University of Medicine and Dentistry of New Jersey

About: University of Medicine and Dentistry of New Jersey is a based out in . It is known for research contribution in the topics: Population & Poison control. The organization has 14634 authors who have published 19610 publications receiving 1041794 citations.

Dual role of TFIIH in DNA excision repair and in transcription by RNA polymerase II

Abstract: THE RNA polymerase II general transcription factor TFIIH is composed of several polypeptides. The observation that the largest subunit of TFIIH is the excision-repair protein XPB/ERCC3 (ref. 1), a helicase implicated in the human DNA-repair disorders xeroderma pigmentosum (XP) and Cockayne's syndrome2,3, suggests a functional link between transcription and DNA repair4,5. To understand the connection between these two cellular processes, we have extensively purified and functionally analysed TFIIH. We find that TFIIH has a dual role, being required for basal transcription of class II genes and for participation in DNA-excision repair. TFIIH is shown to complement three different cell extracts deficient in excision repair: XPB/ERCC3, XPC and XPD/ ERCC2. The complementation of XPB and XPD is a consequence of ERCC3 and ERCC2 being integral subunits of TFIIH, whereas complementation of XPC is due to an association of this polypeptide with TFIIH. We found that the general transcription factor IIE negatively modulates the helicase activity of TFIIH through a direct interaction between TFIIE and the ERCC3 subunit of TFIIH.

Mesenchymal stem cells: a new strategy for immunosuppression and tissue repair.

Abstract: Mesenchymal stem cells (MSCs) have great potential for treating various diseases, especially those related to tissue damage involving immune reactions. Various studies have demonstrated that MSCs are strongly immunosuppressive in vitro and in vivo. Our recent studies have shown that un-stimulated MSCs are indeed incapable of immunosuppression; they become potently immunosuppressive upon stimulation with the supernatant of activated lymphocytes, or with combinations of IFN-gamma with TNF-alpha, IL-1alpha or IL-1beta. This observation revealed that under certain circumstances, inflammatory cytokines can actually become immunosuppressive. We showed that there is a species variation in the mechanisms of MSC-mediated immunosuppression: immunosuppression by cytokine-primed mouse MSCs is mediated by nitric oxide (NO), whereas immunosuppression by cytokine-primed human MSCs is executed through indoleamine 2, 3-dioxygenase (IDO). Additionally, upon stimulation with the inflammatory cytokines, both mouse and human MSCs secrete several leukocyte chemokines that apparently serve to attract immune cells into the proximity with MSCs, where NO or IDO is predicted to be most active. Therefore, immunosuppression by inflammatory cytokine-stimulated MSCs occurs via the concerted action of chemokines and immune-inhibitory NO or IDO produced by MSCs. Thus, our results provide novel information about the mechanisms of MSC-mediated immunosuppression and for better application of MSCs in treating tissue injuries induced by immune responses.

Regulation of Translation in Eukaryotic Systems

Abstract: The striking differences between prokaryotes and eukaryotes in cell structure, in the mechanism of initiation of translation, and in the structure of messenger RNAs dictate strikingly different approaches to regulating translation. The first section of this review gives a thumbnail comparison of translational regulation in prokaryotic and eukaryotic systems. The remaining sections expand the discussion of regulatory mechanisms that operate during the initiation phase of protein synthesis in eukaryotes .

Veto-Like Activity of Mesenchymal Stem Cells: Functional Discrimination Between Cellular Responses to Alloantigens and Recall Antigens

Abstract: Trans-differentiation of stem cells shows promise for use in tissue repair medicine. Although poorly defined, mesenchymal stem cells (MSC) appear useful for applications in repair medicine. Despite the low frequency of MSC, they are relatively easy to expand. The expression of MHC class II on MSC, however, could deter their use in repair medicine, since these molecules could stimulate an allogeneic host response. This study sought to compare the immune stimulatory and suppressive effects of MSC. Primary human MSC were cultured from bone marrow aspirates and then passaged at least three times before use in assays. Morphologically, MSC were symmetrical; were SH2(+), MHC class II(+), CD45(-), CD44(+), CD31(-), CD14(-), proly-4-hydroxylase(-); and showed normal karyotype patterns and elevated telomerase activities. MSC elicited significant stimulatory responses when cocultured with allogeneic PBMC. Despite the production of different types of growth factors, allogeneic effects of MSC could not be explained by the production of these growth factors. One-way MLR reactions were significantly blunted by third-party MSC. Similar suppression was not observed for responses to three different recall Ags. Based on these functional differences by MSC in responses to allo- and recall Ags, we examined whether MSC could exert veto-like functions. We showed that MSC could blunt the cytotoxic effects of allogeneic-induced effectors to mitogen-activated targets. The results showed that although MSC elicited allogeneic responses in a model that mimics a graft-vs-host reaction, they also exerted veto-like activity, but caused no effect on responses to recall Ags.