Virulence factor secretion and assembly occurs at spatially restricted foci in some Gram-positive bacteria. Given the essentiality of the general secretion pathway in bacteria and the contribution of virulence factors to disease progression, the foci that coordinate these processes are attractive antimicrobial targets. In this study, we show in Enterococcus faecalis that SecA and Sortase A, required for the attachment of virulence factors to the cell wall, localize to discrete domains near the septum or nascent septal site as the bacteria proceed through the cell cycle. We also demonstrate that cationic human β-defensins interact with E. faecalis at discrete septal foci, and this exposure disrupts sites of localized secretion and sorting. Modification of anionic lipids by multiple peptide resistance factor, a protein that confers antimicrobial peptide resistance by electrostatic repulsion, renders E. faecalis more resistant to killing by defensins and less susceptible to focal targeting by the cationic antimicrobial peptides. These data suggest a paradigm in which focal targeting by antimicrobial peptides is linked to their killing efficiency and to disruption of virulence factor assembly.focal localization | immunofluorescence | microscopy | MprF
Survivors of pediatric acute lymphoblastic leukemia (ALL) are at increased risk for cognitive impairments that disrupt everyday functioning and decrease quality of life. The specific biological mechanisms underlying cognitive impairment following ALL remain largely unclear, but previous studies consistently demonstrate significant white matter pathology. We aimed to extend this literature by examining the organization of the white matter connectome in young patients with a history of ALL treated with chemotherapy only. We applied graph theoretical analysis to diffusion tensor imaging obtained from 31 survivors of ALL age 5-19 years and 39 matched healthy controls. Results indicated significantly lower small-worldness ( p = 0.007) and network clustering coefficient ( p = 0.019), as well as greater cognitive impairment ( p = 0.027) in the ALL group. Regional analysis indicated that clustered connectivity in parietal, frontal, hippocampal, amygdalar, thalamic, and occipital regions was altered in the ALL group. Random forest analysis revealed a model of connectome and demographic variables that could automatically classify survivors of ALL as having cognitive impairment or not (accuracy = 0.89, p < 0.0001). These findings provide further evidence of brain injury in young survivors of ALL, even those without a history of central nervous system (CNS) disease or cranial radiation. Efficiency of local information processing, reorganization of hub connectivity, and cognitive reserve may contribute to cognitive outcome in these children. Certain connectome properties showed U-shaped relationships with cognitive impairment suggesting an optimal range of regional connectivity.
The goal of this study was to evaluate the extent to which training that emphasizes the process of executive function (EF) and self-regulated learning (SRL) would result in increased reading comprehension; we also evaluated interrelationships of EF, SRL, and reading. We report an experiment (N = 75 fourth graders) that contrasted two researcher-implemented conditions (text-based reading [TB] and text-based reading plus executive function [TB+EF]) to a control. We also evaluated relationships among measures of SRL, EF, and reading. Both the TB and TB+EF groups outperformed the control group for proximal text comprehension (where the topic was similar to that covered in training) and background knowledge related to it, but the two researcher-led groups performed similarly. There were no significant differences for less proximal text, and again similar performance for both TB and TB+EF. Correlations among measures were weak in general, although the pattern was similar to that found in the extant literature. The findings speak to the difficulty in separating these components from those of strong instruction more generally. The relationships of these constructs to reading comprehension will likely be enhanced by more sensitive measurement of EF and reading comprehension, particularly where tied to active treatment components.
all patient and tumor factors, adults were associated with less chance of receiving RT (pZ0.002) but not surgery (pZ0.084). The median and 5 year OS of adults continued to be significantly worse than those of pediatrics (p < 0.0001) which could be partially secondary to a lower chance of having RT in adults. Conclusion: Adult patients with PMS had inferior survival as compared to pediatric patients even following propensity matching of all patient and tumor factors. Adults had less odds of receiving RT which could be partially responsible for the poor outcomes. Further studies on adults adopting pediatric treatment regimens are warranted.
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