TY - JOUR A1 - Beckmann, Nadine A1 - Becker, Katrin Anne A1 - Kadow, Stephanie A1 - Schumacher, Fabian A1 - Kramer, Melanie A1 - Kuehn, Claudine A1 - Schulz-Schaeffer, Walter J. A1 - Edwards, Michael J. A1 - Kleuser, Burkhard A1 - Gulbins, Erich A1 - Carpinteiro, Alexander T1 - Acid Sphingomyelinase Deficiency Ameliorates Farber Disease JF - International journal of molecular sciences N2 - Farber disease is a rare lysosomal storage disorder resulting from acid ceramidase deficiency and subsequent ceramide accumulation. No treatments for Farber disease are clinically available, and affected patients have a severely shortened lifespan. We have recently reported a novel acid ceramidase deficiency model that mirrors the human disease closely. Acid sphingomyelinase is the enzyme that generates ceramide upstream of acid ceramidase in the lysosomes. Using our acid ceramidase deficiency model, we tested if acid sphingomyelinase could be a potential novel therapeutic target for the treatment of Farber disease. A number of functional acid sphingomyelinase inhibitors are clinically available and have been used for decades to treat major depression. Using these as a therapeutic for Farber disease, thus, has the potential to improve central nervous symptoms of the disease as well, something all other treatment options for Farber disease can’t achieve so far. As a proof-of-concept study, we first cross-bred acid ceramidase deficient mice with acid sphingomyelinase deficient mice in order to prevent ceramide accumulation. Double-deficient mice had reduced ceramide accumulation, fewer disease manifestations, and prolonged survival. We next targeted acid sphingomyelinase pharmacologically, to test if these findings would translate to a setting with clinical applicability. Surprisingly, the treatment of acid ceramidase deficient mice with the acid sphingomyelinase inhibitor amitriptyline was toxic to acid ceramidase deficient mice and killed them within a few days of treatment. In conclusion, our study provides the first proof-of-concept that acid sphingomyelinase could be a potential new therapeutic target for Farber disease to reduce disease manifestations and prolong survival. However, we also identified previously unknown toxicity of the functional acid sphingomyelinase inhibitor amitriptyline in the context of Farber disease, strongly cautioning against the use of this substance class for Farber disease patients. KW - Farber disease KW - lysosomal storage disorders KW - acid ceramidase KW - acid sphingomyelinase KW - amitriptyline Y1 - 2019 U6 - https://doi.org/10.3390/ijms20246253 SN - 1422-0067 VL - 20 IS - 24 PB - MDPI CY - Basel ER - TY - JOUR A1 - Lang, Judith A1 - Bohn, Patrick A1 - Bhat, Hilal A1 - Jastrow, Holger A1 - Walkenfort, Bernd A1 - Cansiz, Feyza A1 - Fink, Julian A1 - Bauer, Michael A1 - Schumacher, Fabian A1 - Kleuser, Burkhard A1 - Lang, Karl S. T1 - Acid ceramidase of macrophages traps herpes simplex virus in multivesicular bodies and protects from severe disease JF - Nature Communications N2 - Macrophages have important protective functions during infection with herpes simplex virus type 1 (HSV-1). However, molecular mechanisms that restrict viral propagation and protect from severe disease are unclear. Here we show that macrophages take up HSV-1 via endocytosis and transport the virions into multivesicular bodies (MVBs). In MVBs, acid ceramidase (aCDase) converts ceramide into sphingosine and increases the formation of sphingosine-rich intraluminal vesicles (ILVs). Once HSV-1 particles reach MVBs, sphingosine-rich ILVs bind to HSV-1 particles, which restricts fusion with the limiting endosomal membrane and prevents cellular infection. Lack of aCDase in macrophage cultures or in Asah1(-/-) mice results in replication of HSV-1 and Asah1(-/-) mice die soon after systemic or intravaginal inoculation. The treatment of macrophages with sphingosine enhancing compounds blocks HSV-1 propagation, suggesting a therapeutic potential of this pathway. In conclusion, aCDase loads ILVs with sphingosine, which prevents HSV-1 capsids from penetrating into the cytosol. KW - immunology KW - infection KW - membrane fusion KW - phagocytosis KW - sphingolipids Y1 - 2020 U6 - https://doi.org/10.1038/s41467-020-15072-8 SN - 2041-1723 VL - 11 IS - 1 SP - 1 EP - 15 PB - Nature Publishing Group UK CY - London ER - TY - JOUR A1 - Graf, Lukas A1 - Moreno-de-las-Heras, Mariano A1 - Ruiz, Maurici A1 - Calsamiglia, Aleix A1 - García-Comendador, Julián A1 - Fortesa, Josep A1 - López-Tarazón, José A. A1 - Estrany, Joan T1 - Accuracy assessment of digital terrain model dataset sources for hydrogeomorphological modelling in small mediterranean catchments JF - Remote sensing N2 - Digital terrain models (DTMs) are a fundamental source of information in Earth sciences. DTM-based studies, however, can contain remarkable biases if limitations and inaccuracies in these models are disregarded. In this work, four freely available datasets, including Shuttle Radar Topography Mission C-Band Synthetic Aperture Radar (SRTM C-SAR V3 DEM), Advanced Spaceborne Thermal Emission and Reflection Radiometer Global Digital Elevation Map (ASTER GDEM V2), and two nationwide airborne light detection and ranging (LiDAR)-derived DTMs (at 5-m and 1-m spatial resolution, respectively) were analysed in three geomorphologically contrasting, small (3–5 km2) catchments located in Mediterranean landscapes under intensive human influence (Mallorca Island, Spain). Vertical accuracy as well as the influence of each dataset’s characteristics on hydrological and geomorphological modelling applicability were assessed by using ground-truth data, classic geometric and morphometric parameters, and a recently proposed index of sediment connectivity. Overall vertical accuracy—expressed as the root mean squared error (RMSE) and normalised median deviation (NMAD)—revealed the highest accuracy for the 1-m (RMSE = 1.55 m; NMAD = 0.44 m) and 5-m LiDAR DTMs (RMSE = 1.73 m; NMAD = 0.84 m). Vertical accuracy of the SRTM data was lower (RMSE = 6.98 m; NMAD = 5.27 m), but considerably higher than for the ASTER data (RMSE = 16.10 m; NMAD = 11.23 m). All datasets were affected by systematic distortions. Propagation of these errors and coarse horizontal resolution caused negative impacts on flow routing, stream network, and catchment delineation, and to a lower extent, on the distribution of slope values. These limitations should be carefully considered when applying DTMs for catchment hydrogeomorphological modelling. KW - digital terrain models KW - DTM vertical accuracy KW - DTM comparison KW - hydrogeomorphological modelling KW - Mediterranean catchments Y1 - 2018 U6 - https://doi.org/10.3390/rs10122014 SN - 2072-4292 VL - 10 IS - 12 PB - MDPI CY - Basel ER - TY - JOUR A1 - Göldel, Julia Marlen A1 - Kamrath, Clemens A1 - Minden, Kirsten A1 - Wiegand, Susanna A1 - Lanzinger, Stefanie A1 - Sengler, Claudia A1 - Weihrauch-Blüher, Susann A1 - Holl, Reinhard A1 - Tittel, Sascha René A1 - Warschburger, Petra T1 - Access to Healthcare for Children and Adolescents with a Chronic Health Condition during the COVID-19 Pandemic: First Results from the KICK-COVID Study in Germany JF - Children N2 - This study examines the access to healthcare for children and adolescents with three common chronic diseases (type-1 diabetes (T1D), obesity, or juvenile idiopathic arthritis (JIA)) within the 4th (Delta), 5th (Omicron), and beginning of the 6th (Omicron) wave (June 2021 until July 2022) of the COVID-19 pandemic in Germany in a cross-sectional study using three national patient registries. A paper-and-pencil questionnaire was given to parents of pediatric patients (<21 years) during the routine check-ups. The questionnaire contains self-constructed items assessing the frequency of healthcare appointments and cancellations, remote healthcare, and satisfaction with healthcare. In total, 905 parents participated in the T1D-sample, 175 in the obesity-sample, and 786 in the JIA-sample. In general, satisfaction with healthcare (scale: 0–10; 10 reflecting the highest satisfaction) was quite high (median values: T1D 10, JIA 10, obesity 8.5). The proportion of children and adolescents with canceled appointments was relatively small (T1D 14.1%, JIA 11.1%, obesity 20%), with a median of 1 missed appointment, respectively. Only a few parents (T1D 8.6%; obesity 13.1%; JIA 5%) reported obstacles regarding health services during the pandemic. To conclude, it seems that access to healthcare was largely preserved for children and adolescents with chronic health conditions during the COVID-19 pandemic in Germany. KW - chronic health condition KW - children and adolescents KW - health care KW - COVID-19 pandemic KW - diabetes KW - rheumatic diseases KW - obesity Y1 - 2022 U6 - https://doi.org/10.3390/children10010010 SN - 2227-9067 VL - 10 SP - 1 EP - 11 PB - MDPI CY - Basel, Schweiz ET - 1 ER - TY - JOUR A1 - Kulawiak, Pawel R. T1 - Academic benefits of wearing noise-cancelling headphones during class for typically developing students and students with special needs BT - a scoping review JF - Cogent education N2 - Classroom noise impairs students' cognition and learning. At a first glance, it seems useful to prevent the negative effects of noise on academic learning by wearing noise-cancelling (NC) headphones during class. The literature and guidelines emphasize the academic benefits of wearing NC headphones (decreased auditory distraction, increased concentration, learning improvement, and decreased distress). These benefits are particularly expected for students with special needs. None of the recommendations to wear NC headphones during class refer to any empirical studies, indicating a potential research gap and lack of evidence. Therefore, the question arises: Is there any empirical evidence supporting academic benefits of wearing NC headphones during class for typically developing students or students with special needs? A total of 13 empirical studies (quantitative and qualitative) were identified through a systematic scoping review of the existing literature. A wide range of outcomes (cognition, learning, academic performance, behaviour, and emotions) were reported related to the use of NC headphones. Most of the studies refer to specific groups of students with special needs (learning disabilities, autism, ADHD, etc.). In view of the limited number of studies, small sample sizes, and lack of replication studies, all studies give the impression of being pilot studies on the academic benefits of wearing NC headphones. The practice of wearing NC headphones during class is an understudied topic. The current body of evidence does not meet the standards for evidence-based practices in both general and special education. Implications for educational practice and future research are discussed. KW - classroom noise KW - academic performance KW - noise-cancelling headphones KW - special needs KW - scoping review Y1 - 2021 U6 - https://doi.org/10.1080/2331186X.2021.1957530 SN - 2331-186X VL - 8 IS - 1 PB - Taylor & Francis CY - Abingdon ER - TY - JOUR A1 - Guggenberger, Tobias A1 - Chechkin, Aleksei A1 - Metzler, Ralf T1 - Absence of stationary states and non-Boltzmann distributions of fractional Brownian motion in shallow external potentials JF - New journal of physics : the open-access journal for physics N2 - We study the diffusive motion of a particle in a subharmonic potential of the form U(x) = |x|( c ) (0 < c < 2) driven by long-range correlated, stationary fractional Gaussian noise xi ( alpha )(t) with 0 < alpha <= 2. In the absence of the potential the particle exhibits free fractional Brownian motion with anomalous diffusion exponent alpha. While for an harmonic external potential the dynamics converges to a Gaussian stationary state, from extensive numerical analysis we here demonstrate that stationary states for shallower than harmonic potentials exist only as long as the relation c > 2(1 - 1/alpha) holds. We analyse the motion in terms of the mean squared displacement and (when it exists) the stationary probability density function. Moreover we discuss analogies of non-stationarity of Levy flights in shallow external potentials. KW - diffusion KW - Boltzmann distribution KW - fractional Brownian motion Y1 - 2022 U6 - https://doi.org/10.1088/1367-2630/ac7b3c SN - 1367-2630 VL - 24 IS - 7 PB - Dt. Physikalische Ges. CY - [Bad Honnef] ER - TY - RPRT A1 - Meyer, André A1 - Richter, Eric A1 - Richter, Dirk T1 - Abschlussbericht zur wissenschaftlichen Evaluation der Werkstatt "Schule leiten" N2 - Der vorliegende Abschlussbericht umfasst die Ergebnisse der wissenschaftlichen Evaluation der Werkstatt „Schule leiten“. Bei dieser Werkstatt handelt es sich um ein 18-monatiges Fortbildungsangebot für Schulleitungen, das durch die Deutsche Schulakademie konzipiert und in Kooperation mit dem saarländischen Kultusministerium für Bildung und Kultur sowie dem saarländischen Landesinstitut für Pädagogik und Medien durchgeführt wurde. Im Zeitraum 2016–2020 absolvierten jeweils zwei Personen des Schulleitungsteams allgemeinbildender Schulen erstmalig in insgesamt drei Durchgängen verschiedene Angebote der Werkstatt. Weiterhin erhielten die Teilnehmenden die Aufgaben, im Zuge ihres Fortbildungsbesuches ein individuelles Schulentwicklungsprojekt zu planen, zu entwickeln und unter Anleitung der Werkstatt in der Schule zu implementieren. Zur Überprüfung der wahrgenommenen Qualität sowie der Wirksamkeit des Fortbildungsangebotes wurde die Universität Potsdam, Arbeitsbereich Prof. Dr. Dirk Richter, beauftragt. Der vorliegende Bericht präsentiert die Evaluationsergebnisse der Durchgänge 2 und 3. Im Zentrum der Evaluation stehen die folgenden Forschungsfragen: (1) Wie beurteilen die Teilnehmenden die Qualität der Werkstatt „Schule leiten“? (2) Inwiefern hat die Werkstatt „Schule leiten“ dazu beigetragen, die Leitungskompetenzen (u.a. Einstellungen und Führungshandeln) der Teilnehmenden zu stärken? sowie (3) Wie haben sich schulische Strukturen und Prozesse zur Förderung von Schulentwicklung in den teilnehmenden Schulen durch die Werkstatt „Schule leiten“ verändert? Zur Beantwortung der Fragestellungen wurden eine Reihe schriftlicher Befragungen mit den teilnehmenden Schulleitungen sowie den Lehrkräften der teilnehmenden Schulen durchgeführt. Diese Befragungen erfolgten sowohl begleitend zum Fortbildungsprogramm (nach Absolvieren der einzelnen Angebote) sowie in einem Prä-Post-Follow-Up-Design. Weiterhin wurden im Rahmen einer qualitativen Begleitstudie verschiedene Personen (Schulleitung, Mitglieder des Schulleitungsteams, Lehrkräfte) von insgesamt fünf Schulen über drei Zeitpunkte dazu befragt, wie die Planung, Entwicklung und Implementation der Schulentwicklungsprojekte erfolgten. Die Befunde der Evaluation deuten insgesamt darauf hin, dass die Qualität der Werkstatt „Schule leiten“ als Gesamtprogramm sowie die einzelnen Angebote der Werkstatt sehr positiv bewertet werden. Dabei nehmen die Teilnehmenden von Durchgang 2 die Werkstatt in einer Reihe von Merkmalen positiver wahr als die Teilnehmenden von Durchgang 3. Weiterhin deuten die Ergebnisse darauf hin, dass sich bestimmte Facetten des Führungshandelns der Teilnehmenden im zeitlichen Verlauf positiv verändert haben. Hierfür existieren Hinweise sowohl aus Perspektive der Teilnehmenden selbst als auch aus Perspektive der Lehrkräfte ihrer Schulen. Motivationale Merkmale der Teilnehmenden sowie Aspekte des Führungshandelns, die sich auf Tätigkeiten zur Unterstützung der innerschulischen Kooperation beziehen, bleiben aus Perspektive der Teilnehmenden hingegen weitestgehend konstant. Hinsichtlich der Veränderungen schulischer Strukturen zur Schulentwicklung deuten die Ergebnisse auf eine positive Entwicklung der wahrgenommenen Offenheit gegenüber Kooperation im Kollegium aus Perspektive der Lehrkräfte hin. Die Befunde der qualitativen Begleitstudie liefern weitere Informationen über die wahrgenommene Qualität der Werkstatt sowie über Veränderungen aufseiten der Teilnehmenden und der schulischen Strukturen. KW - Schulleitungen KW - Forbildung KW - Evaluation KW - Schulentwicklung Y1 - 2022 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:kobv:517-opus4-548869 ER - TY - JOUR A1 - Goswami, Bedartha A1 - Boers, Niklas A1 - Rheinwalt, Aljoscha A1 - Marwan, Norbert A1 - Heitzig, Jobst A1 - Breitenbach, Sebastian Franz Martin A1 - Kurths, Jürgen T1 - Abrupt transitions in time series with uncertainties JF - Nature Communications N2 - Identifying abrupt transitions is a key question in various disciplines. Existing transition detection methods, however, do not rigorously account for time series uncertainties, often neglecting them altogether or assuming them to be independent and qualitatively similar. Here, we introduce a novel approach suited to handle uncertainties by representing the time series as a time-ordered sequence of probability density functions. We show how to detect abrupt transitions in such a sequence using the community structure of networks representing probabilities of recurrence. Using our approach, we detect transitions in global stock indices related to well-known periods of politico-economic volatility. We further uncover transitions in the El Niño-Southern Oscillation which coincide with periods of phase locking with the Pacific Decadal Oscillation. Finally, we provide for the first time an ‘uncertainty-aware’ framework which validates the hypothesis that ice-rafting events in the North Atlantic during the Holocene were synchronous with a weakened Asian summer monsoon. Y1 - 2018 U6 - https://doi.org/10.1038/s41467-017-02456-6 SN - 2041-1723 VL - 9 PB - Nature Publ. Group CY - London ER - TY - JOUR A1 - Doering, Ulrike A1 - Grigoriev, Dmitry A1 - Tapio, Kosti A1 - Rosencrantz, Sophia A1 - Rosencrantz, Ruben R. A1 - Bald, Ilko A1 - Böker, Alexander T1 - About the mechanism of ultrasonically induced protein capsule formation JF - RSC Advances : an international journal to further the chemical sciences / Royal Society of Chemistry N2 - In this paper, we propose a consistent mechanism of protein microcapsule formation upon ultrasound treatment. Aqueous suspensions of bovine serum albumin (BSA) microcapsules filled with toluene are prepared by use of high-intensity ultrasound following a reported method. Stabilization of the oil-in-water emulsion by the adsorption of the protein molecules at the interface of the emulsion droplets is accompanied by the creation of the cross-linked capsule shell due to formation of intermolecular disulfide bonds caused by highly reactive species like superoxide radicals generated sonochemically. The evidence for this mechanism, which until now remained elusive and was not proven properly, is presented based on experimental data from SDS-PAGE, Raman spectroscopy and dynamic light scattering. Y1 - 2021 U6 - https://doi.org/10.1039/d0ra08100k SN - 2046-2069 VL - 11 IS - 27 SP - 16152 EP - 16157 PB - RSC Publishing CY - London ER - TY - JOUR A1 - Corti, Giacomo A1 - Cioni, Raffaello A1 - Franceschini, Zara A1 - Sani, Federico A1 - Scaillet, Stephane A1 - Molin, Paola A1 - Isola, Ilaria A1 - Mazzarini, Francesco A1 - Brune, Sascha A1 - Keir, Derek A1 - Erbello Doelesso, Asfaw A1 - Muluneh, Ameha A1 - Illsley-Kemp, Finnigan A1 - Glerum, Anne T1 - Aborted propagation of the Ethiopian rift caused by linkage with the Kenyan rift JF - Nature Communications N2 - Continental rift systems form by propagation of isolated rift segments that interact, and eventually evolve into continuous zones of deformation. This process impacts many aspects of rifting including rift morphology at breakup, and eventual ocean-ridge segmentation. Yet, rift segment growth and interaction remain enigmatic. Here we present geological data from the poorly documented Ririba rift (South Ethiopia) that reveals how two major sectors of the East African rift, the Kenyan and Ethiopian rifts, interact. We show that the Ririba rift formed from the southward propagation of the Ethiopian rift during the Pliocene but this propagation was short-lived and aborted close to the Pliocene-Pleistocene boundary. Seismicity data support the abandonment of laterally offset, overlapping tips of the Ethiopian and Kenyan rifts. Integration with new numerical models indicates that rift abandonment resulted from progressive focusing of the tectonic and magmatic activity into an oblique, throughgoing rift zone of near pure extension directly connecting the rift sectors. Y1 - 2019 U6 - https://doi.org/10.1038/s41467-019-09335-2 SN - 2041-1723 VL - 10 PB - Nature Publ. Group CY - London ER -