Q-dependence of the inelastic neutron scattering cross section for molecular spin clusters with high molecular symmetry

For powder samples of polynuclear metal complexes the dependence of the inelastic neutron scattering intensity on the momentum transfer Q is known to be described by a combination of so called interference terms. They reflect the interplay between the geometrical structure of the compound and the spatial properties of the wave functions involved in the transition. In this work, it is shown that the Q-dependence is strongly interrelated with the molecular symmetry of molecular nanomagnets, and, if the molecular symmetry is high enough, is actually completely determined by it. A general formalism connecting spatial symmetry and interference terms is developed. The arguments are detailed for cyclic spin clusters, as experimentally realized by e.g. the octanuclear molecular wheel Cr8, and the star like tetranuclear cluster Fe4.Comment: 8 pages, 1 figures, REVTEX

An Evolutionarily Conserved Arginine Is Essential for Tre1 G Protein-Coupled Receptor Function During Germ Cell Migration in Drosophila melanogaster

BACKGROUND: G protein-coupled receptors (GPCRs) play central roles in mediating cellular responses to environmental signals leading to changes in cell physiology and behaviors, including cell migration. Numerous clinical pathologies including metastasis, an invasive form of cell migration, have been linked to abnormal GPCR signaling. While the structures of some GPCRs have been defined, the in vivo roles of conserved amino acid residues and their relationships to receptor function are not fully understood. Trapped in endoderm 1 (Tre1) is an orphan receptor of the rhodopsin class that is necessary for primordial germ cell migration in Drosophila melanogaster embryos. In this study, we employ molecular genetic approaches to identify residues in Tre1 that are critical to its functions in germ cell migration. METHODOLOGY/PRINCIPAL FINDINGS: First, we show that the previously reported scattershot mutation is an allele of tre1. The scattershot allele results in an in-frame deletion of 8 amino acids at the junction of the third transmembrane domain and the second intracellular loop of Tre1 that dramatically impairs the function of this GPCR in germ cell migration. To further refine the molecular basis for this phenotype, we assayed the effects of single amino acid substitutions in transgenic animals and determined that the arginine within the evolutionarily conserved E/N/DRY motif is critical for receptor function in mediating germ cell migration within an intact developing embryo. CONCLUSIONS/SIGNIFICANCE: These structure-function studies of GPCR signaling in native contexts will inform future studies into the basic biology of this large and clinically important family of receptors

A Macroecological Analysis of SERA Derived Forest Heights and Implications for Forest Volume Remote Sensing

Individual trees have been shown to exhibit strong relationships between DBH, height and volume. Often such studies are cited as justification for forest volume or standing biomass estimation through remote sensing. With resolution of common satellite remote sensing systems generally too low to resolve individuals, and a need for larger coverage, these systems rely on descriptive heights, which account for tree collections in forests. For remote sensing and allometric applications, this height is not entirely understood in terms of its location. Here, a forest growth model (SERA) analyzes forest canopy height relationships with forest wood volume. Maximum height, mean, H100, and Lorey's height are examined for variability under plant number density, resource and species. Our findings, shown to be allometrically consistent with empirical measurements for forested communities world-wide, are analyzed for implications to forest remote sensing techniques such as LiDAR and RADAR. Traditional forestry measures of maximum height, and to a lesser extent H100 and Lorey's, exhibit little consistent correlation with forest volume across modeled conditions. The implication is that using forest height to infer volume or biomass from remote sensing requires species and community behavioral information to infer accurate estimates using height alone. SERA predicts mean height to provide the most consistent relationship with volume of the height classifications studied and overall across forest variations. This prediction agrees with empirical data collected from conifer and angiosperm forests with plant densities ranging between 102–106 plants/hectare and heights 6–49 m. Height classifications investigated are potentially linked to radar scattering centers with implications for allometry. These findings may be used to advance forest biomass estimation accuracy through remote sensing. Furthermore, Lorey's height with its specific relationship to remote sensing physics is recommended as a more universal indicator of volume when using remote sensing than achieved using either maximum height or H100

DNA Interactions of Monofunctional Organometallic Ruthenium(II) Antitumor Complexes in Cell-free Media

Modifications of natural DNA in a cell-free medium by antitumor monodentate Ru(II) arene compounds of the general formula [(eta 6-arene)Ru(en)Cl]+ (arene ) biphenyl, dihydroanthracene, tetrahydroanthracene, p-cymene, or benzene; en ) ethylenediamine) were studied by atomic absorption, melting behavior, transcription mapping, circular and linear dichroism, plasmid unwinding, competitive ethidium displacement, and differential pulse polarography. The results indicate that these complexes bind preferentially to guanine residues in double-helical DNA. The data are consistent with DNA binding of the complexes containing biphenyl, dihydroanthracene, or tetrahydroanthracene ligands that involves combined coordination to G N7 and noncovalent, hydrophobic interactions between the arene ligand and DNA, which may include arene intercalation and minor groove binding. In contrast, the single hydrocarbon rings in the p-cymene and benzene ruthenium complexes cannot interact with double-helical DNA by intercalation. Interestingly, the adducts of the complex containing p-cymene ligand, which has methyl and isopropyl substituents, distort the conformation and thermally destabilize double-helical DNA distinctly more than the adducts of the three multiring ruthenium arene compounds. It has been suggested that the different character of conformational alterations induced in DNA, and the resulting thermal destabilization, may affect differently further “downstream” effects of damaged DNA and consequently may result in different biological effects of this new class of metal-based antitumor compounds. The results point to a unique profile of DNA binding for Ru(II) arene compounds, suggesting that a search for new anticancer compounds based on this class of complexes may also lead to an altered profile of biological activity in comparison with that of metal-based antitumor drugs already used in the clinic or currently on clinical trials

The V471A polymorphism in autophagy-related gene ATG7 modifies age at onset specifically in Italian Huntington disease patients

The cause of Huntington disease (HD) is a polyglutamine repeat expansion of more than 36 units in the huntingtin protein, which is inversely correlated with the age at onset of the disease. However, additional genetic factors are believed to modify the course and the age at onset of HD. Recently, we identified the V471A polymorphism in the autophagy-related gene ATG7, a key component of the autophagy pathway that plays an important role in HD pathogenesis, to be associated with the age at onset in a large group of European Huntington disease patients. To confirm this association in a second independent patient cohort, we analysed the ATG7 V471A polymorphism in additional 1,464 European HD patients of the “REGISTRY” cohort from the European Huntington Disease Network (EHDN). In the entire REGISTRY cohort we could not confirm a modifying effect of the ATG7 V471A polymorphism. However, analysing a modifying effect of ATG7 in these REGISTRY patients and in patients of our previous HD cohort according to their ethnic origin, we identified a significant effect of the ATG7 V471A polymorphism on the HD age at onset only in the Italian population (327 patients). In these Italian patients, the polymorphism is associated with a 6-years earlier disease onset and thus seems to have an aggravating effect. We could specify the role of ATG7 as a genetic modifier for HD particularly in the Italian population. This result affirms the modifying influence of the autophagic pathway on the course of HD, but also suggests population-specific modifying mechanisms in HD pathogenesis

Identification of genetic variants associated with Huntington's disease progression: a genome-wide association study

Background Huntington's disease is caused by a CAG repeat expansion in the huntingtin gene, HTT. Age at onset has been used as a quantitative phenotype in genetic analysis looking for Huntington's disease modifiers, but is hard to define and not always available. Therefore, we aimed to generate a novel measure of disease progression and to identify genetic markers associated with this progression measure. Methods We generated a progression score on the basis of principal component analysis of prospectively acquired longitudinal changes in motor, cognitive, and imaging measures in the 218 indivduals in the TRACK-HD cohort of Huntington's disease gene mutation carriers (data collected 2008–11). We generated a parallel progression score using data from 1773 previously genotyped participants from the European Huntington's Disease Network REGISTRY study of Huntington's disease mutation carriers (data collected 2003–13). We did a genome-wide association analyses in terms of progression for 216 TRACK-HD participants and 1773 REGISTRY participants, then a meta-analysis of these results was undertaken. Findings Longitudinal motor, cognitive, and imaging scores were correlated with each other in TRACK-HD participants, justifying use of a single, cross-domain measure of disease progression in both studies. The TRACK-HD and REGISTRY progression measures were correlated with each other (r=0·674), and with age at onset (TRACK-HD, r=0·315; REGISTRY, r=0·234). The meta-analysis of progression in TRACK-HD and REGISTRY gave a genome-wide significant signal (p=1·12 × 10−10) on chromosome 5 spanning three genes: MSH3, DHFR, and MTRNR2L2. The genes in this locus were associated with progression in TRACK-HD (MSH3 p=2·94 × 10−8 DHFR p=8·37 × 10−7 MTRNR2L2 p=2·15 × 10−9) and to a lesser extent in REGISTRY (MSH3 p=9·36 × 10−4 DHFR p=8·45 × 10−4 MTRNR2L2 p=1·20 × 10−3). The lead single nucleotide polymorphism (SNP) in TRACK-HD (rs557874766) was genome-wide significant in the meta-analysis (p=1·58 × 10−8), and encodes an aminoacid change (Pro67Ala) in MSH3. In TRACK-HD, each copy of the minor allele at this SNP was associated with a 0·4 units per year (95% CI 0·16–0·66) reduction in the rate of change of the Unified Huntington's Disease Rating Scale (UHDRS) Total Motor Score, and a reduction of 0·12 units per year (95% CI 0·06–0·18) in the rate of change of UHDRS Total Functional Capacity score. These associations remained significant after adjusting for age of onset. Interpretation The multidomain progression measure in TRACK-HD was associated with a functional variant that was genome-wide significant in our meta-analysis. The association in only 216 participants implies that the progression measure is a sensitive reflection of disease burden, that the effect size at this locus is large, or both. Knockout of Msh3 reduces somatic expansion in Huntington's disease mouse models, suggesting this mechanism as an area for future therapeutic investigation

Extraartikuläre weichteilrheumatische Erkrankungen (Weichteilrheumatismus) und Rückenschmerzen

Extraartikuläre oder weichteilrheumatische Erkrankungen umfassen ca. ein Viertel aller Erkrankungen des rheumatischen Formenkreises. Dazu gehören generalisierte Phänomene (wie z.B. Fibromyalgie) sowie lokalisierte Schmerzmechanismen im Bereich der Wirbelsäule und der Gelenke. Erkrankungen des subcutanen Binde- und Fettgewebes gehören genauso zu dieser Kategorie wie Myopathien und deren Differentialdiagnosen. Die entzündlichen Myopathien werden im Kapitel O 27 abgehandelt. Aufgrund der Häufigkeit dieser Erkrankungen sind sie nicht nur Alltag in einer rheumatologischen Sprechstunde sondern auch in einer hausärztlichen Praxis. Bei den nicht-entzündlichen Formen fehlen häufig spezifische Bluttests. Durch die Verbesserung der bildgebenden Verfahren (z.B. Ultraschall, Magnetresonanz-Tomographie) ist es in den letzten Jahren jedoch möglich geworden, auch lokale „Reizungen“ für den Untersucher sichtbar zu machen. In der Mehrzahl der Fälle wird die Diagnose jedoch aufgrund der Anamnese und der klinischen Untersuchungen gestellt. Häufig finden sich auslösende Faktoren wie mechanische Überbelastungen oder ungewohnte Belastungen sowie repetitive Tätigkeiten, die sich ergonomisch ungünstig auf die jeweiligen Strukturen auswirken. Psychische Faktoren lassen die Schmerzintensität als auch die Ausdehnung der Symptomatik häufig exazerbieren und erschweren die Differentialdiagnose. Die folgenden Kapitel beschreiben die wichtigsten weichteilrheumatischen Erkrankungen und geben diagnostische sowie therapeutische Hinweise

Digital playing desk: A case study for Augmented Reality

Abstract To compare the advantages and disadvantages of a "Natural User Interface" (se

Direct observation of dislocations in smectics

We have been able to observe dislocations in liquid crystals by taking advantage of the characteristics of the second order smectic A-to-smectic C transition. The two materials N-p-heptyloxybenzylidene-p-heptylaniline and n-undecyl-p-azoxy-a-methyl-cinnamate (AMC 11) have been studied so far. In a series of micrographs at small temperature intervals we show how the dislocations become gradually visible when the phase transition point is approached from above or from below. We discuss the phenomenon by making a Landau development of the free energy density, allowing an order of magnitude estimation of the temperature range for observations. The Burgers’ vector of the dislocations is determined by an interference measurement and found equal to one unit of smectic layer thickness

Electrophysiological Study of Femoral Nerve Function After a Continuous Femoral Nerve Block for Anterior Cruciate Ligament Reconstruction.

A continuous femoral nerve block (CFNB) is an effective analgesic treatment after anterior cruciate ligament (ACL) reconstruction but may result in transient femoral nerve injuries and quadriceps muscle weakness, which in turn contribute to worsened functional outcomes. To compare electrophysiological criteria of a femoral nerve injury as well as functional and pain-related outcomes after ACL reconstruction when analgesia was provided by a CFNB or intravenous patient-controlled analgesic of morphine (IV PCA). Randomized controlled clinical trial; Level of evidence, 1. A total of 74 patients scheduled for ACL reconstruction were randomized to receive a CFNB before surgery, followed by a ropivacaine infusion for 2 days and oxycodone, or IV PCA. The primary outcome was the rate of femoral nerve injuries at 4 weeks postoperatively, defined as a reduction of the compound muscle action potential (CMAP) area from the vastus medialis muscle after supramaximal femoral nerve stimulation at the groin, associated with an absent H-reflex of the femoral nerve and signs of vastus medialis muscle denervation. Secondary functional outcomes were quadriceps muscle strength, active flexion range, and distance walked, as measured on postoperative days 1 and 2. Secondary pain-related outcomes were IV morphine consumption and pain scores at rest and on movement in phase 1 recovery and on postoperative days 1 and 2. No patients met the electrophysiological criteria of a femoral nerve injury. The mean CMAP area at 4 weeks was equivalent in both the CFNB and IV PCA groups (47 ± 16 mV·ms and 51 ± 13 mV·ms, respectively; P = .50). While no differences were detected in functional outcomes or pain scores, the consumption of an IV morphine equivalent was reduced by the administration of a CFNB in phase 1 recovery (6 ± 5 mg and 13 ± 7 mg, respectively; P = .0003), on postoperative day 1 (6 ± 7 mg and 19 ± 17 mg, respectively; P = .0005), and on postoperative day 2 (11 ± 10 mg and 19 ± 17 mg, respectively; P = .03) compared with an IV PCA. Despite prior contrary reports, a CFNB did not result in femoral nerve injuries or worsened functional outcomes after ACL reconstruction. The improvement of analgesia with a CFNB was only marginal and not clinically relevant beyond 24 hours. Registration: NCT01321138 ( ClinicalTrials.gov identifier)