215 research outputs found

    Adipocyte lipolysis links obesity to breast cancer growth: adipocyte-derived fatty acids drive breast cancer cell proliferation and migration.

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    BACKGROUND: Obesity is associated with increased recurrence and reduced survival of breast cancer. Adipocytes constitute a significant component of breast tissue, yet their role in provisioning metabolic substrates to support breast cancer progression is poorly understood. RESULTS: Here, we show that co-culture of breast cancer cells with adipocytes revealed cancer cell-stimulated depletion of adipocyte triacylglycerol. Adipocyte-derived free fatty acids were transferred to breast cancer cells, driving fatty acid metabolism via increased CPT1A and electron transport chain complex protein levels, resulting in increased proliferation and migration. Notably, fatty acid transfer to breast cancer cells was enhanced from "obese" adipocytes, concomitant with increased stimulation of cancer cell proliferation and migration. This adipocyte-stimulated breast cancer cell proliferation was dependent on lipolytic processes since HSL/ATGL knockdown attenuated cancer cell responses. CONCLUSIONS: These findings highlight a novel and potentially important role for adipocyte lipolysis in the provision of metabolic substrates to breast cancer cells, thereby supporting cancer progression

    Human tribbles-1 controls proliferation and chemotaxis of smooth muscle cells via MAPK signaling pathways

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    Migration and proliferation of smooth muscle cells are key to a number of physiological and pathological processes, including wound healing and the narrowing of the vessel wall.Previous work has shown links between inflammatory stimuli and vascular smooth muscle cell proliferation and migration through mitogen activated protein kinase (MAPK) activation, though the molecular mechanisms of this process are poorly understood. Here we report that tribbles-1, a recently described modulator of MAPK activation controls vascular smooth muscle cell proliferation and chemotaxis via the Jun Kinase pathway. Our findings demonstrate that this regulation takes place via direct interactions between tribbles-1 and MKK4/SEK1, a Jun activator kinase. The activity of this kinase is dependent on tribbles-1 levels, whilst the activation and the expression of MKK4/SEK1 is not. In addition, tribbles-1 expression is elevated in human atherosclerotic arteries compared to non-atherosclerotic controls, suggesting that this protein may pay a role in disease in vivo. In summary, the data presented here suggest an important regulatory role for trb-1 in vascular smooth muscle cell biology

    MicroRNA-regulated, systemically delivered rAAV9: a step closer to CNS-restricted transgene expression

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    Recombinant adeno-associated viruses (rAAVs) that can cross the blood-brain-barrier and achieve efficient and stable transvascular gene transfer to the central nervous system (CNS) hold significant promise for treating CNS disorders. However, following intravascular delivery, these vectors also target liver, heart, skeletal muscle, and other tissues, which may cause untoward effects. To circumvent this, we used tissue-specific, endogenous microRNAs (miRNAs) to repress rAAV expression outside the CNS, by engineering perfectly complementary miRNA-binding sites into the rAAV9 genome. This approach allowed simultaneous multi-tissue regulation and CNS-directed stable transgene expression without detectably perturbing the endogenous miRNA pathway. Regulation of rAAV expression by miRNA was primarily via site-specific cleavage of the transgene mRNA, generating specific 5\u27 and 3\u27 mRNA fragments. Our findings promise to facilitate the development of miRNA-regulated rAAV for CNS-targeted gene delivery and other applications

    Evolution of spin excitations from bulk to monolayer FeSe

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    In ultrathin films of FeSe grown on SrTiO (FeSe/STO), the superconducting transition temperature T is increased by almost an order of magnitude, raising questions on the pairing mechanism. As in other superconductors, antiferromagnetic spin fluctuations have been proposed to mediate SC making it essential to study the evolution of the spin dynamics of FeSe from the bulk to the ultrathin limit. Here, we investigate the spin excitations in bulk and monolayer FeSe/STO using resonant inelastic x-ray scattering (RIXS) and quantum Monte Carlo (QMC) calculations. Despite the absence of long-range magnetic order, bulk FeSe displays dispersive magnetic excitations reminiscent of other Fe-pnictides. Conversely, the spin excitations in FeSe/STO are gapped, dispersionless, and significantly hardened relative to its bulk counterpart. By comparing our RIXS results with simulations of a bilayer Hubbard model, we connect the evolution of the spin excitations to the Fermiology of the two systems revealing a remarkable reconfiguration of spin excitations in FeSe/STO, essential to understand the role of spin fluctuations in the pairing mechanism

    Molecular genetics and phenotypic assessment of foxtail millet (Setaria italica (L.) P. Beauv.) landraces revealed remarkable variability of morpho-physiological, yield, and yield‐related traits

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    Foxtail millet (Setaria italica (L.) P. Beauv.) is highly valued for nutritional traits, stress tolerance and sustainability in resource-poor dryland agriculture. However, the low productivity of this crop in semi-arid regions of Southern India, is further threatened by climate stress. Landraces are valuable genetic resources, regionally adapted in form of novel alleles that are responsible for cope up the adverse conditions used by local farmers. In recent years, there is an erosion of genetic diversity. We have hypothesized that plant genetic resources collected from the semi-arid climatic zone would serve as a source of novel alleles for the development of climate resilience foxtail millet lines with enhanced yield. Keeping in view, there is an urgent need for conservation of genetic resources. To explore the genetic diversity, to identify superior genotypes and novel alleles, we collected a heterogeneous mixture of foxtail millet landraces from farmer fields. In an extensive multi-year study, we developed twenty genetically fixed foxtail millet landraces by single seed descent method. These landraces characterized along with four released cultivars with agro-morphological, physiological, yield and yield-related traits assessed genetic diversity and population structure. The landraces showed significant diversity in all the studied traits. We identified landraces S3G5, Red, Black and S1C1 that showed outstanding grain yield with earlier flowering, and maturity as compared to released cultivars. Diversity analysis using 67 simple sequence repeat microsatellite and other markers detected 127 alleles including 11 rare alleles, averaging 1.89 alleles per locus, expected heterozygosity of 0.26 and an average polymorphism information content of 0.23, collectively indicating a moderate genetic diversity in the landrace populations. Euclidean Ward’s clustering, based on the molecular markers, principal coordinate analysis and structure analysis concordantly distinguished the genotypes into two to three sub-populations. A significant phenotypic and genotypic diversity observed in the landraces indicates a diverse gene pool that can be utilized for sustainable foxtail millet crop improvement

    Magmatic plumbing at Lucky Strike volcano based on olivine-hosted melt inclusion compositions

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    Author Posting. © American Geophysical Union, 2015. This article is posted here by permission of American Geophysical Union for personal use, not for redistribution. The definitive version was published in Geochemistry, Geophysics, Geosystems 16 (2015): 126–147, doi:10.1002/2014GC005517.Here we present volatile, major, and trace element concentrations of 64 olivine-hosted melt inclusions from the Lucky Strike segment on the mid-Atlantic ridge. Lucky Strike is one of two locations where a crustal melt lens has been seismically imaged on a slow-spreading ridge. Vapor-saturation pressures, calculated from CO2 and H2O contents of Lucky Strike melt inclusions, range from approximately 300–3000 bars, corresponding to depths of 0.5–9.9 km below the seafloor. Approximately 50% of the melt inclusions record crystallization depths of 3–4 km, corresponding to the seismically imaged melt lens depth, while an additional ∼35% crystallize at depths > 4 km. This indicates that while crystallization is focused within the melt lens, significant crystallization also occurs in the lower crust and/or upper mantle. The melt inclusions span a range of major and trace element concentrations from normal to enriched basalts. Trace element ratios at all depths are heterogeneous, suggesting that melts are not efficiently homogenized in the mantle or crust, despite the presence of a melt lens. This is consistent with the transient nature of magma chambers proposed for slower-spreading ridges. To investigate the petrogenesis of the melt inclusion compositions, we compare the measured trace element compositions to theoretical melting calculations that consider variations in the melting geometry and heterogeneities in the mantle source. The full range of compositions can be produced by slight variations in the proportion of an Azores plume and depleted upper mantle components and changes in the total extent of melting.thanked for his help with sample preparation. The GRAVILUCK'06 and Bathyluck'08 cruises where financed by the French Ministry of Research. This work was supported by NSF grant OCE-0926422 to A.M.S., OCE-PRF-1226130 to V.D.W., OCE-1333492 to S.A.S., and EAR-09-48666 to M.D.B., and by ANR (France) Mothseim Project NT05-342213 to J.E.2015-07-2

    Novel features of ARS selection in budding yeast Lachancea kluyveri

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    <p>Abstract</p> <p>Background</p> <p>The characterization of DNA replication origins in yeast has shed much light on the mechanisms of initiation of DNA replication. However, very little is known about the evolution of origins or the evolution of mechanisms through which origins are recognized by the initiation machinery. This lack of understanding is largely due to the vast evolutionary distances between model organisms in which origins have been examined.</p> <p>Results</p> <p>In this study we have isolated and characterized autonomously replicating sequences (ARSs) in <it>Lachancea kluyveri </it>- a pre-whole genome duplication (WGD) budding yeast. Through a combination of experimental work and rigorous computational analysis, we show that <it>L. kluyveri </it>ARSs require a sequence that is similar but much longer than the ARS Consensus Sequence well defined in <it>Saccharomyces cerevisiae</it>. Moreover, compared with <it>S. cerevisiae </it>and <it>K. lactis</it>, the replication licensing machinery in <it>L. kluyveri </it>seems more tolerant to variations in the ARS sequence composition. It is able to initiate replication from almost all <it>S. cerevisiae </it>ARSs tested and most <it>Kluyveromyces lactis </it>ARSs. In contrast, only about half of the <it>L. kluyveri </it>ARSs function in <it>S. cerevisiae </it>and less than 10% function in <it>K. lactis</it>.</p> <p>Conclusions</p> <p>Our findings demonstrate a replication initiation system with novel features and underscore the functional diversity within the budding yeasts. Furthermore, we have developed new approaches for analyzing biologically functional DNA sequences with ill-defined motifs.</p
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