The nuclear factor-B (NF-B) transcription factors play important roles in cancer development by preventing apoptosis and facilitating the tumor cell growth. However, the precise mechanisms by which NF-B is constitutively activated in specific cancer cells remain largely unknown. In our current study, we now report that NF-B-inducing kinase (NIK) is overexpressed at the pretranslational IntroductionThe nuclear factor-B (NF-B) transcription factors are known to regulate the expression of a wide range of genes involved in development, immune responses, apoptosis, and carcinogenesis as dimers of the REL family members, RelA, RelB, c-Rel, p50, and p52. 1 The p50 and p52 proteins are generated by proteasomemediated processing of their precursors, p105 and p100, respectively. In resting cells, Rel proteins are sequestered in the cytoplasm through their interactions with the ankyrin repeats of the inhibitory proteins IB␣, -␤, and -⑀, as well as the precursor proteins p105 and p100. On stimulation, signals converge at the multiprotein IB kinase (IKK) complex, which is composed of 2 catalytic subunits, IKK1/␣ and IKK2/␤, and the scaffolding proteins, NF-B essential modulator (NEMO, also known as IKK␥) and ELKS. 2 Phosphorylation by the IKK complex of specific serine residues on the IB or precursor proteins results in their poly-ubiquitination and proteasome-dependent degradation or processing. 2 Released NF-B then translocates to the nucleus and regulates expression of target genes.NF-B signaling pathways are largely classified as either canonical or noncanonical based on the stimuli and targets of the IKK complex. 2 Canonical activation is induced by stimuli, such as tumor necrosis factor-␣ (TNF␣) and interleukin-1␤, and involves NEMO-and IKK2/␤-dependent phosphorylation and the subsequent degradation of IB proteins. Noncanonical NF-B pathways are activated after the stimulation of a range of TNF receptor family members, such as B-cell activating factor belonging to the TNF family (BAFF) receptor, lymphotoxin-␤ receptor, Fn14 and CD40, and direct NF-B-inducing kinase (NIK)-and IKK1/␣-dependent phosphorylation and subsequent processing of p100, leading to activation of NF-B complexes containing RelB. 2,3 Of note in this context, the noncanonical pathways operate in a delayed fashion and are sensitive to protein synthesis inhibition. 4,5 Compared with the mechanisms underlying the transduction of ligand-induced signaling to NF-B activation, much less is known about how NF-B is constitutively activated in a variety of cancer cells. 6 Constitutively high NF-B activity has typically been demonstrated in human hematopoietic cancer cells, including adult T-cell leukemia (ATL), Hodgkin lymphoma, and multiple myeloma cells. 7,8 We have previously reported the aberrant expression of p52 in ATL and Hodgkin Reed-Sternberg (H-RS) cells that do not express viral regulatory proteins, such as Tax of the human T-cell leukemia virus or latent membrane protein 1 of the Epstein-Barr virus. 9,10 In addition, IKK activation in ATL and H-RS c...

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Four of the nine sigmodontine tribes have species that serve as reservoirs of rodent-borne hantaviruses (RBO-HV), few have been studied in any depth. Several viruses have been associated with human cases of hantavirus pulmonary syndrome often through peridomestic exposure. Jabora (JABV) and Juquitiba (JUQV), harbored by Akodon montensis and Oligoryzomys nigripes, respectively, are endemic and sympatric in the Reserva Natural de Bosque Mbaracayú (RNBM), Paraguay, a protected area of the Interior Atlantic Forest. Rodent communities were surveyed along a 30 km stretch of the RNBM in eight vegetation classifications (Low, High, Bamboo, Riparian and Liana Forests, Bamboo Understory, Cerrado, and Meadow/Grasslands). We collected 417 rodents from which 11 species were identified; Akodon montensis was the predominant species (72%; 95%CI: 64.7%-76.3%), followed by Hylaeamys megacephalus (15% (11.2%-18.2%)) and Oligoryzomys nigripes (9% (6.6%-12.4%)). We examined the statistical associations among habitat (vegetation class) type, rodent species diversity, population structure (age, sex, and weight), and prevalence of RBO-HV antibody and/or viral RNA (Ab/RNA) or characteristic Leishmania tail lesions. Ab/RNA positive rodents were not observed in Cerrado and Low Forest. A. montensis had an overall Ab/RNA prevalence of 7.7% (4.9%-11.3%) and O. nigripes had an overall prevalence of 8.6% (1.8%-23.1%). For A. montensis, the odds of being Ab/RNA positive in High Forest was 3.73 times of the other habitats combined. There was no significant difference among age classes in the proportion of Ab/RNA positive rodents overall (p = 0.66), however, all 11 RNA-positive individuals were adult. Sex and habitat had independent prognostic value for hantaviral Ab/RNA in the study population; age, presence of tail scar/lesion (19% of the rodents) and weight did not. Adjusting for habitat, female rodents had less risk of becoming infected. Importantly, these data suggest habitat preferences of two sympatric rodent reservoirs for two endemic hantaviruses and the importance of including habitat in models of species diversity and habitat fragmentation.

Small mammal communities in the Neotropics are composed largely of sigmodontine rodents. However, many questions regarding these communities remain unanswered, especially those pertaining to fine-scale sympatry and habitat selection. To address this, we examined sigmodontine community structure and vegetation in the western margin of the Upper Paraná Atlantic Forest and the southwestern-most extent of the Cerrado (CE) (an extensive South American savanna ecoregion) of Paraguay. Vegetation classifications were derived from satellite imagery combined with maps based on extensive ground-based surveys. The three most abundant species (Akodon montensis, Hylaeamys megacephalus, and Oligoryzomys nigripes) were found most often in microsympatry with conspecifics, and were negatively associated with other species. Akodon montensis was associated with high forest (HF), and H. megacephalus with bamboo understory (BU), whereas O. nigripes did not exhibit a habitat preference. The first two species’ distributions within the landscape were found to be driven primarily by habitat selection, and O. nigripes by a behavioral response (avoidance) to the presence of the other two species. Moreover, habitat influences whether or not a particular species associates with, or avoids, conspecifics or other species.