55 research outputs found

    Refinement of 1p36 Alterations Not Involving PRDM16 in Myeloid and Lymphoid Malignancies

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    Fluorescence in situ hybridization was performed to characterize 81 cases of myeloid and lymphoid malignancies with cytogenetic 1p36 alterations not affecting the PRDM16 locus. In total, three subgroups were identified: balanced translocations (N = 27) and telomeric rearrangements (N = 15), both mainly observed in myeloid disorders; and unbalanced non-telomeric rearrangements (N = 39), mainly observed in lymphoid proliferations and frequently associated with a highly complex karyotype. The 1p36 rearrangement was isolated in 12 cases, mainly myeloid disorders. The breakpoints on 1p36 were more widely distributed than previously reported, but with identifiable rare breakpoint cluster regions, such as the TP73 locus. We also found novel partner loci on 1p36 for the known multi-partner genes HMGA2 and RUNX1. We precised the common terminal 1p36 deletion, which has been suggested to have an adverse prognosis, in B-cell lymphomas [follicular lymphomas and diffuse large B-cell lymphomas with t(14;18)(q32;q21) as well as follicular lymphomas without t(14;18)]. Intrachromosomal telomeric repetitive sequences were detected in at least half the cases of telomeric rearrangements. It is unclear how the latter rearrangements occurred and whether they represent oncogenic events or result from chromosomal instability during oncogenesis

    Voltage-dependent charge movement associated with activation of the CLC-5 2Cl−/1H+ exchanger

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    The family of CLC proteins comprises both Cl− channels and Cl−/H+ exchange transporters with varying degrees of voltage dependence. The human CLC-5 is an electrogenic voltage-dependent 2Cl−/1H+ exchanger that gives rise to strongly outwardly rectifying currents when expressed. We conducted whole-cell recordings from HEK293 cells transiently transfected with either wild-type CLC-5 or a permeation-deficient mutant, E268A. With E268A CLC-5 we recorded transient voltage-dependent currents that represent the gating currents associated with CLC-5 activation and had kinetics that could be described by voltage-dependent forward and reverse transition rates. In extracellular solutions rich in Cl− or Br−, CLC-5 exhibited a gating charge of 1.3, but this was reduced to 0.9 in solutions comprising the impermeant anions aspartate, methanesulfonate, sulfate, or HEPES. Extracellular ion depletion by local perfusion with isotonic mannitol failed to reduce the gating charge further. Lowering intracellular pH from 7.4 to 5.4 did not shift the voltage-dependence of the gating currents, but reducing and increasing intracellular Cl− shifted the charge-voltage relationship to more negative and positive potentials, respectively. Our data suggest that voltage sensing is an intrinsic property of the CLC-5 protein and that permeant anions, particularly Cl−, modulate a voltage-dependent transition to an activated state from which Cl−/H+ exchange can occur.—Smith, A. J., Lippiat, J. D. Voltage-dependent charge movement associated with activation of the CLC-5 2Cl−/1H+ exchanger

    Reproducibility and robustness of graph measures of the associative-semantic network

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    Graph analysis is a promising tool to quantify brain connectivity. However, an essential requirement is that the graph measures are reproducible and robust. We have studied the reproducibility and robustness of various graph measures in group based and in individual binary and weighted networks derived from a task fMRI experiment during explicit associative-semantic processing of words and pictures. The nodes of the network were defined using an independent study and the connectivity was based on the partial correlation of the time series between any pair of nodes. The results showed that in case of binary networks, global graph measures exhibit a good reproducibility and robustness for networks which are not too sparse and these figures of merit depend on the graph measure and on the density of the network. Furthermore, group based binary networks should be derived from groups of sufficient size and the lower the density the more subjects are required to obtain robust values. Local graph measures are very variable in terms of reproducibility and should be interpreted with care. For weighted networks, we found good reproducibility (average test-retest variability <5% and ICC values >0.4) when using subject specific networks and this will allow us to relate network properties to individual subject information

    Treatment of chronic phantom limb pain using a trauma-focused psychological approach

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    BACKGROUND: Chronic phantom limb pain (PLP) is a disabling chronic pain syndrome for which regular pain treatment is seldom effective. Pain memories resulting from long-lasting preamputation pain or pain flashbacks, which are part of a traumatic memory, are reported to be powerful elicitors of PLP

    Arts handbook

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    1995 handbook for the faculty of Art
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