Zweitveröffentlichungen der Universität Potsdam : Mathematisch-Naturwissenschaftliche Reihe
ISSN (online) 1866-8372
URN urn:nbn:de:kobv:517-series-403
Herausgegeben von der Universität Potsdam
URN urn:nbn:de:kobv:517-series-403
Herausgegeben von der Universität Potsdam
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1407
Inhibition of acid sphingomyelinase (ASM), a lysosomal enzyme that catalyzes the hydrolysis of sphingomyelin into ceramide and phosphorylcholine, may serve as an investigational tool or a therapeutic intervention to control many diseases. Specific ASM inhibitors are currently not sufficiently characterized. Here, we found that 1-aminodecylidene bis-phosphonic acid (ARC39) specifically and efficiently (>90%) inhibits both lysosomal and secretory ASM in vitro. Results from investigating sphingomyelin phosphodiesterase 1 (SMPD1/Smpd1) mRNA and ASM protein levels suggested that ARC39 directly inhibits ASM's catalytic activity in cultured cells, a mechanism that differs from that of functional inhibitors of ASM. We further provide evidence that ARC39 dose- and time-dependently inhibits lysosomal ASM in intact cells, and we show that ARC39 also reduces platelet- and ASM-promoted adhesion of tumor cells. The observed toxicity of ARC39 is low at concentrations relevant for ASM inhibition in vitro, and it does not strongly alter the lysosomal compartment or induce phospholipidosis in vitro. When applied intraperitoneally in vivo, even subtoxic high doses administered short-term induced sphingomyelin accumulation only locally in the peritoneal lavage without significant accumulation in plasma, liver, spleen, or brain. These findings require further investigation with other possible chemical modifications. In conclusion, our results indicate that ARC39 potently and selectively inhibits ASM in vitro and highlight the need for developing compounds that can reach tissue concentrations sufficient for ASM inhibition in vivo.
1387
Due to the high concentration of people and infrastructures in European cities, the possible impacts of climate change are particularly high (cities' social, economic and technical vulnerabilities). Adaptation measures to reduce the sensitivity of a city to climate risks are therefore of particular importance. Nevertheless, it is also common to develop compact and dense urban areas to reduce urban sprawl. Urban infill development and sustainable spatial climate policies are thus in apparent conflict with each other. This article examines how German cities deal with the tensions between these two policy fields. Using six case studies, a new heuristic analysis method is applied. This study identifies three key governance aspects that are essential for promoting the joint implementation: instruments, organisation and interaction. Based on our case studies, we conclude that successful implementation can only be achieved through integrative governance including all three domains.
1368
The Salt Range in Pakistan exposes Precambrian to Pleistocene strata outcropping along the Salt Range Thrust (SRT). To better understand the in-situ Cambrian and Pliocene tectonic evolution of the Pakistan Subhimalaya, we have conducted low-temperature thermochronological analysis using apatite (U-Th-Sm)/He and fission track dating. We combine cooling ages from different samples located along the thrust front of the SRT into a thermal model that shows two major cooling events associated with rifting and regional erosion in the Late Palaeozoic and SRT activity since the Pliocene. Our results suggest that the SRT maintained a long-term average shortening rate of similar to 5-6 mm/yr and a high exhumation rate above the SRT ramp since similar to 4 Ma.
1367
Background:
Epidemiological evidence indicates that diets rich in plant foods are associated with a lower risk of ischaemic heart disease (IHD), but there is sparse information on fruit and vegetable subtypes and sources of dietary fibre. This study examined the associations of major plant foods, their subtypes and dietary fibre with risk of IHD in the European Prospective Investigation into Cancer and Nutrition (EPIC).
Methods:
We conducted a prospective analysis of 490 311 men and women without a history of myocardial infarction or stroke at recruitment (12.6 years of follow-up, n cases = 8504), in 10 European countries. Dietary intake was assessed using validated questionnaires, calibrated with 24-h recalls. Multivariable Cox regressions were used to estimate hazard ratios (HR) of IHD.
Results:
There was a lower risk of IHD with a higher intake of fruit and vegetables combined [HR per 200 g/day higher intake 0.94, 95% confidence interval (CI): 0.90-0.99, P-trend = 0.009], and with total fruits (per 100 g/day 0.97, 0.95-1.00, P-trend = 0.021). There was no evidence for a reduced risk for fruit subtypes, except for bananas. Risk was lower with higher intakes of nuts and seeds (per 10 g/day 0.90, 0.82-0.98, Ptrend = 0.020), total fibre (per 10 g/day 0.91, 0.85-0.98, P-trend = 0.015), fruit and vegetable fibre (per 4 g/day 0.95, 0.91-0.99, P-trend = 0.022) and fruit fibre (per 2 g/day 0.97, 0.95-1.00, P-trend = 0.045). No associations were observed between vegetables, vegetables subtypes, legumes, cereals and IHD risk.
Conclusions:
In this large prospective study, we found some small inverse associations between plant foods and IHD risk, with fruit and vegetables combined being the most strongly inversely associated with risk. Whether these small associations are causal remains unclear.
1365
Mycotoxins and pesticides regularly co-occur in agricultural products worldwide. Thus, humans can be exposed to both toxic contaminants and pesticides simultaneously, and multi-methods assessing the occurrence of various food contaminants and residues in a single method are necessary. A two-dimensional high performance liquid chromatography tandem mass spectrometry method for the analysis of 40 (modified) mycotoxins, two plant growth regulators, two tropane alkaloids, and 334 pesticides in cereals was developed. After an acetonitrile/water/formic acid (79:20:1, v/v/v) multi-analyte extraction procedure, extracts were injected into the two-dimensional setup, and an online clean-up was performed. The method was validated according to Commission Decision (EC) no. 657/2002 and document N° SANTE/12682/2019. Good linearity (R2 > 0.96), recovery data between 70-120%, repeatability and reproducibility values < 20%, and expanded measurement uncertainties < 50% were obtained for a wide range of analytes, including very polar substances like deoxynivalenol-3-glucoside and methamidophos. However, results for fumonisins, zearalenone-14,16-disulfate, acid-labile pesticides, and carbamates were unsatisfying. Limits of quantification meeting maximum (residue) limits were achieved for most analytes. Matrix effects varied highly (−85 to +1574%) and were mainly observed for analytes eluting in the first dimension and early-eluting analytes in the second dimension. The application of the method demonstrated the co-occurrence of different types of cereals with 28 toxins and pesticides. Overall, 86% of the samples showed positive findings with at least one mycotoxin, plant growth regulator, or pesticide.
1364
Manganese (Mn) and zinc (Zn) are not only essential trace elements, but also potential exogenous risk factors for various diseases. Since the disturbed homeostasis of single metals can result in detrimental health effects, concerns have emerged regarding the consequences of excessive exposures to multiple metals, either via nutritional supplementation or parenteral nutrition. This study focuses on Mn-Zn-interactions in the nematode Caenorhabditis elegans (C. elegans) model, taking into account aspects related to aging and age-dependent neurodegeneration.
1361
The Big Naryn Complex (BNC) in the East Djetim-Too Range of the Kyrgyz Middle Tianshan block is a tectonized, at least 2 km thick sequence of predominantly felsic to intermediate volcanic rocks intruded by porphyric rhyolite sills. It overlies a basement of metamorphic rocks and is overlain by late Neoproterozoic Djetim-Too Formation sediments; these also occur as tectonic intercalations in the BNC. The up to ca. 1100 m thick Lower Member is composed of predominantly rhyolites-to-dacites and minor basalts, while the at least 900 m thick pyroclastic Upper Member is dominated by rhyolitic-to-dacitic ignimbrites. Porphyric rhyolite sills are concentrated at the top of the Lower Member. A Lower Member rhyolite and a sill sample have LA-ICP-MS U-Pb zircon crystallization ages of 726.1 +/- 2.2 Ma and 720.3 +/- 6.5 Ma, respectively, showing that most of the magmatism occurred within a short time span in the late Tonian-early Cryogenian. Inherited zircons in the sill sample have Neoarchean (2.63, 2.64 Ga), Paleo- (2.33-1.81 Ga), Meso- (1.55 Ga), and Neoproterozoic (ca. 815 Ma) ages, and were derived from a heterogeneous Kuilyu Complex basement. A 1751 +/- 7 Ma Ar-40/Ar-39 age for amphibole from metagabbro is the age of cooling subsequent to Paleoproterozoic metamorphism of the Kuilyu Complex. The large amount of pyroclastic rocks, and their major and trace element compositions, the presence of Neoarchean to Neoproterozoic inherited zircons and a depositional basement of metamorphic rocks point to formation of the BNC in a continental magmatic arc setting.
1360
Large rock slope failures play a pivotal role in long-term landscape evolution and are a major concern in land use planning and hazard aspects. While the failure phase and the time immediately prior to failure are increasingly well studied, the nature of the preparation phase remains enigmatic. This knowledge gap is due, to a large degree, to difficulties associated with instrumenting high mountain terrain and the local nature of classic monitoring methods, which does not allow integral observation of large rock volumes. Here, we analyse data from a small network of up to seven seismic sensors installed during July-October 2018 (with 43 days of data loss) at the summit of the Hochvogel, a 2592 m high Alpine peak. We develop proxy time series indicative of cyclic and progressive changes of the summit. Modal analysis, horizontal-to-vertical spectral ratio data and end-member modelling analysis reveal diurnal cycles of increasing and decreasing coupling stiffness of a 260,000 m(3) large, instable rock volume, due to thermal forcing. Relative seismic wave velocity changes also indicate diurnal accumulation and release of stress within the rock mass. At longer time scales, there is a systematic superimposed pattern of stress increased over multiple days and episodic stress release within a few days, expressed in an increased emission of short seismic pulses indicative of rock cracking. Our data provide essential first order information on the development of large-scale slope instabilities towards catastrophic failure. (c) 2020 The Authors. Earth Surface Processes and Landforms published by John Wiley & Sons Ltd
1359
The sediment profile from Lake Goscia(z) over dot in central Poland comprises a continuous, seasonally resolved and exceptionally well-preserved archive of the Younger Dryas (YD) climate variation. This provides a unique opportunity for detailed investigation of lake system responses during periods of rapid climate cooling (YD onset) and warming (YD termination). The new varve record of Lake Goscia(z) over dot presented here spans 1662 years from the late Allerod (AL) to the early Preboreal (PB). Microscopic varve counting provides an independent chronology with a YD duration of 1149+14/-22 years, which confirms previous results of 1140 +/- 40 years. We link stable oxygen isotopes and chironomid-based air temperature reconstructions with the response of various geochemical and varve microfacies proxies especially focusing on the onset and termination of the YD. Cooling at the YD onset lasted similar to 180 years, which is about a century longer than the terminal warming that was completed in similar to 70 years. During the AL/YD transition, environmental proxy data lagged the onset of cooling by similar to 90 years and revealed an increase of lake productivity and internal lake re-suspension as well as slightly higher detrital sediment input. In contrast, rapid warming and environmental changes during the YD/PB transition occurred simultaneously. However, initial changes such as declining diatom deposition and detrital input occurred already a few centuries before the rapid warming at the YD/PB transition. These environmental changes likely reflect a gradual increase in summer air temperatures already during the YD. Our data indicate complex and differing environmental responses to the major climate changes related to the YD, which involve different proxy sensitivities and threshold processes.
1255
We study the probability density function (PDF) of the first-reaction times between a diffusive ligand and a membrane-bound, immobile imperfect target region in a restricted 'onion-shell' geometry bounded by two nested membranes of arbitrary shapes. For such a setting, encountered in diverse molecular signal transduction pathways or in the narrow escape problem with additional steric constraints, we derive an exact spectral form of the PDF, as well as present its approximate form calculated by help of the so-called self-consistent approximation. For a particular case when the nested domains are concentric spheres, we get a fully explicit form of the approximated PDF, assess the accuracy of this approximation, and discuss various facets of the obtained distributions. Our results can be straightforwardly applied to describe the PDF of the terminal reaction event in multi-stage signal transduction processes.