Publications by authors named "Jason Hustedt"

4 Publications

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Characterizing Family Contextual Factors and Relationships with Child Behavior and Sleep Across the Buffering Toxic Stress Consortium.

Prev Sci 2021 May 26. Epub 2021 May 26.

Department of Psychology, University of Denver, Denver, CO, USA.

The Buffering Toxic Stress (BTS) consortium included six sites in locations that varied widely in racial/ethnic composition and population density. Each site tested a promising parent-child intervention designed to supplement Early Head Start (EHS) services and prevent "toxic stress." To better understand family risk in a large and diverse EHS sample, studies gathered extensive data on family risk exposure, including demographic risk factors (single mother, unemployed, less than high school education or its equivalent, and neighborhood safety), income-to-needs ratio, household resource constraints, perceptions of economic hardship and pressure, caregiver mental health, and caregiver-reported dysfunctional parent-child interactions. Results presented here for all six sites offer context for the more targeted studies in this special issue. Average levels of family characteristics and child behavior varied by site. We also characterized associations between family characteristics, observer-rated child temperament, and child outcomes (i.e., caregiver-reported child behavior problems and behavioral sleep quality), controlling for child age; these relationships were similar across sites. Demographic risk and caregiver mental health problems were positively associated with child behavior problems, with low income-to-needs ratio and increased financial strain relating to behavioral problems in infancy and toddlerhood. Caregiver mental health problems, financial strain, and social and affect temperament dimensions were related to increased behavioral sleep problems. Dysfunctional parent-child interactions and household resource constraints did not demonstrate statistically significant associations. Findings suggest helpful targets to increase effectiveness of parent-child interventions in early childhood on behavior and sleep outcomes.
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http://dx.doi.org/10.1007/s11121-021-01243-6DOI Listing
May 2021

EARLY HEAD START FAMILIES' EXPERIENCES WITH STRESS: UNDERSTANDING VARIATIONS WITHIN A HIGH-RISK, LOW-INCOME SAMPLE.

Infant Ment Health J 2017 09 26;38(5):602-616. Epub 2017 Aug 26.

University of Delaware.

The federal Early Head Start program provides a relevant context to examine families' experiences with stress since participants qualify on the basis of poverty and risk. Building on previous research that has shown variations in demographic and economic risks even among qualifying families, we examined possible variations in families' perceptions of stress. Family, parent, and child data were collected to measure stressors and risk across a variety of domains in families' everyday lives, primarily from self-report measures, but also including assay results from child cortisol samples. A cluster analysis was employed to examine potential differences among groups of Early Head Start families. Results showed that there were three distinct subgroups of families, with some families perceiving that they experienced very high levels of stress while others perceived much lower levels of stress despite also experiencing poverty and heightened risk. These findings have important implications in that they provide an initial step toward distinguishing differences in low-income families' experiences with stress, thereby informing interventions focused on promoting responsive caregiving as a possible mechanism to buffer the effects of family and social stressors on young children.
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http://dx.doi.org/10.1002/imhj.21667DOI Listing
September 2017

Direct observation of dynamic mechanical regulation of DNA condensation by environmental stimuli.

Angew Chem Int Ed Engl 2014 Sep 21;53(40):10631-5. Epub 2014 Aug 21.

Fischell Department of Bioengineering, University of Maryland, College Park, MD 20742 (USA).

Gene delivery is a promising way to treat hereditary diseases and cancer; however, there is little understanding of DNA:carrier complex mechanical properties, which may be critical for the protection and release of nucleic acids. We applied optical tweezers to directly measure single-molecule mechanical properties of DNA condensed using 19-mer poly-L-lysine (PLL) or branched histidine-lysine (HK) peptides. Force-extension profiles indicate that both carriers condense DNA actively, showing force plateaus during stretching and relaxation cycles. As the environment such as carrier concentration, pH, and the presence of zinc ions changes, DNA:HK complexes showed dynamically regulated mechanical properties at multiple force levels. The fundamental knowledge from this study can be applied to design a mechanically tailored complex which may enhance transfection efficiency by controlling the stability of the complex temporally and spatially.
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http://dx.doi.org/10.1002/anie.201403499DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5517097PMC
September 2014

Enhanced silencing and stabilization of siRNA polyplexes by histidine-mediated hydrogen bonds.

Biomaterials 2014 Jan 22;35(2):846-55. Epub 2013 Oct 22.

Department of Pathology, University of Maryland Baltimore, MSTF Building, 10 South Pine Street, Baltimore, MD 21201, United States; Department of Chemical and Biomolecular Engineering, University of Maryland, College Park, MD 20742, United States. Electronic address:

Branched peptides containing histidines and lysines (HK) have been shown to be effective carriers for DNA and siRNA. We anticipate that elucidation of the binding mechanism of HK with siRNA will provide greater insight into the self-assembly and delivery of the HK:siRNA polyplex. Non-covalent bonds between histidine residues and nucleic acids may enhance the stability of siRNA polyplexes. We first compared the polyplex biophysical properties of a branched HK with those of branched asparagine-lysine peptide (NK). Consistent with siRNA silencing experiments, gel electrophoresis demonstrated that the HK siRNA polyplex maintained its integrity with prolonged incubation in serum, whereas siRNA in complex with NK was degraded in a time-dependent manner. Isothermal titration calorimetry of various peptides binding to siRNA at pH 7.3 showed that branched polylysine, interacted with siRNA was initially endothermic, whereas branched HK exhibited an exothermic reaction at initial binding. The exothermic interaction indicates formation of non-ionic bonds between histidines and siRNA; purely electrostatic interaction is entropy-driven and endothermic. To investigate the type of non-ionic bond, we studied the protonation state of imidazole rings of a selectively (15)N labeled branched HK by heteronuclear single quantum coherence NMR. The peak of Nδ1-H tautomers of imidazole shifted downfield (in the direction of deprotonation) by 0.5-1.0 ppm with addition of siRNA, providing direct evidence that histidines formed hydrogen bonds with siRNA at physiological pH. These results establish that histidine-rich peptides form hydrogen bonds with siRNA, thereby enhancing the stability and biological activity of the polyplex in vitro and in vivo.
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http://dx.doi.org/10.1016/j.biomaterials.2013.10.019DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3920840PMC
January 2014
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