Myosin-1a powers the sliding of apical membrane along microvillar actin bundles

Microvilli are actin-rich membrane protrusions common to a variety of epithelial cell types. Within microvilli of the enterocyte brush border (BB), myosin-1a (Myo1a) forms an ordered ensemble of bridges that link the plasma membrane to the underlying polarized actin bundle. Despite decades of investigation, the function of this unique actomyosin array has remained unclear. Here, we show that addition of ATP to isolated BBs induces a plus end–directed translation of apical membrane along microvillar actin bundles. Upon reaching microvillar tips, membrane is “shed” into solution in the form of small vesicles. Because this movement demonstrates the polarity, velocity, and nucleotide dependence expected for a Myo1a-driven process, and BBs lacking Myo1a fail to undergo membrane translation, we conclude that Myo1a powers this novel form of motility. Thus, in addition to providing a means for amplifying apical surface area, we propose that microvilli function as actomyosin contractile arrays that power the release of BB membrane vesicles into the intestinal lumen

The Shifting Landscape of Amish Agriculture: Balancing Tradition and Innovation in an Organic Farming Cooperative

In the context of the recent proliferation of alternative operations and marketing schemes across the agricultural landscape, this article examines an Amish organic farming cooperative in northeast Ohio. Contrary to popular perception, the large majority of Amish are not full-time farmers, and those who do farm typically use conventional, chemical-intensive methods. The adoption of certified organic among the Amish is a pragmatic decision that stems from concerns over the sociocultural effects of losing their agrarian heritage, but it also raises challenges that require a careful balance between market imperatives and cultural traditions. We investigate these challenges and the Amish response to them, including: how a culture group largely antithetical to bureaucracy and economic regulation has responded to the demands of external certification standards, how the cooperative has found markets for its products given their reluctance to use the Amish name in advertising, and how a people known for adherence to conservative cultural traditions manages to embrace the alternative nature of organic farming. Our study illustrates the complex ways culture can both facilitate and constrain agricultural innovation

Seasonally resolved ice core records from West Antarctica indicate a sea ice source of sea-salt aerosol and a biomass burning source of ammonium

Author Posting. © American Geophysical Union, 2014. This article is posted here by permission of American Geophysical Union for personal use, not for redistribution. The definitive version was published in Journal of Geophysical Research: Atmospheres 119 (2014): 9168–9182, doi:10.1002/2013JD020720.The sources and transport pathways of aerosol species in Antarctica remain uncertain, partly due to limited seasonally resolved data from the harsh environment. Here, we examine the seasonal cycles of major ions in three high-accumulation West Antarctic ice cores for new information regarding the origin of aerosol species. A new method for continuous acidity measurement in ice cores is exploited to provide a comprehensive, charge-balance approach to assessing the major non-sea-salt (nss) species. The average nss-anion composition is 41% sulfate (SO42−), 36% nitrate (NO3−), 15% excess-chloride (ExCl−), and 8% methanesulfonic acid (MSA). Approximately 2% of the acid-anion content is neutralized by ammonium (NH4+), and the remainder is balanced by the acidity (Acy ≈ H+ − HCO3−). The annual cycle of NO3− shows a primary peak in summer and a secondary peak in late winter/spring that are consistent with previous air and snow studies in Antarctica. The origin of these peaks remains uncertain, however, and is an area of active research. A high correlation between NH4+ and black carbon (BC) suggests that a major source of NH4+ is midlatitude biomass burning rather than marine biomass decay, as previously assumed. The annual peak in excess chloride (ExCl−) coincides with the late-winter maximum in sea ice extent. Wintertime ExCl− is correlated with offshore sea ice concentrations and inversely correlated with temperature from nearby Byrd station. These observations suggest that the winter peak in ExCl− is an expression of fractionated sea-salt aerosol and that sea ice is therefore a major source of sea-salt aerosol in the region.This work was supported by grants from the NSF Antarctic Program (0632031 and 1142166), NSF-MRI (1126217), the NASA Cryosphere Program (NNX10AP09G), and by an award from the Department of Energy Office of Science Graduate Fellowship Program (DOE SCGF) to ASC.2015-01-2

Five millennia of surface temperatures and ice core bubble characteristics from the WAIS Divide deep core, West Antarctica

Bubble number densities from the West Antarctic Ice Sheet (WAIS) Divide deep core in West Antarctica record relatively stable temperatures during the middle Holocene followed by late Holocene cooling. We measured bubble number density, shape, size, and arrangement on new samples of the main WAIS Divide deep core WDC06A from similar to 580m to similar to 1600 depth. The bubble size, shape, and arrangement data confirm that the samples satisfy the requirements for temperature reconstructions. A small correction for cracks formed after core recovery allows extension of earlier work through the brittle ice zone, and a site-specific calibration reduces uncertainties. Using an independently constructed accumulation rate history and a steady state bubble number density model, we determined a temperature reconstruction that agrees closely with other independent estimates, showing a stable middle Holocene, followed by a cooling of similar to 1.25 degrees C in the late Holocene. Over the last similar to 5 millennia, accumulation has been higher during warmer times by similar to 12%degrees C-1, somewhat stronger than for thermodynamic control alone, suggesting dynamic processes

A generalizable data-driven multicellular model of pancreatic ductal adenocarcinoma.

BACKGROUND: Mechanistic models, when combined with pertinent data, can improve our knowledge regarding important molecular and cellular mechanisms found in cancer. These models make the prediction of tissue-level response to drug treatment possible, which can lead to new therapies and improved patient outcomes. Here we present a data-driven multiscale modeling framework to study molecular interactions between cancer, stromal, and immune cells found in the tumor microenvironment. We also develop methods to use molecular data available in The Cancer Genome Atlas to generate sample-specific models of cancer. RESULTS: By combining published models of different cells relevant to pancreatic ductal adenocarcinoma (PDAC), we built an agent-based model of the multicellular pancreatic tumor microenvironment, formally describing cell type-specific molecular interactions and cytokine-mediated cell-cell communications. We used an ensemble-based modeling approach to systematically explore how variations in the tumor microenvironment affect the viability of cancer cells. The results suggest that the autocrine loop involving EGF signaling is a key interaction modulator between pancreatic cancer and stellate cells. EGF is also found to be associated with previously described subtypes of PDAC. Moreover, the model allows a systematic exploration of the effect of possible therapeutic perturbations; our simulations suggest that reducing bFGF secretion by stellate cells will have, on average, a positive impact on cancer apoptosis. CONCLUSIONS: The developed framework allows model-driven hypotheses to be generated regarding therapeutically relevant PDAC states with potential molecular and cellular drivers indicating specific intervention strategies

GRB Polarimetry with POET

POET (Polarimeters for Energetic Transients) represents a concept for a Small Explorer (SMEX) satellite mission, whose principal scientific goal is to understand the structure of GRB sources through sensitive X‐ray and γ‐ray polarization measurements. The payload consists of two wide field‐of‐view (FoV) instruments: a Low Energy Polarimeter (LEP) capable of polarization measurements in the energy range from 2–15 keV and a high energy polarimeter (Gamma‐Ray Polarimeter Experiment or GRAPE) that would measure polarization in the 60–500 keV energy range. The POET spacecraft provides a zenith‐pointed platform for maximizing the exposure to deep space. Spacecraft rotation provides a means of effectively dealing with any residual systematic effects in the polarization response. POET provides sufficient sensitivity and sky coverage to measure statistically significant polarization (for polarization levels in excess of 20%) for ∼80 GRBs in a two‐year mission. High energy polarization data would also be obtained for SGRs, solar flares, pulsars and other sources of astronomical interest

MUC1 Is a Downstream Target of STAT3 and Regulates Lung Cancer Cell Survival and Invasion

Signal transducer and activator of transcription 3 (STAT3) is aberrantly activated in human cancer including lung cancer and has been implicated in transformation, tumorigenicity, and metastasis. One putative downstream gene regulated by Stat3 is MUC1 which also has important roles in tumorigenesis. We determined if Stat3 regulates MUC1 in lung cancer cell lines and what function MUC1 plays in lung cancer cell biology. We examined MUC1 expression in non-small cell lung cancer (NSCLC) cell lines and found high levels of MUC1 protein expression associated with higher levels of tyrosine phosphorylated STAT3. STAT3 knockdown downregulated MUC1 expression whereas constitutive STAT3 expression increased MUC1 expression at mRNA and protein levels. MUC1 knockdown induced cellular apoptosis concomitant with reduced Bcl-XL and sensitized cells to cisplatin treatment. MUC1 knockdown inhibited tumor growth and metastasis in an orthotopic mouse model of lung cancer by activating apoptosis and inhibiting cell proliferation in vivo. These results demonstrate that constitutively activated STAT3 regulates expression of MUC1, which mediates lung cancer cell survival and metastasis in vitro and in vivo. MUC1 appears to be a cooperating oncoprotein with multiple oncogenic tyrosine kinase pathways and could be an effective target for the treatment of lung cancer

PASCal: A principal-axis strain calculator for thermal expansion and compressibility determination

We describe a web-based tool (PASCal; Principal Axis Strain Calculator) aimed at simplifying the determination of principal coefficients of thermal expansion and compressibilities from variable-temperature and variable-pressure lattice parameter data. In a series of three case studies, we use PASCal to re-analyse previously-published lattice parameter data and show that additional scientific insight is obtainable in each case. First, the two-dimensional metal-organic framework Cu-SIP-3 is found to exhibit the strongest area-negative thermal expansion (NTE) effect yet observed; second, the widely-used explosive HMX exhibits much stronger mechanical anisotropy than had previously been anticipated, including uniaxial NTE driven by thermal changes in molecular conformation; and, third, the high-pressure form of the mineral malayaite is shown to exhibit a strong negative linear compressibility (NLC) effect that arises from correlated tilting of SnO6 and SiO4 coordination polyhedra.Comment: 31 pages, 8 figures, formatted as preprint for J. Appl. Crys