Tumor angiogenic switch determines sustained proliferative malignant transformation in tumorigenesis and overlaps with para-inflammatory phenomena

Contextual BCR-ABL tyrosine kinase over-activity determines in formulated fashion the emergence of proliferation and anti-apoptosis that arise largely as derived phenomena of otherwise homeostatic mechanisms of the c-ABL gene within hematopoietic stem cells and hemangioblasts in the bone marrow. The ability to suppress almost completely, both in terms of phenotype and cytogenetically, the myeloid cell line expansion by imatinib mesylate is indicative of a phenomenon that depends strictly on the transformed status of the cell of origin in the chronic myeloid leukemia process. It is with relevance to complex participation of the dynamics of the fused BCR- ABL protein product that contextual conditioning of the cells of origin of the gene translocation further motivates the dimensional expansion of the transformed myeloid cell clones to increasing proliferative rates, thus leading to blast crisis as eventual loss of differentiating potential.peer-reviewe

A dual origin for Bcr-Abl gene translocation/fusion as dynamics of synergism of the hematopoietic stem cell and hemangioblast in chronic myeloid leukemia

Contextual BCR-ABL tyrosine kinase over-activity determines in formulated fashion the emergence of proliferation and anti-apoptosis that arise largely as derived phenomena of otherwise homeostatic mechanisms of the c-ABL gene within hematopoietic stem cells and hemangioblasts in the bone marrow. The ability to suppress almost completely, both in terms of phenotype and cytogenetically, the myeloid cell line expansion by imatinib mesylate is indicative of a phenomenon that depends strictly on the transformed status of the cell of origin in the chronic myeloid leukemia process. It is with relevance to complex participation of the dynamics of the fused BCR- ABL protein product that contextual conditioning of the cells of origin of the gene translocation further motivates the dimensional expansion of the transformed myeloid cell clones to increasing proliferative rates, thus leading to blast crisis as eventual loss of differentiating potential.peer-reviewe

ANTI-NMDA ENCEPHALITIS IN THE ACUTE SETTING

Background: Encephalitis associated with antibodies targeted against the N-methyl-D-aspartate (NMDA) receptor is increasingly recognised as a major cause of an acute presentation of organic psychosis. Misdiagnosis and subsequent inappropriate referral to psychiatric services is common and avoidable. This review focuses on addressing this issue in the acute setting. Methods: The authors present a review of existing literature relating to the pathophysiology and presentation of anti-NMDA receptor encephalitis, prior to proposing a management pathway avoiding delays to treatment incurred through misdiagnosis or inappropriate referral. Conclusions: Acute care physicians should have a low threshold for suspecting anti-NMDA receptor encephalitis in any patient presenting with acute psychosis in the context of non-specific coryzal and constitutional symptoms in whom infective causes have been excluded. The presence of pleocytosis and reduced protein in routine CSF analysis should further raise suspicion, and samples should be sent for immunohistochemical testing. Availability and efficiency of this testing is currently suboptimal

ANTI-NMDA ENCEPHALITIS IN THE ACUTE SETTING

Background: Encephalitis associated with antibodies targeted against the N-methyl-D-aspartate (NMDA) receptor is increasingly recognised as a major cause of an acute presentation of organic psychosis. Misdiagnosis and subsequent inappropriate referral to psychiatric services is common and avoidable. This review focuses on addressing this issue in the acute setting. Methods: The authors present a review of existing literature relating to the pathophysiology and presentation of anti-NMDA receptor encephalitis, prior to proposing a management pathway avoiding delays to treatment incurred through misdiagnosis or inappropriate referral. Conclusions: Acute care physicians should have a low threshold for suspecting anti-NMDA receptor encephalitis in any patient presenting with acute psychosis in the context of non-specific coryzal and constitutional symptoms in whom infective causes have been excluded. The presence of pleocytosis and reduced protein in routine CSF analysis should further raise suspicion, and samples should be sent for immunohistochemical testing. Availability and efficiency of this testing is currently suboptimal

A Linear Model for Transcription Factor Binding Affinity Prediction in Protein Binding Microarrays

Protein binding microarrays (PBM) are a high throughput technology used to characterize protein-DNA binding. The arrays measure a protein's affinity toward thousands of double-stranded DNA sequences at once, producing a comprehensive binding specificity catalog. We present a linear model for predicting the binding affinity of a protein toward DNA sequences based on PBM data. Our model represents the measured intensity of an individual probe as a sum of the binding affinity contributions of the probe's subsequences. These subsequences characterize a DNA binding motif and can be used to predict the intensity of protein binding against arbitrary DNA sequences. Our method was the best performer in the Dialogue for Reverse Engineering Assessments and Methods 5 (DREAM5) transcription factor/DNA motif recognition challenge. For the DREAM5 bonus challenge, we also developed an approach for the identification of transcription factors based on their PBM binding profiles. Our approach for TF identification achieved the best performance in the bonus challenge

A Herschel*-ATLAS study of dusty spheroids : Probing the minor-merger process in the local Universe

We use multiwavelength (0.12-500 μm) photometry from Herschel-ATLAS, WISE, UKIDSS, SDSS and GALEX to study 23 nearby spheroidal galaxies with prominent dust lanes (DLSGs). DLSGs are considered to be remnants of recent minor mergers, making them ideal laboratories for studying both the interstellar medium (ISM) of spheroids and minor-merger-driven star formation in thenearby Universe. The DLSGs exhibit star formation rates (SFRs) between 0.01and 10M yr with a median of 0.26M yr (a factor of 3.5 greater thanthe average SG). The median dust mass, dust-to-stellar mass ratio and dust temperature in these galaxies are around 107.6M, ≈0.05 per cent and ≈19.5K, respectively. The dust masses are at least a factor of 50 greater than that expected from stellar mass loss and, like the SFRs, show no correlationwith galaxy luminosity, suggesting that both the ISM and the star formationhave external drivers. Adopting literature gas-to-dust ratios and star formation histories derived from fits to the panchromatic photometry, we estimate that the median current and initial gasto- stellar mass ratios in these systems are ≈4 and ≈7 per cent, respectively. If, as indicated by recent work, minor mergers that drive star formation in spheroids with (NUV - r) > 3.8 (the colour range of our DLSGs) have stellar mass ratios between 1:6 and 1:10, then the satellite gas fractions are likely =50 per cent.Peer reviewedSubmitted Versio

Galaxy and Mass Assembly (GAMA): Variation in Galaxy Structure Across the Green Valley

Using a sample of 472 local Universe (z < 0.06) galaxies in the stellar mass range 10.25 < log M*/MG < 10.75, we explore the variation in galaxy structure as a function of morphology and galaxy colour. Our sample of galaxies is sub-divided into red, green and blue colour groups and into elliptical and non-elliptical (disk-type) morphologies. Using KiDS and VIKING derived postage stamp images, a group of eight volunteers visually classified bars, rings, morphological lenses, tidal streams, shells and signs of merger activity for all systems. We find a significant surplus of rings (2.3σ) and lenses (2.9σ) in disk-type galaxies as they transition across the green valley. Combined, this implies a joint ring/lens green valley surplus significance of 3.3σ relative to equivalent disk-types within either the blue cloud or the red sequence. We recover a bar fraction of ∼ 44% which remains flat with colour, however, we find that the presence of a bar acts to modulate the incidence of rings and (to a lesser extent) lenses, with rings in barred disk-type galaxies more common by ∼ 20 − 30 percentage points relative to their unbarred counterparts, regardless of colour. Additionally, green valley disk-type galaxies with a bar exhibit a significant 3.0σ surplus of lenses relative to their blue/red analogues. The existence of such structures rules out violent transformative events as the primary end-of-life evolutionary mechanism, with a more passive scenario the favoured candidate for the majority of galaxies rapidly transitioning across the green valley. Key words: galaxies: elliptical and lenticular, cD – galaxies: spiral – galaxies: evo- lution – galaxies: star formation – galaxies: statistics – galaxies: structur