1,130 research outputs found
Slow Temperature Equilibration Behind the Shock Front of SN 1006
We report on the observation of OVII Doppler line broadening in a compact
knot at the edge of SN 1006 detected with the Reflective Grating Spectrometer
on board XMM-Newton. The observed line width of sigma = 3.4+/-0.5 eV at a line
energy of 574 eV indicates an oxygen temperature of kT = 528+/-150 keV.
Combined with the observed electron temperature of 1.5 keV the observed
broadening is direct evidence for temperature non-equilibration in high Mach
number shocks, and slow subsequent equilibration. The OVII line emission allows
an accurate determination of the ionization state of the plasma, which is
characterized by a relatively high forbidden line contribution, indicating
log(n_e t) ~ 9.2.Comment: Accepted by Astrophysical Journal Letters, 4 pages, 4 figures. One of
the original figures has been replaced by a color version (Fig. 1a
Enhanced activation of an amino-terminally truncated isoform of the voltage-gated proton channel HVCN1 enriched in malignant B cells
The final published version can be found here: http://dx.doi.org/10.1073/pnas.1411390111M.C. is the recipient of a Bennett Fellowship from Leukaemia and Lymphoma Research (ref. 12002). M.A.B. is supported by a GlaxoSmithKline OncologyâBiotechnology and Biological Sciences Research Council Collaborative Awards in Science and Engineering PhD studentship. This work was supported by National Institutes of Health Grants GM087507 and GM102336 (to T.E.D.)
A comprehensive microarray-based DNA methylation study of 367 hematological neoplasms
Background: Alterations in the DNA methylation pattern are a hallmark of leukemias and lymphomas. However, most epigenetic studies in hematologic neoplasms (HNs) have focused either on the analysis of few candidate genes or many genes and few HN entities, and comprehensive studies are required. Methodology/Principal Findings: Here, we report for the first time a microarray-based DNA methylation study of 767 genes in 367 HNs diagnosed with 16 of the most representative B-cell (n = 203), T-cell (n = 30), and myeloid (n = 134) neoplasias, as well as 37 samples from different cell types of the hematopoietic system. Using appropriate controls of B-, T-, or myeloid cellular origin, we identified a total of 220 genes hypermethylated in at least one HN entity. In general, promoter hypermethylation was more frequent in lymphoid malignancies than in myeloid malignancies, being germinal center mature B-cell lymphomas as well as B and T precursor lymphoid neoplasias those entities with highest frequency of gene-associated DNA hypermethylation. We also observed a significant correlation between the number of hypermethylated and hypomethylated genes in several mature B-cell neoplasias, but not in precursor B- and T-cell leukemias. Most of the genes becoming hypermethylated contained promoters with high CpG content, and a significant fraction of them are targets of the polycomb repressor complex. Interestingly, T-cell prolymphocytic leukemias show low levels of DNA hypermethylation and a comparatively large number of hypomethylated genes, many of them showing an increased gene expression. Conclusions/Significance: We have characterized the DNA methylation profile of a wide range of different HNs entities. As well as identifying genes showing aberrant DNA methylation in certain HN subtypes, we also detected six genesâDBC1, DIO3, FZD9, HS3ST2, MOS, and MYOD1âthat were significantly hypermethylated in B-cell, T-cell, and myeloid malignancies. These might therefore play an important role in the development of different HNs
Efficacy of venetoclax monotherapy in patients with relapsed, refractory mantle cell lymphoma post BTK inhibitor therapy
Mantle-cell lymphoma genotypes identified with CGH to BAC microarrays define a leukemic subgroup of disease and predict patient outcome
To identify recurrent genomic changes in mantle cell lymphoma (MCL), we used high-resolution comparative genomic hybridization (CGH) to bacterial artificial chromosome (BAC) microarrays in 68 patients and 9 MCL-derived cell lines. Array CGH defined an MCL genomic signature distinct from other B-cell lymphomas, including deletions of 1p21 and 11q22.3-ATM gene with coincident 10p12-BMI1 gene amplification and 10p14 deletion, along with a previously unidentified loss within 9q21-q22. Specific genomic alterations were associated with different subgroups of disease. Notably, 11 patients with leukemic MCL showed a different genomic profile than nodal cases, including 8p21.3 deletion at tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) receptor gene cluster (55% versus 19%; P = .01) and gain of 8q24.1 at MYC locus (46% versus 14%; P = .015). Additionally, leukemic MCL exhibited frequent IGVH mutation (64% versus 21%; P = .009) with preferential VH4-39 use (36% versus 4%; P = .005) and followed a more indolent clinical course. Blastoid variants, increased number of genomic gains, and deletions of P16/INK4a and TP53 genes correlated with poorer outcomes, while 1p21 loss was associated with prolonged survival (P = .02). In multivariate analysis, deletion of 9q21-q22 was the strongest predictor for inferior survival (hazard ratio [HR], 6; confidence interval [CI], 2.3 to 15.7). Our study highlights the genomic profile as a predictor for clinical outcome and suggests that "genome scanning" of chromosomes 1p21, 9q21-q22, 9p21.3-P16/INK4a, and 17p13.1-TP53 may be clinically useful in MCL
'Drowning in here in his bloody sea' : exploring TV cop drama's representations of the impact of stress in modern policing
The Criminal Justice System is a part of society that is both familiar and hidden. It is familiar in that a large part of daily news and television drama is devoted to it (Carrabine, 2008; Jewkes, 2011). It is hidden in the sense that the majority of the population have little, if any, direct contact with the Criminal Justice System, meaning that the media may be a major force in shaping their views on crime and policing (Carrabine, 2008). As Reiner (2000) notes, the debate about the relationship between the media, policing, and crime has been a key feature of wider societal concerns about crime since the establishment of the modern police force. He outlines the recurring themes in post-war debates in this field. For Conservatives there has been an ongoing concern that the media is criminongenic, as it serves to undermine traditional institutions, including the police. From the viewpoint of radical criminology, the impact of the media is two-fold: it exaggerates legitimate concerns about crime and emphasises the bureaucratic and other restrictions under which the police operate (Reiner, 2000). This is seen as undermining due process and legitimatising what can be termed a âmaverickâ approach to policing. An early example of this can be seen in Clint Eastwoodâs Dirty Harry movies (Siegel, 1971) where Harry Callaghan acts as a one-man law enforcement system outside of the formal legal process, a process portrayed as corrupt, inefficient, and concerned with offendersâ rights rather than protecting victims. From a policing perspective, Reiner (2000) argues that film and TV drama creates a simplistic narrative of crime solving that is almost completely divorced from the reality of modern police work, a finding consistent with more recent work by Cummins et al., (2014)
Therapy-related leukaemias with balanced translocations can arise from pre-existing clonal haematopoiesis
High Levels of Human Immunodeficiency Virus Type 1 in Blood and Semen of Seropositive Men in Sub-Saharan Africa
High levels of human immunodeficiency virus type 1 (HIV-1) replication, as reflected in HIV-1 RNA concentrations in blood and semen, probably contribute to both rapid disease progression and enhanced sexual transmission. Semen and blood were collected from 49 Malawian and 61 US and Swiss (US/Swiss) HIV-1.seropositive men with similar CD4 cell counts and no urethritis or exposure to antiretroviral drugs. Median seminal plasma and blood plasma HIV-1 RNA concentrations were > 3-fold (P = .034) and 5-fold (P = .0003) higher, respectively, in the Malawian men. Similar differences were observed in subsets of the Malawian and US/Swiss study groups matched individually for CD4 cell count (P = .035 and P <.002, respectively). These observations may help explain the high rates of HIV-1 sexual transmission and accelerated HIV-1 disease progression in sub-Saharan Afric
GeneChip analyses point to novel pathogenetic mechanisms in mantle cell lymphoma
The translocation t(11;14)(q13;q32) is the genetic hallmark of mantle cell lymphoma (MCL) but is not sufficient for inducing lymphomagenesis. Here we performed genome-wide 100K GeneChip Mapping in 26 t(11;14)-positive MCL and six MCL cell lines. Partial uniparental disomy (pUPD) was shown to be a recurrent chromosomal event not only in MCL cell lines but also in primary MCL. Remarkably, pUPD affected recurrent targets of deletion like 11q, 13q and 17p. Moreover, we identified 12 novel regions of recurrent gain and loss as well as 12 high-level amplifications and eight homozygously deleted regions hitherto undescribed in MCL. Interestingly, GeneChip analyses identified different genes, encoding proteins involved in microtubule dynamics, such as MAP2, MAP6 and TP53, as targets for chromosomal aberration in MCL. Further investigation, including mutation analyses, fluorescence in situ hybridisation as well as epigenetic and expression studies, revealed additional aberrations frequently affecting these genes. In total, 19 of 20 MCL cases, which were subjected to genetic and epigenetic analyses, and five of six MCL cell lines harboured at least one aberration in MAP2, MAP6 or TP53. These findings provide evidence that alterations of microtubule dynamics might be one of the critical events in MCL lymphomagenesis contributing to chromosomal instability
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