RNAi-Mediated c-Rel Silencing Leads to Apoptosis of B Cell Tumor Cells and Suppresses Antigenic Immune Response In Vivo

c-Rel is a member of the Rel/NF-κB transcription factor family and is predominantly expressed in lymphoid and myeloid cells, playing a critical role in lymphocyte proliferation and survival. Persistent activation of the c-Rel signal transduction pathway is associated with allergies, inflammation, autoimmune diseases, and a variety of human malignancies. To explore the potential of targeting c-Rel as a therapeutic agent for these disorders, we designed a small interfering RNA (siRNA) to silence c-Rel expression in vitro and in vivo. C-Rel-siRNA expression via a retroviral vector in a B cell tumor cell line leads to growth arrest and apoptosis of the tumor cells. Silencing c-Rel in primary B cells in vitro compromises their proliferative and survival response to CD40 activation signals, similar to the impaired response of c-Rel knockout B cells. Most important, in vivo silencing of c-Rel results in significant impairment in T cell-mediated immune responses to antigenic stimulation. Our study thus validates the efficacy of c-Rel-siRNA, and suggests the development of siRNA-based therapy, as well as small molecular inhibitors for the treatment of B cell tumors as well as autoimmune diseases

Late Pleistocene echimyid rodents (Rodentia, Hystricognathi) from northern Brazil

ABSTRACT Echimyidae (spiny rats, tree rats and the coypu) is the most diverse family of extant South American hystricognath rodents (caviomorphs). Today, they live in tropical forests (Amazonian, coastal and Andean forests), occasionally in more open xeric habitats in the Cerrado and Caatinga of northern South America, and open areas across the southern portion of the continent (Myocastor). The Quaternary fossil record of this family remains poorly studied. Here, we describe the fossil echimyids found in karst deposits from southern Tocantins, northern Brazil. The analyzed specimens are assigned to Thrichomys sp., Makalata cf. didelphoides and Proechimys sp. This is the first time that a fossil of Makalata is reported. The Pleistocene record of echimyids from this area is represented by fragmentary remains, which hinders their determination at specific levels. The data reported here contributes to the understanding of the ancient diversity of rodents of this region, evidenced until now in other groups, such as the artiodactyls, cingulates, carnivores, marsupials, and squamate reptiles