TY - JOUR A1 - Krstic, Jelena A1 - Reinisch, Isabel A1 - Schupp, Michael A1 - Schulz, Tim Julius A1 - Prokesch, Andreas T1 - p53 functions in adipose tissue metabolism and homeostasis JF - International journal of molecular sciences N2 - As a tumor suppressor and the most frequently mutated gene in cancer, p53 is among the best-described molecules in medical research. As cancer is in most cases an age-related disease, it seems paradoxical that p53 is so strongly conserved from early multicellular organisms to humans. A function not directly related to tumor suppression, such as the regulation of metabolism in nontransformed cells, could explain this selective pressure. While this role of p53 in cellular metabolism is gradually emerging, it is imperative to dissect the tissue-and cell-specific actions of p53 and its downstream signaling pathways. In this review, we focus on studies reporting p53's impact on adipocyte development, function, and maintenance, as well as the causes and consequences of altered p53 levels in white and brown adipose tissue (AT) with respect to systemic energy homeostasis. While whole body p53 knockout mice gain less weight and fat mass under a high-fat diet owing to increased energy expenditure, modifying p53 expression specifically in adipocytes yields more refined insights: (1) p53 is a negative regulator of in vitro adipogenesis; (2) p53 levels in white AT are increased in diet-induced and genetic obesity mouse models and in obese humans; (3) functionally, elevated p53 in white AT increases senescence and chronic inflammation, aggravating systemic insulin resistance; (4) p53 is not required for normal development of brown AT; and (5) when p53 is activated in brown AT in mice fed a high-fat diet, it increases brown AT temperature and brown AT marker gene expression, thereby contributing to reduced fat mass accumulation. In addition, p53 is increasingly being recognized as crucial player in nutrient sensing pathways. Hence, despite existence of contradictory findings and a varying density of evidence, several functions of p53 in adipocytes and ATs have been emerging, positioning p53 as an essential regulatory hub in ATs. Future studies need to make use of more sophisticated in vivo model systems and should identify an AT-specific set of p53 target genes and downstream pathways upon different (nutrient) challenges to identify novel therapeutic targets to curb metabolic diseases KW - p53 KW - adipose tissue KW - metabolic syndrome KW - obesity KW - adipogenesis KW - insulin resistance Y1 - 2018 U6 - https://doi.org/10.3390/ijms19092622 SN - 1422-0067 VL - 19 IS - 9 PB - MDPI CY - Basel ER - TY - JOUR A1 - Schulze, Sven A1 - Wehrhold, Michel A1 - Hille, Carsten T1 - Femtosecond-Pulsed laser written and etched fiber bragg gratings for fiber-optical biosensing JF - Sensors N2 - We present the development of a label-free, highly sensitive fiber-optical biosensor for online detection and quantification of biomolecules. Here, the advantages of etched fiber Bragg gratings (eFBG) were used, since they induce a narrowband Bragg wavelength peak in the reflection operation mode. The gratings were fabricated point-by-point via a nonlinear absorption process of a highly focused femtosecond-pulsed laser, without the need of prior coating removal or specific fiber doping. The sensitivity of the Bragg wavelength peak to the surrounding refractive index (SRI), as needed for biochemical sensing, was realized by fiber cladding removal using hydrofluoric acid etching. For evaluation of biosensing capabilities, eFBG fibers were biofunctionalized with a single-stranded DNA aptamer specific for binding the C-reactive protein (CRP). Thus, the CRP-sensitive eFBG fiber-optical biosensor showed a very low limit of detection of 0.82 pg/L, with a dynamic range of CRP detection from approximately 0.8 pg/L to 1.2 mu g/L. The biosensor showed a high specificity to CRP even in the presence of interfering substances. These results suggest that the proposed biosensor is capable for quantification of CRP from trace amounts of clinical samples. In addition, the adaption of this eFBG fiber-optical biosensor for detection of other relevant analytes can be easily realized. KW - fiber Bragg gratings KW - ultra-fast laser inscription KW - fiber etching KW - nanostructure fabrication KW - fiber-optical sensors KW - aptamers KW - C-reactive protein KW - biomarker Y1 - 2018 U6 - https://doi.org/10.3390/s18092844 SN - 1424-8220 VL - 18 IS - 9 PB - MDPI CY - Basel ER - TY - JOUR A1 - Biterova, Ekaterina A1 - Esmaeeli Moghaddam Tabalvandani, Mariam A1 - Alanen, Heli I. A1 - Saaranen, Mirva A1 - Ruddock, Lloyd W. T1 - Structures of Angptl3 and Angptl4, modulators of triglyceride levels and coronary artery disease JF - Scientific reports N2 - Coronary artery disease is the most common cause of death globally and is linked to a number of risk factors including serum low density lipoprotein, high density lipoprotein, triglycerides and lipoprotein(a). Recently two proteins, angiopoietin-like protein 3 and 4, have emerged from genetic studies as being factors that significantly modulate plasma triglyceride levels and coronary artery disease. The exact function and mechanism of action of both proteins remains to be elucidated, however, mutations in these proteins results in up to 34% reduction in coronary artery disease and inhibition of function results in reduced plasma triglyceride levels. Here we report the crystal structures of the fibrinogen-like domains of both proteins. These structures offer new insights into the reported loss of function mutations, the mechanisms of action of the proteins and open up the possibility for the rational design of low molecular weight inhibitors for intervention in coronary artery disease. Y1 - 2018 U6 - https://doi.org/10.1038/s41598-018-25237-7 SN - 2045-2322 VL - 8 PB - Nature Publ. Group CY - London ER - TY - JOUR A1 - Xiong, Chao A1 - Stolle, Claudia A1 - Park, Jaeheung T1 - Climatology of GPS signal loss observed by Swarm satellites JF - Annales geophysicae N2 - By using 3-year global positioning system (GPS) measurements from December 2013 to November 2016, we provide in this study a detailed survey on the climatology of the GPS signal loss of Swarm onboard receivers. Our results show that the GPS signal losses prefer to occur at both low latitudes between +/- 5 and +/- 20 degrees magnetic latitude (MLAT) and high latitudes above 60 degrees MLAT in both hemispheres. These events at all latitudes are observed mainly during equinoxes and December solstice months, while totally absent during June solstice months. At low latitudes the GPS signal losses are caused by the equatorial plasma irregularities shortly after sunset, and at high latitude they are also highly related to the large density gradients associated with ionospheric irregularities. Additionally, the high-latitude events are more often observed in the Southern Hemisphere, occurring mainly at the cusp region and along nightside auroral latitudes. The signal losses mainly happen for those GPS rays with elevation angles less than 20 degrees, and more commonly occur when the line of sight between GPS and Swarm satellites is aligned with the shell structure of plasma irregularities. Our results also confirm that the capability of the Swarm receiver has been improved after the bandwidth of the phase-locked loop (PLL) widened, but the updates cannot radically avoid the interruption in tracking GPS satellites caused by the ionospheric plasma irregularities. Additionally, after the PLL bandwidth increased larger than 0.5 Hz, some unexpected signal losses are observed even at middle latitudes, which are not related to the ionospheric plasma irregularities. Our results suggest that rather than 1.0 Hz, a PLL bandwidth of 0.5 Hz is a more suitable value for the Swarm receiver. KW - Ionosphere KW - equatorial ionosphere KW - ionospheric irregularities KW - radio science KW - radio wave propagation Y1 - 2018 U6 - https://doi.org/10.5194/angeo-36-679-2018 SN - 0992-7689 SN - 1432-0576 VL - 36 IS - 2 SP - 679 EP - 693 PB - Copernicus CY - Göttingen ER - TY - JOUR A1 - Kucian, Karin A1 - Zuber, Isabelle A1 - Kohn, Juliane A1 - Poltz, Nadine A1 - Wyschkon, Anne A1 - Esser, Günter A1 - von Aster, Michael G. T1 - Relation Between Mathematical Performance, Math Anxiety, and Affective Priming in Children With and Without Developmental Dyscalculia JF - Frontiers in psychology N2 - Many children show negative emotions related to mathematics and some even develop mathematics anxiety. The present study focused on the relation between negative emotions and arithmetical performance in children with and without developmental dyscalculia (DD) using an affective priming task. Previous findings suggested that arithmetic performance is influenced if an affective prime precedes the presentation of an arithmetic problem. In children with DD specifically, responses to arithmetic operations are supposed to be facilitated by both negative and mathematics-related primes (= negative math priming effect). We investigated mathematical performance, math anxiety, and the domain-general abilities of 172 primary school children (76 with DD and 96 controls). All participants also underwent an affective priming task which consisted of the decision whether a simple arithmetic operation (addition or subtraction) that was preceded by a prime (positive/negative/neutral or mathematics-related) was true or false. Our findings did not reveal a negative math priming effect in children with DD. Furthermore, when considering accuracy levels, gender, or math anxiety, the negative math priming effect could not be replicated. However, children with DD showed more math anxiety when explicitly assessed by a specific math anxiety interview and showed lower mathematical performance compared to controls. Moreover, math anxiety was equally present in boys and girls, even in the earliest stages of schooling, and interfered negatively with performance. In conclusion, mathematics is often associated with negative emotions that can be manifested in specific math anxiety, particularly in children with DD. Importantly, present findings suggest that in the assessed age group, it is more reliable to judge math anxiety and investigate its effects on mathematical performance explicitly by adequate questionnaires than by an affective math priming task. KW - developmental dyscalculia KW - mathematics KW - affective priming KW - calculation KW - arithmetic KW - anxiety KW - gender KW - children Y1 - 2018 U6 - https://doi.org/10.3389/fpsyg.2018.00263 SN - 1664-1078 VL - 9 PB - Frontiers Research Foundation CY - Lausanne ER - TY - JOUR A1 - Coesfeld, Jacqueline A1 - Kuester, Theres A1 - Kuechly, Helga U. A1 - Kyba, Christopher C. M. T1 - Reducing variability and removing natural light from nighttime satellite imagery: A case study using the VIIRS DNB JF - Sensors N2 - Temporal variation of natural light sources such as airglow limits the ability of night light sensors to detect changes in small sources of artificial light (such as villages). This study presents a method for correcting for this effect globally, using the satellite radiance detected from regions without artificial light emissions. We developed a routine to define an approximate grid of locations worldwide that do not have regular light emission. We apply this method with a 5 degree equally spaced global grid (total of 2016 individual locations), using data from the Visible Infrared Imaging Radiometer Suite (VIIRS) Day-Night Band (DNB). This code could easily be adapted for other future global sensors. The correction reduces the standard deviation of data in the Earth Observation Group monthly DNB composites by almost a factor of two. The code and datasets presented here are available under an open license by GFZ Data Services, and are implemented in the Radiance Light Trends web application. KW - airglow KW - artificial light KW - calibration KW - VIIRS DNB KW - nightlights KW - remote sensing Y1 - 2020 VL - 20 PB - MDPI CY - Basel ER - TY - JOUR A1 - Dunsing, Valentin A1 - Luckner, Madlen A1 - Zuehlke, Boris A1 - Petazzi, Roberto Arturo A1 - Herrmann, Andreas A1 - Chiantia, Salvatore T1 - Optimal fluorescent protein tags for quantifying protein oligomerization in living cells JF - Scientific reports N2 - Fluorescence fluctuation spectroscopy has become a popular toolbox for non-disruptive analysis of molecular interactions in living cells. The quantification of protein oligomerization in the native cellular environment is highly relevant for a detailed understanding of complex biological processes. An important parameter in this context is the molecular brightness, which serves as a direct measure of oligomerization and can be easily extracted from temporal or spatial fluorescence fluctuations. However, fluorescent proteins (FPs) typically used in such studies suffer from complex photophysical transitions and limited maturation, inducing non-fluorescent states. Here, we show how these processes strongly affect molecular brightness measurements. We perform a systematic characterization of non-fluorescent states for commonly used FPs and provide a simple guideline for accurate, unbiased oligomerization measurements in living cells. Further, we focus on novel red FPs and demonstrate that mCherry2, an mCherry variant, possesses superior properties with regards to precise quantification of oligomerization. Y1 - 2018 U6 - https://doi.org/10.1038/s41598-018-28858-0 SN - 2045-2322 VL - 8 PB - Nature Publ. Group CY - London ER - TY - JOUR A1 - Zeeden, Christian A1 - Obreht, Igor A1 - Veres, Daniel A1 - Kaboth-Bahr, Stefanie A1 - Hošek, Jan A1 - Marković, Slobodan B. A1 - Bösken, Janina A1 - Lehmkuhl, Frank A1 - Rolf, Christian A1 - Hambach, Ulrich T1 - Smoothed millennial-scale palaeoclimatic reference data as unconventional comparison targets: Application to European loess records JF - Scientific Reports N2 - Millennial-scale palaeoclimate variability has been documented in various terrestrial and marine palaeoclimate proxy records throughout the Northern Hemisphere for the last glacial cycle. Its clear expression and rapid shifts between different states of climate (Greenland Interstadials and Stadials) represents a correlation tool beyond the resolution of e.g. luminescence dating, especially relevant for terrestrial deposits. Usually, comparison of terrestrial proxy datasets and the Greenland ice cores indicates a complex expression of millennial-scale climate variability as recorded in terrestrial geoarchives including loess. Loess is the most widespread terrestrial geoarchive of the Quaternary and especially widespread over Eurasia. However, loess often records a smoothed representation of millennial-scale variability without all fidelity when compared to the Greenland data, this being a relevant limiting feature in integrating loess with other palaeoclimate records. To better understand the loess proxy-response to millennial-scale climate variability, we simulate a proxy signal smoothing by natural processes through application of low-pass filters of delta O-18 data from Greenland, a high-resolution palaeoclimate reference record, alongside speleothem isotope records from the Black Sea-Mediterranean region. We show that low-pass filters represent rather simple models for better constraining the expression of millennial-scale climate variability in low sedimentation environments, and in sediments where proxy-response signals are most likely affected by natural smoothing (by e.g. bioturbation). Interestingly, smoothed datasets from Greenland and the Black Sea-Mediterranean region are most similar in the last similar to 15 ka and between similar to 50-30 ka. Between similar to 30-15 ka, roughly corresponding to the Last Glacial Maximum and the deglaciation, the records show dissimilarities, challenging the construction of robust correlative time-scales in this age range. From our analysis it becomes apparent that patterns of palaeoclimate signals in loess-palaeosol sequences often might be better explained by smoothed Greenland reference data than the original high-resolution Greenland dataset, or other reference data. This opens the possibility to better assess the temporal resolution and palaeoclimate potential of loess-palaeosol sequences in recording supra-regional climate patterns, as well as to securely integrate loess with other chronologically better-resolved palaeoclimate records. KW - last glacial period KW - Western Interior Basin KW - high-resolution record KW - Greenland ice cores KW - paleosol sequence KW - time-scale KW - Chinese loess KW - astronomical calibration KW - chronology (AICC2012) KW - Antarctic ice Y1 - 2020 VL - 10 IS - 1 PB - Springer Nature CY - Berlin ER - TY - JOUR A1 - Richly, Keven A1 - Brauer, Janos A1 - Schlosser, Rainer T1 - Predicting location probabilities of drivers to improved dispatch decisions of transportation network companies based on trajectory data JF - Proceedings of the 9th International Conference on Operations Research and Enterprise Systems - ICORES N2 - The demand for peer-to-peer ridesharing services increased over the last years rapidly. To cost-efficiently dispatch orders and communicate accurate pick-up times is challenging as the current location of each available driver is not exactly known since observed locations can be outdated for several seconds. The developed trajectory visualization tool enables transportation network companies to analyze dispatch processes and determine the causes of unexpected delays. As dispatching algorithms are based on the accuracy of arrival time predictions, we account for factors like noise, sample rate, technical and economic limitations as well as the duration of the entire process as they have an impact on the accuracy of spatio-temporal data. To improve dispatching strategies, we propose a prediction approach that provides a probability distribution for a driver’s future locations based on patterns observed in past trajectories. We demonstrate the capabilities of our prediction results to ( i) avoid critical delays, (ii) to estimate waiting times with higher confidence, and (iii) to enable risk considerations in dispatching strategies. KW - trajectory data KW - location prediction algorithm KW - Peer-to-Peer ridesharing KW - transport network companies KW - risk-aware dispatching Y1 - 2020 PB - Springer CY - Berlin ER - TY - JOUR A1 - Söchting, Maximilian A1 - Trapp, Matthias T1 - Controlling image-stylization techniques using eye tracking JF - Science and Technology Publications N2 - With the spread of smart phones capable of taking high-resolution photos and the development of high-speed mobile data infrastructure, digital visual media is becoming one of the most important forms of modern communication. With this development, however, also comes a devaluation of images as a media form with the focus becoming the frequency at which visual content is generated instead of the quality of the content. In this work, an interactive system using image-abstraction techniques and an eye tracking sensor is presented, which allows users to experience diverting and dynamic artworks that react to their eye movement. The underlying modular architecture enables a variety of different interaction techniques that share common design principles, making the interface as intuitive as possible. The resulting experience allows users to experience a game-like interaction in which they aim for a reward, the artwork, while being held under constraints, e.g., not blinking. The co nscious eye movements that are required by some interaction techniques hint an interesting, possible future extension for this work into the field of relaxation exercises and concentration training. KW - Eye-tracking KW - Image Abstraction KW - Image Processing KW - Artistic Image Stylization KW - Interactive Media Y1 - 2020 SN - 2184-4321 PB - Springer CY - Berlin ER -