Inflammatory response in the dental pulp can alter the collagen matrix formation by dental pulp stem cells and lead to a delay or poor healing of the pulp. This inflammatory response is mediated by cytokines, including interleukin-1β and tumor necrosis factor-α. In this study, it is hypothesized that suppressing the actions of these inflammatory cytokines by knocking down the activity of transcription factor Nuclear Factor–κB will lead to dental pulp stem cell differentiation into odontoblasts and the production of collagen. Here, the role of Nuclear Factor–κB signaling and its reduction was examined during odontogenic behavior in the presence of these cytokines. The results showed a significant increase in Nuclear Factor–κB gene expression and p65 protein expression by interleukin-1β and tumor necrosis factor-α. Nuclear Factor–κB activation in the presence of these cytokines decreased significantly in a dose-dependent manner by a Nuclear Factor–κB inhibitor (MG132) and p65 siRNA. Down-regulation of Nuclear Factor–κB activity also enhanced the gene expression of the odontoblastic markers (dentin sialophosphoprotein, Nestin, and alkaline phosphatase) and displayed an odontoblastic cell morphology indicating the promotion of odontogenic differentiation of dental pulp stem cells. Finally, dental pulp stem cells exposed to reduced Nuclear Factor–κB activity resulted in a significant increase in collagen (I)-α1 expression in the presence of these cytokines. In conclusion, a decrease in Nuclear Factor-κB in dental pulp stem cells in the presence of inflammatory cytokines enhanced odontoblastic differentiation and collagen matrix formation.

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Aberrant activation of endoplasmic reticulum (ER) stress by extrinsic and intrinsic factors contributes to tumorigenesis and resistance to chemotherapies in various cancer types. Our previous studies have shown that the downregulation of PHLPP, a novel family of Ser/Thr protein phosphatases, promotes tumor initiation, and progression. Here we investigated the functional interaction between the ER stress and PHLPP expression in colon cancer. We found that induction of ER stress significantly decreased the expression of PHLPP proteins through a proteasome-dependent mechanism. Knockdown of PHLPP increased the phosphorylation of eIF2α as well as the expression of autophagy-associated genes downstream of the eIF2α/ATF4 signaling pathway. In addition, results from immunoprecipitation experiments showed that PHLPP interacted with eIF2α and this interaction was enhanced by ER stress. Functionally, knockdown of PHLPP improved cell survival under ER stress conditions, whereas overexpression of a degradation-resistant mutant PHLPP1 had the opposite effect. Taken together, our studies identified ER stress as a novel mechanism that triggers PHLPP downregulation; and PHLPP-loss promotes chemoresistance by upregulating the eIF2α/ATF4 signaling axis in colon cancer cells.

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As traffic volumes increase across the nation, transportation projects also increase. With that increase comes the responsibility of expanding the current roadway system while protecting the social and cultural values of each community affected by such expansion. One of the greatest concerns in social and cultural preservation comes from tribal entities. The necessity of advancing the transportation network while ensuring agreement with tribal governments on transportation projects has proved difficult, as recurring issues can lead to difficulty in project execution. However, several transportation agencies have overcome geographical, political, institutional, and cultural barriers to provide transportation networks crossing tribal lands. Across the transportation sector, steps have been taken to alleviate common issues on such projects in the form of programs for the establishment of government-to-government relationships and the implementation of projects. Government-to-government relationships are crucial for the success of transportation improvements, whether state or tribal. Cooperation on transportation issues is affected by complex issues such as tribal sovereignty, intergovernmental agreements, jurisdiction, regional planning efforts, right-of-way acquisition, funding, and maintenance. Similarly, planning, design, and implementation of transportation projects require collaboration among tribal, federal, and state agencies. This paper identifies and categorizes issues surrounding transportation projects affected by–-or of interest to–-tribal communities, and initiatives taken to alleviate issues. It also defines steps for future research in order to refine issues as they are identified in the paper and context-specific strategies implemented to alleviate each issue.

The transportation project environment is complex as project stakeholders most often represent multiple governments because transportation systems are owned and operated by local, state, federal, and tribal governments. Surface transportation projects concerning tribal communities introduce additional complexity to the project environment as an additional layer of institutional relationships and protocols must be recognized. To achieve success on complex transportation projects, a collaborative environment must be established among project stakeholders. One strategy is to use intergovernmental networks for transportation planning and programming to address complex issues within the intergovernmental framework. These intergovernmental networks have been used in states across the nation, and specific cases that resulted from such networks have been documented. This paper investigates the intergovernmental network as a tool for creating a collaborative environment among project stakeholders. The paper also presents best practices by profiling states that have utilized intergovernmental networks for transportation planning as well as success stories resulting from intergovernmental utilization in each state.

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