The efficacy of halofantrine in the treatment of acute malaria in nonimmune travelers

A multicenter prospective trial was performed to investigate the efficacy and the tolerability of halofantrine in nonimmune patients with malaria imported from areas with drug-resistant falciparum parasites (mainly Africa). Forty-five of the 74 subjects were treated with a one-day regimen (3 x 500 mg) of halofantrine, and the other 29 received the same regimen with an additional treatment on day 7. In the second group, a 100% efficacy rate was demonstrated, but in the group receiving the one-day regimen, four recrudescences were observed in patients with falciparum malaria. Only five mild adverse reactions were seen, which disappeared spontaneously after the end of the treatment. We conclude that halofantrine is highly effective in curing malaria in nonimmune subjects. The treatment scheme for such persons should include an additional treatment on day 7 for nonimmune individuals. This drug was well tolerated in our patients, indicating that halofantrine will be useful in the treatment of multidrug-resistant malaria in nonimmune persons

1,25-Dihydroxyvitamin D Induces Lipoprotein Lipase Expression in 3T3-L1 Cells in Association with Adipocyte Differentiation

1,25-dihydroxyvitamin D3 [1,25-(OH)2D3] is known to modulate the development of hone and other mesenchymal cell types. Since osteoblasts and adipocytes are thought to arise in bone marrow from a common progenitor, this work examined the effects of 1,25-(OH)2D3 on adipocyte development, and in particular on the expression of lipoprotein lipase (LPL), which is an early marker for the differentiated adipocyte. 3T3-L1 preadipocytes were cultured in the presence of 1.25-(OH)2D3 (10-9 to 10-7 M) for up to 7 days. LPL activity was measured in the medium and cell extracts, and LPL messenger RNA levels were measured by Northern blotting. When compared to control cells, 10-7 M 1,25-(OH)2D3 increased medium LPL activity by 2- to 3-fold and cellular LPL by 1.5-fold. Significant increases in medium and cellular LPL were observed at 10-9 M and were maximal at 10-7 M. Along with the increase in LPL activity, there was an increase in LPL messenger RNA by 2- fold at 5 days, and by 5-fold at 7 days. In addition to an increase in LPL, 1,25-(OH)2D3 increased expression of aP2, an adipocyte-specific marker associated with differentiation. After the addition of 1,25-(OH)2D3, there was a decrease in 3T3-L1 cell number, which is consistent with differentiation, and a decrease in vitamin D receptors. Finally, these cells developed a different morphology. 1,25-(OH)2D3-treated cells assumed a rounded appearance, although without detachment from the dish and without the degree of lipid accumulation usually associated with the addition of insulin, isobutylmethylxanthine, and dexamethasone. It is concluded that 1,25- (OH)2D3 induced LPL expression in 3T3-L1 cells through an induction of differentiation-dependent mechanism(s). These findings suggest an important role for 1,25-(OH)2D3 in normal adipocyte differentiation

Проблемы информационного обеспечения физической культуры и спорта

A formation process for semiconductor quantum dots based on a surface instability induced by ion sputtering under normal incidence is presented. Crystalline dots 35 nanometers in diameter and arranged in a regular hexagonal lattice were produced on gallium antimonide surfaces. The formation mechanism relies on a natural self-organization mechanism that occurs during the erosion of surfaces, which is based on the interplay between roughening induced by ion sputtering and smoothing due to surface diffusion

Event-wise <pt> fluctuations in Au-Au collisions at sqrt[sNN]=130 GeV

We present the first large-acceptance measurement of event-wise mean transverse momentum fluctuations for Au-Au collisions at nucleon-nucleon center-of-momentum collision energy sqrt[sNN] = 130 GeV. The observed nonstatistical fluctuations substantially exceed in magnitude fluctuations expected from the finite number of particles produced in a typical collision. The r.m.s. fractional width excess of the event-wise distribution is 13.7±0.1(stat) ±1.3(syst)% relative to a statistical reference, for the 15% most-central collisions and for charged hadrons within pseudorapidity range | eta | fluctuation excess is qualitatively larger than those observed at lower energies and differs markedly from theoretical expectations. Contributions to fluctuations from semihard parton scattering in the initial state and dissipation in the bulk colored medium are discussed

Structure and stimuli-responsiveness of all-DNA dendrimers: theory and experiment

We present a comprehensive theoretical and experimental study of the solution phase properties of DNA-based family of nanoparticles - dendrimer-like DNA molecules (DL-DNA). These charged DNA dendrimers are novel macromolecular aggregates, which hold high promise in targeted self-assembly of soft matter systems in the bulk and at interfaces. To describe the behavior of this family of dendrimers (with generations ranging from G1 to G7), we use a theoretical model in which base-pairs of a single DL-DNA molecule are modeled by charged monomers, whose interactions are chosen to mimic the equilibrium properties of DNA correctly. Experimental results on the sizes and conformations of DL-DNA are based on static and 1dynamic light scattering; at the same time, Molecular Dynamics simulations are employed to model the equilibrium properties of DL-DNA, which compare favorably with the findings from experiments while at the same time providing a host of additional information and insight into the molecular structure of the nanostructures. We also examine the salt-responsiveness of these macromolecules, finding that despite the strong screening of electrostatic interactions, brought about by the added salt, the macromolecules shrink only slightly, their size robustness stemming from the high bending rigidity of the DNA-segments. The study of these charged dendrimer systems is an important field of research in the area of soft matter due to their potential role for various interdisciplinary applications, ranging from molecular cages and carriers for drug delivery in a living organism to the development of dendrimer- and dendron-based ultra-thin films in the area of nanotechnology. These findings are essential to determine if DL-DNA is a viable candidate for the experimental realization of cluster crystals in the bulk, a novel form of solids with multiple site occupancy.Comment: 38 pages, 17 figure

chloroExtractor: extraction and assembly of the chloroplast genome from whole genome shotgun data

The chloroExtractor is a perl based program which provides a pipeline for DNA extraction of chloroplast DNA from whole genome plant data.The authors MJA and SP contributed equally to this work. MJA was supported by a grant of the German Excellence Initiative to the Graduate School of Life Sciences, University of Würzburg

Discrepancy in exchangeable and soluble ammonium-induced effects on aerobic methane oxidation: a microcosm study of a paddy soil

Ammonium-induced stimulatory, inhibitory, and/or neutral effects on soil methane oxidation have been attributable to the ammonium concentration and mineral forms, confounded by other edaphic properties (e.g., pH, salinity), as well as the site-specific composition of the methanotrophic community. We hypothesize that this inconsistency may stem from the discrepancy in the cation adsorption capacity of the soil. We postulate that the effects of ammonium on the methanotrophic activity in soil are more accurately portrayed by relating methane uptake rates to the soluble ammonium (bioavailable), rather than the exchangeable (total) ammonium. To reduce adsorption (exchangeable) sites for ammonium in a paddy soil, two successive pre-incubation steps were introduced resulting in a 1000-fold soil dilution (soil enrichment), to be compared to a soil slurry (tenfold dilution) incubation. Ammonium was supplemented as NH4Cl at 0.5–4.75gL−1 after pre-incubation. While NH4Cl significantly stimulated the methanotrophic activity at all concentrations in the soil slurry incubation, methane uptake showed a dose-dependent effect in the soil enrichment. The trend in methane uptake could be explained by the soluble ammonium concentration, which was proportionate to the supplemented ammonium in the soil enrichment. In the soil slurry incubation, a fraction (36–63%) of the supplemented ammonium was determined to be adsorbed to the soil. Accordingly, Methylosarcina was found to predominate the methanotrophic community after the incubation, suggesting the relevance of this methanotroph at elevated ammonium levels (< 3.25gL−1 NH4Cl). Collectively, our results showed that the soluble, rather than the exchangeable ammonium concentration, is relevant when determining the effects of ammonium on methane oxidation, but this does not exclude other (a)biotic factors concurrently influencing methanotrophic activity

TrkA+ Neurons Induce Pathologic Regeneration After Soft Tissue Trauma

Heterotopic ossification (HO) is a dynamic, complex pathologic process that often occurs after severe polytrauma trauma, resulting in an abnormal mesenchymal stem cell differentiation leading to ectopic bone growth in soft-tissues including tendons, ligaments, and muscles. The abnormal bone structure and location induce pain and loss of mobility. Recently, we observed that NGF (Nerve growth factor)-responsive TrkA (Tropomyosin receptor kinase A)-expressing nerves invade sites of soft-tissue trauma, and this is a necessary feature for heterotopic bone formation at sites of injury. Here, we assayed the effects of the partial TrkA agonist Gambogic amide (GA) in peritendinous heterotopic bone after extremity trauma. Mice underwent HO induction using the burn/tenotomy model with or without systemic treatment with GA, followed by an examination of the injury site via radiographic imaging, histology, and immunohistochemistry. Single-cell RNA Sequencing confirmed an increase in neurotrophin signaling activity after HO-inducing extremity trauma. Next, TrkA agonism led to injury site hyper-innervation, more brisk expression of cartilage antigens within the injured tendon, and a shift from FGF to TGF beta signaling activity among injury site cells. Nine weeks after injury, this culminated in higher overall levels of heterotopic bone among GA-treated animals. In summary, these studies further link injury site hyper-innervation with increased vascular ingrowth and ultimately heterotopic bone after trauma. In the future, modulation of TrkA signaling may represent a potent means to prevent the trauma-induced heterotopic bone formation and improve tissue regeneration