Faculty Bibliography

Presenilin 1 (PS1), a polytopic membrane protein, has a critical role in the trafficking and proteolysis of a selected set of transmembrane proteins. The vast majority of individuals affected with early onset familial Alzheimer's disease (FAD) carry missense mutations in PS1. Two studies have suggested that loss of PS1 function, or expression of FAD-linked PS1 variants, compromises the mammalian unfolded-protein response (UPR), and we sought to evaluate the potential role of PS1 in the mammalian UPR. Here we show that that neither the endoplasmic reticulum (ER) stress-induced accumulation of BiP and CHOP messenger RNA, nor the activation of ER stress kinases IRE1alpha and PERK, is compromised in cells lacking both PS1 and PS2 or in cells expressing FAD-linked PS1 variants. We also show that the levels of BiP are not significantly different in the brains of individuals with sporadic Alzheimer's disease or PS1-mediated FAD to levels in control brains. Our findings provide evidence that neither loss of PS1 and PS2 function, nor expression of PS1 variants, has a discernable impact on ER stress-mediated induction of the several established 'readouts' of the UPR pathway.

No studies have demonstrated a direct relationship between pregnancy and rib fracture. A case of spontaneous rib fracture in the third trimester presents the opportunity to examine factors unique to pregnancy that may predispose the patient to stress fractures of the lower ribs. A 28-year old woman in week 31 of her pregnancy presented with the chief complaint of acute onset of right upper quadrant pain. A chest radiograph demonstrated a minimally displaced fracture of the right 10th rib. During pregnancy, the enlarging uterus causes certain opposing muscular forces to act on the ribs, making them more susceptible to fracture after minimal trauma or after repeated stresses such as a chronic cough