HNRNPK maintains epidermal progenitor function through transcription of proliferation genes and degrading differentiation promoting mRNAs.

Maintenance of high-turnover tissues such as the epidermis requires a balance between stem cell proliferation and differentiation. The molecular mechanisms governing this process are an area of investigation. Here we show that HNRNPK, a multifunctional protein, is necessary to prevent premature differentiation and sustains the proliferative capacity of epidermal stem and progenitor cells. To prevent premature differentiation of progenitor cells, HNRNPK is necessary for DDX6 to bind a subset of mRNAs that code for transcription factors that promote differentiation. Upon binding, these mRNAs such as GRHL3, KLF4, and ZNF750 are degraded through the mRNA degradation pathway, which prevents premature differentiation. To sustain the proliferative capacity of the epidermis, HNRNPK is necessary for RNA Polymerase II binding to proliferation/self-renewal genes such as MYC, CYR61, FGFBP1, EGFR, and cyclins to promote their expression. Our study establishes a prominent role for HNRNPK in maintaining adult tissue self-renewal through both transcriptional and post-transcriptional mechanisms

The effect of Matmo typhoon on mixed zone between the Yellow sea and Bohai sea

The results of remote sensing, buoy and profile based on measured data indicate that the wind speed, H-1/3 and salinity increased, sea surface temperature declined, and wind direction changed greatly during the transit of the Matmo typhoon on July 25. It was found that the typhoon transport the Yellow Sea Cold Water Mass into the the Yellow and Bohai seas mixed zone

Extremes and limit theorems for difference of chi-type processes

Let {ζm,k(κ)(t), t ≥ 0}, κ > 0 be random processes defined as the differences of two independent stationary chi-type processes with m and k degrees of freedom. In this paper we derive the asymptotics of ℙ{supt∈[0,T]ζm,k(κ)(t) > u }, u → ∞ under some assumptions on the covariance structures of the underlying Gaussian processes. Further, we establish a Berman sojourn limit theorem and a Gumbel limit result

Comparison inequalities for order statistics of Gaussian arrays

Normal comparison lemma and Slepian’s inequality are essential tools for the analysis of extremes of Gaussian processes. In this paper we show that the Normal comparison lemma for Gaussian vectors can be extended to order statistics of Gaussian arrays. Our applications include the derivation of mixed Gumbel limit laws for the order statistics of stationary Gaussian processes and the investigation of lower tail behavior of order statistics of self-similar Gaussian processes

Extremes of order statistics of stationary processes

Let be independent copies of a stationary process . For given positive constants , define the set of th conjunctions with the th largest order statistics of . In numerous applications such as brain mapping and digital communication systems, of interest is the approximation of the probability that the set of conjunctions is not empty. Imposing the Albin's conditions on , in this paper we obtain an exact asymptotic expansion of this probability as tends to infinity. Furthermore, we establish the tail asymptotics of the supremum of the order statistics processes of skew-Gaussian processes and a Gumbel limit theorem for the minimum order statistics of stationary Gaussian processes

Moving Beyond Dichotomies: How the Intersection of Race, Class and Place Impacts High School Graduation Rates for African American Students

Over thirty years ago, William Julius Wilson declared that class trumped race as the more significant determinant of social mobility and economic opportunity. Despite the acclaim and scrutiny for Wilson\u27s work, the United States has grown increasingly divided by intersecting factors of race, class and other demographic factors such as place (Massey, 2007). These divisions are especially evident in the public education system. We analyze how race, class and place interact to predict high school graduation rates in a national sample of schools and students. Results confirm that a singular focus on race, class, or locale is insufficient to explain high school graduation rates. However, a more contextualized focus on the interactions between multiple determinants of inequality (e.g. race, class and place) can yield a more nuanced understanding of the indicators driving educational inequalities. Scholars and practitioners need to focus on the manner in which multiple positionalities influence the academic achievement of African American children and young adults

Mesenchymal stem cells and immunomodulation: current status and future prospects

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Reduced EGFR signaling enhances cartilage destruction in a mouse osteoarthritis model

Osteoarthritis (OA) is a degenerative joint disease and a major cause of pain and disability in older adults. We have previously identified epidermal growth factor receptor (EGFR) signaling as an important regulator of cartilage matrix degradation during epiphyseal cartilage development. To study its function in OA progression, we performed surgical destabilization of the medial meniscus (DMM) to induce OA in two mouse models with reduced EGFR activity, one with genetic modification (Egfr Wa5/+ mice) and the other one with pharmacological inhibition (gefitinib treatment). Histological analyses and scoring at 3 months post-surgery revealed increased cartilage destruction and accelerated OA progression in both mouse models. TUNEL staining demonstrated that EGFR signaling protects chondrocytes from OA-induced apoptosis, which was further confirmed in primary chondrocyte culture. Immunohistochemistry showed increased aggrecan degradation in these mouse models, which coincides with elevated amounts of ADAMTS5 and matrix metalloproteinase 13 (MMP13), the principle proteinases responsible for aggrecan degradation, in the articular cartilage after DMM surgery. Furthermore, hypoxia-inducible factor 2α (HIF2α), a critical catabolic transcription factor stimulating MMP13 expression during OA, was also upregulated in mice with reduced EGFR signaling. Taken together, our findings demonstrate a primarily protective role of EGFR during OA progression by regulating chondrocyte survival and cartilage degradation

The critical role of the epidermal growth factor receptor in endochondral ossification

Loss of epidermal growth factor receptor (EGFR) activity in mice alters growth plate development, impairs endochondral ossification, and retards growth. However, the detailed mechanism by which EGFR regulates endochondral bone formation is unknown. Here, we show that administration of an EGFR-specific small-molecule inhibitor, gefitinib, into 1-month-old rats for 7 days produced profound defects in long bone growth plate cartilage characterized by epiphyseal growth plate thickening and massive accumulation of hypertrophic chondrocytes. Immunostaining demonstrated that growth plate chondrocytes express EGFR, but endothelial cells and osteoclasts show little to no expression. Gefitinib did not alter chondrocyte proliferation or differentiation and vascular invasion into the hypertrophic cartilage. However, osteoclast recruitment and differentiation at the chondro-osseous junction were attenuated owing to decreased RANKL expression in the growth plate. Moreover, gefitinib treatment inhibited the expression of matrix metalloproteinases (MMP-9, -13, and -14), increased the amount of collagen fibrils, and decreased degraded extracellular matrix products in the growth plate. In vitro, the EGFR ligand transforming growth factor α (TGF-α) strongly stimulated RANKL and MMPs expression and suppressed osteoprotegerin (OPG) expression in primary chondrocytes. In addition, a mouse model of cartilage-specific EGFR inactivation exhibited a similar phenotype of hypertrophic cartilage enlargement. Together our data demonstrate that EGFR signaling supports osteoclastogenesis at the chondro-osseous junction and promotes chondrogenic expression of MMPs in the growth plate. Therefore, we conclude that EGFR signaling plays an essential role in the remodeling of growth plate cartilage extracellular matrix into bone during endochondral ossification. © 2011 American Society for Bone and Mineral Research