regenerate and instead forms scars that may interfere with normal endometrial function and contribute to infertility. Thus, the endometrium provides an exceptional platform to answer a central question of regenerative medicine: Why do some systems regenerate while others scar? Here, we review our current understanding of diverse endometrial disruption events in humans, nonhuman primates, and rodents, and the associated mechanisms of regenerative success and failure. Elucidating the determinants of these disparate repair processes promises insights into fundamental mechanisms of mammalian regeneration with substantial implications for reproductive health.
Subject(s)
Endometrium , Uterus , Female , Animals , Humans , Endometrium/pathology , Endometrium/physiology , Uterus/pathology , Uterus/physiology , Fibrosis , MammalsABSTRACT
The authors report the case of a 4-year-old male child with a background of Down's syndrome (Trisomy 21) and a definitive repair of a balanced complete atrioventricular septal defect (CAVSD) at 3 months of age who experienced acute pulmonary oedema at high altitude (2000 m) while on holiday with his parents. The authors discuss and review the literature on the effect of altitude on children with Down's syndrome and postoperative CAVSD repair. The authors propose that further research is needed into this area in this specific group of patients, so advice can be given to families prior to flying or travelling.
Subject(s)
Altitude , Down Syndrome/complications , Hypoxia/etiology , Mitral Valve Insufficiency/complications , Mitral Valve Insufficiency/surgery , Postoperative Complications/etiology , Acute Disease , Child, Preschool , Heart Septal Defects , Humans , MaleABSTRACT
UNLABELLED: Craniopagus twinning is a rare form of the already uncommon entity of conjoint twins. With advances in medical technology and expertise, future attempts at surgical separation of these increasingly complex cases are likely to occur. Despite this, medical literature on the anesthetic management of these cases is sparse. The following case report details the anesthetic management and planning leading to and including the 5-dy separation of 11-mo-old craniopagus twins. The report emphasizes the importance of teamwork, communication, and advanced planning required in cases such as this. IMPLICATIONS: The following case report documents the anesthetic planning and management leading to and including a 5-day separation of twins joined at the head. This case report also details the difficulties encountered during the unique combination of a rarely performed procedure and a long operating time.