Maternal dietary deficiencies in folic acid or choline reduce primary neuron viability after exposure to hypoxia through increased levels of apoptosis.

: Ischemic stroke is the leading cause of death and disability globally. By addressing modifiable risk factors, particularly nutrition, the prevalence of stroke and its dire consequences can be mitigated. One-carbon (1C) metabolism is a critical biosynthetic process that is involved in neural tube closure, DNA synthesis, plasticity, and cellular proliferation.

A maternal-effect variant causes nuclear and cytoplasmic abnormalities in oocytes, as well as failure of epigenetic reprogramming and zygotic genome activation in embryos.

Maternal inactivation of genes encoding components of the subcortical maternal complex (SCMC) and its associated member, PADI6, generally results in early embryo lethality. In humans, SCMC gene variants were found in the healthy mothers of children affected by multilocus imprinting disturbances (MLID). However, how the SCMC controls the DNA methylation required to regulate imprinting remains poorly defined.

Maternal dietary deficiencies in folic acid or choline worsen stroke outcomes in adult male and female mouse offspring.

Maternal one-carbon metabolism plays an important role in early life programming. There is a well-established connection between the fetal environment and the health status of the offspring. However, there is a knowledge gap on how maternal nutrition impacts stroke outcomes in offspring.

GDNF-RET signaling and EGR1 form a positive feedback loop that promotes tamoxifen resistance via cyclin D1.

Background: Rearranged during transfection (RET) tyrosine kinase signaling has been previously implicated in endocrine resistant breast cancer, however the mechanism by which this signaling cascade promotes resistance is currently not well described. We recently reported that glial cell-derived neurotrophic factor (GDNF)-RET signaling appears to promote a positive feedback loop with the transcription factor early growth response 1 (EGR1). Here we investigate the mechanism behind this feedback loop and test the hypothesis that GDNF-RET signaling forms a regulatory loop with EGR1 to upregulate cyclin D1 (CCND1) transcription, leading to cell cycle progression and tamoxifen resistance.

Delayed puberty, gonadotropin abnormalities and subfertility in male Padi2/Padi4 double knockout mice.

Background: Peptidylarginine deiminase enzymes (PADs) convert arginine residues to citrulline in a process called citrullination or deimination. Recently, two PADs, PAD2 and PAD4, have been linked to hormone signaling in vitro and the goal of this study was to test for links between PAD2/PAD4 and hormone signaling in vivo.

Methods: Preliminary analysis of Padi2 and Padi4 single knockout (SKO) mice did not find any overt reproductive defects and we predicted that this was likely due to genetic compensation.