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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 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
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.
In nature, plants are constantly exposed to many transient, but recurring, stresses. Thus, to complete their life cycles, plants require a dynamic balance between capacities to recover following cessation of stress and maintenance of stress memory. Recently, we uncovered a new functional role for macroautophagy/autophagy in regulating recovery from heat stress (HS) and resetting cellular memory of HS inArabidopsis thaliana. Here, we demonstrated that NBR1 (next to BRCA1 gene 1) plays a crucial role as a receptor for selective autophagy during recovery from HS. Immunoblot analysis and confocal microscopy revealed that levels of the NBR1 protein, NBR1-labeled puncta, and NBR1 activity are all higher during the HS recovery phase than before. Co-immunoprecipitation analysis of proteins interacting with NBR1 and comparative proteomic analysis of annbr1-null mutant and wild-type plants identified 58 proteins as potential novel targets of NBR1. Cellular, biochemical and functional genetic studies confirmed that NBR1 interacts with HSP90.1 (heat shock protein 90.1) and ROF1 (rotamase FKBP 1), a member of the FKBP family, and mediates their degradation by autophagy, which represses the response to HS by attenuating the expression ofHSPgenes regulated by the HSFA2 transcription factor. Accordingly, loss-of-function mutation ofNBR1resulted in a stronger HS memory phenotype. Together, our results provide new insights into the mechanistic principles by which autophagy regulates plant response to recurrent HS.
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.
Magnetite containing aerogels were synthesized by freeze-drying olive oil/silicone oil-based Janus emulsion gels containing gelatin and sodium carboxymethylcellulose (NaCMC). The magnetite nanoparticles dispersed in olive oil are processed into the gel and remain in the macroporous aerogel after removing the oil components. The coexistence of macropores from the Janus droplets and mesopores from freeze-drying of the hydrogels in combination with the magnetic properties offer a special hierarchical pore structure, which is of relevance for smart supercapacitors, biosensors, and spilled oil sorption and separation. The morphology of the final structure was investigated in dependence on initial compositions. More hydrophobic aerogels with magnetic responsiveness were synthesized by bisacrylamide-crosslinking of the hydrogel. The crosslinked aerogels can be successfully used in magnetically responsive clean up experiments of the cationic dye methylene blue.
Abiotic stresses cause oxidative damage in plants. Here, we demonstrate that foliar application of an extract from the seaweed Ascophyllum nodosum, SuperFifty (SF), largely prevents paraquat (PQ)-induced oxidative stress in Arabidopsis thaliana. While PQ-stressed plants develop necrotic lesions, plants pre-treated with SF (i.e., primed plants) were unaffected by PQ. Transcriptome analysis revealed induction of reactive oxygen species (ROS) marker genes, genes involved in ROS-induced programmed cell death, and autophagy-related genes after PQ treatment. These changes did not occur in PQ-stressed plants primed with SF. In contrast, upregulation of several carbohydrate metabolism genes, growth, and hormone signaling as well as antioxidant-related genes were specific to SF-primed plants. Metabolomic analyses revealed accumulation of the stress-protective metabolite maltose and the tricarboxylic acid cycle intermediates fumarate and malate in SF-primed plants. Lipidome analysis indicated that those lipids associated with oxidative stress-induced cell death and chloroplast degradation, such as triacylglycerols (TAGs), declined upon SF priming. Our study demonstrated that SF confers tolerance to PQ-induced oxidative stress in A. thaliana, an effect achieved by modulating a range of processes at the transcriptomic, metabolic, and lipid levels.
Bayesian Data Assimilation to Support Informed Decision Making in Individualized Chemotherapy
(2020)
An essential component of therapeutic drug/biomarker monitoring (TDM) is to combine patient data with prior knowledge for model-based predictions of therapy outcomes. Current Bayesian forecasting tools typically rely only on the most probable model parameters (maximum a posteriori (MAP) estimate). This MAP-based approach, however, does neither necessarily predict the most probable outcome nor does it quantify the risks of treatment inefficacy or toxicity. Bayesian data assimilation (DA) methods overcome these limitations by providing a comprehensive uncertainty quantification. We compare DA methods with MAP-based approaches and show how probabilistic statements about key markers related to chemotherapy-induced neutropenia can be leveraged for more informative decision support in individualized chemotherapy. Sequential Bayesian DA proved to be most computationally efficient for handling interoccasion variability and integrating TDM data. For new digital monitoring devices enabling more frequent data collection, these features will be of critical importance to improve patient care decisions in various therapeutic areas.
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.
Spiked gold nanotriangles
(2020)
We show the formation of metallic spikes on the surface of gold nanotriangles (AuNTs) by using the same reduction process which has been used for the synthesis of gold nanostars. We confirm that silver nitrate operates as a shape-directing agent in combination with ascorbic acid as the reducing agent and investigate the mechanism by dissecting the contribution of each component, i.e., anionic surfactant dioctyl sodium sulfosuccinate (AOT), ascorbic acid (AA), and AgNO3. Molecular dynamics (MD) simulations show that AA attaches to the AOT bilayer of nanotriangles, and covers the surface of gold clusters, which is of special relevance for the spike formation process at the AuNT surface. The surface modification goes hand in hand with a change of the optical properties. The increased thickness of the triangles and a sizeable fraction of silver atoms covering the spikes lead to a blue-shift of the intense near infrared absorption of the AuNTs. The sponge-like spiky surface increases both the surface enhanced Raman scattering (SERS) cross section of the particles and the photo-catalytic activity in comparison with the unmodified triangles, which is exemplified by the plasmon-driven dimerization of 4-nitrothiophenol (4-NTP) to 4,4'-dimercaptoazobenzene (DMAB).