Performance of Lambs Fed Green Chop

Management is important in controlling internal parasitism of lambs, as proved by research at various locations in recent years. The following experiment at the Agricultural Research Center, Beltsville, Maryland, evaluated some control procedures for internal parasitism in the Middle Atlantic States

Surface Composition of a Highly Active Pt3Y Alloy Catalyst for Application in Low Temperature Fuel Cells

Currently, platinum is the most widely used catalyst for low temperature proton exchange membrane fuel cells (PEMFC). However, the kinetics at the cathode are slow, and the price of platinum is high. To improve oxygen reduction reaction (ORR) kinetics at the cathode, platinum can be alloyed with rare earth elements, such as yttrium. We report that Pt3Y has the potential to be over 2 times more active for the ORR compared with Pt inside a real fuel cell. We present detailed photoemission analysis into the nature of the sputtered catalyst surface, using synchrotron radiation photoelectron spectroscopy (SRPES) to examine if surface adsorbates or impurities are present and can be removed. Pretreatment removes most of the yttrium oxide in the surface leaving behind a Pt overlayer which is only a few monolayers thick. Evidence of a substochiometric oxide peak in the Y 3d core level is presented, this oxide extends into the surface even after Ar+ sputter cleaning in-situ. This information will aid the development of new highly active nanocatalysts for employment in real fuel cell electrodes

Jak3, STAT3, and STAT5 inhibit expression of miR-22, a novel tumor suppressor microRNA, in cutaneous T-Cell lymphoma

Aberrant activation of Janus kinase-3 (Jak3) and its key down-stream effectors, Signal Transducer and Activator of Transcription-3 (STAT3) and STAT5, is a key feature of malignant transformation in cutaneous T-cell lymphoma (CTCL). However, it remains only partially understood how Jak3/STAT activation promotes lymphomagenesis. Recently, non-coding microRNAs (miRNAs) have been implicated in the pathogenesis of this malignancy. Here, we show that (i) malignant T cells display a decreased expression of a tumor suppressor miRNA, miR-22, when compared to non-malignant T cells, (ii) STAT5 binds the promoter of the miR-22 host gene, and (iii) inhibition of Jak3, STAT3, and STAT5 triggers increased expression of pri-miR-22 and miR-22. Curcumin, a nutrient with anti-Jak3 activity and histone deacetylase inhibitors (HDACi) also trigger increased expression of pri-miR-22 and miR-22. Transfection of malignant T cells with recombinant miR-22 inhibits the expression of validated miR-22 targets including NCoA1, a transcriptional co-activator in others cancers, as well as HDAC6, MAX, MYCBP, PTEN, and CDK2, which have all been implicated in CTCL pathogenesis. In conclusion, we provide the first evidence that de-regulated Jak3/STAT3/STAT5 signalling in CTCL cells represses the expression of the gene encoding miR-22, a novel tumor suppressor miRNA

Jak3, STAT3, and STAT5 inhibit expression of miR-22, a novel tumor suppressor microRNA, in cutaneous T-Cell lymphoma

Aberrant activation of Janus kinase-3 (Jak3) and its key down-stream effectors, Signal Transducer and Activator of Transcription-3 (STAT3) and STAT5, is a key feature of malignant transformation in cutaneous T-cell lymphoma (CTCL). However, it remains only partially understood how Jak3/STAT activation promotes lymphomagenesis. Recently, non-coding microRNAs (miRNAs) have been implicated in the pathogenesis of this malignancy. Here, we show that (i) malignant T cells display a decreased expression of a tumor suppressor miRNA, miR-22, when compared to non-malignant T cells, (ii) STAT5 binds the promoter of the miR-22 host gene, and (iii) inhibition of Jak3, STAT3, and STAT5 triggers increased expression of pri-miR-22 and miR-22. Curcumin, a nutrient with anti-Jak3 activity and histone deacetylase inhibitors (HDACi) also trigger increased expression of pri-miR-22 and miR-22. Transfection of malignant T cells with recombinant miR-22 inhibits the expression of validated miR-22 targets including NCoA1, a transcriptional co-activator in others cancers, as well as HDAC6, MAX, MYCBP, PTEN, and CDK2, which have all been implicated in CTCL pathogenesis. In conclusion, we provide the first evidence that de-regulated Jak3/STAT3/STAT5 signalling in CTCL cells represses the expression of the gene encoding miR-22, a novel tumor suppressor miRNA

MicroRNAs in the pathogenesis, diagnosis, prognosis and targeted treatment of cutaneous T-cell lymphomas

Cutaneous T-cell lymphoma (CTCL) represents a heterogeneous group of potentially devastating primary skin malignancies. Despite decades of intense research efforts, the pathogenesis is still not fully understood. In the early stages, both clinical and histopathological diagnosis is often difficult due to the ability of CTCL to masquerade as benign skin inflammatory dermatoses. Due to a lack of reliable biomarkers, it is also difficult to predict which patients will respond to therapy or progress towards severe recalcitrant disease. In this review, we discuss recent discoveries concerning dysregulated microRNA (miR) expression and putative pathological roles of oncogenic and tumor suppressive miRs in CTCL. We also focus on the interplay between miRs, histone deacetylase inhibitors, and oncogenic signaling pathways in malignant T cells as well as the impact of miRs in shaping the inflammatory tumor microenvironment. We highlight the potential use of miRs as diagnostic and prognostic markers, as well as their potential as therapeutic targets. Finally, we propose that the combined use of miR-modulating compounds with epigenetic drugs may provide a novel avenue for boosting the clinical efficacy of existing anti-cancer therapies in CTCL

<i>Staphylococcus aureus</i> enterotoxins induce FOXP3 in neoplastic T cells in Sézary syndrome

Sezary syndrome (SS) is a heterogeneous leukemic subtype of cutaneous T-cell lymphoma (CTCL) with generalized erythroderma, lymphadenopathy, and a poor prognosis. Advanced disease is invariably associated with severe immune dysregulation and the majority of patients die from infectious complications caused by microorganisms such as, Staphylococcus aureus, rather than from the lymphoma per se. Here, we examined if staphylococcal enterotoxins (SE) may shape the phenotype of malignant SS cells, including expression of the regulatory T-cell-associated marker FOXP3. Our studies with primary and cultured malignant cells show that SE induce expression of FOXP3 in malignant cells when exposed to nonmalignant cells. Mutations in the MHC class II binding domain of SE-A (SEA) largely block the effect indicating that the response relies at least in part on the MHC class II-mediated antigen presentation. Transwell experiments show that the effect is induced by soluble factors, partly blocked by anti-IL-2 antibody, and depends on STAT5 activation in malignant cells. Collectively, these findings show that SE stimulate nonmalignant cells to induce FOXP3 expression in malignant cells. Thus, differences in exposure to environmental factors, such as bacterial toxins may explain the heterogeneous FOXP3 expression in malignant cells in SS.Dermatology-oncolog

STAT5 induces miR-21 expression in cutaneous T cell lymphoma

In cutaneous T cell lymphomas (CTCL), miR-21 is aberrantly expressed in skin and peripheral blood and displays anti-apoptotic properties in malignant T cells. It is, however, unclear exactly which cells express miR-21 and what mechanisms regulate miR-21. Here, we demonstrate miR-21 expression in situ in both malignant and reactive lymphocytes as well as stromal cells. qRT-PCR analysis of 47 patients with mycosis fungoides (MF) and Sezary Syndrome (SS) confirmed an increased miR-21 expression that correlated with progressive disease. In cultured malignant T cells miR-21 expression was inhibited by Tofacitinib (CP-690550), a clinical-grade JAK3 inhibitor. Chromatin immunoprecipitation (ChIP) analysis showed direct binding of STAT5 to the miR-21 promoter. Cytokine starvation ex vivo triggered a decrease in miR-21 expression, whereas IL-2 induced an increased miR-21 expression in primary SS T cells and cultured cytokine-dependent SS cells (SeAx). siRNA-mediated depletion of STAT5 inhibited constitutive- and IL-2-induced miR-21 expression in cytokine-independent and dependent T cell lines, respectively. IL-15 and IL-2 were more potent than IL-21 in inducing miR-21 expression in the cytokine-dependent T cells. In conclusion, we provide first evidence that miR-21 is expressed in situ in CTCL skin lesions, induced by IL-2 and IL-15 cytokines, and is regulated by STAT5 in malignant T cells. Thus, our data provide novel evidence for a pathological role of IL-2Rg cytokines in promoting expression of the oncogenic miR-21 in CTCL