The role of serendipity in our investigation of embryo implantation.

Serendipity plays a huge role in science, and having a prepared mind that can seize upon a serendipitous observation or occurrence can drive a project forward. This happened in my lab with a project centered on the regulation of trophoblast cell behavior at implantation. We discovered that amino acids regulate the onset of trophoblast motility through the activation of the kinase complex mTORC1, and that this acts as a checkpoint to trophoblast differentiation.

Synthesis and evaluation of 6-arylaminobenzamides as positron emission tomography imaging ligands for the sphingosine-1-phosphate-5 receptor.

The sphingosine-1-phosphate-5 (S1P) receptor is one of the five membrane G protein-coupled receptors that are activated by the lysophospholipid, sphingosine-1-phosphate, resulting in regulation of many cellular processes. S1P receptors are located on oligodendrocytes and are proposed to influence oligodendrocyte physiology. Understanding S1P modulation during processes such as remyelination could have potential applications for demyelinating CNS disorders such as multiple sclerosis (MS).

Assessment of a 6-arylaminobenzamide lead derivative as a potential core scaffold for S1P positron emission tomography radiotracer development.

Sphingosine-1-phosphate-5 receptors (S1P) are predominantly expressed in oligodendrocytes and as a result have been proposed as an important target in Multiple Sclerosis (MS). Selective S1P radiotracers could enable in vivo positron emission tomography (PET) imaging of oligodendrocytes activity. Here we report the synthesis, radiolabelling and first preclinical evaluation of the pharmacokinetics and binding properties of a lead 6-arylaminobenzamide derivative, 6-(mesitylamino)-2-methoxy-3-methylbenzamide (also named as TEFM180), as a potential core scaffold for development of novel S1P PET radiotracers.

Clinical and immunological outcomes after randomized trial of baked milk oral immunotherapy for milk allergy.

BACKGROUNDCow's milk (CM) allergy is the most common food allergy in young children. Treatment with oral immunotherapy (OIT) has shown efficacy, but high rates of adverse reactions. The aim of this study was to determine whether baked milk OIT (BMOIT) could reduce adverse reactions while still inducing desensitization, and to identify immunological correlates of successful BMOIT.

Fetal growth restriction adversely impacts trajectory of hippocampal neurodevelopment and function.

The last pregnancy trimester is critical for fetal brain development but is a vulnerable period if the pregnancy is compromised by fetal growth restriction (FGR). The impact of FGR on the maturational development of neuronal morphology is not known, however, studies in fetal sheep allow longitudinal analysis in a long gestation species. Here we compared hippocampal neuron dendritogenesis in FGR and control fetal sheep at three timepoints equivalent to the third trimester of pregnancy, complemented by magnetic resonance image for brain volume, and electrophysiology for synaptic function.