Discovery of a pathway for terminal-alkyne amino acid biosynthesis.

Living systems can generate an enormous range of cellular functions, from mechanical infrastructure and signalling networks to enzymatic catalysis and information storage, using a notably limited set of chemical functional groups. This observation is especially notable when compared to the breadth of functional groups used as the basis for similar functions in synthetically derived small molecules and materials. The relatively small cross-section between biological and synthetic reactivity space forms the foundation for the development of bioorthogonal chemistry, in which the absence of a pair of reactive functional groups within the cell allows for a selective in situ reaction1-4. However, biologically 'rare' functional groups, such as the fluoro5, chloro6,7, bromo7,8, phosphonate9, enediyne10,11, cyano12, diazo13, alkene14 and alkyne15-17 groups, continue to be discovered in natural products made by plants, fungi and microorganisms, which offers a potential route to genetically encode the endogenous biosynthesis of bioorthogonal reagents within living organisms. In particular, the terminal alkyne has found broad utility via the Cu(I)-catalysed azide-alkyne cycloaddition 'click' reaction18. Here we report the discovery and characterization of a unique pathway to produce a terminal alkyne-containing amino acid in the bacterium Streptomyces cattleya. We found that L-lysine undergoes an unexpected reaction sequence that includes halogenation, oxidative C-C bond cleavage and triple bond formation through a putative allene intermediate. This pathway offers the potential for de novo cellular production of halo-, alkene- and alkyne-labelled proteins and natural products from glucose for a variety of downstream applications.

The ultrafast Einstein-de Haas effect.

The Einstein-de Haas effect was originally observed in a landmark experiment1 demonstrating that the angular momentum associated with aligned electron spins in a ferromagnet can be converted to mechanical angular momentum by reversing the direction of magnetization using an external magnetic field. A related problem concerns the timescale of this angular momentum transfer. Experiments have established that intense photoexcitation in several metallic ferromagnets leads to a drop in magnetization on a timescale shorter than 100 femtoseconds-a phenomenon called ultrafast demagnetization2-4. Although the microscopic mechanism for this process has been hotly debated, the key question of where the angular momentum goes on these femtosecond timescales remains unanswered. Here we use femtosecond time-resolved X-ray diffraction to show that most of the angular momentum lost from the spin system upon laser-induced demagnetization of ferromagnetic iron is transferred to the lattice on sub-picosecond timescales, launching a transverse strain wave that propagates from the surface into the bulk. By fitting a simple model of the X-ray data to simulations and optical data, we estimate that the angular momentum transfer occurs on a timescale of 200 femtoseconds and corresponds to 80 per cent of the angular momentum that is lost from the spin system. Our results show that interaction with the lattice has an essential role in the process of ultrafast demagnetization in this system.

A clinical decision support system improves antibiotic therapy for upper urinary tract infection in a randomized single-blinded study.

BACKGROUND: Due to increasing bacterial resistance rates choosing a correct empiric antibiotic therapy is getting more and more complex. Often medical doctors use information tools to make the right treatment choice. METHODS: One hundred sixty six participants (77 medical doctors and 89 medical students) were asked to provide a diagnosis and antibiotic therapy in a simple fictive paper case of upper urinary tract infection (UTI) in a randomized single-blinded study. Participants were randomized to one of four information tools they were allowed to use in the study or control: 1. free internet access, 2. pharmaceutical pocket guide, 3. pocket guide antibiotic therapy, 4. clinical decision support system (CDSS), and control (no information tool). The CDSS was designed for the study. The adherence to the national German UTI guideline was evaluated. RESULTS: Only 27.1% (n = 45/166) provided a correct diagnosis of upper UTI and 19.4% (n = 32/166) an antibiotic treatment recommended by national German treatment guidelines indicating their need for information tools. This result was not significantly different between medical doctors and medical students, residents and medical specialists or level of working experience. Using CDSS improved results significantly compared to conventional tools (diagnosis 57.1%; treatment recommendation 40.5%; p < 0,01). Processing time was not different between the use of CDSS and conventional information tools. CDSS users based their decision making on their assigned information tool more than users of conventional tools (73.8% vs. 48.0%; p < 0.01). Using CDSS improved the confidence of participants in their recommendation significantly compared to conventional tools (p < 0.01). CONCLUSIONS: Our study suggests that medical professionals require information tools in diagnosing and treating a simple case of upper UTI correctly. CDSS appears to be superior to conventional tools as an information source.

Ultrafast Relaxation Dynamics of the Antiferrodistortive Phase in Ca Doped SrTiO_{3}.

The ultrafast dynamics of the octahedral rotation in Ca:SrTiO_{3} is studied by time-resolved x-ray diffraction after photoexcitation over the band gap. By monitoring the diffraction intensity of a superlattice reflection that is directly related to the structural order parameter of the soft-mode driven antiferrodistortive phase in Ca:SrTiO_{3}, we observe an ultrafast relaxation on a 0.2 ps timescale of the rotation of the oxygen octahedron, which is found to be independent of the initial temperature despite large changes in the corresponding soft-mode frequency. A further, much smaller reduction on a slower picosecond timescale is attributed to thermal effects. Time-dependent density-functional-theory calculations show that the fast response can be ascribed to an ultrafast displacive modification of the soft-mode potential towards the normal state induced by holes created in the oxygen 2p states.

Coupling between a Charge Density Wave and Magnetism in an Heusler Material.

The prototypical magnetic memory shape alloy Ni_{2}MnGa undergoes various phase transitions as a function of the temperature, pressure, and doping. In the low-temperature phases below 260 K, an incommensurate structural modulation occurs along the [110] direction which is thought to arise from the softening of a phonon mode. It is not at present clear how this phenomenon is related, if at all, to the magnetic memory effect. Here we report time-resolved measurements which track both the structural and magnetic components of the phase transition from the modulated cubic phase as it is brought into the high-symmetry phase. The results suggest that the photoinduced demagnetization modifies the Fermi surface in regions that couple strongly to the periodicity of the structural modulation through the nesting vector. The amplitude of the periodic lattice distortion, however, appears to be less affected by the demagnetization.

[Cognitive-perceptive approaches in the treatment of chronic pain]. / Kognitiv-perzeptive Ansätze bei chronischen Schmerzen.

In the treatment of difficult chronic pain conditions, cognitive-perceptive approaches offer an alternative to conventional therapies. Especially phantom limb pain and complex regional pain syndrome (CRPS) are frequently treated with these promising modalities. This article provides an overview of the most important cognitive-perceptive therapies and the research results concerning their clinical efficacy. In addition, we discuss their neurobiological foundation and clinical perspectives.

The quasi-stationary and transient States of the solar wind.

There are two states of the solar wind: quasi-stationary and transient. After 30 years of measurements by interplanetary spacecraft, the differences in the physical properties of the two types of wind are fairly well determined, but the physical processes involved in their accelerations are not yet understood in detail. The solar wind exists in part because the upper solar atmosphere, called the corona, is very hot, but the heating mechanisms are also not well understood. Recent research suggests a link between the heating and acceleration mechanisms.

Mariner Mark II and the Exploration of the Solar System.

Mariner Mark II is a concept for the next generatioon of deep-space missions. The project would provide limited, focused sets of Voyager- and Galileo-quality planetary observations at a fraction of the cost of the Voyager and Galileo projects. This article discusses Mariner Mark II's cost goals, scientific objectives, and mission requirements. Strategies for limiting costs include the use of a reconfigurable spacecraft, a multimission ground-support system, and selected new technologies.

Jupiter's Magnetosphere: Plasma Description from the Ulysses Flyby.

Plasma observations at Jupiter show that the outer regions of the Jovian magnetosphere are remarkably similar to those of Earth. Bow-shock precursor electrons and ions were detected in the upstream solar wind, as at Earth. Plasma changes across the bow shock and properties of the magnetosheath electrons were much like those at Earth, indicating that similar processes are operating. A boundary layer populated by a varying mixture of solar wind and magnetospheric plasmas was found inside the magnetopause, again as at Earth. In the middle magnetosphere, large electron density excursions were detected with a 10-hour periodicity as planetary rotation carried the tilted plasma sheet past Ulysses. Deep in the magnetosphere, Ulysses crossed a region, tentatively described as magnetically connected to the Jovian polar cap on one end and to the interplanetary magnetic field on the other. In the inner magnetosphere and lo torus, where corotation plays a dominant role, measurements could not be made because of extreme background rates from penetrating radiation belt particles.

Ulysses solar wind plasma observations at high southerly latitudes.

Solar wind plasma observations made by the Ulysses spacecraft through -80.2 degrees solar latitude and continuing equatorward to -40.1 degrees are summarized. Recurrent high-speed streams and corotating interaction regions dominated at middle latitudes. The speed of the solar wind was typically 700 to 800 kilometers per second poleward of -35 degrees . Corotating reverse shocks persisted farther south than did forward shocks because of the tilt of the heliomagnetic streamer belt. Sporadic coronal mass ejections were seen as far south as -60.5 degrees . Proton temperature was higher and the electron strahl was broader at higher latitudes. The high-latitude wind contained compressional, pressure-balanced, and Alfvénic structures.

A comprehensive search for segregation distortion in HLA.

Segregation distortion, the non-Mendelian segregation of gametes, has been well documented among diverse groups of organisms. These cases are characterized by extreme segregation ratios found only in males. Previous reports have suggested the existence of segregation distortion operating in the HLA system of humans, a tightly linked complex of genes which regulates the immune system. In mice, some alleles of the T/t complex, which is linked to H-2 (the HLA homologue of mice), cause extreme segregation distortion in wild mice populations. Here we report on the examination of a large body of pedigree data on non-diseased families, scored for the alleles of five HLA region loci. We searched for segregation distortion on the basis of five different models of inheritance: allelic, haplotypic, genotypic, diffuse occurrence in families, and autosomal effects on the sex ratio. There was no clear evidence for segregation distortion. In particular, the possibility of extreme levels of segregation distortion was firmly rejected in the populations examined, thus reducing the likelihood of common distortion-causing HLA associated haplotypes in our species.

Gene localization in a family with X-linked syndromal mental retardation (Prieto syndrome).

A mapping study was performed on a 3-generation Spanish family with X-linked syndromal mental retardation. Affected males have a typical facial appearance, ear malformations, abnormal growth of teeth, clinodactyly, dimpled skin at the lower back, and patellar luxation. In pneumoencephalography a marked subcortical cerebral atrophy was evident. In the linkage studies with polymorphic DNA markers, no recombination was found between the disease locus and the loci OTC and DXS148, both assigned to Xp21.1. One or more recombinants were observed between the disease locus and loci from the distal part of Xp and the pericentromeric region. Close linkage to loci of Xq has also been excluded. The analysis of multiple informative meioses suggests that the disease locus maps between DXS255 (Xp11.22) and DXS84 (Xp21.1) on Xp.

Gene for non-specific X-linked mental retardation maps in the pericentromeric region.

Linkage analysis was carried out in a large four-generation German family segregating for non-specific X-linked mental retardation. Affected males have moderate intellectual handicap. Speech delay, deviant behaviour, and hyperactivity have also been reported. Head circumference and testicular volumes are normal. Cytogenetic analysis failed to show evidence for fragile site or structural abnormality of the X chromosome. None of the obligatory carriers shows any clinical symptoms. Close linkage without recombination (lod scores 1.74 to 2.05) has been found between the disease locus (MRX1) and the polymorphic DNA loci DXS7 (Xp11.4-p11.3), MAOA (Xp11.3-p11.23), DXS255 (Xp11.22), and DXS159 (Xq12) suggesting that the gene responsible for the disease in this family maps in the pericentromeric region of the X chromosome. Linkage data obtained with the flanking marker loci OTC (Xp21.1) and DXS95 (Xq21.2-q21.3) also were compatible with this localization of the MRX1 gene. Close linkage to loci from Xp22, Xq22, Xq24-25, or Xq28 could be excluded.

MASA syndrome: clinical variability and linkage analysis.

We report on a family with three males with MASA syndrome (mental retardation, aphasia, shuffling gait, and adducted thumbs). One patient demonstrated spastic paraplegia and psychomotor retardation but no adducted thumbs. The described family underlines the clinical variability in MASA syndrome. DNA studies confirm linkage to DNA markers of the Xq28 region. Analysis of published cases with hereditary spastic paraplegia (HSP), where linkage studies have been carried out, emphasizes the clinical variability in MASA syndrome and other types of HSP, thus making a definite diagnosis in single cases often impossible.

Carotid artery aneurysm of granulomatous origin.

A native of the Western Caroline Islands presented with a granulomatous aneurysm of the right common carotid artery measuring 7 to 8 cm, which was resected and replaced with a reversed segment of saphenous vein. Adequacy of the collateral circulation to the brain was established by occlusion of the common carotid artery with local anesthesia. This was followed by definitive operation with general endotracheal anesthesia and induced hypertension. Although tuberculosis was the most likely etiologic agent, sarcoid could not be ruled out. Granulomatous aneurysms of the common carotid are extremely rare, and if this case was sarcoid in origin, it is the first such case reported. Only one other similar aneurysm could be found in the literature. Of the various methods of reconstruction of the common carotid artery reported, autogenous reversed saphenous vein is recommended strongly.

Some new urinary metabolites of famprofazone and morazone in man.

The human urinary metabolism of two pyrazolone derivatives, morazone and famprofazone, has been investigated. After administration of morazone, the metabolites p-hydroxymorazone and phenazone-4-carboxylic acid were excreted in addition to the known metabolite, phenmetrazine, and unchanged morazone. Metabolism of famprofazone led to the formation of methamphetamine; the pyrazolone moiety was excreted as 3-hydroxymethyl-propyphenazone.

[Biotransformation of (+)-methamphetamine in fertile hen's eggs]. / Biotransformation von (+)-Metamfetamin im bebrüteten Hühnerei.

On application of (+)-methamphetamine (1) to the albumen of embryonated hen's eggs it is possible to detect phase I as well as phase II metabolites of 1 in the allantois liquid. When application is effected on the first day of incubation, methamphetamine is less toxic than when effected on the sixth day of incubation. Besides unchanged 1 ten metabolites have been identified. Principal pathways of biotransformation are N-dealkylation as well as aromatic p-hydroxylation and--as phase II reactions--N-acetylation and other conjugation reactions. The total amount of the metabolites produced depends on time of incubation and is up to about 25% of the applied dose. Differences from, but also similarities to human metabolism have been noticed. Consequently, the experiment is likely to be suitable as an alternative method for testing biotransformation reactions.

[Quantitative determination of alpha-peroxyachifolide in yarrow by HPLC with amperometric detection]. / Quantitative Bestimmung von alpha-Peroxyachifolid in der Schafgarbe durch HPLC mit amperometrischer Detektion.

A HPLC method with amperometric detection is established for the contact allergen alpha-peroxyachifolid (1) from yarrow (Achillea millefolium L., s. str.). The amounts of 1 are between 0.25 and 0.60% in blossoms, dried 2 h at room temperature, and between 0.01 and 0.05% in the leaves. In completely dried material and in some preparations from the market 1 could also be quantified.

The Suess-Urey mission (return of solar matter to Earth).

The Suess-Urey (S-U) mission has been proposed as a NASA Discovery mission to return samples of matter from the Sun to the Earth for isotopic and chemical analyses in terrestrial laboratories to provide a major improvement in our knowledge of the average chemical and isotopic composition of the solar system. The S-U spacecraft and sample return capsule will be placed in a halo orbit around the L1 Sun-Earth libration point for two years to collect solar wind ions which implant into large passive collectors made of ultra-pure materials. Constant Spacecraft-Sun-Earth geometries enable simple spin stabilized attitude control, simple passive thermal control, and a fixed medium gain antenna. Low data requirements and the safety of a Sun-pointed spinner, result in extremely low mission operations costs.

Automatic generation of anatomic characteristics from cerebral aneurysm surface models.

PURPOSE: Computer-aided research on cerebral aneurysms often depends on a polygonal mesh representation of the vessel lumen. To support a differentiated, anatomy-aware analysis, it is necessary to derive anatomic descriptors from the surface model. We present an approach on automatic decomposition of the adjacent vessels into near- and far-vessel regions and computation of the axial plane. We also exemplarily present two applications of the geometric descriptors: automatic computation of a unique vessel order and automatic viewpoint selection. METHODS: Approximation methods are employed to analyze vessel cross-sections and the vessel area profile along the centerline. The resulting transition zones between near- and far- vessel regions are used as input for an optimization process to compute the axial plane. The unique vessel order is defined via projection into the plane space of the axial plane. The viewing direction for the automatic viewpoint selection is derived from the normal vector of the axial plane. RESULTS: The approach was successfully applied to representative data sets exhibiting a broad variability with respect to the configuration of their adjacent vessels. A robustness analysis showed that the automatic decomposition is stable against noise. A survey with 4 medical experts showed a broad agreement with the automatically defined transition zones. CONCLUSION: Due to the general nature of the underlying algorithms, this approach is applicable to most of the likely aneurysm configurations in the cerebral vasculature. Additional geometric information obtained during automatic decomposition can support correction in case the automatic approach fails. The resulting descriptors can be used for various applications in the field of visualization, exploration and analysis of cerebral aneurysms.