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The relevance for in vitro three-dimensional (3D) tissue culture of skin has been present for almost a century. From using skin biopsies in organ culture, to vascularized organotypic full-thickness reconstructed human skin equivalents, in vitro tissue regeneration of 3D skin has reached a golden era. However, the reconstruction of 3D skin still has room to grow and develop. The need for reproducible methodology, physiological structures and tissue architecture, and perfusable vasculature are only recently becoming a reality, though the addition of more complex structures such as glands and tactile corpuscles require advanced technologies. In this review, we will discuss the current methodology for biofabrication of 3D skin models and highlight the advantages and disadvantages of the existing systems as well as emphasize how new techniques can aid in the production of a truly physiologically relevant skin construct for preclinical innovation.
The centrosome is not only the largest and most sophisticated protein complex within a eukaryotic cell, in the light of evolution, it is also one of its most ancient organelles. This special issue of "Cells" features representatives of three main, structurally divergent centrosome types, i.e., centriole-containing centrosomes, yeast spindle pole bodies (SPBs), and amoebozoan nucleus-associated bodies (NABs). Here, I discuss their evolution and their key-functions in microtubule organization, mitosis, and cytokinesis. Furthermore, I provide a brief history of centrosome research and highlight recently emerged topics, such as the role of centrioles in ciliogenesis, the relationship of centrosomes and centriolar satellites, the integration of centrosomal structures into the nuclear envelope and the involvement of centrosomal components in non-centrosomal microtubule organization.
A considerable number of German dialects exhibit doubled R-pronouns with pronominal adverbs (dadamit, dadafur, dadagegen). At first sight, this type of in situ replication seems to be completely redundant since its occurrence is independent of R-pronoun extraction/movement. The main purpose of this paper is to account for (i) the difference between dialects with regard to replication of R-pronouns and (ii) why an (apparently redundant) process of replication occurs. Following Muller (2000a), who considers R-pronouns to be a repair phenomenon, we present an analysis in the framework of Optimality Theory. We argue that replication of R-pronouns is a consequence of different rankings of universal requirements like e.g. the Inclusiveness Condition, the Lexical Integrity Hypothesis and Antilocality and that the interaction of these constraints results in the occurrence of replication.
We present a general analysis of the cooling produced by losses on condensates or quasi-condensates. We study how the occupations of the collective phonon modes evolve in time, assuming that the loss process is slow enough so that each mode adiabatically follows the decrease of the mean density. The theory is valid for any loss process whose rate is proportional to the jth power of the density, but otherwise spatially uniform. We cover both homogeneous gases and systems confined in a smooth potential. For a low-dimensional gas, we can take into account the modified equation of state due to the broadening of the cloud width along the tightly confined directions, which occurs for large interactions. We find that at large times, the temperature decreases proportionally to the energy scale mc(2), where m is the mass of the particles and c the sound velocity. We compute the asymptotic ratio of these two quantities for different limiting cases: a homogeneous gas in any dimension and a one-dimensional gas in a harmonic trap.
DNA nanostructures enable the attachment of functional molecules to nearly any unique location on their underlying structure. Due to their single-base-pair structural resolution, several ligands can be spatially arranged and closely controlled according to the geometry of their desired target, resulting in optimized binding and/or signaling interactions. Here, the efficacy of SWL, an ephrin-mimicking peptide that binds specifically to EphrinA2 (EphA2) receptors, increased by presenting up to three of these peptides on small DNA nanostructures in an oligovalent manner. Ephrin signaling pathways play crucial roles in tumor development and progression. Moreover, Eph receptors are potential targets in cancer diagnosis and treatment. Here, the quantitative impact of SWL valency on binding, phosphorylation (key player for activation) and phenotype regulation in EphA2-expressing prostate cancer cells was demonstrated. EphA2 phosphorylation was significantly increased by DNA trimers carrying three SWL peptides compared to monovalent SWL. In comparison to one of EphA2’s natural ligands ephrin-A1, which is known to bind promiscuously to multiple receptors, pinpointed targeting of EphA2 by oligovalent DNA-SWL constructs showed enhanced cell retraction. Overall, we show that DNA scaffolds can increase the potency of weak signaling peptides through oligovalent presentation and serve as potential tools for examination of complex signaling pathways.
Same but different
(2018)
The maturation of bacterial molybdoenzymes is a complex process leading to the insertion of the bulky bis-molybdopterin guanine dinucleotide (bis-MGD) cofactor into the apoenzyme. Most molybdoenzymes were shown to contain a specific chaperone for the insertion of the bis-MGD cofactor. Formate dehydrogenases (FDH) together with their molecular chaperone partner seem to display an exception to this specificity rule, since the chaperone FdhD has been proven to be involved in the maturation of all three FDH enzymes present in Escherichia colt. Multiple roles have been suggested for FdhD-like chaperones in the past, including the involvement in a sulfur transfer reaction from the L-cysteine desulfurase IscS to bis-MGD by the action of two cysteine residues present in a conserved CXXC motif of the chaperones. However, in this study we show by phylogenetic analyses that the CXXC motif is not conserved among FdhD-like chaperones. We compared in detail the FdhD-like homologues from Rhodobacter capsulatus and E. colt and show that their roles in the maturation of FDH enzymes from different subgroups can be exchanged. We reveal that bis-MGDbinding is a common characteristic of FdhD-like proteins and that the cofactor is bound with a sulfido-ligand at the molybdenum atom to the chaperone. Generally, we reveal that the cysteine residues in the motif CXXC of the chaperone are not essential for the production of active FDH enzymes.
Flood risk is impacted by a range of physical and socio-economic processes. Hence, the quantification of flood risk ideally considers the complete flood risk chain, from atmospheric processes through catchment and river system processes to damage mechanisms in the affected areas. Although it is generally accepted that a multitude of changes along the risk chain can occur and impact flood risk, there is a lack of knowledge of how and to what extent changes in influencing factors propagate through the chain and finally affect flood risk. To fill this gap, we present a comprehensive sensitivity analysis which considers changes in all risk components, i.e. changes in climate, catchment, river system, land use, assets, and vulnerability. The application of this framework to the mesoscale Mulde catchment in Germany shows that flood risk can vary dramatically as a consequence of plausible change scenarios. It further reveals that components that have not received much attention, such as changes in dike systems or in vulnerability, may outweigh changes in often investigated components, such as climate. Although the specific results are conditional on the case study area and the selected assumptions, they emphasize the need for a broader consideration of potential drivers of change in a comprehensive way. Hence, our approach contributes to a better understanding of how the different risk components influence the overall flood risk.
Mechanical and/or chemical removal of material from the subsurface may generate large subsurface cavities, the destabilisation of which can lead to ground collapse and the formation of sinkholes. Numerical simulation of the interaction of cavity growth, host material deformation and overburden collapse is desirable to better understand the sinkhole hazard but is a challenging task due to the involved high strains and material discontinuities. Here, we present 2-D distinct element method numerical simulations of cavity growth and sinkhole development. Firstly, we simulate cavity formation by quasi-static, stepwise removal of material in a single growing zone of an arbitrary geometry and depth. We benchmark this approach against analytical and boundary element method models of a deep void space in a linear elastic material. Secondly, we explore the effects of properties of different uniform materials on cavity stability and sinkhole development. We perform simulated biaxial tests to calibrate macroscopic geotechnical parameters of three model materials representative of those in which sinkholes develop at the Dead Sea shoreline: mud, alluvium and salt. We show that weak materials do not support large cavities, leading to gradual sagging or suffusion-style subsidence. Strong materials support quasi-stable to stable cavities, the overburdens of which may fail suddenly in a caprock or bedrock collapse style. Thirdly, we examine the consequences of layered arrangements of weak and strong materials. We find that these are more susceptible to sinkhole collapse than uniform materials not only due to a lower integrated strength of the overburden but also due to an inhibition of stabilising stress arching. Finally, we compare our model sinkhole geometries to observations at the Ghor Al-Haditha sinkhole site in Jordan. Sinkhole depth / diameter ratios of 0.15 in mud, 0.37 in alluvium and 0.33 in salt are reproduced successfully in the calibrated model materials. The model results suggest that the observed distribution of sinkhole depth / diameter values in each material type may partly reflect sinkhole growth trends.
The variabilities of the semidiurnal solar and lunar tides of the equatorial electrojet (EEJ) are investigated during the 2003, 2006, 2009 and 2013 major sudden stratospheric warming (SSW) events in this study. For this purpose, ground-magnetometer recordings at the equatorial observatories in Huancayo and Fuquene are utilized. Results show a major enhancement in the amplitude of the EEJ semidiurnal lunar tide in each of the four warming events. The EEJ semidiurnal solar tidal amplitude shows an amplification prior to the onset of warmings, a reduction during the deceleration of the zonal mean zonal wind at 60 degrees N and 10 hPa, and a second enhancement a few days after the peak reversal of the zonal mean zonal wind during all four SSWs. Results also reveal that the amplitude of the EEJ semidiurnal lunar tide becomes comparable or even greater than the amplitude of the EEJ semidiurnal solar tide during all these warming events. The present study also compares the EEJ semidiurnal solar and lunar tidal changes with the variability of the migrating semidiurnal solar (SW2) and lunar (M2) tides in neutral temperature and zonal wind obtained from numerical simulations at E-region heights. A better agreement between the enhancements of the EEJ semidiurnal lunar tide and the M2 tide is found in comparison with the enhancements of the EEJ semidiurnal solar tide and the SW2 tide in both the neutral temperature and zonal wind at the E-region altitudes.
At Saturn electrons are trapped in the planet’s magnetic field and accelerated to relativistic energies to form the radiation belts, but how this dramatic increase in electron energy occurs is still unknown. Until now the mechanism of radial diffusion has been assumed but we show here that in-situ acceleration through wave particle interactions, which initial studies dismissed as ineffectual at Saturn, is in fact a vital part of the energetic particle dynamics there. We present evidence from numerical simulations based on Cassini spacecraft data that a particular plasma wave, known as Z-mode, accelerates electrons to MeV energies inside 4 RS (1 RS = 60,330 km) through a Doppler shifted cyclotron resonant interaction. Our results show that the Z-mode waves observed are not oblique as previously assumed and are much better accelerators than O-mode waves, resulting in an electron energy spectrum that closely approaches observed values without any transport effects included.
The phi(ev) is calculated from high-resolution discharge and precipitation data for several rain events with a cumulative precipitation P-cum ranging from less than 5mm to more than 80 mm. Because of the high uncertainty of phi(ev) associated with the hydrograph separation method, phi(ev) is calculated with several methods, including graphical methods, digital filters and a tracer-based method. The results indicate that the hydrological response depends on (theta) over bar (ini): during dry conditions phi(ev) is consistently below 0.1, even for events with high and intense precipitation. Above a threshold of (theta) over bar (ini) = 34 vol % phi(ev) can reach values up to 0.99 but there is a high scatter. Some variability can be explained with a weak correlation of phi(ev) with P-cum and rain intensity, but a considerable part of the variability remains unexplained. It is concluded that threshold-based methods can be helpful to prevent overestimation of the hydrological response during dry catchment conditions. The impact of soil moisture on the hydrological response during wet catchment conditions, however, is still insufficiently understood and cannot be generalized based on the present results.
This work reviews the literature on an alleged global warming 'pause' in global mean surface temperature (GMST) to determine how it has been defined, what time intervals are used to characterise it, what data are used to measure it, and what methods used to assess it. We test for 'pauses', both in the normally understood meaning of the term to mean no warming trend, as well as for a 'pause' defined as a substantially slower trend in GMST. The tests are carried out with the historical versions of GMST that existed for each pause-interval tested, and with current versions of each of the GMST datasets. The tests are conducted following the common (but questionable) practice of breaking the linear fit at the start of the trend interval ('broken' trends), and also with trends that are continuous with the data bordering the trend interval. We also compare results when appropriate allowance is made for the selection bias problem. The results show that there is little or no statistical evidence for a lack of trend or slower trend in GMST using either the historical data or the current data. The perception that there was a 'pause' in GMST was bolstered by earlier biases in the data in combination with incomplete statistical testing.
Dating growth strata and basin fill by combining Al-26/Be-10 burial dating and magnetostratigraphy
(2018)
Cosmogenic burial dating enables dating of coarse-grained, Pliocene-Pleistocene sedimentary units that are typically difficult to date with traditional methods, such as magnetostratigraphy. In the actively deforming western Tarim Basin in NW China, Pliocene-Pleistocene conglomerates were dated at eight sites, integrating Al-26/Be-10 burial dating with previously published magnetostratigraphic sections. These samples were collected from growth strata on the flanks of growing folds and from sedimentary units beneath active faults to place timing constraints on the initiation of deformation of structures within the basin and on shortening rates on active faults. These new basin-fill and growthstrata ages document the late Neogene and Quaternary growth of the Pamir and Tian Shan orogens between >5 and 1 Ma and delineate the eastward propagation of deformation at rates up to 115 km/m.y. and basinward growth of both mountain belts at rates up to 12 km/m.y.
Lanthanide-doped upconverting nanoparticles (UCNP) are being extensively studied for bioapplications due to their unique photoluminescence properties and low toxicity. Interest in RET applications involving UCNP is also increasing, but due to factors such as large sizes, ion emission distributions within the particles, and complicated energy transfer processes within the UCNP, there are still many questions to be answered. In this study, four types of core and core-shell NaYF4-based UCNP co-doped with Yb3+ and Tm3+ as sensitizer and activator, respectively, were investigated as donors for the Methyl 5-(8-decanoylbenzo[1,2-d:4,5-d ']bis([1,3]dioxole)-4-yl)-5-oxopentanoate (DBD-6) dye. The possibility of resonance energy transfer (RET) between UCNP and the DBD-6 attached to their surface was demonstrated based on the comparison of luminescence intensities, band ratios, and decay kinetics. The architecture of UCNP influenced both the luminescence properties and the energy transfer to the dye: UCNP with an inert shell were the brightest, but their RET efficiency was the lowest (17%). Nanoparticles with Tm3+ only in the shell have revealed the highest RET efficiencies (up to 51%) despite the compromised luminescence due to surface quenching.
A new micro/mesoporous hybrid clay nanocomposite prepared from kaolinite clay, Carica papaya seeds, and ZnCl2 via calcination in an inert atmosphere is presented. Regardless of the synthesis temperature, the specific surface area of the nanocomposite material is between approximate to 150 and 300 m(2)/g. The material contains both micro- and mesopores in roughly equal amounts. X-ray diffraction, infrared spectroscopy, and solid-state nuclear magnetic resonance spectroscopy suggest the formation of several new bonds in the materials upon reaction of the precursors, thus confirming the formation of a new hybrid material. Thermogravimetric analysis/differential thermal analysis and elemental analysis confirm the presence of carbonaceous matter. The new composite is stable up to 900 degrees C and is an efficient adsorbent for the removal of a water micropollutant, 4-nitrophenol, and a pathogen, E. coli, from an aqueous medium, suggesting applications in water remediation are feasible.
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.
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.
By using an integrative approach, we describe a new species of mayfly, Bungona (Chopralla) pontica sp. n., from Turkey. The discovery of a representative of the tropical mayfly genus Bungona in the Middle East is rather unexpected. The new species shows all the main morphological characters of the subgenus Chopralla, which has its closest related species occurring in southeastern Asia. Barcoding clearly indicated that the new species represents an independent lineage isolated for a very long time from other members of the complex. The claw is equipped with two rows of three or four flattened denticles. This condition is a unique feature of Bungona (Chopralla) pontica sp. n. among West Palaearctic mayfly species. Within the subgenus Chopralla, the species can be identified by the presence of a simple, not bifid right prostheca (also present only in Bungona (Chopralla) liebenauae (Soldan, Braasch & Muu, 1987)), the shape of the labial palp, and the absence of protuberances on pronotum.
Using two crystals for spontaneous parametric down-conversion in a parallel setup, we observe two-photon interference with high visibility. The high visibility is consistent with complementarity and the absence of which-path information. The observations are explained as the effects of entanglement or equivalently in terms of interfering probability amplitudes and also by the calculation of a second-order field correlation function in the Heisenberg picture. The latter approach brings out explicitly the role of the vacuum fields in the down-conversion at the crystals and in the photon coincidence counting. For comparison, we show that the Hong-Ou-Mandel dip can be explained by the same approach in which the role of the vacuum signal and idler fields, as opposed to entanglement involving vacuum states, is emphasized. We discuss the fundamental limitations of a theory in which these vacuum fields are treated as classical, stochastic fields.
Background: There is a growing interest in the role of inflammageing for chronic disease development. Cytokines are potent soluble immune mediators that can be used as target biomarkers of inflammageing; however, their measurement in human samples has been challenging. This study aimed to assess the reliability of a pro- and anti-inflammatory cytokine panel in a sample of healthy people measured with a novel electrochemiluminescent multiplex immunoassay platform (Meso Scale Discovery, MSD), and to characterize their associations with metabolic and inflammatory phenotypes.