Interference during the implicit learning of two different motor sequences

It has been demonstrated that learning a second motor task after having learned a first task may interfere with the long-term consolidation of the first task. However, little is known about immediate changes in the representation of the motor memory in the early acquisition phase within the first minutes of the learning process. Therefore, we investigated such early interference effects with an implicit serial reaction time task in 55 healthy subjects. Each subject performed either a sequence learning task involving two different sequences, or a random control task. The results showed that learning the first sequence led to only a slight, short-lived interference effect in the early acquisition phase of the second sequence. Overall, learning of neither sequence was impaired. Furthermore, the two processes, sequence-unrelated task learning (i.e. general motor training) and the sequence learning itself did not appear to interfere with each other. In conclusion, although the long-term consolidation of a motor memory has been shown to be sensitive to other interfering memories, the present study suggests that the brain is initially able to acquire more than one new motor sequence within a short space of time without significant interferenc

A nuclear localization signal targets tail-anchored membrane proteins to the inner nuclear envelope in plants

Protein targeting to the inner nuclear membrane (INM) is one of the least understood protein targeting pathways. INM proteins are important for chromatin organization, nuclear morphology and movement, and meiosis, and have been implicated in human diseases. In opisthokonts, one mechanism for INM targeting is transport factor-mediated trafficking, in which nuclear localization signals (NLSs) function in nuclear import of transmembrane proteins. To explore whether this pathway exists in plants, we fused the SV40 NLS to a plant ER tail-anchored protein and showed that the GFP-tagged fusion protein was significantly enriched at the nuclear envelope (NE) of leaf epidermal cells. Airyscan subdiffraction limited confocal microscopy showed that this protein displays a localization consistent with an INM protein. Nine different monopartite and bipartite NLSs from plants and opisthokonts, fused to a chimeric tail-anchored membrane protein, were all sufficient for NE enrichment, and both monopartite and bipartite NLSs were sufficient for trafficking to the INM. Tolerance for different linker lengths and protein conformations suggests that INM trafficking rules might differ from those in opisthokonts. The INM proteins developed here can be used to target new functionalities to the plant nuclear periphery

Modell zur Quantifizierung des Energieverbrauchs und der Treibhausgasemissionen von Biobetrieben

Zusammenfassung Während der Jahre 2009-2011 wurden am FiBL über verschiedene Projekte Grundlagen zur betrieblichen und produktbezogenen Energie- und Klimabilanzierung erarbeitet. Daraus wurde ein Modellansatz entwickelt, mit dem der Energieverbrauch und die Treibhausgasemissionen (THG-Emissionen) auf Betriebsebene abgeschätzt werden können. Aus diesen Vorarbeiten ist 2011 und 2012 das FiBL-Betriebsmodell entstanden, mit dem es möglich ist: 1. detaillierte Klimabilanzen von Schweizer Biobetrieben durchzuführen, 2. zwischenbetriebliche Vergleiche anzustellen und 3. die Auswirkungen von betrieblichen Veränderungen oder Anpassungsstrategien auf die THG-Emissionen zu berechnen. Die grosse Stärke des Betriebsmodells ist seine hohe Flexibilität in Bezug auf die Datenerfordernisse. So werden zur Analyse und Optimierung des Energieverbrauchs und der THG-Emissionen auf Schweizer Biobetrieben – wo vorhanden – betriebsindividuelle Daten berücksichtigt. Fehlen diese, werden Standarddaten verwendet. Im Modell werden alle erforderlichen Betriebsmittel und Prozesse zur Bewirtschaftung eines Betriebes, bzw. zur Produktion von Nahrungsmitteln berücksichtigt. Hauptbestandteile des Betriebsmodells sind das sogenannte Pflanzenbau- und das Tierproduktionsmodell, welche untereinander über innerbetrieblicher Stoff- und Energieflüsse (organische Dünger, Futtermittel, Stroh) verknüpft sind. Bei einer betrieblichen Bilanz werden die Emissionen der einzelnen Module aufsummiert und bezogen auf die funktionellen Einheiten Fläche*Jahr-1 und Produktion (Masse, Kalorien, Protein, Wertschöpfung) ausgedrückt. Der Energieverbrauch und die THG-Emissionen lassen sich für alle einzelnen Verfahren aus dem Tier- und Pflanzenbaumodell (z.B. Weizenproduktion, Milchproduktion) bilanzieren. Durch seine Flexibilität was Datenerfordernisse, Systemgrenzen und funktionelle Einheiten betrifft, ist das Betriebsmodell sowohl für wissenschaftliche Analysen als auch Betriebsberatungen geeignet. Ein grosser Vorteil des Modells ist die Möglichkeit, verschiedene Klimaschutz und Energieeinsparmassnahmen zu modellieren und so betriebsspezifisch die Auswirkungen der Massnahmen zu untersuchen. Derzeit sind 11 Massnahmen implementiert (z.B. reduzierte Bodenbearbeitung oder Weideanteil vergrössern bzw. standortangepasste Umstellung auf Vollweide), weitere Massnahmen können problemlos integriert werden. Weiterhin ist geplant, das Modell auf andere Nachhaltigkeitskategorien (Luft- und Gewässerbelastung, Humusaufbau, Biodiversität, Ökonomie und Soziales) zu erweitern. Bisher wurde das Betriebsmodell nur auf Bio-Milchvieh und Bio-Gemischtbetrieben angewendet. Für die Abbildung weiterer Betriebstypen (z.B. Obst- und Gemüsebau) sind teilweise Anpassungen am Modell erforderlich. Ziel dieses Papieres ist es, die Funktionsweise und Annahme des Modells transparent zu machen und zur Diskussion zu stellen. Dabei gehen wir zunächst auf das grundlegende Konzept ein und stellen danach die unterschiedlichen Module vor. Für Fragen, Anregungen und konstruktive Kritik sind wir dankbar, da dies für uns ein Mittel ist das Modell stetig weiterzuentwickeln und zu verbessern

Individualized versus Standardized Risk Assessment in Patients at High Risk for Adverse Drug Reactions (The IDrug Randomized Controlled Trial)–Never Change a Running System?

The aim of this study was to compare effects of an individualized with a standardized risk assessment for adverse drug reactions to improve drug treatment with antithrombotic drugs in older adults. A randomized controlled trial was conducted in general practitioner (GP) offices. Patients aged 60 years and older, multi-morbid, taking antithrombotic drugs and at least one additional drug continuously were randomized to individualized and standardized risk assessment groups. Patients were followed up for nine months. A composite endpoint defined as at least one bleeding, thromboembolic event or death reported via a trigger list was used. Odds ratios (OR) and 95% confidence intervals (CI) were calculated. In total, N = 340 patients were enrolled from 43 GP offices. Patients in the individualized risk assessment group met the composite endpoint more often than in the standardized group (OR 1.63 [95%CI 1.02–2.63]) with multiple adjustments. The OR was higher in patients on phenprocoumon treatment (OR 1.99 [95%CI 1.05–3.76]), and not significant on DOAC treatment (OR 1.52 [95%CI 0.63–3.69]). Pharmacogenenetic variants of CYP2C9, 2C19 and VKORC1 were not observed to be associated with the composite endpoint. The results of this study may indicate that the time point for implementing individualized risk assessments is of importance

FACT - Long-term Monitoring of Bright TeV-Blazars

Since October 2011, the First G-APD Cherenkov Telescope (FACT) is operated successfully on the Canary Island of La Palma. Apart from the proof of principle for the use of G-APDs in Cherenkov telescopes, the major goal of the project is the dedicated long-term monitoring of a small sample of bright TeV blazars. The unique properties of G-APDs permit stable observations also during strong moon light. Thus a superior sampling density is provided on time scales at which the blazar variability amplitudes are expected to be largest, as exemplified by the spectacular variations of Mrk 501 observed in June 2012. While still in commissioning, FACT monitored bright blazars like Mrk 421 and Mrk 501 during the past 1.5 years so far. Preliminary results including the Mrk 501 flare from June 2012 will be presented.Comment: 4 pages, 4 figures, presented at the 33rd ICRC (2013

Wasp controls oriented migration of endothelial cells to achieve functional vascular patterning

Endothelial cell migration and proliferation are essential for the establishment of a hierarchical organization of blood vessels and optimal distribution of blood. However, how these cellular processes are coordinated remains unknown. Here, using the zebrafish trunk vasculature we show that in future veins endothelial cells proliferate more than in future arteries and migrate preferentially towards neighboring arteries. In future arteries endothelial cells show a biphasic migration profile. During sprouting cells move away from the dorsal aorta, during remodelling cells stop or move towards the feeding aorta. The final morphology of blood vessels is thus established by local proliferation and oriented cell migration to and from neighboring vessels. Additionally, we identify WASp to be essential for this differential migration. Loss of WASp leads to irregular distribution of endothelial cells, substantially enlarged veins and persistent arteriovenous shunting. Mechanistically, we report that WASp drives the assembly of junctional associated actin filaments and is required for junctional expression of PECAM-1. Together, our data identify that functional vascular patterning in the zebrafish trunk utilizes differential cell movement regulated by junctional actin, and that interruption of differential migration may represent a pathomechanism in vascular malformations

Comparison of drug-eluting stents with bare metal stents in patients with ST-segment elevation myocardial infarction

Aims To evaluate safety and effectiveness of early generation drug-eluting stents (DES) compared with bare-metal stents (BMS) in patients with ST-segment elevation myocardial infarction (STEMI) undergoing primary percutaneous coronary intervention (PCI), and to determine whether benefits and risks vary over time. Methods and results We performed a meta-analysis of 15 randomized controlled trials enrolling a total of 7867 patients comparing first-generation FDA-approved DES with BMS in patients with STEMI. Random effect models were used to assess differences in outcomes between DES and BMS among different time periods with regard to the pre-specified primary outcomes stent thrombosis (ST) and target vessel revascularization (TVR). The overall risk of definite ST was similar for DES and BMS [risk ratio (RR) = 1.08, 95% CI 0.82-1.43]. However, there were time-dependent effects, with a RR of 0.80 during the first year (95% CI 0.58-1.12) and 2.10 during subsequent years (95% CI 1.20-3.69), with a positive test for interaction between RR of ST and time (P for interaction = 0.009). Results were similar for definite or probable ST (P for interaction = 0.015). In the overall analysis, TVR was performed less frequently in patients with DES when compared with BMS (RR 0.51, 95% CI 0.43-0.61), with a greater benefit in the first year (RR 0.46, 95% CI 0.38-0.55) when compared with subsequent years (RR 0.75, 95% CI 0.59-0.94; P for interaction = 0.007). Conclusion An early benefit of early generation DES in primary PCI for STEMI with a reduction in TVR and a trend towards less definite ST is offset in subsequent years by an increased risk of very late S

The state of the Martian climate

60°N was +2.0°C, relative to the 1981–2010 average value (Fig. 5.1). This marks a new high for the record. The average annual surface air temperature (SAT) anomaly for 2016 for land stations north of starting in 1900, and is a significant increase over the previous highest value of +1.2°C, which was observed in 2007, 2011, and 2015. Average global annual temperatures also showed record values in 2015 and 2016. Currently, the Arctic is warming at more than twice the rate of lower latitudes