bluuebunny/crossref_metadata_2025_split huggingface dataset:
Size dependent effects of Gold Nanoparticles in ISO-induced Hyperthyroid Rats
Authors: Zhang Jingwen , Xue Yanbo , Ni Yajuan , Ning Feifei , Shang Lijun , Ma Aiqun 
Published: July 2018

AbstractIn this study, we applied different sizes of gold nanoparticles (Au-NPs) to isoproterenol (ISO)-induced hyperthyroid heart disease rats (HHD rats). Single dose of 5, 40, 100 nm Au-NPs were injected intravenously. Cardiac safety tests were evaluated by cardiac marker enzymes in serum and cardiac accumulation of Au-NPs were measured by ICP-MS. Our results showed that size-dependent cardiac effects of Au-NPs in ISO-induced hyperthyroid rats. 5 nm Au-NPs had some cardiac protective effect but little accumulation in heart, probably due to smaller size Au-NPs can adapt to whole body easily in vivo. Histological analysis and TUNEL staining showed that Au-NPs can induce pathological alterations including cardiac fibrosis, apoptosis in control groups, however they can protect HHD groups from these harmful effects. Furthermore, transmission electron microscopy and western blotting employed on H9C2 cells showed that autophagy presented in Au-NPs treated cells and that Au-NPs can decrease LC3 II turning to LC3 I and decrease APG7 and caspase 12 in the process in HHD groups, while opposite effects on control groups were presented, which could be an adaptive inflammation reacts. As there are few animal studies about using nanoparticles in the treatment of heart disease, our in vivo and in vitro studies would provide valuable information before they can be considered for clinical use in general.
Small molecule activator of Nm23/NDPK as an inhibitor of metastasis
Authors: Lee Jae-Jin , Kim Hwang Suk , Lee Ji-Sun , Park Jimin , Shin Sang Chul , Song Soonwha , Lee Eunsun , Choi Jung-Eun , Suh Ji-Wan , Lee Hongsoo , Kim Eunice EunKyeong , Seo Eun Kyoung , Shin Dong Hae , Lee Ho-Young , Lee Hee-Yoon , Lee Kong-Joo 
Published: July 2018

AbstractNm23-H1/NDPK-A is a tumor metastasis suppressor having NDP kinase (NDPK) activity. Nm23-H1 is positively associated with prolonged disease-free survival and good prognosis of cancer patients. Approaches to increasing the cellular levels of Nm23-H1 therefore have significance in the therapy of metastatic cancers. We found a small molecule, (±)-trans-3-(3,4-dimethoxyphenyl)-4-[(E)-3,4-dimethoxystyryl]cyclohex-1-ene, that activates Nm23, hereafter called NMac1. NMac1 directly binds to Nm23-H1 and increases its NDPK activity. Employing various NMac1 derivatives and hydrogen/deuterium mass spectrometry (HDX-MS), we identified the pharmacophore and mode of action of NMac1. We found that NMac1 binds to the C-terminal of Nm23-H1 and induces the NDPK activation through its allosteric conformational changes. NMac1-treated MDA-MB-231 breast cancer cells showed dramatic changes in morphology and actin-cytoskeletal organization following inhibition of Rac1 activation. NMac1 also suppressed invasion and migration in vitro, and metastasis in vivo, in a breast cancer mouse model. NMac1 as an activator of NDPK has potential as an anti-metastatic agent.
Chromatin remodeling in Drosophila preblastodermic embryo extract
Authors: Šatović Eva , Font-Mateu Jofre , Carbonell Albert , Beato Miguel , Azorín Fernando 
Published: July 2018

AbstractChromatin is known to undergo extensive remodeling during nuclear reprogramming. However, the factors and mechanisms involved in this remodeling are still poorly understood and current experimental approaches to study it are not best suited for molecular and genetic analyses. Here we report on the use of Drosophila preblastodermic embryo extracts (DREX) in chromatin remodeling experiments. Our results show that incubation of somatic nuclei in DREX induces changes in chromatin organization similar to those associated with nuclear reprogramming, such as rapid binding of the germline specific linker histone dBigH1 variant to somatic chromatin, heterochromatin reorganization, changes in the epigenetic state of chromatin, and nuclear lamin disassembly. These results raise the possibility of using the powerful tools of Drosophila genetics for the analysis of chromatin changes associated with this essential process.
Investigating the Association between Chronic Kidney Disease and Ischaemic Stroke from a Health Examination Database
Authors: Ou-Yang Chao , Handaruputri Theresa Lalita , Wang Han-Cheng , Chen Chiehfeng 
Published: July 2018

AbstractStroke has become one of the leading causes of death, with ischaemic stroke as the most common type of stroke occurrence compared to haemorrhagic stroke. Chronic kidney disease(CKD), another important cause of death, shares several traditional cardiovascular riskfactors with ischaemic stroke. Therefore, it is important to examine the existence of shared risk factors in the association between CKD and ischaemic stroke. This study used a health examination database from a medical centre in Taiwan. A generalized linear regression analysis was used to determine the association between CKD and ischaemic stroke. The Maentel-Haenszel test was performed to analyse the effect of possible confounding factors on the association between CKD and ischaemic stroke. A prevalence rate study showed that more subjects with CKD suffered from ischaemic stroke than subjects without CKD. Diabetes, hypertension, hypertriglyceridemia, and hypercholesterolemia were associated with increased risks of ischaemic stroke in CKD subjects. There was an inverse association of the odds ratio of ischaemic stroke between CKD and non-CKD patients, which implied that younger subjects with CKD should be made aware of ischaemic stroke prevention.
Structure of the replication regulator Sap1 reveals functionally important interfaces
Authors: Jørgensen Maria M. , Ekundayo Babatunde , Zaratiegui Mikel , Skriver Karen , Thon Geneviève , Schalch Thomas 
Published: July 2018

AbstractThe mechanism by which specific protein-DNA complexes induce programmed replication fork stalling in the eukaryotic genome remains poorly understood. In order to shed light on this process we carried out structural investigations on the essential fission yeast protein Sap1. Sap1 was identified as a protein involved in mating-type switching in Schizosaccharomyces pombe, and has been shown to be involved in programmed replication fork stalling. Interestingly, Sap1 assumes two different DNA binding modes. At the mating-type locus dimers of Sap1 bind the SAS1 sequence in a head-to-head arrangement, while they bind to replication fork blocking sites at rDNA and Tf2 transposons in a head-to-tail mode. In this study, we have solved the crystal structure of the Sap1 DNA binding domain and we observe that Sap1 molecules interact in the crystal using a head-to-tail arrangement that is compatible with DNA binding. We find that Sap1 mutations which alleviate replication-fork blockage at Tf2 transposons in CENP-B mutants map to the head-to-tail interface. Furthermore, several other mutations introduced in this interface are found to be lethal. Our data suggests that essential functions of Sap1 depend on its head-to-tail oligomerization.
A Multifunctional Interlayer for Solution Processed High Performance Indium Oxide Transistors
Authors: Kyndiah Adrica , Ablat Abduleziz , Guyot-Reeb Seymour , Schultz Thorsten , Zu Fengshuo , Koch Norbert , Amsalem Patrick , Chiodini Stefano , Yilmaz Alic Tugbahan , Topal Yasemin , Kus Mahmut , Hirsch Lionel , Fasquel Sophie , Abbas Mamatimin 
Published: July 2018

AbstractMultiple functionality of tungsten polyoxometalate (POM) has been achieved applying it as interfacial layer for solution processed high performance In2O3 thin film transistors, which results in overall improvement of device performance. This approach not only reduces off-current of the device by more than two orders of magnitude, but also leads to a threshold voltage reduction, as well as significantly enhances the mobility through facilitated charge injection from the electrode to the active layer. Such a mechanism has been elucidated through morphological and spectroscopic studies.
Permafrost Degradation and Subsidence Observations during a Controlled Warming Experiment
Authors: Wagner Anna M. , Lindsey Nathaniel J. , Dou Shan , Gelvin Arthur , Saari Stephanie , Williams Christopher , Ekblaw Ian , Ulrich Craig , Borglin Sharon , Morales Alejandro , Ajo-Franklin Jonathan 
Published: July 2018

AbstractGlobal climate change has resulted in a warmer Arctic, with projections indicating accelerated modifications to permafrost in the near future. The thermal, hydrological, and mechanical physics of permafrost thaw have been hypothesized to couple in a complex fashion but data collection efforts to study these feedbacks in the field have been limited. As a result, laboratory and numerical models have largely outpaced field calibration datasets. We present the design, execution, and initial results from the first decameter-scale controlled thawing experiment, targeting coupled thermal/mechanical response, particularly the temporal sequence of surface subsidence relative to permafrost degradation at depth. The warming test was conducted in Fairbanks, AK, and utilized an array of in-ground heaters to induce thaw of a ~11 × 13 × 1.5 m soil volume over 63 days. The 4-D temperature evolution demonstrated that the depth to permafrost lowered 1 m during the experiment. The resulting thaw-induced surface deformation was ~10 cm as observed using a combination of measurement techniques. Surface deformation occurred over a smaller spatial domain than the full thawed volume, suggesting that gradients in cryotexture and ice content were significant. Our experiment provides the first large field calibration dataset for multiphysics thaw models.
Faster growth with shorter antigens can explain a VSG hierarchy during African trypanosome infections: a feint attack by parasites
Authors: Liu Dianbo , Albergante Luca , Newman T. J. , Horn David 
Published: July 2018

AbstractThe parasitic African trypanosome,Trypanosoma brucei, evades the adaptive host immune response by a process of antigenic variation that involves the clonal switching of variant surface glycoproteins (VSGs). The VSGs that come to dominatein vivoduring an infection are not entirely random, but display a hierarchical order. How this arises is not fully understood. Combining available genetic data with mathematical modelling, we report a VSG-length-dependent hierarchical timing of clonal VSG dominance in a mouse model, consistent with an inverse correlation between VSG length and trypanosome growth-rate. Our analyses indicate that, among parasites switching to new VSGs, those expressing shorter VSGs preferentially accumulate to a detectable level that is sufficient to trigger a targeted immune response. This may be due to the increased metabolic cost of producing longer VSGs. Subsequent elimination of faster-growing parasites then allows slower-growing parasites with longer VSGs to accumulate. This interaction between the host and parasite is able to explain the temporal distribution of VSGs observedin vivo. Thus, our findings reveal a length-dependent hierarchy that operates duringT. bruceiinfection. This represents a ‘feint attack’ diversion tactic utilised by these persistent parasites to out-maneuver the host adaptive immune system.
Transcriptome Profiles of Nod Factor-independent Symbiosis in the Tropical Legume Aeschynomene evenia
Authors: Gully Djamel , Czernic Pierre , Cruveiller Stéphane , Mahé Frédéric , Longin Cyrille , Vallenet David , François Philippe , Nidelet Sabine , Rialle Stéphanie , Giraud Eric , Arrighi Jean-François , DasGupta Maitrayee , Cartieaux Fabienne 
Published: July 2018

AbstractNod factors (NF) were assumed to be indispensable for the establishment of a rhizobium-legume symbiosis until the discovery that certain Bradyrhizobium strains interacting with certain Aeschynomene species lack the canonical nodABC genes required for their synthesis. So far, the molecular dialogue between Aeschynomene and its symbionts remains an open question. Here we report a time course transcriptional analysis of Aeschynomene evenia in response to inoculation with Bradyrhizobium ORS278. The NF-independent symbiotic process was monitored at five time points between bacterial infection and nodule maturity. The five time points correspond to three specific events, root infection by crack entry, nodule organogenesis, and the establishment of the nitrogen fixing process. During the third stage, about 80 NCR-like genes and eight symbiotic genes known to be involved in signaling, bacterial infection or nodulation regulation were highly expressed. Comparative gene expression analyses at the five time points also enabled the selection of genes with an expression profile that makes them promising markers to monitor early plant responses to bacteria. Such markers could be used in bioassays to identify the nature of the bacterial signal(s). Our data represent valuable resources for investigation of this Nod factor-independent symbiosis.
Characterization of the effects of immunomodulatory drug fingolimod (FTY720) on human T cell receptor signaling pathways
Authors: Baer Alan , Colon-Moran Winston , Bhattarai Nirjal 
Published: July 2018

AbstractImmune responses against gene therapy products limit its therapeutic efficacy and present a safety risk. Identification of agents that blunt immune reactions may aid in developing novel immunomodulatory therapies. Fingolimod (FTY720) is an FDA approved immunomodulatory drug for treating multiple sclerosis that inhibits lymphocyte egress from lymphoid tissues by down regulating sphingosine-1 phosphate receptor (S1PR). Recent studies found that FTY720 inhibits T cell activation (TCA) in a S1PR-independent manner; however, the mechanism is incompletely understood. Here we characterized the effects of FTY720 on human T cell receptor (TCR) signaling pathways. FTY720 inhibited both the TCR-dependent and independent activation of primary human T cells. FTY720 did not affect proximal TCR signaling events as measured by phosphorylation of Lck, ZAP-70 and LAT; however, inhibited PMA/Ionomycin induced distal TCR signaling as measured by IL-2, IFN-γ release and CD25 expression. FTY720 induced aberrant NFAT1, AP1 and NFκB activation which were associated with increased acetylation of histone (H3K9). Phosphorylated FTY720 did not inhibit TCA, and arachidonic acid did not rescue FTY720 mediated inhibition of TCA. These data suggest that FTY720 mediated inhibition of TCA is due to inhibition of distal TCR signaling. Understanding FTY720-mediated inhibition of TCA may aid in developing novel FTY720-based immunomodulatory agents.
Mapping the 13CO/C18O abundance ratio in the massive star-forming region G29.96−0.02
Authors: Paron S. , Areal M. B. , Ortega M. E. 
Published: July 2018

Aims. Estimating molecular abundances ratios from directly measuring the emission of the molecules toward a variety of interstellar environments is indeed very useful to advance our understanding of the chemical evolution of the Galaxy, and hence of the physical processes related to the chemistry. It is necessary to increase the sample of molecular clouds, located at different distances, in which the behavior of molecular abundance ratios, such as the 13CO/C18O ratio, is studied in detail.
Methods. We selected the well-studied high-mass star-forming region G29.96−0.02, located at a distance of about 6.2 kpc, which is an ideal laboratory to perform this type of study. To study the 13CO/C18O abundance ratio (X13∕18) toward this region, we used 12CO J = 3–2 data obtained from the CO High-Resolution Survey, 13CO and C18O J = 3–2 data from the 13CO/C18O (J = 3–2) Heterodyne Inner Milky Way Plane Survey, and 13CO and C18O J = 2–1 data retrieved from the CDS database that were observed with the IRAM 30 m telescope. The distribution of column densities and X13∕18 throughout the extension of the analyzed molecular cloud was studied based on local thermal equilibrium (LTE) and non-LTE methods.
Results. Values of X13∕18 between 1.5 and 10.5, with an average of about 5, were found throughout the studied region, showing that in addition to the dependency of X13∕18 and the galactocentric distance, the local physical conditions may strongly affect this abundance ratio. We found that correlating the X13∕18 map with the location of the ionized gas and dark clouds allows us to suggest in which regions the far-UV radiation stalls in dense gaseous components, and in which regions it escapes and selectively photodissociates the C18O isotope. The non-LTE analysis shows that the molecular gas has very different physical conditions, not only spatially throughout the cloud, but also along the line of sight. This type of study may represent a tool for indirectly estimating (from molecular line observations) the degree of photodissociation in molecular clouds, which is indeed useful to study the chemistry in the interstellar medium.
„Kritische Diskussion sollte mehr gefördert werden!“– Eine qualitative Auswertung der Lehrevaluation von Medizinstudierenden zur komplementärmedizinischen Lehre
Authors: Valentini Jan , Glassen Katharina , Eicher Christiane , Washington-Dorando Phoebe , Weinschenk Stefan , Musselmann Berthold , Steinhaeuser Jost , Joos Stefanie 
Published: July 2018

Zusammenfassung
Hintergrund In der deutschen Approbationsordnung für Ärzte sind Inhalte aus den Bereichen der Naturheilverfahren und Komplementärmedizin im Querschnittsbereich 12 „Rehabilitation, physikalische Medizin, Naturheilverfahren“ (QB12) curricular verankert. Diese werden an der Universität Heidelberg als Pflicht- und Prüfungsfach in Form von Vorlesungen und Praktika in Kleingruppen unterrichtet. In der vorliegenden Studie wurde die Evaluation von Medizinstudierenden im Bereich der Komplementärmedizin ausgewertet mit dem Ziel, Haltung, Lernbedürfnisse und Interessen von Studierenden in diesem Bereich zu explorieren.
Methoden Die Lehrveranstaltungen wurden von Beginn an im Rahmen der fakultätseigenen Lehrevaluation wissenschaftlich begleitet. Die Freitexte der Evaluationen zwischen dem Wintersemester 2011/2012 und dem Sommersemester 2013 wurden gesammelt und mittels qualitativer Inhaltsanalyse nach Mayring ausgewertet.
Ergebnisse Die Freitexte wurden in 3 deduktive Hauptkategorien (Haltung, Lernbedürfnisse und Interessen) und in weitere Subkategorien unterteilt. Als zentrales Thema fällt die Polarisierung unter den Medizinstudierenden im Hinblick auf Komplementärmedizin auf, die von regem Widerstand bis zu großer Begeisterung reicht. Auffällig häufig waren Kommentare, die erkennen ließen, dass Studierende eine hohe Erwartungshaltung in dem Sinne zeigen, dass sie von einem komplementärmedizinischen Thema oder einer Methode überzeugt werden wollen. Dies war insbesondere bei Lehrinhalten zu nicht medikamentösen Verfahren zu erkennen.
Diskussion Aus den Ergebnissen geht hervor, dass die theoretische Vermittlung komplementärmedizinischer Lehrinhalte kombiniert mit praktischen Erfahrungen „am eigenen Leib“ zur kritischen Reflexion und zur Entwicklung einer ganzheitlichen, patientenorientierten Haltung unter Medizinstudierenden beitragen kann. Diese Ergebnisse können als Grundlage für die Planung, Implementierung und Umsetzung komplementärmedizinischer Lehre an anderen universitären Standorten dienen.
Mechanische Schwingungstherapie in der Orthopädischen Rehabilitation
Authors: Grote Vincent , Böttcher Elke , Zahirovic Seada , Moser Maximilian , Puff Henry 
Published: July 2018

Zusammenfassung
Fragestellung Klinische Anwendungen von mechanischen Schwingungstherapien werden widersprüchlich diskutiert. Orthopädische Krankheitsbilder, wie Endoprothesen, gelten als Kontraindikation.
Material und Methoden Im Rahmen einer 3-wöchigen stationären Rehabilitation wurden 109 orthopädischen PatientInnen (61,4±8 Jahre) stratifiziert einer Versuchsgruppe zugeteilt: Schwingungstherapieliege (Tiktaalik), Überwassermassage (Hydrojet) und Scheinbehandlung (Placebo). Auswirkungen auf medizinische Ergebnisqualität und Herzfrequenzvariabilität wurden geprüft.
Ergebnisse Bei einer Therapiedauer von 12 Min lagen die selbst wählbaren Schwingungsfrequenzen der Therapieliege zwischen 11 und 15 Hz im Brustbereich (Vibrationsschwingung) und 3 bis sieben Hz im Beckenbereich (Lateralschwingung). 2 PatientInnen mussten die Schwingungstherapie vorzeitig abbrechen (Kopfschmerz, Schwindel). Als Folge der Mobilisierung durch die Rehabilitationsmaßnahmen kam es zu einer Zunahme der sympathikotonen Aktivierung. Es konnten Verbesserungen in Schmerzempfinden (VAS) und motorischer Funktion (Beweglichkeit, Muskelkraft) festgestellt werden. Eine Interaktion des Rehabilitationsverlauf mit den Versuchsgruppen wurde unmittelbar zu den Therapieeinheiten beobachtet: Die Beweglichkeit, Muskelkraft und Wachheit nahm in der Tiktaalik-Gruppe stärker zu. Dabei zeichnete sich mechanische Schwingungstherapie insbesondere durch eine stärkere parasympathische Aktivierung aus - es kam in der Nachruhephase zu einer signifikant stärkeren Entspannung.
Diskussion und Schlussfolgerung Die Studienergebnisse zeigen, dass eine mechanische Schwingungsbehandlung im Liegen eine Erweiterung des bestehenden Therapieangebots in der orthopädischen Rehabilitation darstellt.
Medikationspläne bei Krankenhausaufnahme – eine multizentrische Analyse unter Nutzung von Routinedaten einer gesetzlichen Krankenversicherung
Authors: Wilke Dominik , Schiek Susanne , Knoth Holger , Bertsche Thilo 
Published: July 2018

Zusammenfassung
Einleitung Veränderungen der Arzneimitteltherapie an intersektoralen Schnittstellen können zu klinisch relevanten arzneimittelbezogenen Problemen führen. Ziel dieser Studie war ein Vergleich der Kontinuität in der Arzneimittelverordnung von Patienten mit und ohne Medikationsplan (MP) bei Krankenhausaufnahme.
Methoden Nach Erhalt des Ethikvotums wurden in 6 Krankenhäusern in Sachsen von November 2011 bis Januar 2012 konsekutiv Patienten einer gesetzlichen Krankenversicherung (GKV) nach schriftlicher Einwilligung aufgenommen. Für Patienten mit und ohne MP bei Krankenhausaufnahme wurden diese Daten ausgewertet: (1) die am Tag der Krankenhausaufnahme vom Krankenhausarzt verordneten Arzneimittel aus der Patientenkurve, (2) die Arzneimittel des Krankenhausentlassungsbriefes. Diesen Daten wurden patientenbezogene ambulante Arzneimittelverordnungsdaten einer GKV für den Zeitraum 6 Monate vor und nach der stationären Therapie zugeordnet (Datenlinkage).
Ergebnisse Bei 173 (62 %) der 279 Studienteilnehmer lag ein MP bei Krankenhausaufnahme vor. Patienten mit MP hatten ein statistisch signifikant höheres Lebensalter, eine höhere Anzahl an Arzneimitteln und Diagnosen und wurden bei diesem Krankenhausaufenthalt seltener als Notfallbehandlung aufgenommen. Bei Krankenhausaufnahme weitergeführt wurden 53 % der Arzneimittel bei Patienten mit mitgebrachtem MP und 40 % bei Patienten ohne MP (p < 0,001). Bei Krankenhausentlassung wurden 66 % bzw. 64 % der Medikation fortgesetzt (n. s.). Am häufigsten wurde der mitgebrachte MP vom Hausarzt erstellt (38 %) und in 12 % vom Patienten selbst.
Diskussion Noch vor der gesetzlich vorgesehenen Einführung des MP besaßen bei Krankenhausaufnahme fast zwei Drittel der Patienten einen MP. Dieser war allerdings in vielen Fällen vom Patienten selbst erstellt worden. Das Vorliegen eines MP kann einen Einfluss auf die Kontinuität der Arzneimittelverordnung im Krankenhaus nehmen, jedoch nicht auf die Weiterverordnung bei Krankenhausentlassung.