Mice lacking NF-κB1 exhibit marked DNA damage responses and more severe gastric pathology in response to intraperitoneal tamoxifen administration

Tamoxifen (TAM) has recently been shown to cause acute gastric atrophy and metaplasia in mice. We have previously demonstrated that the outcome of Helicobacter felis infection, which induces similar gastric lesions in mice, is altered by deletion of specific NF-κB subunits. Nfkb1-/- mice developed more severe gastric atrophy than wild-type (WT) mice 6 weeks after H. felis infection. In contrast, Nfkb2-/- mice were protected from this pathology. We therefore hypothesized that gastric lesions induced by TAM may be similarly regulated by signaling via NF-κB subunits. Groups of five female C57BL/6 (WT), Nfkb1-/-, Nfkb2-/- and c-Rel-/- mice were administered 150 mg/kg TAM by IP injection. Seventy-two hours later, gastric corpus tissues were taken for quantitative histological assessment. In addition, groups of six female WT and Nfkb1-/- mice were exposed to 12 Gy γ-irradiation. Gastric epithelial apoptosis was quantified 6 and 48 h after irradiation. TAM induced gastric epithelial lesions in all strains of mice, but this was more severe in Nfkb1-/- mice than in WT mice. Nfkb1-/- mice exhibited more severe parietal cell loss than WT mice, had increased gastric epithelial expression of Ki67 and had an exaggerated gastric epithelial DNA damage response as quantified by γH2AX. To investigate whether the difference in gastric epithelial DNA damage response of Nfkb1-/- mice was unique to TAM-induced DNA damage or a generic consequence of DNA damage, we also assessed gastric epithelial apoptosis following γ-irradiation. Six hours after γ-irradiation, gastric epithelial apoptosis was increased in the gastric corpus and antrum of Nfkb1-/- mice. NF-κB1-mediated signaling regulates the development of gastric mucosal pathology following TAM administration. This is associated with an exaggerated gastric epithelial DNA damage response. This aberrant response appears to reflect a more generic sensitization of the gastric mucosa of Nfkb1-/- mice to DNA damage

State of Florida Division of Administrative Hearings: Fifth Motion to Dismiss

Legal documents related to a dispute between the Sawmill Slough Conservation Club vs. the University of North Floridahttps://digitalcommons.unf.edu/sawmill_history/1021/thumbnail.jp

South Dakota Grasslands, Their Condition and Management

Statewide surveys of South Dakota grasslands have been made in 1940, 1942, and 1946. The stocking rates presented on the map (center pages) were determined from the 1946 survey, based upon the past ten years\u27 actual use-grazing records from representative farms and ranches. The range and pasture condition method of study was introduced into the 1946 resurvey of South Dakota grassland. The condition approach is much more usable by stockmen and agricultural workers alike than former methods of making grassland inventories. The 1946 inventory of range and pasture condition shows South Dakota grasslands are near the peak of productivity. Above-average rainfall is largely responsible for this condition. When the precipitation cycle becomes less favorable and dry years come and they surely will-then only good management of our grasslands can maintain their productivity and prevent the unfavorable conditions of the mid-thirties. Further studies and follow-up surveys will be made periodically to keep abreast of changes in condition and stocking rates for South Dakota grassland

Submicromolar quantification of pyocyanin in complex biological fluids using pad-printed carbon electrodes

Pyocyanin, a toxin produced by Pseudomonas aeruginosa, offers potential as a biomarker for the indirect detection of this bacterium of major importance for infections in burns, woundcare and cystic fibrosis. Pad-printed carbon electrodes are herein explored using square wave voltammetry to detect pyocyanin in a range of buffered and biological media. Third-order polynomial baseline fitting was explored to enhance the analytical sensitivity and extend the linear range to submicromolar concentrations. These modelling baselines showed excellent correlation with the experimental data, confirmed by high Interclass Correlation Coefficients of 0.995–0.998, and enabled the quantification of pyocyanin – with linearity extended down to 0.18 μM in Human Serum and 0.336 μM in both Britton-Robinson buffer and Simulated Wound Fluid, and derived Limits of Detection of 0.17, 0.15 and 0.09 μM, respectively, in this proof-of-concept study. Therefore, the use of very simple, cost-effective printed carbon materials enabled the detection of clinically relevant concentrations of this important biomarker through a new baseline fitting model and offers a novel approach for point-of-care diagnostics where Pseudomonas aeruginosa infections are critical

The geographical distribution of Kaposi's sarcoma and of lymphomas in Africa before the AIDS epidemic.

Estimated incidence rates are presented for three human immunodeficiency virus (HIV)-associated cancers [Kaposi's sarcoma (KS), Burkitt's lymphoma (BL) and other non-Hodgkin's lymphomas (NHLs)] from across the African continent, based on data collected before the HIV epidemic. Mapping of the rates and comparisons with a range of geographical variables indicate completely different distributions for KS and BL but a degree of similarity in the occurrence of Burkitt's lymphoma and other NHLs. Comparisons with rates elsewhere in the world suggest, most notably, that KS was as common in some regions of sub-Saharan Africa as was cancer of the colon in much of Western Europe. Comparison with data from the era of AIDS indicates 20-fold increases in the occurrence of Kaposi's sarcoma in Uganda and Zimbabwe. The highest rates for BL were three to four times the rates for leukaemia at young ages in Western populations, but the general incidence of other NHL was no higher than in the West and very low rates were indicated for much of southern Africa

Extracting non-linear integrate-and-fire models from experimental data using dynamic I–V curves

The dynamic I–V curve method was recently introduced for the efficient experimental generation of reduced neuron models. The method extracts the response properties of a neuron while it is subject to a naturalistic stimulus that mimics in vivo-like fluctuating synaptic drive. The resulting history-dependent, transmembrane current is then projected onto a one-dimensional current–voltage relation that provides the basis for a tractable non-linear integrate-and-fire model. An attractive feature of the method is that it can be used in spike-triggered mode to quantify the distinct patterns of post-spike refractoriness seen in different classes of cortical neuron. The method is first illustrated using a conductance-based model and is then applied experimentally to generate reduced models of cortical layer-5 pyramidal cells and interneurons, in injected-current and injected- conductance protocols. The resulting low-dimensional neuron models—of the refractory exponential integrate-and-fire type—provide highly accurate predictions for spike-times. The method therefore provides a useful tool for the construction of tractable models and rapid experimental classification of cortical neurons