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- Potsdam Research Institute for Multilingualism (PRIM) (1)
- Strukturbereich Bildungswissenschaften (1)
The thermal structure of subduction zones exerts a major influence on deep-seated mechanical and chemical processes controlling arc magmatism, seismicity, and global element cycles. Accretionary complexes exposed inland may comprise tectonic blocks with contrasting pressure-temperature (P-T) histories, making it possible to investigate the dynamics and thermal evolution of former subduction interfaces. With this aim, we present new Lu-Hf geochronological results for mafic rocks of the Halilbagi Complex (Anatolia) that evolved along different thermal gradients. Samples include a lawsonite-epidote blueschist, a lawsonite-epidote eclogite, and an epidote eclogite (all with counter-clockwise P-T paths), a prograde lawsonite blueschist with a "hairpin"-type P-T path, and a garnet amphibolite from the overlying sub-ophiolitic metamorphic sole. Equilibrium phase diagrams suggest that the garnet amphibolite formed at similar to 0.6-0.7 GPa and 800-850 degrees C, whereas the prograde lawsonite blueschist records burial from 2.1 GPa and 420 degrees C to 2.6 GPa and 520 degrees C. Well-defined Lu-Hf isochrons were obtained for the epidote eclogite (92.38 +/- 0.22 Ma) and the lawsonite-epidote blueschist (90.19 +/- 0.54 Ma), suggesting rapid garnet growth. The lawsonite-epidote eclogite (87.30 +/- 0.39 Ma) and the prograde lawsonite blueschist (ca. 86 Ma) are younger, whereas the garnet amphibolite (104.5 +/- 3.5 Ma) is older. Our data reveal a consistent trend of progressively decreasing geothermal gradient from granulite-facies conditions at similar to 104 Ma to the epidote-eclogite facies around 92 Ma, and the lawsonite blueschist-facies between 90 Ma and 86 Ma. Three Lu-Hf garnet dates (between 92 Ma and 87 Ma) weighted toward the growth of post-peak rims (as indicated by Lu distribution in garnet) suggest that the HP/LT rocks were exhumed continuously and not episodically. We infer that HP/LT metamorphic rocks within the Halilbagi Complex were subjected to continuous return flow, with "warm" rocks being exhumed during the tectonic burial of "cold" ones. Our results, combined with regional geological constraints, allow us to speculate that subduction started at a transform fault near a mid-oceanic spreading centre. Following its formation, this ancient subduction interface evolved thermally over more than 15 Myr, most likely as a result of heat dissipation rather than crustal underplating. (C) 2018, China University of Geosciences (Beijing) and Peking University. Production and hosting by Elsevier B.V.
During the earliest Triassic microbial mats flourished in the photic zones of marginal seas, generating widespread microbialites. It has been suggested that anoxic conditions in shallow marine environments, linked to the end-Permian mass extinction, limited mat-inhibiting metazoans allowing for this microbialite expansion. The presence of a diverse suite of proxies indicating oxygenated shallow sea-water conditions (metazoan fossils, biomarkers and redox proxies) from microbialite successions have, however, challenged the inference of anoxic conditions. Here, the distribution and faunal composition of Griesbachian microbialites from China, Iran, Turkey, Armenia, Slovenia and Hungary are investigated to determine the factors that allowed microbialite-forming microbial mats to flourish following the end-Permian crisis. The results presented here show that Neotethyan microbial buildups record a unique faunal association due to the presence of keratose sponges, while the Palaeotethyan buildups have a higher proportion of molluscs and the foraminifera Earlandia. The distribution of the faunal components within the microbial fabrics suggests that, except for the keratose sponges and some microconchids, most of the metazoans were transported into the microbial framework via wave currents. The presence of both microbialites and metazoan associations were limited to oxygenated settings, suggesting that a factor other than anoxia resulted in a relaxation of ecological constraints following the mass extinction event. It is inferred that the end-Permian mass extinction event decreased the diversity and abundance of metazoans to the point of significantly reducing competition, allowing photosynthesis-based microbial mats to flourish in shallow water settings and resulting in the formation of widespread microbialites.
Proteasomes are key proteases in regulating protein homeostasis. Their holo-enzymes are composed of 40 different subunits which are arranged in a proteolytic core (CP) flanked by one to two regulatory particles (RP). Proteasomal proteolysis is essential for the degradation of proteins which control time-sensitive processes like cell cycle progression and stress response. In dividing yeast and human cells, proteasomes are primarily nuclear suggesting that proteasomal proteolysis is mainly required in the nucleus during cell proliferation. In yeast, which have a closed mitosis, proteasomes are imported into the nucleus as immature precursors via the classical import pathway. During quiescence, the reversible absence of proliferation induced by nutrient depletion or growth factor deprivation, proteasomes move from the nucleus into the cytoplasm. In the cytoplasm of quiescent yeast, proteasomes are dissociated into CP and RP and stored in membrane-less cytoplasmic foci, named proteasome storage granules (PSGs). With the resumption of growth, PSGs clear and mature proteasomes are transported into the nucleus by Blm10, a conserved 240 kDa protein and proteasome-intrinsic import receptor. How proteasomes are exported from the nucleus into the cytoplasm is unknown.
Estimating parameters from multiple time series of population dynamics using bayesian inference
(2019)
Empirical time series of interacting entities, e.g., species abundances, are highly useful to study ecological mechanisms. Mathematical models are valuable tools to further elucidate those mechanisms and underlying processes. However, obtaining an agreement between model predictions and experimental observations remains a demanding task. As models always abstract from reality one parameter often summarizes several properties. Parameter measurements are performed in additional experiments independent of the ones delivering the time series. Transferring these parameter values to different settings may result in incorrect parametrizations. On top of that, the properties of organisms and thus the respective parameter values may vary considerably. These issues limit the use of a priori model parametrizations. In this study, we present a method suited for a direct estimation of model parameters and their variability from experimental time series data. We combine numerical simulations of a continuous-time dynamical population model with Bayesian inference, using a hierarchical framework that allows for variability of individual parameters. The method is applied to a comprehensive set of time series from a laboratory predator-prey system that features both steady states and cyclic population dynamics. Our model predictions are able to reproduce both steady states and cyclic dynamics of the data. Additionally to the direct estimates of the parameter values, the Bayesian approach also provides their uncertainties. We found that fitting cyclic population dynamics, which contain more information on the process rates than steady states, yields more precise parameter estimates. We detected significant variability among parameters of different time series and identified the variation in the maximum growth rate of the prey as a source for the transition from steady states to cyclic dynamics. By lending more flexibility to the model, our approach facilitates parametrizations and shows more easily which patterns in time series can be explained also by simple models. Applying Bayesian inference and dynamical population models in conjunction may help to quantify the profound variability in organismal properties in nature.
The size structure of autotroph communities - the relative abundance of small vs. large individuals - shapes the functioning of ecosystems. Whether common mechanisms underpin the size structure of unicellular and multicellular autotrophs is, however, unknown. Using a global data compilation, we show that individual body masses in tree and phytoplankton communities follow power-law distributions and that the average exponents of these individual size distributions (ISD) differ. Phytoplankton communities are characterized by an average ISD exponent consistent with three-quarter-power scaling of metabolism with body mass and equivalence in energy use among mass classes. Tree communities deviate from this pattern in a manner consistent with equivalence in energy use among diameter size classes. Our findings suggest that whilst universal metabolic constraints ultimately underlie the emergent size structure of autotroph communities, divergent aspects of body size (volumetric vs. linear dimensions) shape the ecological outcome of metabolic scaling in forest vs. pelagic ecosystems.
Alluvial and transport-limited bedrock rivers constitute the majority of fluvial systems on Earth. Their long profiles hold clues to their present state and past evolution. We currently possess first-principles-based governing equations for flow, sediment transport, and channel morphodynamics in these systems, which we lack for detachment-limited bedrock rivers. Here we formally couple these equations for transport-limited gravel-bed river long-profile evolution. The result is a new predictive relationship whose functional form and parameters are grounded in theory and defined through experimental data. From this, we produce a power-law analytical solution and a finite-difference numerical solution to long-profile evolution. Steady-state channel concavity and steepness are diagnostic of external drivers: concavity decreases with increasing uplift rate, and steepness increases with an increasing sediment-to-water supply ratio. Constraining free parameters explains common observations of river form: to match observed channel concavities, gravel-sized sediments must weather and fine - typically rapidly - and valleys typically should widen gradually. To match the empirical square-root width-discharge scaling in equilibrium-width gravel-bed rivers, downstream fining must occur. The ability to assign a cause to such observations is the direct result of a deductive approach to developing equations for landscape evolution.
In this report, we illustrate the considerable impact of researcher degrees of freedom with respect to exclusion of participants in paradigms with a learning element. We illustrate this empirically through case examples from human fear conditioning research, in which the exclusion of ‘non-learners’ and ‘non-responders’ is common – despite a lack of consensus on how to define these groups. We illustrate the substantial heterogeneity in exclusion criteria identified in a systematic literature search and highlight the potential problems and pitfalls of different definitions through case examples based on re-analyses of existing data sets. On the basis of these studies, we propose a consensus on evidence-based rather than idiosyncratic criteria, including clear guidelines on reporting details. Taken together, we illustrate how flexibility in data collection and analysis can be avoided, which will benefit the robustness and replicability of research findings and can be expected to be applicable to other fields of research that involve a learning element.
Protein interaction and protein imaging strongly benefit from the advancements in time-resolved and superresolution fluorescence microscopic techniques. However, the techniques were typically applied separately and ex vivo because of technical challenges and the absence of suitable fluorescent protein pairs. Here, we show correlative in vivo fluorescence lifetime imaging microscopy Forster resonance energy transfer (FLIM-FRET) and stimulated emission depletion (STED) microscopy to unravel protein mechanics and structure in living cells. We use magnetotactic bacteria as a model system where two proteins, MamJ and MamK, are used to assemble magnetic particles called magnetosomes. The filament polymerizes out of MamK and the magnetosomes are connected via the linker MamJ. Our system reveals that bacterial filamentous structures are more fragile than the connection of biomineralized particles to this filament. More importantly, we anticipate the technique to find wide applicability for the study and quantification of biological processes in living cells and at high resolution.
The great auk was once abundant and distributed across the North Atlantic. It is now extinct, having been heavily exploited for its eggs, meat, and feathers. We investigated the impact of human hunting on its demise by integrating genetic data, GPS-based ocean current data, and analyses of population viability. We sequenced complete mitochondrial genomes of 41 individuals from across the species' geographic range and reconstructed population structure and population dynamics throughout the Holocene. Taken together, our data do not provide any evidence that great auks were at risk of extinction prior to the onset of intensive human hunting in the early 16th century. In addition, our population viability analyses reveal that even if the great auk had not been under threat by environmental change, human hunting alone could have been sufficient to cause its extinction. Our results emphasise the vulnerability of even abundant and widespread species to intense and localised exploitation.
NK cells have emerged as promising candidates for cancer immunotherapy, especially due to their ability to fight circulating tumor cells thereby preventing metastases formation. Hence several studies have been performed to generate and expand highly cytotoxic NK cells ex vivo, e.g., by using specific cytokines to upregulate both their proliferation and surface expression of distinct activating receptors. Apart from an enhanced activity, application of NK cells as immunotherapeutic agent further requires sufficient cell numbers and a high purity. All these parameters depend on a variety of different factors including the starting material, additives like cytokines as well as the culture system. Here we analyzed PBMC-derived NK cells of five anonymized healthy donors expanded under specific conditions in an innovative perfusion bioreactor system with respect to their phenotype, IFN gamma production, and cytotoxicity in vitro. Important features of the meander type bioreactors used here are a directed laminar flow of medium and control of relevant process parameters. Cells are cultivated under "steady state" conditions in perfusion mode. Our data demonstrate that expansion of CD3(+) T cell depleted PBMCs in our standardized system generates massive amounts of highly pure (>85%) and potent anticancer active NK cells. These cells express a variety of important receptors driving NK cell recruitment, adhesion as well as activation. More specifically, they express the chemokine receptors CXCR3, CXCR4, and CCR7, the adhesion molecules L-selectin, LFA-1, and VLA-4, the activating receptors NKp30, NKp44, NKp46, NKG2D, DNAM1, and CD16 as well as the death ligands TRAIL and Fas-L. Moreover, the generated NK cells show a strong IFN gamma expression upon cultivation with K562 tumor cells and demonstrate a high cytotoxicity toward leukemic as well as solid tumor cell lines in vitro. Altogether, these characteristics promise a high clinical potency of thus produced NK cells awaiting further evaluation.
Locally delivered anti-inflammatory compounds can restore the homeostasis of the degenerated intervertebral disc (IVD). With beneficial effects on IVD cells, epigallocatechin 3-gallate (EGCG) is a promising therapeutic candidate. However, EGCG is prone to rapid degradation and/or depletion. Therefore, the purpose of this study was to develop a method for controlled EGCG delivery in the degenerated IVD. Primary IVD cells were isolated from human donors undergoing IVD surgeries. EGCG was encapsulated into microparticles by electrospraying of glutaraldehyde-crosslinked gelatin. The resulting particles were characterized in terms of cytocompatibility and anti-inflammatory activity, and combined with a thermoresponsive carrier to produce an injectable EGCG delivery system. Subsequently, electrospraying was scaled up using the industrial NANOSPIDER (TM) technology. The produced EGCG microparticles reduced the expression of inflammatory (IL-6, IL-8, COX-2) and catabolic (MMP1, MMP3, MMP13) mediators in pro-inflammatory 3D cell cultures. Combining the EGCG microparticles with the carrier showed a trend towards modulating EGCG activity/release. Electrospray upscaling was achieved, leading to particles with homogenous spherical morphologies. In conclusion, electrospray-based encapsulation of EGCG resulted in cytocompatible microparticles that preserved the activity of EGCG and showed the potential to control EGCG release, thus favoring IVD health by downregulating local inflammation. Future studies will focus on further exploring the biological activity of the developed delivery system for potential clinical use.
Ecological communities are undeniably diverse, both in terms of the species that compose them as well as the type of interactions that link species to each other. Despite this long recognition of the coexistence of multiple interaction types in nature, little is known about the consequences of this diversity for community functioning. In the ongoing context of global change and increasing species extinction rates, it seems crucial to improve our understanding of the drivers of the relationship between species diversity and ecosystem functioning. Here, using a multispecies dynamical model of ecological communities including various interaction types (e.g. competition for space, predator interference, recruitment facilitation in addition to feeding), we studied the role of the presence and the intensity of these interactions for species diversity, community functioning (biomass and production) and the relationship between diversity and functioning. Taken jointly, the diverse interactions have significant effects on species diversity, whose amplitude and sign depend on the type of interactions involved and their relative abundance. They however consistently increase the slope of the relationship between diversity and functioning, suggesting that species losses might have stronger effects on community functioning than expected when ignoring the diversity of interaction types and focusing on feeding interactions only.
A yeast expression plasmid was constructed containing a cardenolide biosynthetic module, referred to as CARD II, using the AssemblX toolkit, which enables the assembly of large DNA constructs. The genes cloned into the vector were (a) a Δ5‐3β‐hydroxysteroid dehydrogenase gene from Digitalis lanata, (b) a steroid Δ5‐isomerase gene from Comamonas testosteronii, (c) a mutated steroid‐5β‐reductase gene from Arabidopsis thaliana, and (d) a steroid 21‐hydroxylase gene from Mus musculus. A second plasmid bearing an ADR/ADX fusion gene from Bos taurus was also constructed. A Saccharomyces cerevisiae strain bearing these two plasmids was generated. This strain, termed “CARD II yeast”, was capable of producing 5β‐pregnane‐3β,21‐diol‐20‐one, a central intermediate in 5β‐cardenolide biosynthesis, starting from pregnenolone which was added to the culture medium. Using this approach, five consecutive steps in cardenolide biosynthesis were realized in baker's yeast.
The majority of earthquakes occur unexpectedly and can trigger subsequent sequences of events that can culminate in more powerful earthquakes. This self-exciting nature of seismicity generates complex clustering of earthquakes in space and time. Therefore, the problem of constraining the magnitude of the largest expected earthquake during a future time interval is of critical importance in mitigating earthquake hazard. We address this problem by developing a methodology to compute the probabilities for such extreme earthquakes to be above certain magnitudes. We combine the Bayesian methods with the extreme value theory and assume that the occurrence of earthquakes can be described by the Epidemic Type Aftershock Sequence process. We analyze in detail the application of this methodology to the 2016 Kumamoto, Japan, earthquake sequence. We are able to estimate retrospectively the probabilities of having large subsequent earthquakes during several stages of the evolution of this sequence.
A Metabarcoding Analysis of the Mycobiome of Wheat Ears Across a Topographically Heterogeneous Field
(2019)
Movement ecology aims to provide common terminology and an integrative framework of movement research across all groups of organisms. Yet such work has focused on unitary organisms so far, and thus the important group of filamentous fungi has not been considered in this context. With the exception of spore dispersal, movement in filamentous fungi has not been integrated into the movement ecology field. At the same time, the field of fungal ecology has been advancing research on topics like informed growth, mycelial translocations, or fungal highways using its own terminology and frameworks, overlooking the theoretical developments within movement ecology. We provide a conceptual and terminological framework for interdisciplinary collaboration between these two disciplines, and show how both can benefit from closer links: We show how placing the knowledge from fungal biology and ecology into the framework of movement ecology can inspire both theoretical and empirical developments, eventually leading towards a better understanding of fungal ecology and community assembly. Conversely, by a greater focus on movement specificities of filamentous fungi, movement ecology stands to benefit from the challenge to evolve its concepts and terminology towards even greater universality. We show how our concept can be applied for other modular organisms (such as clonal plants and slime molds), and how this can lead towards comparative studies with the relationship between organismal movement and ecosystems in the focus.
Eine Gruppe, gar eine innerlich verbundene Gemeinschaft, können Intellektuelle im Normalfall nur bilden, soweit sie von gleichem Denken und Wollen bewegt werden […]. Wo dagegen die von den Intellektuellen vertretenen Ansichten weit divergieren, da kann es nur unter sehr kritischen Umständen geschehen, daß die verschieden gearteten (sozialen, politischen, rechtlichen, kulturellen, religiösen) Standpunkte und Anliegen – auf Zeit – sich zusammenfinden […]. Das polemische Element, das kritischen Intellektuellen ja wesensmäßig zu eigen ist, bringt am ehesten eine gemeinsame Front zwischen ihnen zustande.
Melancholia
(2019)
Anti-Consumption
(2019)
Transcending the conventional debate around efficiency in sustainable consumption, anti-consumption patterns leading to decreased levels of material consumption have been gaining importance. Change agents are crucial for the promotion of such patterns, so there may be lessons for governance interventions that can be learnt from the every-day experiences of those who actively implement and promote sustainability in the field of anti-consumption. Eighteen social innovation pioneers, who engage in and diffuse practices of voluntary simplicity and collaborative consumption as sustainable options of anti-consumption share their knowledge and personal insights in expert interviews for this research. Our qualitative content analysis reveals drivers, barriers, and governance strategies to strengthen anti-consumption patterns, which are negotiated between the market, the state, and civil society. Recommendations derived from the interviews concern entrepreneurship, municipal infrastructures in support of local grassroots projects, regulative policy measures, more positive communication to strengthen the visibility of initiatives and emphasize individual benefits, establishing a sense of community, anti-consumer activism, and education. We argue for complementary action between top-down strategies, bottom-up initiatives, corporate activities, and consumer behavior. The results are valuable to researchers, activists, marketers, and policymakers who seek to enhance their understanding of materially reduced consumption patterns based on the real-life experiences of active pioneers in the field.
Molecularly imprinted polymers (MIPs) mimic the binding sites of antibodies by substituting the amino acid-scaffold of proteins by synthetic polymers. In this work, the first MIP for the recognition of the diagnostically relevant enzyme butyrylcholinesterase (BuChE) is presented. The MIP was prepared using electropolymerization of the functional monomer o-phenylenediamine and was deposited as a thin film on a glassy carbon electrode by oxidative potentiodynamic polymerization. Rebinding and removal of the template were detected by cyclic voltammetry using ferricyanide as a redox marker. Furthermore, the enzymatic activity of BuChE rebound to the MIP was measured via the anodic oxidation of thiocholine, the reaction product of butyrylthiocholine. The response was linear between 50 pM and 2 nM concentrations of BuChE with a detection limit of 14.7 pM. In addition to the high sensitivity for BuChE, the sensor responded towards pseudo-irreversible inhibitors in the lower mM range.
The concept of a "flow network"-a set of nodes and links which carries one or more flows-unites many different disciplines, including pipe flow, fluid flow, electrical, chemical reaction, ecological, epidemiological, neurological, communications, transportation, financial, economic and human social networks. This Feature Paper presents a generalized maximum entropy framework to infer the state of a flow network, including its flow rates and other properties, in probabilistic form. In this method, the network uncertainty is represented by a joint probability function over its unknowns, subject to all that is known. This gives a relative entropy function which is maximized, subject to the constraints, to determine the most probable or most representative state of the network. The constraints can include "observable" constraints on various parameters, "physical" constraints such as conservation laws and frictional properties, and "graphical" constraints arising from uncertainty in the network structure itself. Since the method is probabilistic, it enables the prediction of network properties when there is insufficient information to obtain a deterministic solution. The derived framework can incorporate nonlinear constraints or nonlinear interdependencies between variables, at the cost of requiring numerical solution. The theoretical foundations of the method are first presented, followed by its application to a variety of flow networks.
Intolerance to lactose or fructose is frequently diagnosed in children with chronic abdominal pain (CAP). However, the causal relationship remains a matter of discussion. A cohort of 253 patients, aged 7-12 years, presenting with unexplained CAP received standardized diagnostics. Additional diagnostic tests were performed based on their medical history and physical and laboratory investigations. Fructose and lactose hydrogen breath tests (H2BT) as well as empiric diagnostic elimination diets were performed in 135 patients reporting abdominal pain related to the consumption of lactose or fructose to evaluate carbohydrate intolerance as a potential cause of CAP. Carbohydrate malabsorption by H2BT was found in 55 (41%) out of 135 patients. An abnormal increase in H2BT was revealed in 30% (35/118) of patients after fructose consumption and in 18% (20/114) of patients after lactose administration. Forty-six percent (25/54) reported pain relief during a diagnostic elimination diet. In total, 17 patients had lactose malabsorption, 29 fructose malabsorption, and nine combined carbohydrate malabsorption. Carbohydrate intolerance as a cause of CAP was diagnosed at follow-up in only 18% (10/55) of patients with malabsorption after the elimination of the respective carbohydrate. Thus, carbohydrate malabsorption appears to be an incidental finding in children with functional abdominal pain disorders, rather than its cause. Therefore, testing of carbohydrate intolerance should only be considered in children with a strong clinical suspicion and with the goal to prevent long-term unnecessary dietary restrictions in children suffering from CAP.
The movement of microswimmers is often described by active Brownian particle models. Here we introduce a variant of these models with several internal states of the swimmer to describe stochastic strategies for directional swimming such as run and tumble or run and reverse that are used by microorganisms for chemotaxis. The model includes a mechanism to generate a directional bias for chemotaxis and interactions with external fields (e.g., gravity, magnetic field, fluid flow) that impose forces or torques on the swimmer. We show how this modified model can be applied to various scenarios: First, the run and tumble motion of E. coli is used to establish a paradigm for chemotaxis and investigate how it is affected by external forces. Then, we study magneto-aerotaxis in magnetotactic bacteria, which is biased not only by an oxygen gradient towards a preferred concentration, but also by magnetic fields, which exert a torque on an intracellular chain of magnets. We study the competition of magnetic alignment with active reorientation and show that the magnetic orientation can improve chemotaxis and thereby provide an advantage to the bacteria, even at rather large inclination angles of the magnetic field relative to the oxygen gradient, a case reminiscent of what is expected for the bacteria at or close to the equator. The highest gain in chemotactic velocity is obtained for run and tumble with a magnetic field parallel to the gradient, but in general a mechanism for reverse motion is necessary to swim against the magnetic field and a run and reverse strategy is more advantageous in the presence of a magnetic torque. This finding is consistent with observations that the dominant mode of directional changes in magnetotactic bacteria is reversal rather than tumbles. Moreover, it provides guidance for the design of future magnetic biohybrid swimmers. Author summary In this paper, we propose a modified Active Brownian particle model to describe bacterial swimming behavior under the influence of external forces and torques, in particular of a magnetic torque. This type of interaction is particularly important for magnetic biohybrids (i.e. motile bacteria coupled to a synthetic magnetic component) and for magnetotactic bacteria (i.e. bacteria with a natural intracellular magnetic chain), which perform chemotaxis to swim along chemical gradients, but are also directed by an external magnetic field. The model allows us to investigate the benefits and disadvantages of such coupling between two different directionality mechanisms. In particular we show that the magnetic torque can speed chemotaxis up in some conditions, while it can hinder it in other cases. In addition to an understanding of the swimming strategies of naturally magnetotactic organisms, the results may guide the design of future biomedical devices.
Photothermal conversion (PTC) nanostructures have great potential for applications in many fields, and therefore, they have attracted tremendous attention. However, the construction of a PTC nanoreactor with multi-compartment structure to achieve the combination of unique chemical properties and structural feature is still challenging due to the synthetic difficulties. Herein, we designed and synthesized a catalytically active, PTC gold (Au)@polydopamine (PDA) nanoreactor driven by infrared irradiation using assembled PS-b-P2VP nanosphere as soft template. The particles exhibit multi-compartment structure which is revealed by 3D electron tomography characterization technique. They feature permeable shells with tunable shell thickness. Full kinetics for the reduction reaction of 4-nitrophenol has been investigated using these particles as nanoreactors and compared with other reported systems. Notably, a remarkable acceleration of the catalytic reaction upon near-infrared irradiation is demonstrated, which reveals for the first time the importance of the synergistic effect of photothermal conversion and complex inner structure to the kinetics of the catalytic reduction. The ease of synthesis and fresh insights into catalysis will promote a new platform for novel nanoreactor studies.
A comprehensive analysis of the variable temporal and spatial responses of tropical-subtropical high-altitude glaciers to climate change is critical for successful model predictions and environmental risk assessment in the Himalayan-Tibetan orogen. High-frequency Holocene glacier chronostratigraphies are therefore reconstructed in 79 glaciated valleys across the orogen using 519 published and 16 new terrestrial cosmogenic 10Be exposure age dataset. Published 10Be ages are compiled only for moraine boulders (excluding bedrock ages). These ages are recalculated using the latest ICE-D production rate calibration database and the scaling scheme models. Outliers for the individual moraine are detected using the Chauvenet's criterion. In addition, past equilibrium-line altitudes (ELAs) are determined using the area-altitude (AA), area accumulation ratio (AAR), and toe-headwall accumulation ratio (THAR) methods for each glacier advance. The modern maximum elevations of lateral moraines (MELM) are also used to estimate modern ELAs and as an independent check on mean ELAs derived using the above three methods. These data may serve as an essential archive for future studies focusing on the cryospheric and environmental changes in the Himalayan-Tibetan orogen. A more comprehensive analysis of the published and new 10Be ages and ELA results and a list of references are presented in Saha et al. (2019, High-frequency Holocene glacier fluctuations in the Himalayan-Tibetan orogen. Quaternary Science Reviews, 220, 372–400).
In ecological communities, especially the pelagic zones of aquatic ecosystems, certain bodysize ranges are often over-represented compared to others. Community size spectra, the distributions of community biomass over the logarithmic body-mass axis, tend to exhibit regularly spaced local maxima, called "domes", separated by steep troughs. Contrasting established theory, we explain these dome patterns as manifestations of top-down trophic cascades along aquatic food chains. Compiling high quality size-spectrum data and comparing these with a size-spectrum model introduced in this study, we test this theory and develop a detailed picture of the mechanisms by which bottom-up and top-down effects interact to generate dome patterns. Results imply that strong top-down trophic cascades are common in freshwater communities, much more than hitherto demonstrated, and may arise in nutrient rich marine systems as well. Transferring insights from the general theory of nonlinear pattern formation to domes patterns, we provide new interpretations of past lake-manipulation experiments.
Although malnutrition is frequent in the old, little is known about its association with fatigue. We evaluated the relation of self-reported severe weight loss with fatigue and the predictors for fatigue in old patients at hospital discharge. Severe weight loss was defined according to involuntary weight loss >= 5% in the last three months. We determined fatigue with the validated Brief Fatigue Inventory questionnaire. The regression analyses were adjusted for age, sex, number of comorbidities, medications/day, and BMI. Of 424 patients aged between 61 and 98 y, 34.1% had severe weight loss. Fatigue was higher in patients with severe weight loss (3.7 +/- 2.3 vs. 3.2 +/- 2.3 points, p = 0.021). In a multinomial regression model, weight loss was independently associated with higher risk for moderate fatigue (OR:1.172, CI:1.026-1.338, p = 0.019) and with increased risk for severe fatigue (OR:1.209, CI:1.047-1.395, p = 0.010) together with the number of medications/day (OR:1.220, CI:1.023-1.455, p = 0.027). In a binary regression model, severe weight loss predicted moderate-to-severe fatigue in the study population (OR:1.651, CI:1.052-2.590, p = 0.029). In summary, patients with self-reported severe weight loss at hospital discharge exhibited higher fatigue levels and severe weight loss was an independent predictor of moderate and severe fatigue, placing these patients at risk for impaired outcome in the post-hospital period.
For both Lévy flight and Lévy walk search processes we analyse the full distribution of first-passage and first-hitting (or first-arrival) times. These are, respectively, the times when the particle moves across a point at some given distance from its initial position for the first time, or when it lands at a given point for the first time. For Lévy motions with their propensity for long relocation events and thus the possibility to jump across a given point in space without actually hitting it ('leapovers'), these two definitions lead to significantly different results. We study the first-passage and first-hitting time distributions as functions of the Lévy stable index, highlighting the different behaviour for the cases when the first absolute moment of the jump length distribution is finite or infinite. In particular we examine the limits of short and long times. Our results will find their application in the mathematical modelling of random search processes as well as computer algorithms.
Sex determination has evolved in a variety of ways and can depend on environmental and genetic signals. A widespread form of genetic sex determination is haplodiploidy, where unfertilized, haploid eggs develop into males and fertilized diploid eggs into females. One of the molecular mechanisms underlying haplodiploidy in Hymenoptera, the large insect order comprising ants, bees, and wasps, is complementary sex determination (CSD). In species with CSD, heterozygosity at one or several loci induces female development. Here, we identify the genomic regions putatively underlying multilocus CSD in the parasitoid wasp Lysiphlebus fabarum using restriction -site associated DNA sequencing. By analyzing segregation patterns at polymorphic sites among 331 diploid males and females, we identify up to four CSD candidate regions, all on different chromosomes. None of the candidate regions feature evidence for homology with the csd gene from the honey bee, the only species in which CSD has been characterized, suggesting that CSD in L. fabarum is regulated via a novel molecular mechanism. Moreover, no homology is shared between the candidate loci, in contrast to the idea that multilocus CSD should emerge from duplications of an ancestral single -locus system. Taken together, our results suggest that the molecular mechanisms underlying CSD in Hymenoptera are not conserved between species, raising the question as to whether CSD may have evolved multiple times independently in the group.
Entrepreneurial persistence is demonstrated by an entrepreneur’s continued positive maintenance of entrepreneurial motivation and constantly renewed active engagement in a new business venture despite counterforces or enticing alternatives. It thus is a crucial factor for entrepreneurs when pursuing and exploiting their business opportunities and in realizing potential economic gains and benefits. Using rich data on a representative sample of German business founders, we investigated the determinants of entrepreneurial persistence. Next to observed survival, we also constructed a hybrid persistence measure capturing the motivational dimension of persistence. We analyzed the influence of individual-level (human capital and personality) and business-related characteristics on both measures as well as their relative importance. We found that the two indicators emphasize different aspects of persistence. For the survival indicator, the predictive power was concentrated in business characteristics and human capital, while for hybrid persistence the dominant factors were business characteristics and personality. Finally, we showed that results were heterogeneous across subgroups. In particular, formerly unemployed founders did not differ in survival chances, but they were more likely to lack a high psychological commitment to their business ventures.
Sensors composed of a porous silicon monolayer covered with a film of nanostructured gold layer, which provide two optical signal transduction methods, are fabricated and thoroughly characterized concerning their sensing performance. For this purpose, silicon substrates were electrochemically etched in order to obtain porous silicon monolayers, which were subsequently immersed in gold salt solution facilitating the formation of a porous gold nanoparticle layer on top of the porous silicon. The deposition process was monitored by reflectance spectroscopy, and the appearance of a dip in the interference pattern of the porous silicon layer was observed. This dip can be assigned to the absorption of light by the deposited gold nanostructures leading to localized surface plasmon resonance. The bulk sensitivity of these sensors was determined by recording reflectance spectra in media having different refractive indices and compared to sensors exclusively based on porous silicon or gold nanostructures. A thorough analysis of resulting shifts of the different optical signals in the reflectance spectra on the wavelength scale indicated that the optical response of the porous silicon sensor is not influenced by the presence of a gold nanostructure on top. Moreover, the adsorption of thiol-terminated polystyrene to the sensor surface was solely detected by changes in the position of the dip in the reflectance spectrum, which is assigned to localized surface plasmon resonance in the gold nanostructures. The interference pattern resulting from the porous silicon layer is not shifted to longer wavelengths by the adsorption indicating the independence of the optical response of the two nanostructures, namely porous silicon and nanostructured gold layer, to refractive index changes and pointing to the successful realization of two sensors in one spot.
The innovative dual-purpose chicken approach aims at contributing to the transition towards sustainable poultry production by avoiding the culling of male chickens. To successfully integrate sustainability aspects into innovation, goal congruency among actors and clearly communicating the added value within the actor network and to consumers is needed. The challenge of identifying common sustainability goals calls for decision support tools. The objectives of our research were to investigate whether the tool could assist in improving communication and marketing with respect to sustainability and optimizing the value chain organization. Three actor groups participated in the tool application, in which quantitative and qualitative data were collected. The results showed that there were manifold sustainability goals within the innovation network, but only some goals overlapped, and the perception of their implementation also diverged. While easily marketable goals such as ‘animal welfare’ were perceived as being largely implemented, economic goals were prioritized less often, and the implementation was perceived as being rather low. By visualizing congruencies and differences in the goals, the tool helped identify fields of action, such as improved information flows and prompted thinking processes. We conclude that the tool is useful for managing complex decision processes with several actors involved.
Background. In horses and ponies numerous medical conditions are known to be linked with inflammation in different tissues, especially in the liver. Besides affecting other metabolic pathways such as the expression of certain interleukins (IL), inflammation is associated with stress of the endoplasmic reticulum (ER). In particular, ER stress leads to adaptive stress response and can be measured by several markers of inflammatory and stress signalling pathways, like nuclear factor kappa B (NF-kB). Objectives. To investigate lipopolysaccharide (LPS)-induced inflammatory reactions and their modulation in horses and ponies by feeding a polyphenol-rich supplement consisting of green tea and curcuma. Methods. In a cross-over study, 11 animals were allocated to either a placebo or a supplement group and supplemented with 10 g of a blend of green tea and curcuma extract (GCE) or a placebo (calcium carbonate) once daily. After 21 days of supplementation, all animals underwent a LPS challenge to induce moderate systemic inflammation. Blood samples and liver biopsies were taken at standardized time points: 24 hours before and 12 hours after LPS challenge. Inflammatory blood parameters such as serum amyloid A (SAA), haptoglobin and retinol binding protein 4 (RBP4) were measured in serum. Hepatic mRNA levels of selected markers of inflammation such as haptoglobin, tumor necrosis factor alpha (TNF-alpha), IL-1 beta, IL-6, cluster of differentiation 68 (CD68), fibroblast growth factor 21 (FGF-21), NF-kappa B, activating transcription factor 4 (ATF4) were quantified by RT-qPCR. In addition, liver biopsies were examined histologically for inflammatory alterations. Results. Blood markers of acute inflammatory response increased after LPS challenge. In the liver, the proinflammatory cytokine IL-1 beta showed significantly lower mRNA levels after LPS challenge in the supplemented group (P = 0.04) compared to the placebo group. Levels of the hepatic CD68 mRNA increased significantly in the placebo group (P = 0.04). There were no significant differences between supplemented and placebo groups concerning other markers of inflammation and markers of ER stress within the liver. The number of hepatic macrophages were not different after LPS challenge in both feeding groups. Conclusion. LPS was able to induce inflammation but seemed less suitable to induce ER stress in the horses and ponies. The polyphenol-rich supplement showed some potential to reduce inflammatory responses. Nevertheless, the supplementation did not exert an overall anti-inflammatory effect in horses and ponies.
The synthesis of chiral nanoporous carbons based on chiral ionic liquids (CILs) of amino acids as precursors is described. Such unique precursors for the carbonization of CILs yield chiral carbonaceous materials with high surface area (approximate to 620 m(2) g(-1)). The enantioselectivities of the porous carbons are examined by advanced techniques such as selective adsorption of enantiomers using cyclic voltammetry, isothermal titration calorimetry, and mass spectrometry. These techniques demonstrate the chiral nature and high enantioselectivity of the chiral carbon materials. Overall, we believe that the novel approach presented here can contribute significantly to the development of new chiral carbon materials that will find important applications in chiral chemistry, such as in chiral catalysis and separation and in chiral sensors. From a scientific point of view, the approach and results reported here can significantly deepen our understanding of chirality at the nanoscale and of the structure and nature of chiral nonporous materials and surfaces.
The nuclear envelope consists of the outer and the inner nuclear membrane, the nuclear lamina and the nuclear pore complexes, which regulate nuclear import and export.The major constituent of the nuclear lamina of Dictyostelium is the lamin NE81. It can form filaments like B-type lamins and it interacts with Sun 1, as well as with the LEM/HeH-family protein Src1. Sun 1 and Src1 are nuclear envelope transmembrane proteins involved in the centrosome-nucleus connection and nuclear envelope stability at the nucleolar regions, respectively. In conjunction with a KASH-domain protein, Sun 1 usually forms a so-called LINC complex.Two proteins with functions reminiscent of KASH-domain proteins at the outer nuclear membrane of Dictyostelium are known; interaptin which serves as an actin connector and the kinesin Kif9 which plays a role in the microtubule-centrosome connector. However, both of these lack the conserved KASH-domain. The link of the centrosome to the nuclear envelope is essential for the insertion of the centrosome into the nuclear envelope and the appropriate spindle formation. Moreover, centrosome insertion is involved in perm eabilization of the mitotic nucleus, which ensures access of tubulin dimers and spindle assembly factors. Our recent progress in identifying key molecular players at the nuclear envelope of Dictyostelium promises further insights into the mechanisms of nuclear envelope dynamics.
A digital filter is introduced which treats the problem of predictability versus time averaging in a continuous, seamless manner. This seamless filter (SF) is characterized by a unique smoothing rule that determines the strength of smoothing in dependence on lead time. The rule needs to be specified beforehand, either by expert knowledge or by user demand. As a result, skill curves are obtained that allow a predictability assessment across a whole range of time-scales, from daily to seasonal, in a uniform manner. The SF is applied to downscaled SEAS5 ensemble forecasts for two focus regions in or near the tropical belt, the river basins of the Karun in Iran and the Sao Francisco in Brazil. Both are characterized by strong seasonality and semi-aridity, so that predictability across various time-scales is in high demand. Among other things, it is found that from the start of the water year (autumn), areal precipitation is predictable with good skill for the Karun basin two and a half months ahead; for the Sao Francisco it is only one month, longer-term prediction skill is just above the critical level.
Rapid local adaptation frequently occurs during the spread of invading species. It remains unclear, however, how consistent, and therefore potentially predictable, such patterns of local adaptation are. One approach to this question is to measure patterns of local differentiation in functional traits and plasticity levels in invasive species in multiple regions. Finding consistent patterns of local differentiation in replicate regions suggests that these patterns are adaptive. Further, this outcome indicates that the invading species likely responds predictably to selection along environmental gradients, even though standing genetic variation is likely to have been reduced during introduction. We studied local differentiation in the invasive annual plant Erodium cicutarium in two invaded regions, California and Chile. We collected seeds from across strong gradients in precipitation and temperature in Mediterranean-climate parts of the two regions (10 populations per region). We grew seeds from maternal families from these populations through two generations and exposed the second generation to contrasting levels of water and nutrient availability. We measured growth, flowering time and leaf functional traits across these treatments to obtain trait means and plasticity measures. We found strong differentiation among populations in all traits. Plants from drier environments flowered earlier, were less plastic in flowering time and reached greater size in all treatments. Correlations among traits within regions suggested a coordinated evolutionary response along environmental gradients associated with growing season length. There was little divergence in traits and trait intercorrelations between regions, but strongly parallel divergence in traits within regions. Similar, statistically consistent patterns of local trait differentiation across two regions suggest that local adaptation to environmental gradients has aided the spread of this invasive species, and that the formation of ecotypes in newly invaded environments has been relatively consistent and predictable.
Lineament mapping, which is an important part of any structural geological investigation, is made more efficient and easier by the availability of optical as well as radar remote sensing data, such as Landsat and Sentinel with medium and high spatial resolutions. However, the results from these multi-resolution data vary due to their difference in spatial resolution and sensitivity to soil occupation. The accuracy and quality of extracted lineaments depend strongly on the spatial resolution of the imagery. Therefore, the aim of this study was to compare the optical Landsat-8, Sentinel-2A, and radar Sentinel-1A satellite data for automatic lineament extraction. The framework of automatic approach includes defining the optimal parameters for automatic lineament extraction with a combination of edge detection and line-linking algorithms and determining suitable bands from optical data suited for lineament mapping in the study area. For the result validation, the extracted lineaments are compared against the manually obtained lineaments through the application of directional filtering and edge enhancement as well as to the lineaments digitized from the existing geological maps of the study area. In addition, a digital elevation model (DEM) has been utilized for an accuracy assessment followed by the field verification. The obtained results show that the best correlation between automatically extracted lineaments, manual interpretation, and the preexisting lineament map is achieved from the radar Sentinel-1A images. The tests indicate that the radar data used in this study, with 5872 and 5865 lineaments extracted from VH and VV polarizations respectively, is more efficient for structural lineament mapping than the Landsat-8 and Sentinel-2A optical imagery, from which 2338 and 4745 lineaments were extracted respectively.
Cognitive representations and beliefs are what comprise an individual’s self-concept. A positive self-concept is related to and influences academic achievement, and the relationship between a domain-specific self-concept and achievement in the same domain is positive and strong. However, insufficient attention has been paid to these issues among multilingual children. More importantly, since instruction strongly contributes to the development of metacognition and executive functions (EFs), and since the bilingual advantage hypothesis holds that the constant management of multiple languages entails benefits for EF, we bring together these important issues in the present study. We examine the relationship between domain-specific self-concepts and standardized assessment of reading and spelling competences against the background of potential differences in self-concept between monolingual and multilingual German children. While between-group comparisons revealed no significant differences for self-concept nor reading competency, monolinguals outperformed multilinguals in spelling. Correlations between domain-specific self-concepts and academic achievement in reading comprehension, reading fluency, and spelling were positive and significant for both groups. Regardless of language background, children’s evaluations of their academic achievement (reading and spelling) were realistic. We argue, on a theoretical basis, that metacognition and EFs could facilitate a bilingual advantage and improve educational outcomes.
Transient receptor potential (TRP) channels have emerged as potential sensors and transducers of inflammatory pain. The aims of this study were to investigate (1) the expression of TRP channels in intervertebral disc (IVD) cells in normal and inflammatory conditions and (2) the function of Transient receptor potential ankyrin 1 (TRPA1) and Transient receptor potential vanilloid 1 (TRPV1) in IVD inflammation and matrix homeostasis. RT-qPCR was used to analyze human fetal, healthy, and degenerated IVD tissues for the gene expression of TRPA1 and TRPV1. The primary IVD cell cultures were stimulated with either interleukin-1 beta (IL-1) or tumor necrosis factor alpha (TNF-) alone or in combination with TRPA1/V1 agonist allyl isothiocyanate (AITC, 3 and 10 mu M), followed by analysis of calcium flux and the expression of inflammation mediators (RT-qPCR/ELISA) and matrix constituents (RT-qPCR). The matrix structure and composition in caudal motion segments from TRPA1 and TRPV1 wild-type (WT) and knock-out (KO) mice was visualized by FAST staining. Gene expression of other TRP channels (A1, C1, C3, C6, V1, V2, V4, V6, M2, M7, M8) was also tested in cytokine-treated cells. TRPA1 was expressed in fetal IVD cells, 20% of degenerated IVDs, but not in healthy mature IVDs. TRPA1 expression was not detectable in untreated cells and it increased upon cytokine treatment, while TRPV1 was expressed and concomitantly reduced. In inflamed IVD cells, 10 mu M AITC activated calcium flux, induced gene expression of IL-8, and reduced disintegrin and metalloproteinase with thrombospondin motifs 5 (ADAMTS5) and collagen 1A1, possibly via upregulated TRPA1. TRPA1 KO in mice was associated with signs of degeneration in the nucleus pulposus and the vertebral growth plate, whereas TRPV1 KO did not show profound changes. Cytokine treatment also affected the gene expression of TRPV2 (increase), TRPV4 (increase), and TRPC6 (decrease). TRPA1 might be expressed in developing IVD, downregulated during its maturation, and upregulated again in degenerative disc disease, participating in matrix homeostasis. However, follow-up studies with larger sample sizes are needed to fully elucidate the role of TRPA1 and other TRP channels in degenerative disc disease.
The Surface Water and Ocean Topography (SWOT) mission is a next generation satellite mission expected to provide a 2 km-resolution observation of the sea surface height (SSH) on a two-dimensional swath. Processing SWOT data will be challenging because of the large amount of data, the mismatch between a high spatial resolution and a low temporal resolution, and the observation errors. The present paper focuses on the reduction of the spatially structured errors of SWOT SSH data. It investigates a new error reduction method and assesses its performance in an observing system simulation experiment. The proposed error-reduction method first projects the SWOT SSH onto a subspace spanned by the SWOT spatially structured errors. This projection is removed from the SWOT SSH to obtain a detrended SSH. The detrended SSH is then processed within an ensemble data assimilation analysis to retrieve a full SSH field. In the latter step, the detrending is applied to both the SWOT data and an ensemble of model-simulated SSH fields. Numerical experiments are performed with synthetic SWOT observations and an ensemble from a North Atlantic, 1/60 degrees simulation of the ocean circulation (NATL60). The data assimilation analysis is carried out with an ensemble Kalman filter. The results are assessed with root mean square errors, power spectrum density, and spatial coherence. They show that a significant part of the large scale SWOT errors is reduced. The filter analysis also reduces the small scale errors and allows for an accurate recovery of the energy of the signal down to 25 km scales. In addition, using the SWOT nadir data to adjust the SSH detrending further reduces the errors.
Recombinant adeno-associated viruses (rAAV) provide outstanding options for customization and superior capabilities for gene therapy. To access their full potential, facile genetic manipulation is pivotal, including capsid loop modifications. Therefore, we assessed capsid tolerance to modifications of the structural VP proteins in terms of stability and plasticity. Flexible glycine-serine linkers of increasing sizes were, at the genetic level, introduced into the 587 loop region of the VP proteins of serotype 2, the best studied AAV representative. Analyses of biological function and thermal stability with respect to genome release of viral particles revealed structural plasticity. In addition, insertion of the 29 kDa enzyme beta-lactamase into the loop region was tested with a complete or a mosaic modification setting. For the mosaic approach, investigation of VP2 trans expression revealed that a Kozak sequence was required to prevent leaky scanning. Surprisingly, even the full capsid modification with beta-lactamase allowed for the assembly of capsids with a concomitant increase in size. Enzyme activity assays revealed lactamase functionality for both rAAV variants, which demonstrates the structural robustness of this platform technology.
During the last few decades, the rapid separation of the Small Aral Sea from the isolated basin has changed its hydrological and ecological conditions tremendously. In the present study, we developed and validated the hybrid model for the Syr Darya River basin based on a combination of state-of-the-art hydrological and machine learning models. Climate change impact on freshwater inflow into the Small Aral Sea for the projection period 2007-2099 has been quantified based on the developed hybrid model and bias corrected and downscaled meteorological projections simulated by four General Circulation Models (GCM) for each of three Representative Concentration Pathway scenarios (RCP). The developed hybrid model reliably simulates freshwater inflow for the historical period with a Nash-Sutcliffe efficiency of 0.72 and a Kling-Gupta efficiency of 0.77. Results of the climate change impact assessment showed that the freshwater inflow projections produced by different GCMs are misleading by providing contradictory results for the projection period. However, we identified that the relative runoff changes are expected to be more pronounced in the case of more aggressive RCP scenarios. The simulated projections of freshwater inflow provide a basis for further assessment of climate change impacts on hydrological and ecological conditions of the Small Aral Sea in the 21st Century.
Tumor-associated macrophages (TAMs) promote tumor growth and metastasis by suppressing tumor immune surveillance. Herein, we provide evidence that the immunosuppressive phenotype of TAMs is controlled by long-chain fatty acid metabolism, specifically unsaturated fatty acids, here exemplified by oleate. Consequently, en-route enriched lipid droplets were identified as essential organelles, which represent effective targets for chemical inhibitors to block in vitro polarization of TAMs and tumor growth in vivo. In line, analysis of human tumors revealed that myeloid cells infiltrating colon cancer but not gastric cancer tissue indeed accumulate lipid droplets. Mechanistically, our data indicate that oleate-induced polarization of myeloid cells depends on the mammalian target of the rapamycin pathway. Thus, our findings reveal an alternative therapeutic strategy by targeting the pro-tumoral myeloid cells on a metabolic level.
The actin cytoskeleton and its response to external chemical stimuli is fundamental to the mechano-biology of eukaryotic cells and their functions. One of the key players that governs the dynamics of the actin network is the motor protein myosin II. Based on a phase space embedding we have identified from experiments three phases in the cytoskeletal dynamics of starved Dictyostelium discoideum in response to a precisely controlled chemotactic stimulation. In the first two phases the dynamics of actin and myosin II in the cortex is uncoupled, while in the third phase the time scale for the recovery of cortical actin is determined by the myosin II dynamics. We report a theoretical model that captures the experimental observations quantitatively. The model predicts an increase in the optimal response time of actin with decreasing myosin II-actin coupling strength highlighting the role of myosin II in the robust control of cell contraction.
DNA origami nanostructures are widely employed in various areas of fundamental and applied research. Due to the tremendous success of the DNA origami technique in the academic field, considerable efforts currently aim at the translation of this technology from a laboratory setting to real-world applications, such as nanoelectronics, drug delivery, and biosensing. While many of these real-world applications rely on an intact DNA origami shape, they often also subject the DNA origami nanostructures to rather harsh and potentially damaging environmental and processing conditions. Furthermore, in the context of DNA origami mass production, the long-term storage of DNA origami nanostructures or their pre-assembled components also becomes an issue of high relevance, especially regarding the possible negative effects on DNA origami structural integrity. Thus, we investigated the effect of staple age on the self-assembly and stability of DNA origami nanostructures using atomic force microscopy. Different harsh processing conditions were simulated by applying different sample preparation protocols. Our results show that staple solutions may be stored at -20 degrees C for several years without impeding DNA origami self-assembly. Depending on DNA origami shape and superstructure, however, staple age may have negative effects on DNA origami stability under harsh treatment conditions. Mass spectrometry analysis of the aged staple mixtures revealed no signs of staple fragmentation. We, therefore, attribute the increased DNA origami sensitivity toward environmental conditions to an accumulation of damaged nucleobases, which undergo weaker base-pairing interactions and thus lead to reduced duplex stability.
Enhancers are critical for developmental stage-specific gene expression, but their dynamic regulation in plants remains poorly understood. Here we compare genome-wide localization of H3K27ac, chromatin accessibility and transcriptomic changes during flower development in Arabidopsis. H3K27ac prevalently marks promoter-proximal regions, suggesting that H3K27ac is not a hallmark for enhancers in Arabidopsis. We provide computational and experimental evidence to confirm that distal DNase. hypersensitive sites are predictive of enhancers. The predicted enhancers are highly stage-specific across flower development, significantly associated with SNPs for flowering-related phenotypes, and conserved across crucifer species. Through the integration of genome-wide transcription factor (TF) binding datasets, we find that floral master regulators and stage-specific TFs are largely enriched at developmentally dynamic enhancers. Finally, we show that enhancer clusters and intronic enhancers significantly associate with stage-specific gene regulation by floral master TFs. Our study provides insights into the functional flexibility of enhancers during plant development, as well as hints to annotate plant enhancers.
Peroxisome biogenesis disorders (PBDs) are nontreatable hereditary diseases with a broad range of severity. Approximately 65% of patients are affected by mutations in the peroxins Pex1 and Pex6. The proteins form the heteromeric Pex1/Pex6 complex, which is important for protein import into peroxisomes. To date, no structural data are available for this AAA+ ATPase complex. However, a wealth of information can be transferred from low-resolution structures of the yeast scPex1/scPex6 complex and homologous, well-characterized AAA+ ATPases. We review the abundant records of missense mutations described in PBD patients with the aim to classify and rationalize them by mapping them onto a homology model of the human Pex1/Pex6 complex. Several mutations concern functionally conserved residues that are implied in ATP hydrolysis and substrate processing. Contrary to fold destabilizing mutations, patients suffering from function-impairing mutations may not benefit from stabilizing agents, which have been reported as potential therapeutics for PBD patients.