Measuring cellular traction forces on non-planar substrates

Animal cells use traction forces to sense the mechanics and geometry of their environment. Measuring these traction forces requires a workflow combining cell experiments, image processing and force reconstruction based on elasticity theory. Such procedures have been established before mainly for planar substrates, in which case one can use the Green's function formalism. Here we introduce a worksflow to measure traction forces of cardiac myofibroblasts on non-planar elastic substrates. Soft elastic substrates with a wave-like topology were micromolded from polydimethylsiloxane (PDMS) and fluorescent marker beads were distributed homogeneously in the substrate. Using feature vector based tracking of these marker beads, we first constructed a hexahedral mesh for the substrate. We then solved the direct elastic boundary volume problem on this mesh using the finite element method (FEM). Using data simulations, we show that the traction forces can be reconstructed from the substrate deformations by solving the corresponding inverse problem with a L1-norm for the residue and a L2-norm for 0th order Tikhonov regularization. Applying this procedure to the experimental data, we find that cardiac myofibroblast cells tend to align both their shapes and their forces with the long axis of the deformable wavy substrate.Comment: 34 pages, 9 figure

Improved diamond coring bits developed for dry and chip-flush drilling

Two rotary diamond bit designs, one operating with a chip-flushing fluid, the second including auger section to remove drilled chips, enhance usefulness of tool for exploratory and industrial core-drilling of hard, abrasive mineral deposits and structural masonry

Contacting single bundles of carbon nanotubes with alternating electric fields

Single bundles of carbon nanotubes have been selectively deposited from suspensions onto sub-micron electrodes with alternating electric fields. We explore the resulting contacts using several solvents and delineate the differences between Au and Ag as electrode materials. Alignment of the bundles between electrodes occurs at frequencies above 1 kHz. Control over the number of trapped bundles is achieved by choosing an electrode material which interacts strongly with the chemical functional groups of the carbon nanotubes, with superior contacts being formed with Ag electrodes.Comment: 4 pages, RevTe

Mutual Zonated Interactions of Wnt and Hh Signaling Are Orchestrating the Metabolism of the Adult Liver in Mice and Human

The Hedgehog (Hh) and Wnt/β-Catenin (Wnt) cascades are morphogen pathways whose pronounced influence on adult liver metabolism has been identified in recent years. How both pathways communicate and control liver metabolic functions are largely unknown. Detecting core components of Wnt and Hh signaling and mathematical modeling showed that both pathways in healthy liver act largely complementary to each other in the pericentral (Wnt) and the periportal zone (Hh) and communicate mainly by mutual repression. The Wnt/Hh module inversely controls the spatiotemporal operation of various liver metabolic pathways, as revealed by transcriptome, proteome, and metabolome analyses. Shifting the balance to Wnt (activation) or Hh (inhibition) causes pericentralization and periportalization of liver functions, respectively. Thus, homeostasis of the Wnt/Hh module is essential for maintaining proper liver metabolism and to avoid the development of certain metabolic diseases. With caution due to minor species-specific differences, these conclusions may hold for human liver as well

ABC Effect in Basic Double-Pionic Fusion --- Observation of a new resonance?

We report on a high-statistics measurement of the basic double pionic fusion reaction $pn \to d\pi^0\pi^0$ over the energy region of the so-called ABC effect, a pronounced low-mass enhancement in the $\pi\pi$-invariant mass spectrum. The measurements were performed with the WASA detector setup at COSY. The data reveal the ABC effect to be associated with a Lorentzian shaped energy dependence in the integral cross section. The observables are consistent with a resonance with $I(J^P) =0(3^+)$ in both $pn$ and $\Delta\Delta$ systems. Necessary further tests of the resonance interpretation are discussed

Emerging climate-driven disturbance processes: Widespread mortality associated with snow-to-rain transitions across 10° of latitude and half the range of a climate-threatened conifer

Climate change is causing rapid changes to forest disturbance regimes worldwide. While the consequences of climate change for existing disturbance processes, like fires, are relatively well studied, emerging drivers of disturbance such as snow loss and subsequent mortality are much less documented. As the climate warms, a transition from winter snow to rain in high latitudes will cause significant changes in environmental conditions such as soil temperatures, historically buffered by snow cover. The Pacific coast of North America is an excellent test case, as mean winter temperatures are currently at the snow–rain threshold and have been warming for approximately 100 years post-Little Ice Age. Increased mortality in a widespread tree species in the region has been linked to warmer winters and snow loss. Here, we present the first high-resolution range map of this climate-sensitive species, Callitropsis nootkatensis (yellow-cedar), and document the magnitude and location of observed mortality across Canada and the United States. Snow cover loss related mortality spans approximately 10° latitude (half the native range of the species) and 7% of the overall species range and appears linked to this snow–rain transition across its range. Mortality is commonly >70% of basal area in affected areas, and more common where mean winter temperatures is at or above the snow–rain threshold (>0 °C mean winter temperature). Approximately 50% of areas with a currently suitable climate for the species (< 2 °C) are expected to warm beyond that threshold by the late 21st century. Regardless of climate change scenario, little of the range which is expected to remain suitable in the future (e.g., a climatic refugia) is in currently protected landscapes (<1–9%). These results are the first documentation of this type of emerging climate disturbance and highlight the difficulties of anticipating novel disturbance processes when planning for conservation and management.Ye

Epithelial calcineurin controls microbiota-dependent intestinal tumor development.

Inflammation-associated pathways are active in intestinal epithelial cells (IECs) and contribute to the pathogenesis of colorectal cancer (CRC). Calcineurin, a phosphatase required for the activation of the nuclear factor of activated T cells (NFAT) family of transcription factors, shows increased expression in CRC. We therefore investigated the role of calcineurin in intestinal tumor development. We demonstrate that calcineurin and NFAT factors are constitutively expressed by primary IECs and selectively activated in intestinal tumors as a result of impaired stratification of the tumor-associated microbiota and toll-like receptor signaling. Epithelial calcineurin supports the survival and proliferation of cancer stem cells in an NFAT-dependent manner and promotes the development of intestinal tumors in mice. Moreover, somatic mutations that have been identified in human CRC are associated with constitutive activation of calcineurin, whereas nuclear translocation of NFAT is associated with increased death from CRC. These findings highlight an epithelial cell-intrinsic pathway that integrates signals derived from the commensal microbiota to promote intestinal tumor development.This work was supported by the Deutsche Forschungsgemeinschaft (DFG) grants ZE814/5-1 (S.Z.), BA2863/5-1 (J.F.B.) and CH279/5-1 (T.C.), the European Research Council (ERC) starting grant 336528 (S.Z.), a Postdoctoral Fellowship Award from the Crohn's and Colitis Foundation of America (S.Z.), the European Commission (Marie Curie International Reintegration grant 256363; S.Z.), the DFG Excellence Cluster 'Inflammation at Interfaces' (S.Z. and J.F.B.), the DFG Excellence Cluster 'Center for Regenerative Therapies' (S.Z.); the US National Institutes of Health grants DK044319 (R.S.B.), DK051362 (R.S.B.), DK053056 (R.S.B.) and DK088199 (R.S.B.), the Harvard Digestive Diseases Center (HDDC) grant DK0034854 (R.S.B.), and the AIRC grant IG-14233 (M.E.B.).This is the author accepted manuscript. The final version is available from Nature Publishing Group via http://dx.doi.org/10.1038/nm.407

Long-term consistency of spatial patterns of primate seed dispersal

Seed dispersal is a key ecological process in tropical forests, with effects on various levels ranging from plant reproductive success to the carbon storage potential of tropical rainforests. On a local and landscape scale, spatial patterns of seed dispersal create the template for the recruitment process and thus influence the population dynamics of plant species. The strength of this influence will depend on the long‐term consistency of spatial patterns of seed dispersal. We examined the long‐term consistency of spatial patterns of seed dispersal with spatially explicit data on seed dispersal by two neotropical primate species, Leontocebus nigrifrons and Saguinus mystax (Callitrichidae), collected during four independent studies between 1994 and 2013. Using distributions of dispersal probability over distances independent of plant species, cumulative dispersal distances, and kernel density estimates, we show that spatial patterns of seed dispersal are highly consistent over time. For a specific plant species, the legume Parkia panurensis, the convergence of cumulative distributions at a distance of 300 m, and the high probability of dispersal within 100 m from source trees coincide with the dimension of the spatial–genetic structure on the embryo/juvenile (300 m) and adult stage (100 m), respectively, of this plant species. Our results are the first demonstration of long‐term consistency of spatial patterns of seed dispersal created by tropical frugivores. Such consistency may translate into idiosyncratic patterns of regeneration

Present and past climatic effects on the current distribution and genetic diversity of the Iberian spadefoot toad (Pelobates cultripes): an integrative approach

Aim: Predicting species responses to global change is one of the most pressing issues in Conservation Biogeography. A key part of the problem is understanding how organisms have reacted to climatic changes in the past. Here we use species distribution modelling to infer the effects of climate changes since the Last Interglacial (LIG, about 130,000 ybp) on patterns of genetic structure and diversity in the Western Spadefoot toad (Pelobates cultripes) in combination with spatially-explicit phylogeographic analyses. Location: Iberian Peninsula and mainland France. Methods: 524 individuals from 54 populations across the species range were sampled to document patterns of genetic diversity and infer their evolutionary history based on data from mtDNA and fourteen polymorphic microsatellites. Generalized linear models based on distribution data were used to infer climatic favourability for the species in the present and in projected scenarios for the LIG, the Mid Holocene and the last glacial maximum (LGM). Results: Estimates of genetic diversity show a decreasing trend from south to north, suggesting persistence of higher historical population sizes in the southern Iberian Peninsula. Species distribution models show differences in climatic favourability through time, with significant correlations between historically stable favourable areas and current patterns of genetic diversity. These results are corroborated by Bayesian Skyline Plots and continuous diffusion phylogeographic analyses. Main conclusions: The results indicate the presence of southern refugia, with moderate recent expansions at the northern end of the species’ range. Populations at the northern range margin exhibit the lowest genetic diversity and occupy historically unstable areas, classified as marginal in terms of favourability, rendering them most vulnerable to climate-mediated changes in the medium to long term

Temporal and spatial instability in neutral and adaptive (MHC) genetic variation in marginal salmon populations

The role of marginal populations for the long-term maintenance of species’ genetic diversity and evolutionary potential is particularly timely in view of the range shifts caused by climate change. The Centre-Periphery hypothesis predicts that marginal populations should bear reduced genetic diversity and have low evolutionary potential. We analysed temporal stability at neutral microsatellite and adaptive MHC genetic variation over five decades in four marginal Atlantic salmon populations located at the southern limit of the species’ distribution with a complicated demographic history, which includes stocking with foreign and native salmon for at least 2 decades. We found a temporal increase in neutral genetic variation, as well as temporal instability in population structuring, highlighting the importance of temporal analyses in studies that examine the genetic diversity of peripheral populations at the margins of the species’ range, particularly in face of climate change