Immunoprofiling Correlates of Protection Against SHIV Infection in Adjuvanted HIV-1 Pox-Protein Vaccinated Rhesus Macaques.

Human immunodeficiency virus type 1 (HIV-1) infection remains a major public health threat due to its incurable nature and the lack of a highly efficacious vaccine. The RV144 vaccine trial is the only clinical study to date that demonstrated significant but modest decrease in HIV infection risk. To improve HIV-1 vaccine immunogenicity and efficacy, we recently evaluated pox-protein vaccination using a next generation liposome-based adjuvant, Army Liposomal Formulation adsorbed to aluminum (ALFA), in rhesus monkeys and observed 90% efficacy against limiting dose mucosal SHIV challenge in male animals.

From Cell Death to Regeneration: Rebuilding After Injury.

The ability to regrow lost or damaged tissues is widespread, but highly variable among animals. Understanding this variation remains a challenge in regeneration biology. Numerous studies from to mouse have shown that apoptosis acts as a potent and necessary mechanism in regeneration.

Studying In Vivo Retinal Progenitor Cell Proliferation in Xenopus laevis.

The efficient generation and maintenance of retinal progenitor cells (RPCs) are key goals needed for developing strategies for productive eye repair. Although vertebrate eye development and retinogenesis are well characterized, the mechanisms that can initiate RPC proliferation following injury-induced regrowth and repair remain unknown. This is partly because endogenous RPC proliferation typically occurs during embryogenesis while studies of retinal regeneration have largely utilized adult (or mature) models.

Using the Developmental Eye Regrowth System to Distinguish the Role of Developmental Versus Regenerative Mechanisms.

A longstanding challenge in regeneration biology is to understand the role of developmental mechanisms in restoring lost or damaged tissues and organs. As these body structures were built during embryogenesis, it is not surprising that a number of developmental mechanisms are also active during regeneration. However, it remains unclear whether developmental mechanisms act similarly or differently during regeneration as compared to development.

DNA methylation of NR3c1 in infancy: Associations between maternal caregiving and infant sex.

Caregivers play a critical role in scaffolding infant stress reactivity and regulation, but the mechanisms by which this scaffolding occurs is unclear. Animal models strongly suggest that epigenetic processes, such as DNA methylation, are sensitive to caregiving behaviors and, in turn, offspring stress reactivity. We examined the direct effects of caregiving behaviors on DNA methylation in infants and infant stress reactivity.

Maternal smoking during pregnancy is associated with mitochondrial DNA methylation.

Maternal smoking during pregnancy (MSDP) has detrimental effects on fetal development and on the health of the offspring into adulthood. Energy homeostasis through ATP production via the mitochondria (mt) plays a key role during pregnancy. This study aimed to determine if MSDP resulted in differences in DNA methylation to the placental mitochondrial chromosome at the transcription and replication control region, the D-Loop, and if these differences were also present in an alternate neonatal tissue (foreskin) in an independent birth cohort.

Hydroxymethylation is uniquely distributed within term placenta, and is associated with gene expression.

The conversion of cytosine to 5-methylcystosine (5mC) is an important regulator of gene expression. 5mC may be enzymatically converted to 5-hydroxymethylcytosine (5hmC), with a potentially distinct regulatory function. We sought to investigate these cytosine modifications and their effect on gene expression by parallel processing of genomic DNA using bisulfite and oxidative bisulfite conversion in conjunction with RNA sequencing.

The Contributions of Maternal Sensitivity and Maternal Depressive Symptoms to Epigenetic Processes and Neuroendocrine Functioning.

This study tested whether maternal responsiveness may buffer the child to the effects of maternal depressive symptoms on DNA methylation of NR3C1, 11β-HSD2, and neuroendocrine functioning. DNA was derived from buccal epithelial cells and prestress cortisol was obtained from the saliva of 128 infants. Mothers with depressive symptoms who were more responsive and who engaged in more appropriate touch during face-to-face play had infants with less DNA methylation of NR3C1 and 11β-HSD2 compared to mothers with depressive symptoms who were also insensitive.

Placental epigenetic patterning of glucocorticoid response genes is associated with infant neurodevelopment.

Aim: To determine associations between methylation of NR3C1, HSD11B2, FKBP5 and ADCYAP1R1 and newborn neurobehavioral outcomes.

Methods: In 537 newborns, placental methylation was quantified using bisulfite pyrosequencing. Profiles of neurobehavior were derived via the Neonatal Intensive Care Unit Network Neurobehavioral Scales.

Expression of imprinted genes in placenta is associated with infant neurobehavioral development.

Genomic imprinting disorders often exhibit delayed neurobehavioral development, suggesting this unique mechanism of epigenetic regulation plays a role in mental and neurological health. While major errors in imprinting have been linked to adverse health outcomes, there has been little research conducted on how moderate variability in imprinted gene expression within a population contributes to differences in neurobehavioral outcomes, particularly at birth. Here, we profiled the expression of 108 known and putative imprinted genes in human placenta samples from 615 infants assessed by the Neonatal Intensive Care Unit (NICU) Network Neurobehavioral Scales (NNNS).

Prenatal predictors of infant self-regulation: the contributions of placental DNA methylation of NR3C1 and neuroendocrine activity.

We examined whether placental DNA methylation of the glucocorticoid receptor gene, NR3C1 was associated with self-regulation and neuroendocrine responses to a social stressor in infancy. Placenta samples were obtained at birth and mothers and their infants (n = 128) participated in the still-face paradigm when infants were 5 months old. Infant self-regulation following the still-face episode was coded and pre-stress cortisol and cortisol reactivity was assessed in response to the still-face paradigm.

The Role of Placental 11-Beta Hydroxysteroid Dehydrogenase Type 1 and Type 2 Methylation on Gene Expression and Infant Birth Weight.

Maternal stress has been linked to infant birth weight outcomes, which itself may be associated with health later in life. The placenta acts as a master regulator for the fetal environment, mediating intrauterine exposures to stress through the activity of genes regulating glucocorticoids, including the 11beta-hydroxysteroid dehydrogenase (HSD11B) type 1 and 2 genes, and so we hypothesized that variation in these genes will be associated with infant birth weight. We investigated DNA methylation levels at six sites across the two genes, as well as mRNA expression for each, and the relationship to infant birth weight.