ATRA mechanically reprograms pancreatic stellate cells to suppress matrix remodelling and inhibit cancer cell invasion

Pancreatic ductal adenocarcinoma (PDAC) is a highly aggressive malignancy with a dismal survival rate. Persistent activation of pancreatic stellate cells (PSCs) can perturb the biomechanical homoeostasis of the tumour microenvironment to favour cancer cell invasion. Here we report that ATRA, an active metabolite of vitamin A, restores mechanical quiescence in PSCs via a mechanism involving a retinoic acid receptor beta (RAR-β)-dependent downregulation of actomyosin (MLC-2) contractility. We show that ATRA reduces the ability of PSCs to generate high traction forces and adapt to extracellular mechanical cues (mechanosensing), as well as suppresses force-mediated extracellular matrix remodelling to inhibit local cancer cell invasion in 3D organotypic models. Our findings implicate a RAR-β/MLC-2 pathway in peritumoural stromal remodelling and mechanosensory-driven activation of PSCs, and further suggest that mechanical reprogramming of PSCs with retinoic acid derivatives might be a viable alternative to stromal ablation strategies for the treatment of PDAC

Extensive dissolution of live pteropods in the Southern Ocean

The carbonate chemistry of the surface ocean is rapidly changing with ocean acidification, a result of human activities. In the upper layers of the Southern Ocean, aragonite—a metastable form of calcium carbonate with rapid dissolution kinetics—may become undersaturated by 2050 (ref. 2). Aragonite undersaturation is likely to affect aragonite-shelled organisms, which can dominate surface water communities in polar regions. Here we present analyses of specimens of the pteropod Limacina helicina antarctica that were extracted live from the Southern Ocean early in 2008. We sampled from the top 200m of the water column, where aragonite saturation levels were around 1, as upwelled deep water is mixed with surface water containing anthropogenic CO2. Comparing the shell structure with samples from aragonite-supersaturated regions elsewhere under a scanning electron microscope, we found severe levels of shell dissolution in the undersaturated region alone. According to laboratory incubations of intact samples with a range of aragonite saturation levels, eight days of incubation in aragonite saturation levels of 0.94– 1.12 produces equivalent levels of dissolution. As deep-water upwelling and CO2 absorption by surface waters is likely to increase as a result of human activities2,4, we conclude that upper ocean regions where aragonite-shelled organisms are affected by dissolution are likely to expand

The development of the Meaning in Life Index (MILI) and its relationship with personality and religious behaviours and beliefs among UK undergraduate students

The scales available for assessing meaning in life appear to be confounded with several related constructs, including purpose in life, satisfaction with life, and goal-directed behaviour. The Meaning in Life Index (MILI), a new instrument devised as a specific measure of meaning in life, was developed from responses to a pool of 22 items rated by a sample of 501 undergraduate students in Wales. The nine-item scale demonstrated sufficient face validity, internal consistency, and scale reliability to commend the instrument for future use. With respect to personality, the MILI scores were most strongly predicted by neuroticism (negatively), and less strongly by extraversion (positively) and psychoticism (negatively). With respect to several religious behavioural variables, those who attended church at least weekly returned significantly higher MILI scores than those who attended church less frequently. Intrinsic religiosity was the only orientation to be significantly associated with the MILI scale scores, although the magnitude of the association was smaller than anticipated. These results suggest that meaning in life is associated more strongly with individual differences in personality than with specific religious behaviours and attitudes. The implications of these results are discussed in terms of individual's personal values and attitudes that might underlie their experience of a meaning in life

Dissolution dominating calcification process in polar pteropods close to the point of aragonite undersaturation

Thecosome pteropods are abundant upper-ocean zooplankton that build aragonite shells. Ocean acidification results in the lowering of aragonite saturation levels in the surface layers, and several incubation studies have shown that rates of calcification in these organisms decrease as a result. This study provides a weight-specific net calcification rate function for thecosome pteropods that includes both rates of dissolution and calcification over a range of plausible future aragonite saturation states (Omega_Ar). We measured gross dissolution in the pteropod Limacina helicina antarctica in the Scotia Sea (Southern Ocean) by incubating living specimens across a range of aragonite saturation states for a maximum of 14 days. Specimens started dissolving almost immediately upon exposure to undersaturated conditions (Omega_Ar,0.8), losing 1.4% of shell mass per day. The observed rate of gross dissolution was different from that predicted by rate law kinetics of aragonite dissolution, in being higher at Var levels slightly above 1 and lower at Omega_Ar levels of between 1 and 0.8. This indicates that shell mass is affected by even transitional levels of saturation, but there is, nevertheless, some partial means of protection for shells when in undersaturated conditions. A function for gross dissolution against Var derived from the present observations was compared to a function for gross calcification derived by a different study, and showed that dissolution became the dominating process even at Omega_Ar levels close to 1, with net shell growth ceasing at an Omega_Ar of 1.03. Gross dissolution increasingly dominated net change in shell mass as saturation levels decreased below 1. As well as influencing their viability, such dissolution of pteropod shells in the surface layers will result in slower sinking velocities and decreased carbon and carbonate fluxes to the deep ocean

Mechanical Translation

Contains research objectives and reports on two research objectives.National Science Foundation (Grant GN-244

On the Linearization of the First and Second Painleve' Equations

We found Fuchs--Garnier pairs in 3X3 matrices for the first and second Painleve' equations which are linear in the spectral parameter. As an application of our pairs for the second Painleve' equation we use the generalized Laplace transform to derive an invertible integral transformation relating two its Fuchs--Garnier pairs in 2X2 matrices with different singularity structures, namely, the pair due to Jimbo and Miwa and the one found by Harnad, Tracy, and Widom. Together with the certain other transformations it allows us to relate all known 2X2 matrix Fuchs--Garnier pairs for the second Painleve' equation with the original Garnier pair.Comment: 17 pages, 2 figure

A Concurrent Tuple Set Architecture for Call Level Interfaces

Call Level Interfaces (CLI) are low level API aimed at providing services to connect two main components in database applications: client applications and relational databases. Among their functionalities, the ability to manage data retrieved from databases is emphasized. The retrieved data is kept in local memory structures that may be permanently connected to the host database. Client applications, beyond the ability to read their contents, may also execute Insert, Update and Delete actions over the local memory structures, following specific protocols. These protocols are row (tuple) oriented and, while being executed, cannot be preempted to start another protocol. This restriction leads to several difficulties when applications need to deal with several tuples at a time. The most paradigmatic case is the impossibility to cope with concurrent environments where several threads need to access to the same local memory structure instance, each one pointing to a different tuple and executing its particular protocol. To overcome the aforementioned fragility, a Concurrent Tuple Set Architecture (CTSA) is proposed to manage local memory structures. A performance assessment of a Java component based on JDBC (CLI) is also carried out and compared with a common approach. The main outcome of this research is the evidence that in concurrent environments, components relying on the CTSA may significantly improve the overall performance when compared with solutions based on standard JDBC API.(undefined

Theory and observations of ice particle evolution in cirrus using Doppler radar: evidence for aggregation

Vertically pointing Doppler radar has been used to study the evolution of ice particles as they sediment through a cirrus cloud. The measured Doppler fall speeds, together with radar-derived estimates for the altitude of cloud top, are used to estimate a characteristic fall time tc for the `average' ice particle. The change in radar reflectivity Z is studied as a function of tc, and is found to increase exponentially with fall time. We use the idea of dynamically scaling particle size distributions to show that this behaviour implies exponential growth of the average particle size, and argue that this exponential growth is a signature of ice crystal aggregation.Comment: accepted to Geophysical Research Letter

Modification of the ω\omega-Meson Lifetime in Nuclear Matter

The photo production of $\omega$ mesons on the nuclei C, Ca, Nb and Pb has been measured using the Crystal Barrel/TAPS detector at the ELSA tagged photon facility in Bonn. The dependence of the $\omega$ meson cross section on the nuclear mass number has been compared with three different types of models, a Glauber analysis, a BUU analysis of the Giessen theory group and a calculation by the Valencia theory group. In all three cases, the inelastic $\omega$ width is found to be $130-150 \rm{MeV/c^2}$ at normal nuclear matter density for an average 3-momentum of 1.1 GeV/c. In the restframe of the $\omega$ meson, this inelastic $\omega$ width corresponds to a reduction of the $\omega$ lifetime by a factor $\approx 30$. For the first time, the momentum dependent $\omega$N cross section has been extracted from the experiment and is in the range of 70 mb.Comment: 5 pages, 4 figure

Ocean acidification affects marine chemical communication by changing structure and function of peptide signalling molecules

Ocean acidification is a global challenge that faces marine organisms in the near future with a predicted rapid drop in pH of up to 0.4 units by the end of this century. Effects of the change in ocean carbon chemistry and pH on the development, growth and fitness of marine animals are well documented. Recent evidence also suggests that a range of chemically mediated behaviours and interactions in marine fish and invertebrates will be affected. Marine animals use chemical cues, for example, to detect predators, for settlement, homing and reproduction. But while effects of high CO₂ conditions on these behaviours are described across many species, little is known about the underlying mechanisms, particularly in invertebrates. Here we investigate the direct influence of future oceanic pH conditions on the structure and function of three peptide signalling molecules with an interdisciplinary combination of methods. NMR spectroscopy and quantum chemical calculations were used to assess the direct molecular influence of pH on the peptide cues and we tested the functionality of the cues in different pH conditions using behavioural bioassays with shore crabs (Carcinus maenas) as a model system. We found that peptide signalling cues are susceptible to protonation in future pH conditions, which will alter their overall charge. We also show that structure and electrostatic properties important for receptor-binding differ significantly between the peptide forms present today and the protonated signalling peptides likely to be dominating in future oceans. The bioassays suggest an impaired functionality of the signalling peptides at low pH. Physiological changes due to high CO₂ conditions were found to play a less significant role in influencing the investigated behaviour. From our results we conclude that the change of charge, structure and consequently function of signalling molecules presents one possible mechanism to explain altered behaviour under future oceanic pH conditions