Human T-cell leukemia virus type 1 (HTLV-1) infection is linked to the development of adult T-cell leukemia (ATL) and the neuroinflammatory disease HTLV-1 associated myelopathy/tropical spastic paraparesis (HAM/TSP). The HTLV-1 Tax protein functions as a potent viral oncogene that constitutively activates the NF-κB transcription factor to transform T cells; however, the underlying mechanisms remain obscure. Here, using next-generation RNA sequencing we identified the IL-25 receptor subunit IL-17RB as an aberrantly overexpressed gene in HTLV-1 immortalized T cells. Tax induced the expression of IL-17RB in an IκB kinase (IKK) and NF-κB-dependent manner. Remarkably, Tax activation of the canonical NF-κB pathway in T cells was critically dependent on IL-17RB expression. IL-17RB and IL-25 were required for HTLV-1-induced immortalization of primary T cells, and the constitutive NF-κB activation and survival of HTLV-1 transformed T cells. IL-9 was identified as an important downstream target gene of the IL-17RB pathway that drives the proliferation of HTLV-1 transformed cells. Furthermore, IL-17RB was overexpressed in leukemic cells from a subset of ATL patients and also regulated NF-κB activation in some, but not all, Tax-negative ATL cell lines. Together, our results support a model whereby Tax instigates an IL-17RB-NF-κB feed-forward autocrine loop that is obligatory for HTLV-1 leukemogenesis.
Download full-text PDF |
Source |
---|---|
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4207800 | PMC |
http://dx.doi.org/10.1371/journal.ppat.1004418 | DOI Listing |
J Environ Manage
December 2024
Key Laboratory for Utility of Environment-Friendly Composites and Biomass in Universities of Gansu Province, Lanzhou, 730000, China; Key Laboratory of Environment-Friendly Composites of the State Ethnic Affairs Commission, Lanzhou, 730000, China. Electronic address:
The treatment of biodegradable plastics through composting has garnered increasing attention. This study aimed to investigate the effects of Biochar FN1 bacteria and ferrous sulfate on nitrogen retention, greenhouse gas emissions, and degradable plastics during composting and to elucidate their synergistic mechanisms on microbial communities. Compared with the control, applying biochar-loaded FN1 bacteria composites combined with Ferrous sulfate (SGC) markedly accelerated organic matter degradation and reduced cumulative CO and NH emissions.
View Article and Find Full Text PDFJ Environ Manage
December 2024
Shaanxi Key Laboratory of Environmental Engineering, Key Laboratory of Northwest Water Resource, Environment and Ecology, MOE, Xi'an University of Architecture and Technology, Xi'an, 710055, China; School of Environmental and Municipal Engineering, Xi'an University of Architecture and Technology, Xi'an, 710055, China. Electronic address:
NO-N transformation, the vital biological process, determines nitrogen removal and retention in aquatic environment. Suspended sediment (SPS) ubiquitous in freshwater ecosystems can accelerate the transitions from aerobic to anoxic states, inevitably impacting NO-N transformation. To elaborate on the microbial mechanism by which SPS content affected NO-N transformation, we explored nitrogen removal and retention, microbial communities, co-occurrence networks, and electron transfer behavior under different SPS content during the aerobic-anoxic transition.
View Article and Find Full Text PDFJ Environ Manage
December 2024
Nuclear and Engineering Nonproliferation Division, Los Alamos National Laboratory, Los Alamos, NM, 87545, USA.
Monitoring nuclear reactor operations is vital for nuclear safeguards as it ensures that reactors are in compliance with international legal agreements. Validating nuclear facilities and activities, including potential clandestine activities, is currently accomplished by using remotely sensed data from satellites and aircrafts and on-site sampling. However, these techniques are temporally-limited as sampling and interpretation of environmental releases frequently involve labor-intensive, on-site collections.
View Article and Find Full Text PDFJ Environ Manage
December 2024
Institute of Urology, Zhong Da Hospital, Southeast University School of Medicine, Nanjing, China. Electronic address:
Titanium dioxide nanoparticles (TiO NPs) are among the most prevalent nanomaterials utilized in industrial and medical fields. However, their impact on spermatogenesis and male fertility remains insufficiently characterized. This study addresses the reproductive toxicity of TiO NPs and elucidates the underlying molecular mechanisms involved.
View Article and Find Full Text PDFCancer Treat Rev
December 2024
SOLTI Cancer Research Group, Barcelona, Spain; Statistics Unit, Vall d'Hebron Institute of Oncology (VHIO), Barcelona, Spain. Electronic address:
Introduction: Antibody-drug conjugates (ADCs) trastuzumab-deruxtecan (T-DXd) and sacituzumab-govitecan (SG) provided significant progression-free survival (PFS) and overall survival (OS) improvements over chemotherapy (CT) in pretreated hormone receptor-positive (HR+) and triple-negative (TN)/HER2-low metastatic breast cancer (MBC). However, no direct comparison between the two exists, nor with the more recent datopotamab-deruxtecan (Dato-DXd).
Methods: We conducted a network meta-analysis (NMA) to compare efficacy and safety of T-DXd and SG in CT-pretreated HR+ and TN/HER2-low MBC and assess their benefit over standard CT, exploring also a comparison with Dato-DXd.
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!