bluuebunny/crossref_metadata_2025_split huggingface dataset:
Dual action of amitriptyline on NMDA receptors: enhancement of Ca-dependent desensitization and trapping channel block
Authors: Stepanenko Yulia D. , Boikov Sergei I. , Sibarov Dmitry A. , Abushik Polina A. , Vanchakova Nina P. , Belinskaia Daria , Shestakova Natalia N. , Antonov Sergei M. 
Published: December 2019

AbstractAlthough the tricyclic antidepressant amitriptyline (ATL) is widely used in the clinic, the mechanism underlying its high therapeutic efficacy against neuropathic pain remains unclear. NMDA receptors (NMDARs) represent a target for ATL and are involved in sensitization of neuropathic pain. Here we describe two actions of ATL on NMDARs: 1) enhancement of Ca2+-dependent desensitization and 2) trapping channel block. Inhibition of NMDARs by ATL was found to be dependent upon external Ca2+concentration ([Ca2+]) in a voltage-independent manner, with an IC50of 0.72 μM in 4 mM [Ca2+]. The ATL IC50value increased exponentially with decreasing [Ca2+], with ane-fold change observed per 0.69 mM decrease in [Ca2+]. Loading neurons with BAPTA abolished Ca2+-dependent inhibition, suggesting that Ca2+affects NMDARs from the cytosol. Since there is one known Ca2+-dependent process in gating of NMDARs, we conclude that ATL most likely promotes Ca2+-dependent desensitization. We also found ATL to be a trapping open-channel blocker of NMDARs with an IC50of 220 µM at 0 mV. Ane-fold change in ATL IC50was observed to occur with a voltage shift of 50 mV in 0.25 mM [Ca2+]. Thus, we disclose here a robust dependence of ATL potency on extracellular [Ca2+], and demonstrate that ATL bound in the NMDAR pore can be trapped by closure of the channel.
In vitro metabolomic
footprint of the Echinococcus multilocularis
metacestode
Authors: Ritler Dominic , Rufener Reto , Li Jia V. , Kämpfer Urs , Müller Joachim , Bühr Claudia , Schürch Stefan , Lundström-Stadelmann Britta 
Published: December 2019

AbstractAlveolar echinococcosis (AE) is a zoonotic disease that is deadly if
left untreated. AE is caused by the larval metacestode stage of the cestode
Echinococcus multilocularis. Better knowledge
on the host-parasite interface could yield novel targets for improvement of the
treatment against AE. We analyzed culture media incubated with in vitro grown E.
multilocularis metacestodes by 1H nuclear
magnetic resonance spectroscopy to identify the unknown metabolic footprint of the
parasite. Moreover, we quantitatively analyzed all amino acids, acetate, glucose,
lactate, and succinate in time-course experiments using liquid chromatography and
enzymatic assays. The E. multilocularis
metacestodes consumed glucose and, surprisingly, threonine and produced succinate,
acetate, and alanine as major fermentation products. The metabolic composition of
vesicle fluid (VF) from in vitro grown E. multilocularis metacestodes was different from
parasite-incubated culture medium with respect to the abundance, but not the
spectrum, of metabolites, and some metabolites, in particular amino acids,
accumulated in the VF. Overall, this study presents the first characterization of
the in vitro metabolic footprint of E. multilocularis metacestodes and VF composition, and
it provides the basis for analyses of potentially targetable pathways for future
drug development.
Films of rhombohedral graphite as two-dimensional topological semimetals
Authors: Slizovskiy Sergey , McCann Edward , Koshino Mikito , Fal’ko Vladimir I. 
Published: December 2019

AbstractTopologically non-trivial states appear in a number of materials ranging from spin-orbit-coupling driven topological insulators to graphene. In multivalley conductors, such as mono- and bilayer graphene, despite a zero total Chern number for the entire Brillouin zone, Berry curvature with different signs concentrated in different valleys can affect the material’s transport characteristics. Here we consider thin films of rhombohedral graphite, which appear to retain truly two-dimensional properties up to tens of layers of thickness and host two-dimensional electron states with a large Berry curvature, accompanied by a giant intrinsic magnetic moment carried by electrons. The size of Berry curvature and magnetization in the vicinity of each valley can be controlled by electrostatic gating leading to a tuneable anomalous Hall effect and a peculiar structure of the two-dimensional Landau level spectrum.
How mechanical forces can modulate the metal affinity and selectivity of metal binding sites in proteins
Authors: Dudev Todor , Frutos Luis Manuel , Castaño Obis 
Published: December 2019

Abstract
Mechanical forces play a key role in essential biological processes including cell growth, division, deformation, adhesion, migration and intra-cell interactions. The effect of mechanical forces in modulating the structure and properties of metal-occupied protein binding sites has not been fully understood. Here, by employing a combination of density functional theory (DFT) calculations and polarizable continuum model (PCM) computations applied on model metal-loaded EF-hand binding sites, we shed light on the intimate mechanism of the Mg2+/Ca2+ competition impacted by the application of mechanical stimuli. Applying mechanical force with a specific directionality and magnitude may shift the balance between the competing metal cations in favor of a given contestant depending on the composition and strength of the coordinative bonds and robustness of the metal binding site. Furthermore, the calculations help to determine the range of mechanical rupture forces typical for these structures: these range from 0.4 to 1.5 nN depending on the nature of the metal and amino acid residue. This positions the strength of the Mg2+–O and Ca2+–O coordinative bonds between that of typical covalent and hydrogen bonds. The bonds between the metal cation and the charged amino acid residue rupture at higher forces (∼1.2–1.5 nN) relative to those of their metal–noncharged counterparts which dissociate at ∼0.2–0.4 nN.
Expanding Communication Modalities and Functions for Preschoolers With Autism Spectrum Disorder: Secondary Analysis of a Peer Partner Speech-Generating Device Intervention
Authors: Bourque Kathy S. , Goldstein Howard 
Published: December 2019

Purpose

This study reports a secondary analysis of the nature of communicative functions and modalities used in initiations and responses of minimally verbal preschoolers with severe autism spectrum disorder (ASD) from a previously published study (
Thiemann-Bourque, Feldmiller, Hoffman, & Johner, 2018
). This analysis focused on the final cohort (
n =
6) from a group design study (
N
= 45) that examined a peer mediation and speech-generating device (SGD) intervention compared to an SGD-only condition.

Method
After teaching peers to use an iPad as an SGD within a modified stay-play-talk approach, school staff implemented SGD instruction in child–peer dyads during typical preschool activities. To investigate individual differences among children who demonstrated increased communication acts in the peer + SGD condition, changes in reciprocity, modalities used, and communicative functions were examined using a multiple-baseline design across children. Fidelity of implementation and social validity data were also collected.

Results
Six children with ASD and their peers demonstrated more balanced reciprocity, with individual differences in how and why children communicated during exchanges. That is, all children with ASD increased in SGD use as their primary communication mode; 3 children used different modalities including more speech, and 3 children used primarily gestures and SGD. The most frequent function expressed was requests for objects. More modest increases were observed in comments and requests for actions, with negligible changes in gaining attention. Social validity reports by naïve judges reflected clear improvements in communication interactions.

Conclusion
Findings are promising for a preschool SGD intervention that can expand children's modalities and communicative functions to engage in balanced exchanges with peer partners.

Supplemental Material

https://doi.org/10.23641/asha.11374203
A Tutorial for Implementing Strategic Questioning in the Clinical Teaching Environment
Authors: Dalessio (Procaccini) Samantha J. 
Published: December 2019

Purpose
The implementation of strategic questioning within the clinical teaching context has recently gained appeal among clinical educators as a method for stimulating critical thinking and other higher order thinking skills. This article will (a) address evidence for the use of strategic questioning approaches in the clinical teaching environment, (b) examine some of the complexities associated with effectively selecting and implementing questioning types, and (c) discuss the potential significance that supervisory training and self-assessment may have on effective application of strategic questioning.

Conclusion
Strategic questioning can be a highly valuable teaching methodology within the clinical teaching context. Current available external evidence, albeit limited, provides some insight into the complexities involved with effectively implementing strategic questioning methods. Further research is needed to explore the efficacy and feasibility of specific strategic questioning approaches within the scope of communication sciences and disorders.
Spectroscopy and polarimetry of the gravitationally lensed quasar SDSS J1004+4112 with the 6m SAO RAS telescope
Authors: Popović L. Č. , Afanasiev V. L. , Moiseev A. , Smirnova A. , Simić S. , Savić Dj. , Mediavilla E. G. , Fian C. 
Published: December 2019

Context. We present new spectroscopic and polarimetric observations of the gravitational lens SDSS J1004+4112 taken with the 6 m telescope of the Special Astrophysical Observatory (Russia).
Aims. In order to explain the variability that is observed only in the blue wing of the C IV emission line, corresponding to image A, we analyze the spectroscopy and polarimetry of the four images of the lensed system.
Methods. Spectra of the four images were taken in 2007, 2008, and 2018, and polarization was measured in the period 2014–2017. Additionally, we modeled the microlensing effect in the polarized light, assuming that the source of polarization is the equatorial scattering in the inner part of the torus.
Results. We find that a blue enhancement in the C IV line wings affects component A in all three epochs. We also find that the UV continuum of component D was amplified in the period 2007–2008, and that the red wings of CIII] and C IV appear brighter in D than in the other three components. We report significant changes in the polarization parameters of image D, which can be explained by microlensing. Our simulations of microlensing of an equatorial scattering region in the dusty torus can qualitatively explain the observed changes in the polarization degree and angle of image D. We do not detect significant variability in the polarization parameters of the other images (A, B, and C), although the averaged values of the polarization degree and angle are different for the different images.
Conclusions. Microlensing of a broad line region model including a compact outflowing component can qualitatively explain the C IV blue wing enhancement (and variation) in component A. However, to confirmed this hypothesis, we need additional spectroscopic observation in future.
Fragmentation and isomerization of polycyclic aromatic hydrocarbons in the interstellar medium: Coronene as a case study
Authors: Chen Tao , Luo Yi , Li Aigen 
Published: December 2019

Aims. Due to the limitations of current computational technology, the fragmentation and isomerization products of vibrationally-excited polycyclic aromatic hydrocarbon (PAH) molecules and their derivatives have been poorly studied. In this work, we investigate the intermediate products of PAHs and their derivatives as well as the gas-phase reactions relevant to the interstellar medium, with coronene as a case study.
Methods. Based on the semi-empirical method of PM3 as implemented in the CP2K program, molecular dynamics simulations were performed to model the major processes (e.g., vibrations, fragmentations, and isomerizations) of coronene and its derivatives (e.g., methylated coronene, hydrogenated coronene, dehydrogenated coronene, nitrogen-substituted coronene, and oxygen-substituted coronene) at temperatures of 3000 K and 4000 K.
Results. We find that the anharmonic effects are crucial for the simulation of vibrational excitation. For the molecules studied here, H2, CO, HCN, and CH2 are the major fragments. Following the dissociation of these small units, most of the molecules could maintain their ring structures, but a few molecules would completely break into carbon chains. The transformation from a hexagon to a pentagon or a heptagon may occur and the heteroatomic substitutions (e.g., N- or O-substitutions) would facilitate the transformation.
The influence of NLTE effects in Fe I lines on an inverted atmosphere
Authors: Smitha H. N. , Holzreuter R. , van Noort M. , Solanki S. K. 
Published: December 2019

Context. Ultraviolet overionisation of iron atoms in the solar atmosphere leads to deviations in their level populations based on Saha-Boltzmann statistics. This causes their line profiles to form in non-local thermodynamic equilibrium (NLTE) conditions. When inverting such profiles to determine atmospheric parameters, the NLTE effects are often neglected and other quantities are tweaked to compensate for deviations from the LTE.
Aims. We investigate how the routinely employed LTE inversion of iron lines formed in NLTE underestimates or overestimates atmospheric quantities, such as temperature (T), line-of-sight velocity (vLOS), magnetic field strength (B), and inclination (γ) while the earlier papers have focused mainly on T. Our findings has wide-ranging consequences since many results derived in solar physics are based on inversions of Fe I lines carried out in LTE.
Methods. We synthesized the Stokes profiles of Fe I 6301.5 Å and 6302.5 Å lines in both LTE and NLTE using a snapshot of a 3D magnetohydrodynamic simulation. The profiles were then inverted in LTE. We considered the atmosphere inferred from the inversion of LTE profiles as the fiducial model and compared it to the atmosphere resulting from the inversion of NLTE profiles. The observed differences have been attributed to NLTE effects.
Results. Neglecting the NLTE effects introduces errors in the inverted atmosphere. While the errors in T can go up to 13%, in vLOS and B, the errors can go as high as 50% or above. We find these errors to be present at all three inversion nodes. Importantly, they survive degradation from the spatial averaging of the profiles.
Conclusions. We provide an overview of how neglecting NLTE effects influences the values of T, vLOS, B, and γ that are determined by inverting the Fe I 6300 Å line pair, as observed, for example, by Hinode/SOT/SP. Errors are found at the sites of granules, intergranular lanes, magnetic elements, and basically in every region susceptible to NLTE effects. For an accurate determination of the atmospheric quantities and their stratification, it is, therefore, important to take the NLTE effects into account.
Excitation of decay-less transverse oscillations of coronal loops by random motions
Authors: Afanasyev A. N. , Van Doorsselaere T. , Nakariakov V. M. 
Published: December 2019

Context. The relatively large-amplitude decaying regime of transverse oscillations of coronal loops has been known for two decades and has been interpreted in terms of magnetohydrodynamic kink modes of cylindrical plasma waveguides. In this regime oscillations decay in several cycles. Recent observational analysis has revealed so-called decay-less, small-amplitude oscillations, in which a multi-harmonic structure has been detected. Several models have been proposed to explain these oscillations. In particular, decay-less oscillations have been described in terms of standing kink waves driven with continuous mono-periodic motions of loop footpoints, in terms of a simple oscillator model of forced oscillations due to harmonic external force, and as a self-oscillatory process due to the interaction of a loop with quasi-steady flows. However, an alternative mechanism is needed to explain the simultaneous excitation of several longitudinal harmonics of the oscillation.
Aims. We study the mechanism of random excitation of decay-less transverse oscillations of coronal loops.
Methods. With a spatially one-dimensional and time-dependent analytical model taking into account effects of the wave damping and kink speed variation along the loop, we considered transverse loop oscillations driven by random motions of footpoints. The footpoint motions were modelled by broad-band coloured noise.
Results. We found the excitation of loop eigenmodes and analysed their frequency ratios as well as the spatial structure of the oscillations along the loop. The obtained results successfully reproduce the observed properties of decay-less oscillations. In particular, excitation of eigenmodes of a loop as a resonator can explain the observed quasi-monochromatic nature of decay-less oscillations and the generation of multiple harmonics detected recently.
Conclusions. We propose a mechanism that can interpret decay-less transverse oscillations of coronal loops in terms of kink waves randomly driven at the loop footpoints.
Die Zentralsehne
Authors: Corts Magga 
Published: December 2019

SummaryDas Denkmodell der Zentralsehne beschreibt eine Muskel-Faszien-Kette im Körper, die sich in der Region der Medianlinie befindet. Die Strukturen reichen von innerhalb des Schädels bis zur unteren Extremität. Durch dieses Modell kann man den myofaszialen Einfluss auf die Posturologie darstellen.
Evidenz-basierte Prophylaxe, Diagnostik und Therapie der Osteoporose im Jahre 2019
Authors: Buschhorn-Milberger Verena , Erkenberg Judith , Guminski Barbara , Thomasius Friederike , Braun Jürgen , Bühring Björn 
Published: December 2019

ZUSAMMENFASSUNGOsteoporose ist eine Volkskrankheit, die sich durch niedrigtraumatische Frakturen manifestiert. Sie ist durch eine niedrige Knochendichte und verschlechterte ossäre Mikroarchitektur charakterisiert. Osteoporotische Frakturen führen zu Mobilitätsverlusten, Schmerzen und erhöhter Morbidität und Mortalität. Trotz ihrer Häufigkeit und schlimmen Konsequenzen bleibt die Osteoporose untertherapiert. Der Dachverband Osteologie (DVO) hat 2017 seine Leitlinie „Prophylaxe, Diagnostik und Therapie der Osteoporose bei postmenopausalen Frauen und bei Männern“ aktualisiert. Diese Übersichtsarbeit fasst die wichtigsten Empfehlungen und Neuerungen zusammen und gibt einen Ausblick auf Entwicklungen in den nächsten Jahren
„Zur Freiheit des Einzelnen gehört das Recht auf Selbstbestimmung über den eigenen Körper“
Authors: Strasser Benjamin 
Published: December 2019

Summary„DHZ-Herausgeber Siegfried Kämper im Gespräch mit FDP-Politiker Benjamin Strasser über die Gegenwart und Zukunft des Heilpraktikerberufs.“
Herzinsuffizienz und Arrhythmien
Authors: Stellbrink Christoph 
Published: December 2019

ZusammenfassungDie häufigsten und prognostisch bedeutsamsten Arrhythmien bei der Herzinsuffizienz sind Vorhofflimmern und ventrikuläre Arrhythmien. Pathophysiologisch liegen beiden Arrhythmien eine Aktivierung des neurohumoralen Systems im Rahmen des Remodelings, myokardiale Hypertrophie bzw. Fibrose sowie Änderungen der kardialen Erregungsleitung und der Repolarisation zugrunde. Vorhofflimmern führt zu einer Beeinträchtigung der kardialen Hämodynamik, erhöht die Mortalität und das Risiko für thromboembolische Komplikationen. Die Therapie fokussiert daher auf die Antikoagulation, den Erhalt des Sinusrhythmus bzw. eine Frequenzkontrolle, wenn ein Sinusrhythmus nicht mehr dauerhaft erhalten werden kann. Da die antiarrhythmische Therapie praktisch auf Amiodaron beschränkt ist, spielt die Katheterablation eine zunehmende Rolle, wenn ein Erhalt des Sinusrhythmus das therapeutische Ziel ist. Allerdings ist der Eingriff bei herzinsuffizienten Patienten komplex und sollte in erfahrenen Zentren durchgeführt werden. Auch für ventrikuläre Arrhythmien sind die Möglichkeiten der medikamentösen Therapie beschränkt, daher ist bei Patienten mit ausgeprägter systolischer Herzinsuffizienz oft ein implantierbarer Kardioverter-Defibrillator (ICD) indiziert. Allerdings ist die Datenlage für Patienten mit nicht ischämischer Kardiomyopathie etwas schlechter als für Patienten mit linksventrikulärer Dysfunktion nach Infarkt. Auch bei ventrikulären Tachykardien spielt die Katheterablation bei Herzinsuffizienz eine zunehmende Rolle, besonders bei ischämischen Patienten. Sie kann die Häufigkeit von ventrikulären Tachykardien und ICD-Schocks reduzieren, ein Nutzen hinsichtlich Mortalität ist allerdings nicht nachgewiesen.
Medikamenten-assoziierte Kiefernekrosen – Relevanz aus rheumatologischer Sicht?
Authors: Hoefert Sebastian 
Published: December 2019

ZUSAMMENFASSUNGDie Medikamenten-assoziierte Kiefernekrose (MRONJ) ist eine schwere Nebenwirkung einer Antiresorptivatherapie mit Bisphosphonaten und Denosumab sowie von antiangiogenetischen Medikamenten. 16 Jahre nach der Erstbeschreibung der Medikamenten-assoziierten Kiefernekrose konnten noch nicht alle Ursachen geklärt und das Risiko für das Auftreten einer Nekrose minimiert werden. Neue Substanzen und Targeted Therapies können ebenfalls für Nekrosen des Kiefers mit ursächlich sein. Patienten mit rheumatischen Erkrankungen, die mit Biologika und DMARDs behandelt werden, stellen dabei eine besondere Risikogruppe dar und werden nach der neuen S3-Leitlinie „Antiresorptiva-assoziierte Kiefernekrosen (AR-ONJ)“ in ein „mittleres Risikoprofil“ eingeordnet. Aus diesem Grunde ergibt sich eine Relevanz dieses Krankheitsbildes für den rheumatologisch tätigen Mediziner. Dieses soll Anlass sein, über dieses Krankheitsbild zu berichten und für diese Problematik zu sensibilisieren.
Das Kagami-Ogata-Syndrom: Eine Rippenanomalie als pathognomonisches
Korrelat für die klinische Diagnose eines (epi)genetischen
Syndroms
Authors: Westeppe Sarah , Dionysopoulou Anna , Kidszun Andre , Schmeh Isabella , Bartsch Oliver , Mildenberger Eva , Winter Julia 
Published: December 2019

ZusammenfassungInnerhalb von 4 Jahren (2014–2017) haben wir 2 Neugeborene mit der
genetisch gesicherten Diagnose eines Kagami-Ogata-Syndroms (OMIM #608149)
betreut. Pränatal fielen bei beiden Föten ein Polyhydramnion und
in einem Fall eine Hepatomegalie auf. Beide Patienten litten postnatal unter
einer respiratorischen Insuffizienz und wiesen mit einer Muskelhypotonie, einem
vorspringenden Philtrum, vollen Wangen sowie einer breiten Nasenwurzel die
typischen phänotypischen Merkmale dieses Imprinting-Defekts auf.
Wegweisend für die Diagnosestellung waren die
kleiderbügelförmigen Rippen („coat-hanger ribs“)
und der glockenförmige Thorax (bell-shaped thorax) im
Röntgenbild. Das Kagami-Ogata-Syndrom ist auf eine Veränderung
der Genexpression auf dem Chromosom 14 zurückzuführen und wurde
erstmals im Jahr 1991 beschrieben. Als Ursachen werden eine paternale
uniparentale Disomie des Chromosoms 14 von Epimutationen sowie Mikrodeletionen
unterschieden. Bisher sind in der Literatur rund 70 Fälle beschrieben
worden. 34 Betroffene zählen zu der Kohorte der namensgebenden Forscher
M. Kagami und T. Ogata. Die Inzidenz der Erkrankung ist bis heute unbekannt. Die
Patienten zeigen oft eine verzögerte Entwicklung mit einer mentalen
Retardierung, wobei mittlerweile in der Literatur auch Kasuistiken mit milderen
Verläufen zu finden sind. 3 Kinder der Kohorte entwickelten im Verlauf
ein Hepatoblastom, sodass Schnittstellen zu anderen Imprintingdefekten wie dem
Beckwith-Wiedemann-Syndrom nach dem heutigen Stand der Wissenschaft nicht
ausgeschlossen und bei den Nachuntersuchungen berücksichtigt werden
müssen.