2,673 research outputs found

    Effect of Intra-molecular Disorder and Inter-molecular Electronic Interactions on the Electronic Structure of Poly-p-Phenylene Vinylene (PPV)

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    We investigate the role of intra-molecular conformational disorder and inter-molecular electronic interactions on the electronic structure of disorder clusters of poly-p-phenylene vinylene (PPV) oligomers. Classical molecular dynamics is used to determine probable molecular geometries, and first-principle density functional theory (DFT) calculations are used to determine electronic structure. Intra-molecular and inter-molecular effects are disentangled by contrasting results for densely packed oligomer clusters with those for ensembles of isolated oligomers with the same intra-molecular geometries. We find that electron trap states are induced primarily by intra-molecular configuration disorder, while the hole trap states are generated primarily from inter-molecular electronic interactions.Comment: 4 pages, 4 figures. Compile with pdflate

    Lymphoid Enhancer Factor-1 Links Two Hereditary Leukemia Syndromes through Core-binding Factor α Regulation of ELA2

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    Two hereditary human leukemia syndromes are severe congenital neutropenia (SCN), caused by mutations in the gene ELA2, encoding the protease neutrophil elastase, and familial platelet disorder with acute myelogenous leukemia (AML), caused by mutations in the gene AML1, encoding the transcription factor core-binding factor α (CBFα). In mice, CBFα regulates the expression of ELA2, suggesting a common link for both diseases. However, gene-targeted mouse models have failed to reproduce either human disease, thus prohibiting further in vivo studies in mice. Here we investigate CBFα regulation of the human ELA2 promoter, taking advantage of bone marrow obtained from patients with either illness. In particular, we have identified novel ELA2 promoter substitutions (-199 C to A) within a potential motif for lymphoid enhancer factor-1 (LEF-1), a transcriptional mediator of Wnt/β-catenin signaling, in SCN patients. The LEF-1 motif lies adjacent to a potential CBFα binding site that is in a different position in human compared with mouse ELA2. We find that LEF-1 and CBFα co-activate ELA2 expression. In vitro, the high mobility group domain of LEF-1 interacts with the runt DNA binding and proline-, serine-, threonine-rich activation domains of CBFα. ELA2 transcript levels are up-regulated in bone marrow of an SCN patient with the -199 C to A substitution. Conversely, a mutation of the CBFα activation domain, found in a patient with familial platelet disorder with AML, fails to stimulate the ELA2 promoter in vitro, and bone marrow correspondingly demonstrates reduced ELA2 transcript. Observations in these complementary patients indicate that LEF-1 cooperates with CBFα to activate ELA2 in vivo and also suggest the possibility that up-regulating promoter mutations can contribute to SCN. Two hereditary AML predisposition syndromes may therefore intersect via LEF-1, potentially linking them to more generalized cancer mechanisms

    Association between Serum IGF-I levels and Postoperative Delirium in Elderly Subjects Undergoing Elective Knee Arthroplasty.

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    Evidence is mixed for an association between serum insulin-like growth factor-I (IGF-I) levels and postoperative delirium (POD). The current study assessed preoperative serum IGF-I levels as a predictor of incident delirium in non-demented elderly elective knee arthroplasty patients. Preoperative serum levels of total IGF-I were measured using a commercially available Human IGF-I ELISA kit. POD incidence and severity were determined using DSM-IV criteria and the Delirium Rating Scale-Revised-98 (DRS-R98), respectively. Median IGF-I levels in delirious (62.6 ng/ml) and non-delirious groups (65.9 ng/ml) were not significantly different (p = 0.141). The ratio (95% CI) of geometric means, D/ND, was 0.86 (0.70, 1.06). The Hodges-Lehmann median difference estimate was 7.23 ng/mL with 95% confidence interval (−2.32, 19.9). In multivariate logistic regression analysis IGF-I level was not a significant predictor of incident POD after correcting for medical comorbidities. IGF-I levels did not correlate wit

    Groups without cultured representatives dominate eukaryotic picophytoplankton in the oligotrophic South East Pacific Ocean

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    Background: Photosynthetic picoeukaryotes (PPE) with a cell size less than 3 µm play a critical role in oceanic primary production. In recent years, the composition of marine picoeukaryote communities has been intensively investigated by molecular approaches, but their photosynthetic fraction remains poorly characterized. This is largely because the classical approach that relies on constructing 18S rRNA gene clone libraries from filtered seawater samples using universal eukaryotic primers is heavily biased toward heterotrophs, especially alveolates and stramenopiles, despite the fact that autotrophic cells in general outnumber heterotrophic ones in the euphotic zone. Methodology/Principal Findings: In order to better assess the composition of the eukaryotic picophytoplankton in the South East Pacific Ocean, encompassing the most oligotrophic oceanic regions on earth, we used a novel approach based on flow cytometry sorting followed by construction of 18S rRNA gene clone libraries. This strategy dramatically increased the recovery of sequences from putative autotrophic groups. The composition of the PPE community appeared highly variable both vertically down the water column and horizontally across the South East Pacific Ocean. In the central gyre, uncultivated lineages dominated: a recently discovered clade of Prasinophyceae (IX), clades of marine Chrysophyceae and Haptophyta, the latter division containing a potentially new class besides Prymnesiophyceae and Pavlophyceae. In contrast, on the edge of the gyre and in the coastal Chilean upwelling, groups with cultivated representatives (Prasinophyceae clade VII and Mamiellales) dominated. Conclusions/Significance: Our data demonstrate that a very large fraction of the eukaryotic picophytoplankton still escapes cultivation. The use of flow cytometry sorting should prove very useful to better characterize specific plankton populations by molecular approaches such as gene cloning or metagenomics, and also to obtain into culture strains representative of these novel groups

    Monoclonal antibodies provided protection against ocular Pseudomonas aeruginosa infection

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    A panel of well characterized monoclonal antibodies (MAbs) directed against outer membrane proteins H2, or F (porin) of Pseudomonas aeruginosa were examined to determine whether they exhibited any protective effect against subsequent ocular challenge with the bacteria topically applied to the scarified corneal surface. Mice were observed macroscopically following bacterial challenge and the degree of ocular disease graded on a scale of 0 to 4 (0, normal, fully protected cornea; 4, corneal perforation or phthisis, not protected). Mice treated intravenously with either MAb MAI-6 (anti-H2) or MA2-10 (anti-F), or a combination of these two MAbs and MAb MA4-4 (anti-F), two hours before corneal challenge with the viable bacteria, exhibited significantly less corneal disease than mice either not treated with the MAbs, treated with MA4-4 alone or treated with MAb MAI-3 (anti-I). The latter MAb is directed against an outer membrane epitope that is not surface exposed. Light and transmission electron microscopic histopathology also was employed and provided confirmatory evidence to support the macroscopic analyses. Invest Ophthalmol Vis Sci 29: [1277][1278][1279][1280][1281][1282][1283][1284]1988 Ocular disease produced by the opportunistic bacterial pathogen P. aeruginosa often leads to a fulminating and highly destructive infection resulting in rapid liquefaction of the cornea and blindness

    Compositional and expression analyses of the glideosome during the Plasmodium life cycle reveal an additional myosin light chain required for maximum motility

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    Myosin A (MyoA) is a Class XIV myosin implicated in gliding motility and host cell and tissue invasion by malaria parasites. MyoA is part of a membrane-associated protein complex called the glideosome, which is essential for parasite motility and includes the MyoA light chain MTIP, and several glideosome-associated proteins (GAPs). However, most studies of MyoA have focused on single stages of the parasite life cycle. We examined MyoA expression throughout the Plasmodium berghei life cycle in both mammalian and insect hosts. In extracellular ookinetes, sporozoites and merozoites, MyoA was located at the parasite periphery. In the sexual stages, zygote formation and initial ookinete differentiation precede MyoA synthesis and deposition, which occurred only in the developing protuberance. In developing intracellular asexual blood stages, MyoA was synthesized in mature schizonts and was located at the periphery of segmenting merozoites, where it remained throughout maturation, merozoite egress and host cell invasion. Besides the known GAPs in the malaria parasite, the complex included GAP40, an additional myosin light chain designated essential light chain (ELC) and several other candidate components. This ELC bound the MyoA neck region adjacent to the MTIP binding site, and both myosin light chains co-located to the glideosome. Co-expression of MyoA with its two light chains revealed that the presence of both light chains enhances MyoA-dependent actin motility. In conclusion, we have established a system to study the interplay and function of the three glideosome components, enabling the assessment of inhibitors that target this motor complex to block host cell invasion

    Factors influencing the ownership and utilization of long-lasting insecticidal nets for malaria prevention in Ethiopia

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    Background Utilization of long-lasting insecticidal nets (LLINs) is regarded as key malaria prevention and control strategy. However, studies have reported a large gap in terms of both ownership and utilization particularly in the sub-Saharan Africa (SSA). With continual efforts to improve the use of LLIN and to progress malaria elimination, examining the factors influencing the ownership and usage of LLIN is of high importance. Therefore, the current study was conducted to examine the level of ownership and use of LLIN along with identification of associated factors at household level. Methods A cross-sectional study was conducted in Mirab Abaya District, Southern Ethiopia in June and July 2014. A total of 540 households, with an estimated 2690 members, were selected in four kebeles of the district known to have high incidence of malaria. Trained data collectors interviewed household heads to collect information on the knowledge, ownership and utilization of LLINs, which was complemented by direct observation on the conditions and use of the nets through house-to-house visit. Bivariate and multivariable logistic regression analyses were used to determine factors associated to LLIN use. Results Of 540 households intended to be included in the survey, 507 responded to the study (94.24% response rate), covering the homes of 2759 people. More than 58% of the households had family size >5 (the regional average), and 60.2% of them had at least one child below the age of 5 years. The ownership of at least one LLIN among households surveyed was 89.9%, and using at least one LLIN during the night prior to the survey among net owners was 85.1% (n = 456). Only 36.7% (186) mentioned at least as the mean of correct scores of all participants for 14 possible malaria symptoms and 32.7% (166) knew at least as the mean of correct scores of all participants for possible preventive methods. Over 30% of nets owned by the households were out of use. After controlling for confounding factors, having two or more sleeping places (adjusted odds ratio [aOR] = 2.58, 95% CI 1.17, 5.73), knowledge that LLIN prevents malaria (aOR = 2.51, 95% CI 1.17, 5.37), the presence of hanging bed nets (aOR = 19.24, 95% CI 9.24, 40.07) and walls of the house plastered or painted >12 months ago (aOR = 0.09, 95% CI 0.01, 0.71) were important predictors of LLIN utilization. Conclusions This study found a higher proportion of LLIN ownership and utilization by households than had previously been found in similar studies in Ethiopia, and in many studies in SSA. However, poor knowledge of the transmission mechanisms and the symptoms of malaria, and vector control measures to prevent malaria were evident. Moderate proportions of nets were found to be out of use or in poor repair. Efforts should be in place to maintain the current rate of utilization of LLIN in the district and improve on the identified gaps in order to support the elimination of malaria

    Droplet-like Fermi surfaces in the anti-ferromagnetic phase of EuFe2_2As2_2, an Fe-pnictide superconductor parent compound

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    Using angle resolved photoemission it is shown that the low lying electronic states of the iron pnictide parent compound EuFe2_2As2_2 are strongly modified in the magnetically ordered, low temperature, orthorhombic state compared to the tetragonal, paramagnetic case above the spin density wave transition temperature. Back-folded bands, reflected in the orthorhombic/ anti-ferromagnetic Brillouin zone boundary hybridize strongly with the non-folded states, leading to the opening of energy gaps. As a direct consequence, the large Fermi surfaces of the tetragonal phase fragment, the low temperature Fermi surface being comprised of small droplets, built up of electron and hole-like sections. These high resolution ARPES data are therefore in keeping with quantum oscillation and optical data from other undoped pnictide parent compounds.Comment: 4 figures, 6 page
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