A hallmark of aged mesenchymal stem/progenitor cells (MSCs) in bone marrow is the pivot of differentiation potency from osteoblast to adipocyte coupled with a decrease in self-renewal capacity. However, how these cellular events are orchestrated in the aging progress is not fully understood. In this study, we have used molecular and genetic approaches to investigate the role of forkhead box P1 (FOXP1) in transcriptional control of MSC senescence. In bone marrow MSCs, FOXP1 expression levels declined with age in an inverse manner with those of the senescence marker p16INK4A. Conditional depletion of Foxp1 in bone marrow MSCs led to premature aging characteristics, including increased bone marrow adiposity, decreased bone mass, and impaired MSC self-renewal capacity in mice. At the molecular level, FOXP1 regulated cell-fate choice of MSCs through interactions with the CEBPβ/δ complex and recombination signal binding protein for immunoglobulin κ J region (RBPjκ), key modulators of adipogenesis and osteogenesis, respectively. Loss of p16INK4A in Foxp1-deficient MSCs partially rescued the defects in replication capacity and bone mass accrual. Promoter occupancy analyses revealed that FOXP1 directly represses transcription of p16INK4A. These results indicate that FOXP1 attenuates MSC senescence by orchestrating their cell-fate switch while maintaining their replicative capacity in a dose- and age-dependent manner.

Abnormal inflammatory bias in the maternal-fetal interface leads to reproductive failure in mammals. Placental exosomes are involved in maternal-fetal communication during pregnancy. However, whether the placenta or fetus is involved in regulating the balance of uterine local inflammation through exosomes remains unclear, and the mechanism must be further explored. Here we demonstrated that placenta-specific exosomes are abundant in the peripheral blood of dairy cows during early pregnancy and selectively load miRNAs, such as bta-miR-499. In vitro, placental exosome-derived bta-miR-499 inhibits the activation of NF-κB via the Lin28B/let-7 axis, thus repressing LPS-induced inflammation in bovine endometrial epithelial (BEND) cells. Subsequently, inhibition of mmu-miR-499 leads to an impaired balance of inflammation at the maternal-fetal interface in vivo, resulting in an increased risk of pregnancy failure due to placental loss and fetal growth restriction. Thus, our data demonstrate that placental exosomal miR-499 may be a critical immune regulator in the regulation of the inflammation balance at the maternal-fetal interface in the early gestation of dairy cows and other mammals.

We report a systematic study of time-resolved and power-dependent photoresponse in high-efficiency germanium quantum dot photodetectors (Ge-QD PDs), with internal quantum efficiencies greater than 100 over a broad wavelength, reverse bias, and incident power range. Turn-on and turn-off response times (τ on and τ off) are shown to depend on series resistance, bias, optical power, and thickness (W QD) of the Ge-QD layer, with measured τ off values down to ∼40 ns. Two different photoconduction regimes are observed at low and high reverse bias, with a transition around -3 V. A transient current overshoot phenomenon is also observed, which depends on bias and illumination power. © 2012 American Institute of Physics

We report on the noise analysis of high performance germanium quantum dot (Ge QD) photodetectors with responsivity up to $2 A/W and internal quantum efficiency up to $400%, over the 400-1100 nm wavelength range and at a reverse bias of À10 V. Photolithography was performed to define variable active-area devices that show suppressed dark current, leading to a higher signal-to-noise ratio, up to 10 5 , and specific detectivity D Ã ' 6 Â 10 12 cm Hz 1=2 W À1. These figures of merit suggest Ge QDs as a promising alternative material for high-performance photodetectors working in the visible to near-infrared spectral range.