The yeast, , is an increasingly common cause of systemic fungal infections among the immune compromised, including premature infants. Adhesion to host surfaces is an important step in pathogenesis, but this process has not been extensively studied in this organism. A microfluidics assay was developed to test the ability of to adhere to immobilized host extracellular matrix proteins under physiologic fluid shear conditions. Growth in mammalian tissue culture media at 37°C for 3-6 hours led to induction of an adhesive phenotype at shear forces of 1-5 dynes/cm in some isolates of Glutamic acid, proline and calcium appeared to be the minimally necessary requirements for increased adhesion in these assays. To determine whether genes homologous to the gene family of were important for the adhesive phenotype, expression of 5 homologous genes were quantified using qPCR under conditions leading to increased adhesion. () and showed increased expression compared to control yeast. The extent of adhesion was variable among different isolates, and linear regression identified expression of but not to have a strong positive correlation with adhesion. A homozygous deletion strain was deficient in adhesion, whereas expression of in resulted in increased adhesion. Together, these data provide strong evidence that CpAls7 aids in the adherence of to extracellular matrix under shear forces and support its previously reported role in virulence.
Exposures to perinatal, familial, social, and physical environmental stimuli can have substantial effects on human development. We aimed to generate a single measure that capture’s the complex network structure of the environment (i.e., exposome) using multi-level data (participant’s report, parent report and geocoded measures) of environmental exposures (primarily from the psychosocial environment) in two independent adolescent cohorts: The Adolescent Brain Cognitive Development Study (ABCD Study, N = 11,235, mean age 10.9 years, 47.7% females) and an age- and sex-matched sample from the Philadelphia Neurodevelopmental Cohort (PNC, N = 4,993). We conducted a series of data-driven iterative factor analyses and bifactor modeling in the ABCD Study, reducing dimensionality from 348 variables tapping to environment to six orthogonal exposome subfactors and a general (adverse) exposome factor. The general exposome factor was associated with overall psychopathology (B = 0.28, 95%CI 0.26-0.3) and key health-related outcomes: obesity (OR = 1.4, 95%CI 1.3-1.5) and advanced pubertal development (OR = 1.3, 95%CI 1.2-1.5). A similar approach in PNC reduced dimensionality of environment from 29 variables to four exposome subfactors and a general exposome factor. PNC analyses yielded consistent associations of the general exposome factor with psychopathology (B = 0.15, 95%CI 0.13-0.17), obesity (OR = 1.4, 95%CI 1.3-1.6) and advanced pubertal development (OR = 1.3, 95%CI 1-1.6). In both cohorts, inclusion of exposome factors greatly increased variance explained in overall psychopathology compared to models relying solely on demographics and parental education (from <4% to > 38% in ABCD; from <4% to > 18.5% in PNC). Findings suggest that a general exposome factor capturing multi-level environmental exposures can be derived and can consistently explain variance in youth’s mental and general health.
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