198 research outputs found
Calculations of the Exciton Coupling Elements Between the DNA Bases Using the Transition Density Cube Method
Excited states of the of the double-stranded DNA model
(A)(T)_{12} were calculated in the framework of the exciton theory.
The off-diagonal elements of the exciton matrix were calculated using the
transition densities and ideal dipole approximation associated with the lowest
energy excitations of the individual nucleobases obtained from
TDDFT calculations. The values of the coupling calculated with the transition
density cubes (TDC) and ideal-dipole approximation (IDA) methods were found
significantly different for the small inter-chromophore distances. It was shown
that the IDA overestimates the coupling significantly. The effects of the
structural fluctuations were incorporated by averaging the properties of the
excited states over a large number of conformations obtained from the MD
simulations
The N-terminal domain of human GATA1 prevents dyserythropoietic anemia and megakaryocyte dysplasia in vivo
We describe a child with dyserythropoietic anemia, thrombocytosis, functional platelet defect, and megakaryocyte dysplasia. We show that (i) this constellation of hematopoietic abnormalities was due to a germline mutation within the 5′ untranslated region (5′UTR) of globin transcription factor 1 (GATA1); (ii) the mutation impaired a 5′UTR GATA1 splicing site, with promoted production of the shortened GATA1 isoform lacking the N-terminus; and (iii) expression of the GATA1 N-terminus is restricted to erythroblasts and megakaryocytes in normal marrow, consistent with the patient's abnormal erythropoiesis and megakaryopoiesis. Our findings provide insights into the clinically relevant in vivo function of the N-terminal domain of GATA1 in human hematopoiesis
Burkitt lymphoma presenting as multifocal doughnut-shaped masses in the stomach of a patient with AIDS
https://www.thieme-connect.com/products/ejournals/abstract/10.1055/s-0034-136581
Modeling nitrous acid and its impact on ozone and hydroxyl radical during the Texas Air Quality Study 2006
Nitrous acid (HONO) mixing ratios for the Houston metropolitan area were simulated with the Community Multiscale Air Quality (CMAQ) Model for an episode during the Texas Air Quality Study (TexAQS) II in August/September 2006 and compared to in-situ MC/IC (mist-chamber/ion chromatograph) and long path DOAS (Differential Optical Absorption Spectroscopy) measurements at three different altitude ranges. Several HONO sources were accounted for in simulations, such as gas phase formation, direct emissions, nitrogen dioxide (NO<sub>2</sub>) hydrolysis, photo-induced formation from excited NO<sub>2</sub> and photo-induced conversion of NO<sub>2</sub> into HONO on surfaces covered with organic materials. Compared to the gas-phase HONO formation there was about a tenfold increase in HONO mixing ratios when additional HONO sources were taken into account, which improved the correlation between modeled and measured values. Concentrations of HONO simulated with only gas phase chemistry did not change with altitude, while measured HONO concentrations decrease with height. A trend of decreasing HONO concentration with altitude was well captured with CMAQ predicted concentrations when heterogeneous chemistry and photolytic sources of HONO were taken into account. Heterogeneous HONO production mainly accelerated morning ozone formation, albeit slightly. Also HONO formation from excited NO<sub>2</sub> only slightly affected HONO and ozone (O<sub>3</sub>) concentrations. Photo-induced conversion of NO<sub>2</sub> into HONO on surfaces covered with organic materials turned out to be a strong source of daytime HONO. Since HONO immediately photo-dissociates during daytime its ambient mixing ratios were only marginally altered (up to 0.5 ppbv), but significant increase in the hydroxyl radical (OH) and ozone concentration was obtained. In contrast to heterogeneous HONO formation that mainly accelerated morning ozone formation, inclusion of photo-induced surface chemistry influenced ozone throughout the day
Thrombocytopenia and disseminated histoplasmosis in immunocompetent adults
Disseminated histoplasmosis among immunocompetent patients is rare, but may be associated with clinically significant refractory thrombocytopenia. Platelet counts often return to normal levels following antifungal therapy. Therefore, the most important management of this refractory thrombocytopenia is the recognition and treatment of histoplasmosis infection
Successful Modified Therapy in a Patient With Probable Infection-Associated Hemophagocytic Lymphohistiocytosis
Hemophagocytic lymphohistiocytosis (HLH) is a rare, hyperinflammatory syndrome characterized by clinical signs and symptoms of extreme inflammation. In adults, HLH is typically a complication of infections, autoimmune diseases, and malignancies. While the disease is often fatal, classic management of HLH revolves around early diagnosis and initiation of protocolized therapy. We present a case of a previously healthy 56-year-old female who developed distributive shock requiring intubation, vasopressors, and continuous venovenous hemofiltration. In the setting of multiple infectious syndromes, severe cytopenias, and rising direct hyperbilirubinemia, her diagnosis of HLH was confirmed. Therapy was initiated with dexamethasone and two doses of reduced-intensity etoposide based on the patient's clinical course. Over the next few weeks, she continued to improve on dexamethasone monotherapy and has maintained remission up to the present with complete resolution of her cytopenias and return of baseline renal function. Our case highlights the variability in the management of probable infection-associated HLH (IHLH) with a good patient outcome. We demonstrate the potential to treat IHLH with partial protocols and minimal chemotherapeutics
Ref-1/APE1 as Transcriptional Regulator and Novel Therapeutic Target in Pediatric T-cell Leukemia
The increasing characterization of childhood acute lymphoblastic leukemia (ALL) has led to the identification of multiple molecular targets, but have yet to translate into more effective targeted therapies, particularly for high-risk, relapsed T-cell ALL. Searching for master regulators controlling multiple signaling pathways in T-ALL, we investigated the multi-functional protein redox factor-1 (Ref-1/APE1), which acts as a signaling "node" by exerting redox regulatory control of transcription factors important in leukemia. Leukemia patients' transcriptome databases showed increased expression in T-ALL of Ref-1 and other genes of the Ref-1/SET interactome. Validation studies demonstrated that Ref-1 is expressed in high-risk leukemia T-cells, including in patient biopsies. Ref-1 redox function is active in leukemia T-cells, regulating the Ref-1 target NF-kB, and inhibited by the redox-selective Ref-1 inhibitor E3330. Ref-1 expression is not regulated by Notch signaling, but is upregulated by glucocorticoid treatment. E3330 disrupted Ref-1 redox activity in functional studies and resulted in marked inhibition of leukemia cell viability, including T-ALL lines representing different genotypes and risk groups. Potent leukemia cell inhibition was seen in primary cells from ALL patients, relapsed and glucocorticoid-resistant T-ALL cells, and cells from a murine model of Notch-induced leukemia. Ref-1 redox inhibition triggered leukemia cell apoptosis and down-regulation of survival genes regulated by Ref-1 targets. For the first time, this work identifies Ref-1 as a novel molecular effector in T-ALL and demonstrates that Ref-1 redox inhibition results in potent inhibition of leukemia T-cells, including relapsed T-ALL. These data also support E3330 as a specific Ref-1 small molecule inhibitor for leukemia
Quantum Origins of Molecular Recognition and Olfaction in Drosophila
The standard model for molecular recognition of an odorant is that receptor
sites discriminate by molecular geometry as evidenced that two chiral molecules
may smell very differently. However, recent studies of isotopically labeled
olfactants indicate that there may be a molecular vibration-sensing component
to olfactory reception, specifically in the spectral region around 2300
cm. Here we present a donor-bridge-acceptor model for olfaction which
attempts to explain this effect. Our model, based upon accurate quantum
chemical calculations of the olfactant (bridge) in its neutral and ionized
states, posits that internal modes of the olfactant are excited impulsively
during hole transfer from a donor to acceptor site on the receptor,
specifically those modes that are resonant with the tunneling gap. By
projecting the impulsive force onto the internal modes, we can determine which
modes are excited at a given value of the donor-acceptor tunneling gap. Only
those modes resonant with the tunneling gap and are impulsively excited will
give a significant contribution to the inelastic transfer rate. Using
acetophenone as a test case, our model and experiments on D. melanogaster
suggest that isotopomers of a given olfactant give rise to different odorant
qualities. These results support the notion that inelastic scattering effects
play a role in discriminating between isotopomers, but that this is not a
general spectroscopic effectComment: 7 pages, 3 figure
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