Summary Stem cells in many tissues sustain themselves by entering a quiescent state to avoid genomic insults and to prevent exhaustion caused by excessive proliferation. In the mammary gland, the identity and characteristics of quiescent epithelial stem cells are not clear. Here, we identify a quiescent mammary epithelial cell population expressing high levels of Bcl11b and located at the interface between luminal and basal cells. Bcl11bhigh cells are enriched for cells that can regenerate mammary glands in secondary transplants. Loss of Bcl11b leads to a Cdkn2a-dpendent exhaustion of ductal epithelium and loss of epithelial cell regenerative capacity. Gain and loss of function studies show that Bcl11b induces cells to enter the G0 phase of the cell cycle and become quiescent. Taken together, these results suggest that Bcl11b acts as a central intrinsic regulator of mammary epithelial stem cell quiescence and exhaustion, and is necessary for long-term maintenance of the mammary gland.

Veins are exposed to the arterial environment during two common surgical procedures, creation of vein grafts and arteriovenous fistulae (AVF). In both cases veins adapt to the arterial environment that is characterized by different hemodynamic conditions and increased oxygen tension compared to the venous environment. Successful venous adaptation to the arterial environment is critical for long term success of the vein graft or AVF, and in both cases is generally characterized by venous dilation and wall thickening. However, AVF are exposed to a high flow, high shear stress, low pressure arterial environment, and adapt mainly via outward dilation with less intimal thickening. Vein grafts are exposed to a moderate flow, moderate shear stress, high pressure arterial environment, and adapt mainly via increased wall thickening with less outward dilation. We review the data that describe these differences, as well as the underlying molecular mechanisms that mediate these processes. Despite extensive research, there are few differences in the molecular pathways that regulate cell proliferation and migration or matrix synthesis, secretion, or degradation currently identified between vein graft adaptation and AVF maturation that account for the different types of venous adaptation to arterial environments.

Wettability of polyethylene terephthalate) (PET) surfaces was greatly improved by the applications of gaseous glow discharge in argon, nitrogen, and air. The optimum glow discharge condition for producing a durable and wettable PET surface was concluded to be in nitrogen at a power level of 30 W. The most drastic improvement in wettability was achieved during the initial 2 min of exposure. Both moisture regain and water retention values of the substrates were significantly improved by these treatments. Surface morphology of the treated fiber surfaces, revealed by SEM, indicated both etching and redeposition of some previously detached molecules on the surfaces. The treated surfaces were found to undergo some changes as was evident by increasing contact angles and increasing weights up to 3 weeks after the treatments. Major changes occurred within 6 days and were more obvious with shorter exposure periods. Possible oxidation and rearrangement of the surface molecules were suggested to contribute to the decreased wettability and increased weight of the treated materials during storage. The final stabilized surfaces still demonstrated superior wetting characteristics.

Alzheimer's disease (AD) is a progressive neurodegenerative disease observed with aging that represents the most common form of dementia. To date, therapies targeting end-stage disease plaques, tangles, or inflammation have limited efficacy. Therefore, we set out to identify a potential earlier targetable phenotype. Utilizing a mouse model of AD and human fetal cells harboring mutant amyloid precursor protein, we show cell intrinsic neural precursor cell (NPC) dysfunction precedes widespread inflammation and amyloid plaque pathology, making it the earliest defect in the evolution of the disease. We demonstrate that reversing impaired NPC self-renewal via genetic reduction of USP16, a histone modifier and critical physiological antagonist of the Polycomb Repressor Complex 1, can prevent downstream cognitive defects and decrease astrogliosis in vivo. Reduction of USP16 led to decreased expression of senescence gene Cdkn2a and mitigated aberrant regulation of the BMP pathway, a previously unknown function of USP16. Thus, we reveal USP16 as a novel target in an AD model that can both ameliorate the NPC defect and rescue memory and learning through its regulation of both Cdkn2a and BMP signaling.'

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