Roles for Transcription Factors Sp1, NF-kappa B, IRF3, and IRF7 in Expression of the Human IFNL4 Gene

The expression of a biologically active human IFN4 depends on the presence of a frameshift deletion polymorphism within the first exon of the interferon lambda 4 (IFNL4) gene. In this report, we use the lung carcinoma-derived cell line, A549, which is genetically viable to express a functional IFN4, to address transcriptional requirements of the IFNL4 gene. We show that the GC-rich DNA-binding transcription factor (TF) specificity protein 1 (Sp1) is recruited to the IFNL4 promoter and has a role in induction of gene expression upon stimulation with viral RNA mimic poly(I:C). By using RNAi and overexpression strategies, we also show key roles in IFNL4 gene expression for the virus-inducible TFs, nuclear factor kappa-light-chain-enhancer of activated B cells (NF-B), IFN regulatory factor 3 (IRF3), and IRF7. Interestingly, we also observe that overexpression of IFN4 influences IFNL4 promoter activity, which may further be dependent on the retinoic acid-inducible gene-I (RIG-I)-like receptor pathway. Together, our work for the first time reports on the functional characterization of the human IFNL4 promoter.

Role of Monoubiquitylation on the Control of IκBα Degradation and NF-κB Activity

9 p.

Characterization of Navassa National Wildlife Refuge: A preliminary report for NF-06-05 (NOAA ship "Nancy Foster", April 18-30, 2006)

Navassa is a small, undeveloped island in the Windward Passage between Jamaica and Haiti. It was designated a National Wildlife Refuge under the jurisdiction of the U.S. Fish and Wildlife Service in 1999, but the remote location makes management and enforcement challenging, and the area is regularly fished by artisanal fishermen from Haiti. In April 2006, the NOAA Center for Coastal Fisheries and Habitat Research conducted a research cruise to Navassa. The cruise produced the first high-resolution multibeam bathymetry for the area, which will facilitate habitat mapping and assist in refuge management. A major emphasis of the cruise was to study the impact of Haitian fishing gear on benthic habitats and fish communities; however, in 10 days on station only one small boat was observed with five fishermen and seven traps. Fifteen monitoring stations were established to characterize fish and benthic communities along the deep (28-34 m) shelf, as these areas have been largely unstudied by previous cruises. The fish communities included numerous squirrelfishes, triggerfishes, and parrotfishes. Snappers and grouper were also present but no small individuals were observed. Similarly, conch surveys indicated the population was in low abundance and was heavily skewed towards adults. Analysis of the benthic photoquadrats is currently underway. Other cruise activities included installation of a temperature logger network, sample collection for stable isotope analyses to examine trophic structure, and drop camera surveys to ground-truth habitat maps and overhead imagery. (PDF contains 58 pages)

Cruise Report: Summer 2008 Ecological Assessment of Stellwagen Bank National Marine Sanctuary NOAA Ship NANCY FOSTER NF-08-09-CCEHBR (June 14-June 21, 2008)

Summary: This cruise report is a summary of a field survey conducted within the Stellwagen Bank National Marine Sanctuary (SBNMS), located between Cape Cod and Cape Ann at the mouth of Massachusetts Bay. The survey was conducted June 14 – June 21, 2008 on NOAA Ship NANCY FOSTER Cruise NF-08-09-CCEHBR. Multiple indicators of ecological condition and human dimensions were sampled synoptically at each of 30 stations throughout SBNMS using a random probabilistic sampling design. Samples were collected for the analysis of benthic community structure and composition; concentrations of chemical contaminants (metals, pesticides, PAHs, PCBs, PBDEs) in sediments and target demersal biota; nutrient and chlorophyll levels in the water column; and other basic habitat characteristics such as depth, salinity, temperature, dissolved oxygen, turbidity, pH, sediment grain size, and organic carbon content. In addition to the fish samples that were collected for analysis of chemical contaminants relative to human-health consumption limits, other human-dimension indicators were sampled as well including presence or absence of fishing gear, vessels, surface trash, marine mammals, and noxious sediment odors. The overall purpose of the survey was to collect data to assess the status of ecosystem condition and potential stressor impacts throughout SBNMS, based on these various indicators and corresponding management thresholds, and to provide this information as a baseline for determining how such conditions may be changing with time. While sample analysis is still ongoing a few preliminary results and observations are reported here. A final report will be completed once all data have been processed. The results are anticipated to be of value in supporting goals of the SBNMS and National Marine Sanctuary Program aimed at the characterization, protection, and management of sanctuary resources (pursuant to the National Marine Sanctuary Reauthorization Act) as well as a new priority of NCCOS and NOAA to apply Ecosystem Based approaches to the Management of coastal resources (EBM) through Integrated Ecosystem Assessments (IEAs) conducted in various coastal regions of the U.S. including the Northeast Atlantic continental shelf. This was a multi-disciplinary partnership effort made possible by scientists from the following organizations:  NOAA, National Ocean Service (NOS), National Centers for Coastal Ocean Science (NCCOS), Center for Coastal Environmental Health and Biomolecular Research (CCEHBR), Charleston, SC.  U.S. Environmental Protection Agency (EPA), National Health and Environmental Effects Research Laboratory (NHEERL), Atlantic Ecology Division (GED), Narragansett, RI.  U.S. Environmental Protection Agency (EPA), National Health and Environmental Effects Research Laboratory (NHEERL), Gulf Ecology Division (GED), Gulf Breeze, FL.  U.S. Geological Survey (USGS), National Wetlands Research Center, Gulf Breeze Project Office, Gulf Breeze, FL.  NOAA, Office of Marine and Aviation Operations (OMAO), NOAA ship Nancy Foster. (31pp) (PDF contains 58 pages)

Cruise Report: Spring 2007 Survey of ecological conditions along the continental shelf off Florida from Anclote Key to West Palm Beach NOAA Ship NANCY FOSTER NF-07-08-NCCOS (May 15 - May 28, 2007)

This cruise report is a summary of a field survey conducted in coastal-ocean waters off Florida from Anclote Key to West Palm Beach and from approximately 1 nautical mile (nm) offshore seaward to the shelf break (100 m). The survey was conducted May 15 - May 28, 2007 on NOAA Ship NANCY FOSTER Cruise NF-07-08-NCCOS. Multiple indicators of ecological condition were sampled synoptically at each of 50 stations throughout the region including 10 stations within the Florida Keys National Marine Sanctuary (FKNMS) using a random probabilistic sampling design. Samples were collected for the analysis of benthic community structure and composition; concentrations of chemical contaminants (metals, pesticides, PAHs, PCBs, PBDEs) in sediments and target demersal biota; nutrient and chlorophyll levels in the water column; and other basic habitat characteristics such as depth, salinity, temperature, dissolved oxygen, pH, sediment grain size, and organic carbon content. The overall purpose of the survey was to collect data to assess the status of ecological condition in coastal-ocean waters of the region, based on these various indicators, and to provide this information as a baseline for determining how environmental conditions may be changing with time. The results will be of value in helping to broaden our understanding of the status of ecological resources and their controlling factors, including impacts of potential ecosystem stressors, in such strategic coastal areas. (PDF contains 34 pages

Cruise Report: Spring 2006 Survey of ecological conditions of the U.S. Middle Atlantic Bight NOAA Ship Nancy Foster NF-06-06-NCCOS (May 12 - May 21, 2006)

This cruise report is a summary of a field survey conducted in coastal-ocean waters of the Mid-Atlantic Bight from Nags Head, North Carolina to Cape Cod, Massachusetts and from approximately 1 nautical mile (nm) of shore seaward to the shelf break (100 m). The survey was conducted May 12 - May 21, 2006 on NOAA Ship NANCY FOSTER Cruise NF-06-06-NCCOS. Multiple indicators of ecological condition were sampled synoptically at each of 49 stations throughout the region using a random probabilistic sampling design. Samples were collected for the analysis of benthic community structure and composition; concentrations of chemical contaminants (metals, pesticides, PAHs, PCBs, PBDEs) in sediments and target demersal biota; nutrient and chlorophyll levels in the water column; and other basic habitat characteristics such as depth, salinity, temperature, dissolved oxygen, pH, sediment grain size, and organic carbon content. The overall purpose of the survey was to collect data to assess the status of ecological condition in coastal-ocean waters of the region, based on these various indicators, and to provide this information as a baseline for determining how environmental conditions may be changing with time. The results will be of value in helping to broaden our understanding of the status of ecological resources and their controlling factors, including impacts of potential ecosystem stressors, in such strategic coastal areas. (18pp.) (PDF contains 24 pages)

Regulación de la transcripción de los genes SND1 (Homo sapiens) y SNDp102 (Rattus norvegicus)

167 p. : il., graf.

Function of microRNA-146a and NF-κB in physiologic and pathologic hematopoiesis

During inflammation and infection, hematopoietic stem and progenitor cells (HSPCs) are stimulated to proliferate and differentiate into mature immune cells, especially of the myeloid lineage. MicroRNA-146a (miR-146a) is a critical negative regulator of inflammation. Deletion of the gene encoding miR-146a—expressed in all blood cell types—produces effects that appear as dysregulated inflammatory hematopoiesis, leading to a decline in the number and quality of hematopoietic stem cells (HSCs), excessive myeloproliferation, and, ultimately, to exhaustion of the HSCs and hematopoietic neoplasms. Six-week-old deleted mice are normal, with no effect on cell numbers, but by 4 months bone marrow hypercellularity can be seen, and by 8 months marrow exhaustion is becoming evident. The ability of HSCs to replenish the entire hematopoietic repertoire in a myelo-ablated mouse also declines precipitously as miR-146a-deficient mice age. In the absence of miR-146a, LPS-mediated serial inflammatory stimulation accelerates the effects of aging. This chronic inflammatory stress on HSCs in deleted mice involves a molecular axis consisting of upregulation of the signaling protein TRAF6 leading to excessive activity of the transcription factor NF-κB and overproduction of the cytokine IL-6. At the cellular level, transplant studies show that the defects are attributable to both an intrinsic problem in the miR-146a-deficient HSCs and extrinsic effects of miR-146a-deficient lymphocytes and non-hematopoietic cells. This study has identified a microRNA, miR-146a, to be a critical regulator of HSC homeostasis during chronic inflammatory challenge in mice and has provided a molecular connection between chronic inflammation and the development of bone marrow failure and myeloproliferative neoplasms. This may have implications for human hematopoietic malignancies, such as myelodysplastic syndrome, which frequently displays downregulated miR-146a expression.

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Nivel educativo: Grado. Duración (en horas): De 41 a 50 horas

Key to the larvae of the genera of the sub-family Orthocladiinae from Larvae and Pupae of midges of the sub-family Orthocladiinae of the fauna of the USSR. [Translation from: Larvae and pupae of midges of the subfamily Orthocladiinae of the fauna of the USSR (Diptera, Chironomidae = Tendipedidae) (ed. Pankratova V.Ya.), 51-55. Leningrad, Nauka, 1970. ]

A key to the larvae of the genera of the sub-family Orthocladiinae from Larvae and Pupae of midges of the sub-family Orthocladiinae. Parts of the key refer to the rest of the publication which is not included in this partial translation.

The family of chironomids or midges - Chironomidae. Keys to larvae and pupae [Translation from: Guide to the freshwater invertebrates of the European area of the USSR (Plankton and benthos) (ed. L. A. Kutikova and Ya. I. Starobogatov), p.371-431. Leningrad, Gidrometeoizdat, 1977]

The translation of this section of the larger publication ”Opredelitel' presnovodnykh bespozvonochnykh evropeiskoi chasti SSSR. (Plankton i bentos)” provides identification keys to the larvae and pupae of chironomids that occur in the Soviet Union. The morphology of the larvae of Chironomidae is described in the introductory part.

Efeito de ExoU na ativação de NF-κB e na secreção de IL-8 por células humanas infectadas por Pseudomonas aeruginosa

ExoU, uma citotoxina produzida pelo patógeno oportunista Pseudomonas aeruginosa e translocada para o citossol de células hospedeiras via sistema de secreção do tipo III, é associada à gravidade de infecções agudas. Estudos anteriores realizados em nosso laboratório relataram a potente atividade pró-inflamatória de ExoU, responsável por um intenso recrutamento de neutrófilos para o sítio de infecção. No presente trabalho, o efeito de ExoU na modulação da ativação do fator transcricional NF-κB e na regulação da expressão e da secreção da quimiocina para neutrófilos IL-8 foi avaliado em culturas de células epiteliais respiratórias e endoteliais humanas infectadas com a cepa PA103 de P. aeruginosa (produtora de ExoU) ou com a mutante deletada no gene exoU, PA103κexoU. Análises por RT-PCR semi-quantitativo mostraram que a infecção pela cepa produtora de ExoU levou ao aumento dos níveis de mRNA de IL-8, enquanto ensaios de alteração da mobilidade eletroforética (EMSA), supershift e com gene repórter mostraram que ExoU induziu a translocação nuclear do heterodímero transativador p65/p50 de NF-κB e a ativação da transcrição de genes dependente deste fator transcricional. Adicionalmente, o tratamento das culturas celulares com um inibidor de NF-κB antes da infecção bacteriana reduziu significativamente os níveis de mRNA de IL-8 e da secreção desta quimiocina. Em conjunto, estes resultados mostram que ExoU ativa NF-κB e, consequentemente, estimula a expressão e a secreção de IL-8 por células epiteliais respiratórias e células endoteliais infectadas com P. aeruginosa

Differential activity of GSK-3 isoforms regulates NF-kappa B and TRAIL- or TNF alpha induced apoptosis in pancreatic cancer cells

While TRAIL is a promising anticancer agent due to its ability to selectively induce apoptosis in neoplastic cells, many tumors, including pancreatic ductal adenocarcinoma (PDA), display intrinsic resistance, highlighting the need for TRAIL-sensitizing agents. Here we report that TRAIL-induced apoptosis in PDA cell lines is enhanced by pharmacological inhibition of glycogen synthase kinase-3 (GSK-3) or by shRNA-mediated depletion of either GSK-3 alpha or GSK-3 beta. In contrast, depletion of GSK-3 beta, but not GSK-3 alpha, sensitized PDA cell lines to TNF alpha-induced cell death. Further experiments demonstrated that TNF alpha-stimulated I kappa B alpha phosphorylation and degradation as well as p65 nuclear translocation were normal in GSK-3 beta-deficient MEFs. Nonetheless, inhibition of GSK-3 beta function in MEFs or PDA cell lines impaired the expression of the NF-kappa B target genes Bcl-xL and cIAP2, but not I kappa B alpha. Significantly, the expression of Bcl-xL and cIAP2 could be reestablished by expression of GSK-3 beta targeted to the nucleus but not GSK-3 beta targeted to the cytoplasm, suggesting that GSK-3 beta regulates NF-kappa B function within the nucleus. Consistent with this notion, chromatin immunoprecipitation demonstrated that GSK-3 inhibition resulted in either decreased p65 binding to the promoter of BIR3, which encodes cIAP2, or increased p50 binding as well as recruitment of SIRT1 and HDAC3 to the promoter of BCL2L1, which encodes Bcl-xL. Importantly, depletion of Bcl-xL but not cIAP2, mimicked the sensitizing effect of GSK-3 inhibition on TRAIL-induced apoptosis, whereas Bcl-xL overexpression ameliorated the sensitization by GSK-3 inhibition. These results not only suggest that GSK-3 beta overexpression and nuclear localization contribute to TNF alpha and TRAIL resistance via anti-apoptotic NF-kappa B genes such as Bcl-xL, but also provide a rationale for further exploration of GSK-3 inhibitors combined with TRAIL for the treatment of PDA.

Double proximity effect in lateral S-NF-S junctions

We investigate planar Josephson junctions where the intermediate spacer between the two superconductors is an hybrid structure made by a normal metal and a ferromagnet. The different behaviors of the S-N-S junctions with thicknesses of 50 nm in both Cu and Nb layers, and S-N/F-S junctions with 10 nm of Co, 50 nm of Cu and 50 nm of Nb are studied. In this way, we analyze the influence of the ferromagnetic exchange interaction on the proximity effect. A dramatic supression of the josephson critical current of the Nb-(Cu/Co)-Nb junctions is observed. We believe that the reason for this is due to the length scale of the superconducting correlations of the electrons and holes of the weak link is larger than the thickness of Cu/Co bilayer.