Publications by authors named "Jens Als-Nielsen"

The biogenic formation of hemozoin crystals, a crucial process in heme detoxification by the malaria parasite, is reviewed as an antimalarial drug target. We first focus on the in-vivo formation of hemozoin. A model is presented, based on native-contrast 3D imaging obtained by X-ray and electron microscopy, that hemozoin nucleates at the inner membrane leaflet of the parasitic digestive vacuole, and grows in the adjacent aqueous medium.

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The most widely used antimalarial drugs belong to the quinoline family. Their mode of action has not been characterized at the molecular level in vivo. We report the in vivo mode of action of a bromo analog of the drug chloroquine in rapidly frozen -infected red blood cells.

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A key drug target for malaria has been the detoxification pathway of the iron-containing molecule heme, which is the toxic byproduct of hemoglobin digestion. The cornerstone of heme detoxification is its sequestration into hemozoin crystals, but how this occurs remains uncertain. We report new results of in vivo rate of heme crystallization in the malaria parasite, based on a new technique to measure element-specific concentrations at defined locations in cell ultrastructure.

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In recent years powder X-ray diffraction has proven to be a valuable alternative to single-crystal X-ray diffraction for determining electron-density distributions in high-symmetry inorganic materials, including subtle deformation in the core electron density. This was made possible by performing diffraction measurements in vacuum using high-energy X-rays at a synchrotron-radiation facility. Here we present a new version of our custom-built in-vacuum powder diffractometer with the sample-to-detector distance increased by a factor of four.

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Under the experimental condition that all Bragg peaks in a powder X-ray diffraction (PXRD) pattern have the same shape, one can readily obtain the Bragg intensities without fitting any parameters. This condition is fulfilled at the P02.1 beamline at PETRA III using the seventh harmonic from a 23 mm-period undulator (60 keV) at a distance of 65 m.

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In a powder diffraction pattern one measures the intensity of Miller-indexed Bragg peaks versus the wavevector transfer sinθ/λ. With increasing wavevector transfer the density of occurrence of Bragg peaks increases while their intensity decreases until they vanish into the background level. The lowest possible background level is that due to Compton scattering from the powder.

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The human malaria parasite Plasmodium falciparum detoxifies the heme byproduct of hemoglobin digestion in infected red blood cells by sequestration into submicron-sized hemozoin crystals. The crystal is composed of heme units interlinked to form cyclic dimers via reciprocal Fe─O (propionate) bonds. Templated hemozoin nucleation was envisaged to explain a classic observation by electron microscopy of a cluster of aligned hemozoin crystals within the parasite digestive vacuole.

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We present structural studies of Langmuir (L) and Langmuir-Blodgett (LB) films of new amphiphilic hexa-peri-hexabenzocoronene (HBC) discotics, carrying five branched alkyl side chains and one polar group. The polar group is either a carboxylic acid moiety or an electron acceptor moiety (anthraquinone). Grazing-incidence X-ray diffraction (GIXD) and X-ray reflectivity, both utilizing synchrotron radiation, show that these amphiphilic HBCs form well-defined Langmuir monolayers at the air-water interface, with a pi-stacked columnar structure where the HBC cores are rotated around the surface normal and tilted relative to the water surface.

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We report the results of an x-ray scattering study where both the dynamic and the static properties of a liquid crystal (8OCB) near the nematic-smectic A phase transition were probed. The static, time-averaged data show the gradual formation of smectic layers in the nematic phase, and we find that the smectic order correlation length parallel to the molecular axis diverges with the critical exponent nu( parallel )=0.70(4) at the transition.

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