Mammalian sphingoid bases: Biophysical, physiological and pathological properties

Sphingoid bases encompass a group of long chain amino alcohols which form the essential structure of sphingolipids. Over the last years, these amphiphilic molecules were moving more and more into the focus of biomedical research due to their role as bioactive molecules. In fact, free sphingoid bases interact with specific receptors and target molecules, and have been associated with numerous biological and physiological processes. In addition, they can modulate the biophysical properties of biological membranes. Several human diseases are related to pathological changes in the structure and metabolism of sphingoid bases. Yet, the mechanisms underlying their biological and pathophysiological actions remain elusive. Within this review, we aimed to summarize the current knowledge on the biochemical and biophysical properties of the most common sphingoid bases and to discuss their importance in health and disease

Enabled Negatively Regulates Diaphanous-Driven Actin Dynamics In Vitro and In Vivo

Actin regulators facilitate cell migration by controlling cell protrusion architecture and dynamics. As the behavior of individual actin regulators becomes clear, we must address why cells require multiple regulators with similar functions and how they cooperate to create diverse protrusions. We characterized Diaphanous (Dia) and Enabled (Ena) as a model, using complementary approaches: cell culture, biophysical analysis, and Drosophila morphogenesis. We found that Dia and Ena have distinct biochemical properties that contribute to the different protrusion morphologies each induces. Dia is a more processive, faster elongator, paralleling the long, stable filopodia it induces in vivo, while Ena promotes filopodia with more dynamic changes in number, length, and lifetime. Acting together, Ena and Dia induce protrusions distinct from those induced by either alone, with Ena reducing Dia-driven protrusion length and number. Consistent with this, EnaEVH1 binds Dia directly and inhibits DiaFH1FH2-mediated nucleation in vitro. Finally, Ena rescues hemocyte migration defects caused by activated Dia

Drag forces on inclusions in classical fields with dissipative dynamics

We study the drag force on uniformly moving inclusions which interact linearly with dynamical free field theories commonly used to study soft condensed matter systems. Drag forces are shown to be nonlinear functions of the inclusion velocity and depend strongly on the field dynamics. The general results obtained can be used to explain drag forces in Ising systems and also predict the existence of drag forces on proteins in membranes due to couplings to various physical parameters of the membrane such as composition, phase and height fluctuations.Comment: 14 pages, 7 figure

A Screen for Morphological Complexity Identifies Regulators of Switch-like Transitions between Discrete Cell Shapes

The way in which cells adopt different morphologies is not fully understood. Cell shape could be a continuous variable or restricted to a set of discrete forms. We developed quantitative methods to describe cell shape and show that Drosophila hemocytes in culture are a heterogeneous mixture of five discrete morphologies. In an RNAi screen of genes affecting the morphological complexity of heterogeneous populations, we found that most genes regulate the transition between discrete shapes rather than generating new morphologies. In particular, we identified a subset of genes, including the tumour suppressor PTEN, that decrease the heterogeneity of the population leading to populations enriched in rounded or elongated forms. We show that these genes have a highly conserved function as regulators of cell shape in both mouse and human metastatic melanoma cells

Observations of aerosol–vapor pressure deficit–evaporative fraction coupling over India

Northern India is a densely populated subtropical region with heavy aerosol loading (mean aerosol optical depth or AOD is ∼0.7), frequent heat waves, and strong atmosphere–biosphere coupling, making it ideal for studying the impacts of aerosols and the temperature variation in latent heat flux (LH) and evaporative fraction (EF). Here, using in situ observations during the onset of the summer monsoon over a semi-natural grassland site in this region, we confirm that strong co-variability exists among aerosols, LH, air temperature (Tair), and the vapor pressure deficit (VPD). Since the surface evapotranspiration is strongly controlled by both physical (available energy and moisture demand) and physiological (canopy and aerodynamic resistance) factors, we separately analyze our data for different combinations of aerosols and Tair/VPD changes. We find that aerosol loading and warmer conditions both reduce sensible heat (SH). Furthermore, we find that an increase in atmospheric VPD tends to decrease the gross primary production (GPP) and, thus, LH, most likely as a response to stomatal closure of the dominant grasses at this location. In contrast, under heavy aerosol loading, LH is enhanced partly due to the physiological control exerted by the diffuse radiation fertilization effect (thus increasing EF). Moreover, LH and EF increases with aerosol loading even under heat wave conditions, indicating a decoupling of the plant's response to the VPD enhancement (stomatal closure) in the presence of high aerosol conditions. Our results encourage detailed in situ experiments and mechanistic modeling of AOD–VPD–EF coupling for a better understanding of Indian monsoon dynamics and crop vulnerability in a heat stressed and heavily polluted future India

Determinant representation for some transition probabilities in the TASEP with second class particles

We study the transition probabilities for the totally asymmetric simple exclusion process (TASEP) on the infinite integer lattice with a finite, but arbitrary number of first and second class particles. Using the Bethe ansatz we present an explicit expression of these quantities in terms of the Bethe wave function. In a next step it is proved rigorously that this expression can be written in a compact determinantal form for the case where the order of the first and second class particles does not change in time. An independent geometrical approach provides insight into these results and enables us to generalize the determinantal solution to the multi-class TASEP.Comment: Minor revision; journal reference adde

Current Fluctuations of the One Dimensional Symmetric Simple Exclusion Process with Step Initial Condition

For the symmetric simple exclusion process on an infinite line, we calculate exactly the fluctuations of the integrated current $Q_t$ during time $t$ through the origin when, in the initial condition, the sites are occupied with density $\rho_a$ on the negative axis and with density $\rho_b$ on the positive axis. All the cumulants of $Q_t$ grow like $\sqrt{t}$. In the range where $Q_t \sim \sqrt{t}$, the decay $\exp [-Q_t^3/t]$ of the distribution of $Q_t$ is non-Gaussian. Our results are obtained using the Bethe ansatz and several identities recently derived by Tracy and Widom for exclusion processes on the infinite line.Comment: 2 figure

Non-spectral interferences due to the presence of sulfuric acid in inductively coupled plasma mass spectrometry

Results of a systematic study concerning non-spectral interferences from sulfuric acid containing matrices on a large number of elements in inductively coupled plasma–mass spectrometry (ICP-MS) are presented in this work. The signals obtained with sulfuric acid solutions of different concentrations (up to 5% w w− 1) have been compared with the corresponding signals for a 1% w w− 1− nitric acid solution at different experimental conditions (i.e., sample uptake rates, nebulizer gas flows and r.f. powers). The signals observed for 128Te+, 78Se+ and 75As+ were significantly higher when using sulfuric acid matrices (up to 2.2-fold for 128Te+ and 78Se+ and 1.8-fold for 75As+ in the presence of 5 w w-1 sulfuric acid) for the whole range of experimental conditions tested. This is in agreement with previously reported observations. The signal for 31P+ is also higher (1.1-fold) in the presence of sulfuric acid. The signal enhancements for 128Te+, 78Se+, 75As+ and 31P+ are explained in relation to an increase in the analyte ion population as a result of charge transfer reactions involving S+ species in the plasma. Theoretical data suggest that Os, Sb, Pt, Ir, Zn and Hg could also be involved in sulfur-based charge transfer reactions, but no experimental evidence has been found. The presence of sulfuric acid gives rise to lower ion signals (about 10–20% lower) for the other nuclides tested, thus indicating the negative matrix effect caused by changes in the amount of analyte loading of the plasma. The elemental composition of a certified low-density polyethylene sample (ERM-EC681K) was determined by ICP-MS after two different sample digestion procedures, one of them including sulfuric acid. Element concentrations were in agreement with the certified values, irrespective of the acids used for the digestion. These results demonstrate that the use of matrix-matched standards allows the accurate determination of the tested elements in a sulfuric acid matrix

Cell shape analysis of random tessellations based on Minkowski tensors

To which degree are shape indices of individual cells of a tessellation characteristic for the stochastic process that generates them? Within the context of stochastic geometry and the physics of disordered materials, this corresponds to the question of relationships between different stochastic models. In the context of image analysis of synthetic and biological materials, this question is central to the problem of inferring information about formation processes from spatial measurements of resulting random structures. We address this question by a theory-based simulation study of shape indices derived from Minkowski tensors for a variety of tessellation models. We focus on the relationship between two indices: an isoperimetric ratio of the empirical averages of cell volume and area and the cell elongation quantified by eigenvalue ratios of interfacial Minkowski tensors. Simulation data for these quantities, as well as for distributions thereof and for correlations of cell shape and volume, are presented for Voronoi mosaics of the Poisson point process, determinantal and permanental point processes, and Gibbs hard-core and random sequential absorption processes as well as for Laguerre tessellations of polydisperse spheres and STIT- and Poisson hyperplane tessellations. These data are complemented by mechanically stable crystalline sphere and disordered ellipsoid packings and area-minimising foam models. We find that shape indices of individual cells are not sufficient to unambiguously identify the generating process even amongst this limited set of processes. However, we identify significant differences of the shape indices between many of these tessellation models. Given a realization of a tessellation, these shape indices can narrow the choice of possible generating processes, providing a powerful tool which can be further strengthened by density-resolved volume-shape correlations.Comment: Chapter of the forthcoming book "Tensor Valuations and their Applications in Stochastic Geometry and Imaging" in Lecture Notes in Mathematics edited by Markus Kiderlen and Eva B. Vedel Jense