261 research outputs found

    Plasmablastic Lymphoma: A Systematic Review

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    Plasmablastic lymphoma (PBL) is a very aggressive variant of diffuse large B-cell lymphoma initially described in the oral cavity of HIV-infected individuals. PBL represents a diagnostic challenge given its characteristic morphology and lack of CD20 expression, and also a therapeutic challenge, with early responses to therapy, but with high relapse rates and poor prognosis. In recent years, our understanding and clinical experience with PBL has increased in both HIV-positive and -negative settings. However, given its rarity, most of the data available rely on case reports and case series. The main goal of this article is to systematically review the most recent advances in epidemiology; pathophysiology; clinical, pathologic, and molecular characteristics; therapy; and prognosis in patients with PBL. Specific covered topics include new pathological markers for diagnosis, its association with Epstein-Barr virus, and the need of more intensive therapies

    Pscroph, a parasitic plant EST database enriched for parasite associated transcripts

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    BACKGROUND: Parasitic plants in the Orobanchaceae develop invasive root haustoria upon contact with host roots or root factors. The development of haustoria can be visually monitored and is rapid, highly synchronous, and strongly dependent on host factor exposure; therefore it provides a tractable system for studying chemical communications between roots of different plants. DESCRIPTION: Triphysaria is a facultative parasitic plant that initiates haustorium development within minutes after contact with host plant roots, root exudates, or purified haustorium-inducing phenolics. In order to identify genes associated with host root identification and early haustorium development, we sequenced suppression subtractive libraries (SSH) enriched for transcripts regulated in Triphysaria roots within five hours of exposure to Arabidopsis roots or the purified haustorium-inducing factor 2,6 dimethoxybenzoquinone. The sequences of over nine thousand ESTs from three SSH libraries and their subsequent assemblies are available at the Pscroph database . The web site also provides BLAST functions and allows keyword searches of functional annotations. CONCLUSION: Libraries prepared from Triphysaria roots treated with host roots or haustorium inducing factors were enriched for transcripts predicted to function in stress responses, electron transport or protein metabolism. In addition to parasitic plant investigations, the Pscroph database provides a useful resource for investigations in rhizosphere interactions, chemical signaling between organisms, and plant development and evolution

    Nonengraftment Haploidentical Cellular Therapy for Hematologic Malignancies

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    Much of the therapeutic benefit of allogeneic transplant is by a graft versus tumor effect. Further data shows that transplant engraftment is not dependant on myeloablation, instead relying on quantitative competition between donor and host cells. In the clinical setting, engraftment by competition alone is not feasible due to the need for large numbers of infused cells. Instead, low-level host irradiation has proven to be an effective engraftment strategy that is stem cell toxic but not myeloablative. The above observations served as the foundation for clinical trials utilizing allogeneic matched and haploidentical peripheral blood stem cell infusions with minimal conditioning in patients with refractory malignancies. Although engraftment was transient or not apparent, there were compelling responses in a heavily pretreated patient population that appear to result from the breaking of tumor immune tolerance by the host through the actions of IFNγ, invariant NK T cells, CD8 T cells, NK cells, or antigen presenting cells

    Localization of aquaporin CHIP in the human eye: implications in the pathogenesis of glaucoma and other disorders of ocular fluid balance

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    PURPOSE. The existence of integral membrane proteins that serve as selective water channels has been postulated to explain the movement of water across plasma membranes. Aquaporin CHIP (channel-forming integral membrane protein of 28 kd) is the first such channel to be characterized and is abundant in human erythrocytes and a variety of secretory and absorptive epithelia of the rat. Because disturbances in the movement of water characterize several ocular diseases, the distribution of CHIP in the human eye was studied. METHODS. Affinity-purified antibodies against purified CHIP protein were used for the indirect immunofluorescence localization of CHIP in human eye structures. Labeling was confirmed by immunoblot analyses of membrane preparations from eye structures. RESULTS. CHIP immunolabeling was found in the corneal endothelium, the lens epithelium, the nonpigmented epithelium of the ciliary process, the iris epithelium, and the endothelium of the trabecular meshwork and the canal of Schlemm. CONCLUSIONS. The presence of CHIP water channels in the secretory and absorptive tissues of the human eye provides a mechanism for transcellular water movement and may be important for understanding diseases of the eye that involve excess or insufficient movement of ocular fluid such as glaucoma, cataracts, and Fuch's dystrophy. In addition, the existence of CHIP in the outflow pathways of the human eye provides a novel explanation for the movement of water out of the eye

    The 100 most eminent psychologists of the 20th century.

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    A rank-ordered list was constructed that reports the first 99 of the 100 most eminent psychologists of the 20th century. Eminence was measured by scores on 3 quantitative variables and 3 qualitative variables. The quantitative variables were journal citation frequency, introductory psychology textbook citation frequency, and survey response frequency. The qualitative variables were National Academy of Sciences membership, election as American Psychological Association (APA) president or receipt of the APA Distinguished Scientific Contributions Award, and surname used as an eponym. The qualitative variables were quantified and combined with the other 3 quantitative variables to produce a composite score that was then used to construct a rank-ordered list of the most eminent psychologists of the 20th century. The discipline of psychology underwent a remarkable transformation during the 20th cen-tury, a transformation that included a shift away from the European-influenced philosophical psychology of the late 19th century to th

    Bone marrow-specific loss of ABI1 induces myeloproliferative neoplasm with features resembling, human myelofibrosis

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    Although the pathogenesis of primary myelofibrosis (PMF) and other myeloproliferative neoplasms (MPNs) is linked to constitutive activation of the JAK-STAT pathway, JAK inhibitors have neither curative nor MPN-stem cell-eradicating potential, indicating that other targetable mechanisms are contributing to the pathophysiology of MPNs. We previously demonstrated that Abelson interactor 1 (Abi-1), a negative regulator of Abelson kinase 1, functions as a tumor suppressor. Here we present data showing that bone marrow-specific deletion of Abi1 in a novel mouse model leads to development of an MPNlike phenotype resembling human PMF. Abi1 loss resulted in a significant increase in the activity of the Src family kinases (SFKs), STAT3, and NF-κB signaling. We also observed impairment of hematopoietic stem cell self-renewal and fitness, as evidenced in noncompetitive and competitive bone marrow transplant experiments. CD34 + hematopoietic progenitors and granulocytes from patients with PMF showed decreased levels of ABI1 transcript as well as increased activity of SFKs, STAT3, and NF-κB. In aggregate, our data link the loss of Abi-1 function to hyperactive SFKs/STAT3/NF-κB signaling and suggest that this signaling axis may represent a regulatory module involved in the molecular pathophysiology of PMF

    The state of the Martian climate

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    60°N was +2.0°C, relative to the 1981–2010 average value (Fig. 5.1). This marks a new high for the record. The average annual surface air temperature (SAT) anomaly for 2016 for land stations north of starting in 1900, and is a significant increase over the previous highest value of +1.2°C, which was observed in 2007, 2011, and 2015. Average global annual temperatures also showed record values in 2015 and 2016. Currently, the Arctic is warming at more than twice the rate of lower latitudes

    A novel DNA nuclease is stimulated by association with the GINS complex

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    Chromosomal DNA replication requires the spatial and temporal coordination of the activities of several complexes that constitute the replisome. A previously uncharacterized protein, encoded by TK1252 in the archaeon Thermococcus kodakaraensis, was shown to stably interact with the archaeal GINS complex in vivo, a central component of the archaeal replisome. Here, we document that this protein (TK1252p) is a processive, single-strand DNA-specific exonuclease that degrades DNA in the 5′ → 3′ direction. TK1252p binds specifically to the GINS15 subunit of T. kodakaraensis GINS complex and this interaction stimulates the exonuclease activity in vitro. This novel archaeal nuclease, designated GINS-associated nuclease (GAN), also forms a complex in vivo with the euryarchaeal-specific DNA polymerase D. Roles for GAN in replisome assembly and DNA replication are discussed

    Lead isotopic evidence for synextensional lithospheric ductile flow in the Colorado River extensional corridor, western United States

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    This is the published version. Copyright 1998 American Geophysical Union. All Rights Reserved.Temporal changes in the Pb isotopic compositions of Miocene lavas erupted in the northern Colorado River extensional corridor suggest that lithospheric mantle and middle to deep crust migrated from beneath the Colorado Plateau into the corridor during extension. Basaltic to rhyolitic lavas erupted in the extensional corridor prior to 12.2 Ma have Pb isotopic values that are similar to those of Tertiary to Quaternary lavas erupted through Proterozoic Mojave crust, which comprises surface exposures of basement in the corridor and much of the extended territory to the west. In contrast, most post-12.2 Ma lavas from the same region have Pb isotopic compositions similar to those of lavas erupted through Arizona crust, which forms the basement of the Colorado Plateau. The changes in isotopic compositions of the basaltic lavas, and perhaps a portion of the changes in isotopic compositions of silicic lavas, are attributed to a change in the composition of the mantle source. However, the 206Pb/204Pb ratios for lavas erupted before and after 12.2 Ma in the corridor decrease with decreasing MgO concentrations, suggesting that the Pb isotopic compositions of crustal assimilants changed at about the same time as the composition of the mantle. In the area of the Black Mountains accommodation zone, the surface boundary between the Arizona and Mojave crustal provinces lies a minimum of 60–80 km to the east of the westernmost lava with an Arizona Pb isotopic signature. This distance cannot be accounted for by displacements along nearby major faults, suggesting that middle to deep Arizona crust flowed a significant distance to the west during extension
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