1,180 research outputs found

    The NF-ÎșB subunit c-Rel regulates Bach2 tumour suppressor expression in B-cell lymphoma

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    The REL gene, encoding the NF-ÎșB subunit c-Rel, is frequently amplified in B-cell lymphoma and functions as a tumour-promoting transcription factor. Here we report the surprising result that c-rel–/– mice display significantly earlier lymphomagenesis in the c-Myc driven, EÎŒ-Myc model of B-cell lymphoma. c-Rel loss also led to earlier onset of disease in a separate TCL1-Tg-driven lymphoma model. Tumour reimplantation experiments indicated that this is an effect intrinsic to the EÎŒ-Myc lymphoma cells but, counterintuitively, c-rel–/– EÎŒ-Myc lymphoma cells were more sensitive to apoptotic stimuli. To learn more about why loss of c-Rel led to earlier onset of disease, microarray gene expression analysis was performed on B cells from 4-week-old, wild-type and c-rel–/– EÎŒ-Myc mice. Extensive changes in gene expression were not seen at this age, but among those transcripts significantly downregulated by the loss of c-Rel was the B-cell tumour suppressor BTB and CNC homology 2 (Bach2). Quantitative PCR and western blot analysis confirmed loss of Bach2 in c-Rel mutant EÎŒ-Myc tumours at both 4 weeks and the terminal stages of disease. Moreover, Bach2 expression was also downregulated in c-rel–/– TCL1-Tg mice and RelA Thr505Ala mutant EÎŒ-Myc mice. Analysis of wild-type EÎŒ-Myc mice demonstrated that the population expressing low levels of Bach2 exhibited the earlier onset of lymphoma seen in c-rel–/– mice. Confirming the relevance of these findings to human disease, analysis of chromatin immunoprecipitation sequencing data revealed that Bach2 is a c-Rel and NF-ÎșB target gene in transformed human B cells, whereas treatment of Burkitt's lymphoma cells with inhibitors of the NF-ÎșB/IÎșB kinase pathway or deletion of c-Rel or RelA resulted in loss of Bach2 expression. These data reveal a surprising tumour suppressor role for c-Rel in lymphoma development explained by regulation of Bach2 expression, underlining the context-dependent complexity of NF-ÎșB signalling in cancer

    Potential loss of nutrients from different rearing strategies for fattening pigs on pasture

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    Nutrient load and distribution on pasture were investigated with fattening pigs that: 1) spend a proportion of or their entire life on pasture, 2) were fed either restrictively or ad libitum, and 3) were weaned at different times of the year. The N and P retention in pigs decreased the longer they were kept on pasture. The contents of soil inorganic N and exchangeable K were significantly raised compared to the soil outside the enclosures but with no differences between treatments. Pig grazing did not affect extractable soil P. Regular moving of huts, feeding and water troughs was effective in ensuring that nutrients were more evenly distributed on the paddocks. Grass cover, as determined by spectral reflectance, was not related to the experimental treatments but only to time of year. During spring and summer, grass was present in parts of the paddocks, whereas during autumn and winter the pigs kept grass cover below 10%. Fattening pigs on pasture carries a high risk of nutrient loss and it is concluded that the most environmentally acceptable way of keeping fattening pigs on pasture involves a combination of reduced dietary N intake, reduced stocking rate and seasonal rather than all year production

    On the length of chains of proper subgroups covering a topological group

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    We prove that if an ultrafilter L is not coherent to a Q-point, then each analytic non-sigma-bounded topological group G admits an increasing chain <G_a : a of its proper subgroups such that: (i) U_{a in b(L)} G_a=G; and (ii)(ii) For every sigma-bounded subgroup H of G there exists a such that H is a subset of G_a. In case of the group Sym(w) of all permutations of w with the topology inherited from w^w this improves upon earlier results of S. Thomas

    Phylogenetics of Trachylina (Cnidaria: Hydrozoa) with new insights on the evolution of some problematical taxa

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    Some of the most interesting and enigmatic cnidarians are classified within the hydrozoan subclass Trachylina. Despite being relatively depauperate in species richness, the clade contains four taxa typically accorded ordinal status: Actinulida, Limnomedusae, Narcomedusae and Trachymedusae. We bring molecular data (mitochondrial 16S and nuclear small and large subunit ribosomal genes) to bear on the question of phylogenetic relationships within Trachylina. Surprisingly, we find that a diminutive polyp form, Microhydrula limopsicola (classified within Limnomedusae) is actually a previously unknown life stage of a species of Stauromedusae. Our data confirm that the interstitial form Halammohydra sp. (Actinulida) is derived from holopelagic direct developing ancestors, likely within the trachymedusan family Rhopalonematidae. Trachymedusae is shown to be diphyletic, suggesting that the polyp stage has been lost independently at least two times within trachyline evolution. Narcomedusae is supported as a monophyletic group likely also arising from trachymedusan ancestors. Finally, some data, albeit limited, suggest that some trachyline species names refer to cryptic species that have yet to be sorted taxonomicall

    Matching functions for heavy particles

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    We introduce matching functions as a means of summing heavy-quark logarithms to any order. Our analysis is based on Witten's approach, where heavy quarks are decoupled one at a time in a mass-independent renormalization scheme. The outcome is a generalization of the matching conditions of Bernreuther and Wetzel: we show how to derive closed formulas for summed logarithms to any order, and present explicit expressions for leading order and next-to-leading order contributions. The decoupling of heavy quarks in theories lacking asymptotic freedom is also considered.Comment: Revised version to be published in Physical Review D; added section with application to decoupling of heavy particles in non-asymptotically free theorie

    Retinoic Acid Accelerates the Specification of Enteric Neural Progenitors from In-Vitro-Derived Neural Crest

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    The enteric nervous system (ENS) is derived primarily from the vagal neural crest, a migratory multipotent cell population emerging from the dorsal neural tube between somites 1 and 7. Defects in the development and function of the ENS cause a range of enteric neuropathies, including Hirschsprung disease. Little is known about the signals that specify early ENS progenitors, limiting progress in the generation of enteric neurons from human pluripotent stem cells (hPSCs) to provide tools for disease modeling and regenerative medicine for enteric neuropathies. We describe the efficient and accelerated generation of ENS progenitors from hPSCs, revealing that retinoic acid is critical for the acquisition of vagal axial identity and early ENS progenitor specification. These ENS progenitors generate enteric neurons in vitro and, following in vivo transplantation, achieved long-term colonization of the ENS in adult mice. Thus, hPSC-derived ENS progenitors may provide the basis for cell therapy for defects in the ENS. In this article, Frith and colleagues show that retinoic acid (RA) signaling alters the axial identity of hPSC-derived neural crest cells in a time- and dose-dependent manner. They utilized this to derive enteric nervous system (ENS) proge

    Survey of nucleon electromagnetic form factors

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    A dressed-quark core contribution to nucleon electromagnetic form factors is calculated. It is defined by the solution of a Poincare' covariant Faddeev equation in which dressed-quarks provide the elementary degree of freedom and correlations between them are expressed via diquarks. The nucleon-photon vertex involves a single parameter; i.e., a diquark charge radius. It is argued to be commensurate with the pion's charge radius. A comprehensive analysis and explanation of the form factors is built upon this foundation. A particular feature of the study is a separation of form factor contributions into those from different diagram types and correlation sectors, and subsequently a flavour separation for each of these. Amongst the extensive body of results that one could highlight are: r_1^{n,u}>r_1^{n,d}, owing to the presence of axial-vector quark-quark correlations; and for both the neutron and proton the ratio of Sachs electric and magnetic form factors possesses a zero.Comment: 43 pages, 17 figures, 12 tables, 5 appendice

    Saartjie Baartman, Nelisiwe Xaba, and me: the politics of looking at South African bodies

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    Dance Artist/Choreographer Nelisiwe Xaba’s They Look at Me and That Is All They Think (2006) ‘refers to the story of Sara[tjie] Baartman [
] the “Hottentot Venus”’ (2006. 9th Jomba! Contemporary dance experience 2006 programme, p. 7) who was taken from her homeland South Africa, and exhibited in Europe in the nineteenth century. After Baartman died in 1815, her remains were displayed in a museum in Paris until 1982. Xaba parallels the story of Baartman to her own experience of performing in Europe as a black South African woman. This article considers how They Look at Me and That Is All They Think exposes the politics surrounding the act of looking at a particular racial and gendered body in both the historical and contemporary context, and how the concept and articulation of the ‘superior’ European subject was dependent on the classification of Baartman, and other black Africans, as exotic others. In my practice-based research project How I Chased a Rainbow And Bruised My Knee (2007), which was a choreographic response to Xaba’s work, I theatricalize my identity as a white South African woman to make visible whiteness, its associated privilege, and how it is dependent on the representation of a particular type of blackness
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