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Biomembranes are constantly remodeled and in cells, these processes are controlled and modulated by an assortment of membrane proteins. Here, it is shown that such remodeling can also be induced by photoresponsive molecules. The morphological control of giant vesicles in the presence of a water-soluble ortho-tetrafluoroazobenzene photoswitch (F-azo) is demonstrated and it is shown that the shape transformations are based on an increase in membrane area and generation of spontaneous curvature. The vesicles exhibit budding and the buds can be retracted by using light of a different wavelength. In the presence of F-azo, the membrane area can increase by more than 5% as assessed from vesicle electrodeformation. To elucidate the underlying molecular mechanism and the partitioning of F-azo in the membrane, molecular dynamics simulations are employed. Comparison with theoretically calculated shapes reveals that the budded shapes are governed by curvature elasticity, that the spontaneous curvature can be decomposed into a local and a nonlocal contribution, and that the local spontaneous curvature is about 1/(2.5 mu m). The results show that exo- and endocytotic events can be controlled by light and that these photoinduced processes provide an attractive method to change membrane area and morphology.
Losses due to floods have dramatically increased over the past decades, and losses of companies, comprising direct and indirect losses, have a large share of the total economic losses. Thus, there is an urgent need to gain more quantitative knowledge about flood losses, particularly losses caused by business interruption, in order to mitigate the economic loss of companies. However, business interruption caused by floods is rarely assessed because of a lack of sufficiently detailed data. A survey was undertaken to explore processes influencing business interruption, which collected information on 557 companies affected by the severe flood in June 2013 in Germany. Based on this data set, the study aims to assess the business interruption of directly affected companies by means of a Random Forests model. Variables that influence the duration and costs of business interruption were identified by the variable importance measures of Random Forests. Additionally, Random Forest-based models were developed and tested for their capacity to estimate business interruption duration and associated costs. The water level was found to be the most important variable influencing the duration of business interruption. Other important variables, relating to the estimation of business interruption duration, are the warning time, perceived danger of flood recurrence and inundation duration. In contrast, the amount of business interruption costs is strongly influenced by the size of the company, as assessed by the number of employees, emergency measures undertaken by the company and the fraction of customers within a 50 km radius. These results provide useful information and methods for companies to mitigate their losses from business interruption. However, the heterogeneity of companies is relatively high, and sector-specific analyses were not possible due to the small sample size. Therefore, further sector-specific analyses on the basis of more flood loss data of companies are recommended.
The nucleus of Hen 2-428 is a short orbital period (4.2 h) spectroscopic binary, whose status as potential supernovae type Ia progenitor has raised some controversy in the literature. We present preliminary results of a thorough analysis of this interesting system, which combines quantitative non-local thermodynamic (non-LTE) equilibrium spectral modelling, radial velocity analysis, multi-band light curve fitting, and state-of-the art stellar evolutionary calculations. Importantly, we find that the dynamical system mass that is derived by using all available He II lines does not exceed the Chandrasekhar mass limit. Furthermore, the individual masses of the two central stars are too small to lead to an SN Ia in case of a dynamical explosion during the merger process.
Zero-order basins are common features of soil-mantled landscapes, defined as unchanneled basins at the head of a drainage network. Their geometry and volume control how quickly sediment may reaccumulate after landslide evacuation and, more broadly, zero order basins govern the movement of water and sediment from hillslopes to the fluvial network. They also deliver water and sediment to the uppermost portions of the fluvial network. Despite this role as the moderator between hillslope and fluvial processes, little analysis on their morphology has been conducted at the landscape scale. We present a method to identify zero-order basins in landscapes and subsequently quantify their geometric properties using elliptical Fourier analysis. We deploy this method across the Coweeta Hydrologic Laboratory, USA. Properties such as length, relief, width, and concavity follow distinct probability distributions, which may serve as a basis for testing predictions of future landscape evolution models. Surprisingly, in a landscape with an orographic precipitation gradient and large hillslope to channel relief, we observe no correlation between elevation or spatial location and basin geometry. However, we find that two physiographic units in Coweeta have distinct zero-order basin morphologies. These are the steep, thin soiled, high-elevation Nantahala Escarpment and the lower-gradient, lower-elevation, thick soiled remainder of the basin. Our results indicate that basin slope and area negatively covary, producing the distinct forms observed between the two physiographic units, which we suggest arise through competition between spatially variable soil creep and stochastic landsliding.
Interplay of Dietary Fatty Acids and Cholesterol Impacts Brain Mitochondria and Insulin Action
(2020)
Overconsumption of high-fat and cholesterol-containing diets is detrimental for metabolism and mitochondrial function, causes inflammatory responses and impairs insulin action in peripheral tissues. Dietary fatty acids can enter the brain to mediate the nutritional status, but also to influence neuronal homeostasis. Yet, it is unclear whether cholesterol-containing high-fat diets (HFDs) with different combinations of fatty acids exert metabolic stress and impact mitochondrial function in the brain. To investigate whether cholesterol in combination with different fatty acids impacts neuronal metabolism and mitochondrial function, C57BL/6J mice received different cholesterol-containing diets with either high concentrations of long-chain saturated fatty acids or soybean oil-derived poly-unsaturated fatty acids. In addition, CLU183 neurons were stimulated with combinations of palmitate, linoleic acid and cholesterol to assess their effects on metabolic stress, mitochondrial function and insulin action. The dietary interventions resulted in a molecular signature of metabolic stress in the hypothalamus with decreased expression of occludin and subunits of mitochondrial electron chain complexes, elevated protein carbonylation, as well as c-Jun N-terminal kinase (JNK) activation. Palmitate caused mitochondrial dysfunction, oxidative stress, insulin and insulin-like growth factor-1 (IGF-1) resistance, while cholesterol and linoleic acid did not cause functional alterations. Finally, we defined insulin receptor as a novel negative regulator of metabolically stress-induced JNK activation.
Similar Yet Different
(2020)
The importance of intrinsically disordered late embryogenesis abundant (LEA) proteins in the tolerance to abiotic stresses involving cellular dehydration is undisputed. While structural transitions of LEA proteins in response to changes in water availability are commonly observed and several molecular functions have been suggested, a systematic, comprehensive and comparative study of possible underlying sequence-structure-function relationships is still lacking. We performed molecular dynamics (MD) simulations as well as spectroscopic and light scattering experiments to characterize six members of two distinct, lowly homologous clades of LEA_4 family proteins from Arabidopsis thaliana. We compared structural and functional characteristics to elucidate to what degree structure and function are encoded in LEA protein sequences and complemented these findings with physicochemical properties identified in a systematic bioinformatics study of the entire Arabidopsis thaliana LEA_4 family. Our results demonstrate that although the six experimentally characterized LEA_4 proteins have similar structural and functional characteristics, differences concerning their folding propensity and membrane stabilization capacity during a freeze/thaw cycle are obvious. These differences cannot be easily attributed to sequence conservation, simple physicochemical characteristics or the abundance of sequence motifs. Moreover, the folding propensity does not appear to be correlated with membrane stabilization capacity. Therefore, the refinement of LEA_4 structural and functional properties is likely encoded in specific patterns of their physicochemical characteristics.
Optical excitation of spin-ordered rare earth metals triggers a complex response of the crystal lattice since expansive stresses from electron and phonon excitations compete with a contractive stress induced by spin disorder. Using ultrafast x-ray diffraction experiments, we study the layer specific strain response of a dysprosium film within a metallic heterostructure upon femtosecond laser-excitation. The elastic and diffusive transport of energy to an adjacent, non-excited detection layer clearly separates the contributions of strain pulses and thermal excitations in the time domain. We find that energy transfer processes to magnetic excitations significantly modify the observed conventional bipolar strain wave into a unipolar pulse. By modeling the spin system as a saturable energy reservoir that generates substantial contractive stress on ultrafast timescales, we can reproduce the observed strain response and estimate the time- and space dependent magnetic stress. The saturation of the magnetic stress contribution yields a non-monotonous total stress within the nanolayer, which leads to unconventional picosecond strain pulses.
The European rabbit (Oryctolagus cuniculus) is declining in large parts of Europe but populations in some German cities remained so far unaffected by this decline. The question arises of how urbanization affects patterns of population genetic variation and differentiation in German rabbit populations, as urban habitat fragmentation may result in altered meta-population dynamics. To address this question, we used microsatellite markers to genotype rabbit populations occurring along a rural-to-urban gradient in and around the city of Frankfurt, Germany. We found no effect of urbanization on allelic richness. However, the observed heterozygosity was significantly higher in urban than rural populations and also the inbreeding coefficients were lower, most likely reflecting the small population sizes and possibly on-going loss of genetic diversity in structurally impoverished rural areas. Global FST and G'ST-values suggest moderate but significant differentiation between populations. Multiple matrix regression with randomization ascribed this differentiation to isolation-by-environment rather than isolation-by-distance. Analyses of migration rates revealed asymmetrical gene flow, which was higher from rural into urban populations than vice versa and may again reflect intensified agricultural land-use practices in rural areas. We discuss that populations inhabiting urban areas will likely play an important role in the future distribution of European rabbits.
The use of monoclonal antibodies is ubiquitous in science and biomedicine but the generation and validation process of antibodies is nevertheless complicated and time-consuming. To address these issues we developed a novel selective technology based on an artificial cell surface construct by which secreted antibodies were connected to the corresponding hybridoma cell when they possess the desired antigen-specificity. Further the system enables the selection of desired isotypes and the screening for potential cross-reactivities in the same context. For the design of the construct we combined the transmembrane domain of the EGF-receptor with a hemagglutinin epitope and a biotin acceptor peptide and performed a transposon-mediated transfection of myeloma cell lines. The stably transfected myeloma cell line was used for the generation of hybridoma cells and an antigen- and isotype-specific screening method was established. The system has been validated for globular protein antigens as well as for haptens and enables a fast and early stage selection and validation of monoclonal antibodies in one step.
The Feasibility and Effectiveness of a New Practical Multidisciplinary Treatment for Low-Back Pain
(2020)
Low-back pain is a major health problem exacerbated by the fact that most treatments are not suitable for self-management in everyday life. Particularly, interdisciplinary programs consist of intensive therapy lasting several weeks. Additionally, therapy components are rarely coordinated regarding reinforcing effects, which would improve complaints in persons with higher pain. This study assesses the effectiveness of a self-management program, firstly for persons suffering from higher pain and secondly compared to regular routines. Study objectives were treated in a single-blind multicenter controlled trial. A total of n = 439 volunteers (age 18–65 years) were randomly assigned to a twelve-week multidisciplinary sensorimotor training (3-weeks-center- and 9-weeks-homebased) or control group. The primary outcome pain (Chronic-Pain-Grade) as well as mental health were assessed by questionnaires at baseline and follow-up (3/6/12/24 weeks, M2-M5). For statistical analysis, multiple linear regression models were used. N = 291 (age 39.7 ± 12.7 years, female = 61.1%, 77% CPG = 1) completed training (M1/M4/M5), showing a significantly stronger reduction of mental health complaints (anxiety, vital exhaustion) in people with higher than those with lower pain in multidisciplinary treatment. Compared to regular routines, the self-management–multidisciplinary treatment led to a clinically relevant reduction of pain–disability and significant mental health improvements. Low-cost exercise programs may provide enormous relief for therapeutic processes, rehabilitation aftercare, and thus, cost savings for the health system