Tumor suppressor FLCN inhibits tumorigenesis of a FLCN-null renal cancer cell line and regulates expression of key molecules in TGF-β signaling

<p>Abstract</p> <p>Background</p> <p>Germline mutations in the <it>FLCN </it>gene are responsible for the development of fibrofolliculomas, lung cysts and renal neoplasia in Birt-Hogg-Dube' (BHD) syndrome. The encoded protein folliculin (FLCN) is conserved across species but contains no classic motifs or domains and its function remains unknown. Somatic mutations or loss of heterozygosity in the remaining wild type copy of the <it>FLCN </it>gene have been found in renal tumors from BHD patients suggesting that <it>FLCN </it>is a classic tumor suppressor gene.</p> <p>Results</p> <p>To examine the tumor suppressor function of <it>FLCN</it>, wild-type or mutant <it>FLCN </it>(H255R) was stably expressed in a <it>FLCN-null </it>renal tumor cell line, UOK257, derived from a BHD patient. When these cells were injected into nude mice, tumor development was inversely dependent upon the level of wild-type <it>FLCN </it>expression. We identified genes that were differentially expressed in the cell lines with or without wild-type <it>FLCN</it>, many of which are involved in TGF-β signaling, including <it>TGF-β2 </it>(<it>TGFB2</it>)<it>, inhibin β A chain </it>(<it>INHBA</it>)<it>, thrombospondin 1 </it>(<it>THBS1</it>), <it>gremlin </it>(<it>GREM1</it>), and <it>SMAD3</it>. In support of the <it>in vitro </it>data, <it>TGFB2</it>, <it>INHBA</it>, <it>THBS1 </it>and <it>SMAD3 </it>expression levels were significantly lower in BHD-associated renal tumors compared with normal kidney tissue. Although receptor mediated SMAD phosphorylation was not affected, basal and maximal TGF-β-induced levels of <it>TGFB2</it>, <it>INHBA </it>and <it>SMAD7 </it>were dramatically reduced in <it>FLCN-null </it>cells compared with <it>FLCN</it>-restored cells. Secreted TGF-β2 and activin A (homo-dimer of INHBA) protein levels were also lower in <it>FLCN-null </it>cells compared with <it>FLCN</it>-restored cells. Consistent with a growth suppressive function, activin A (but not TGF-β2) completely suppressed anchorage-independent growth of <it>FLCN-null </it>UOK257 cells.</p> <p>Conclusions</p> <p>Our data demonstrate a role for <it>FLCN </it>in the regulation of key molecules in TGF-β signaling and confirm deregulation of their expression in BHD-associated renal tumors. Thus, deregulation of genes involved in TGF-β signaling by <it>FLCN </it>inactivation is likely to be an important step for tumorigenesis in BHD syndrome.</p

Ultrafast Umklapp-assisted electron-phonon cooling in magic-angle twisted bilayer graphene

Understanding electron-phonon interactions is fundamentally important and has crucial implications for device applications. However, in twisted bilayer graphene near the magic angle, this understanding is currently lacking. Here, we study electron-phonon coupling using time- and frequency-resolved photovoltage measurements as direct and complementary probes of phonon-mediated hot-electron cooling. We find a remarkable speedup in cooling of twisted bilayer graphene near the magic angle: The cooling time is a few picoseconds from room temperature down to 5 kelvin, whereas in pristine bilayer graphene, cooling to phonons becomes much slower for lower temperatures. Our experimental and theoretical analysis indicates that this ultrafast cooling is a combined effect of superlattice formation with low-energy moiré phonons, spatially compressed electronic Wannier orbitals, and a reduced superlattice Brillouin zone. This enables efficient electron-phonon Umklapp scattering that overcomes electron-phonon momentum mismatch. These results establish twist angle as an effective way to control energy relaxation and electronic heat flow.</p

A palaeoecological approach to understanding the past and present of Sierra Nevada, a Southwestern European biodiversity hotspot

Mediterranean mountainous environments are biodiversity hotspots and priority areas in conservation agendas. Although they are fragile and threatened by forecasted global change scenarios, their sensitivity to long-term environmental variability is still understudied. The Sierra Nevada range, located in southern Spain on the north-western European flanks of the Mediterranean basin, is a biodiversity hotspot. Consequently, Sierra Nevada provides an excellent model system to apply a palaeoecological approach to detect vegetation changes, explore the drivers triggering those changes, and how vegetation changes link to the present landscape in such a paradigmatic mountain system. A multi-proxy strategy (magnetic susceptibility, grain size, loss-on-ignition, macroremains, charcoal and palynological analyses) is applied to an 8400-year long lacustrine environmental archive from the Laguna de la Mosca (2889 masl). The long-term ecological data show how the Early Holocene pine forests transitioned towards mixed Pinus-Quercus submediterranean forests as a response to a decrease in seasonality at ~7.3 cal. kyr BP. The mixed Pinus-Quercus submediterranean forests collapsed drastically giving way to open evergreen Quercus formations at ~4.2 cal. kyr BP after a well-known aridity crisis. Under the forecasted northward expansion of the Mediterranean area due to global change-related aridity increase, mountain forests inhabiting territories adjacent to the Mediterranean Region could experience analogous responses to those detected in the Sierra Nevada forests to the Mid to Late Holocene aridification, moving from temperate to submediterranean and then Mediterranean formations

Ultrafast Umklapp-assisted electron-phonon cooling in magic-angle twisted bilayer graphene

Understanding electron-phonon interactions is fundamentally important and has crucial implications for device applications. However, in twisted bilayer graphene near the magic angle, this understanding is currently lacking. Here, we study electron-phonon coupling using time- and frequency-resolved photovoltage measurements as direct and complementary probes of phonon-mediated hot-electron cooling. We find a remarkable speedup in cooling of twisted bilayer graphene near the magic angle: The cooling time is a few picoseconds from room temperature down to 5 kelvin, whereas in pristine bilayer graphene, cooling to phonons becomes much slower for lower temperatures. Our experimental and theoretical analysis indicates that this ultrafast cooling is a combined effect of superlattice formation with low-energy moiré phonons, spatially compressed electronic Wannier orbitals, and a reduced superlattice Brillouin zone. This enables efficient electron-phonon Umklapp scattering that overcomes electron-phonon momentum mismatch. These results establish twist angle as an effective way to control energy relaxation and electronic heat flow.</p

Quantifying the Production of Fruit-Bearing Trees Using Image Processing Techniques

[EN] In recent years, the growth rate of world agricultural production and crop yields have decreased. Crop irrigation becomes essential in very dry areas and where rainfall is scarce, as in Egypt. Persimmon needs low humidity to obtain an optimal crop. This article proposes the monitoring of its performance, in order to regulate the amount of water needed for each tree at any time. In our work we present a technique that consists of obtaining images of some of the trees with fruit, which are subsequently treated, to obtain reliable harvest data. This technique allows us to have control and predictions of the harvest. Also, we present the results obtained in a first trial, through which we demonstrate the feasibility of using the system to meet the objectives set. We use 5 different trees in our experiment. Their fruit production is different (between 20 and 47kg of fruit). The correlation coefficient of the obtained regression model is 0.97.This work has been partially supported by European Union through the ERANETMED (Euromediterranean Cooperation through ERANET joint activities and beyond) project ERANETMED3-227 SMARTWATIR by the Conselleria de Educación, Cultura y Deporte with the Subvenciones para la contratación de personal investigador en fase postdoctoral, grant number APOSTD/2019/04, and by the Cooperativa Agrícola Sant Bernat Coop.V.García, L.; Parra-Boronat, L.; Basterrechea-Chertudi, DA.; Jimenez, JM.; Rocher-Morant, J.; Parra-Boronat, M.; García-Navas, JL.... (2019). Quantifying the Production of Fruit-Bearing Trees Using Image Processing Techniques. IARIA XPS Press. 14-19. http://hdl.handle.net/10251/180619S141

Transport properties of strongly correlated metals:a dynamical mean-field approach

The temperature dependence of the transport properties of the metallic phase of a frustrated Hubbard model on the hypercubic lattice at half-filling are calculated. Dynamical mean-field theory, which maps the Hubbard model onto a single impurity Anderson model that is solved self-consistently, and becomes exact in the limit of large dimensionality, is used. As the temperature increases there is a smooth crossover from coherent Fermi liquid excitations at low temperatures to incoherent excitations at high temperatures. This crossover leads to a non-monotonic temperature dependence for the resistance, thermopower, and Hall coefficient, unlike in conventional metals. The resistance smoothly increases from a quadratic temperature dependence at low temperatures to large values which can exceed the Mott-Ioffe-Regel value, hbar a/e^2 (where "a" is a lattice constant) associated with mean-free paths less than a lattice constant. Further signatures of the thermal destruction of quasiparticle excitations are a peak in the thermopower and the absence of a Drude peak in the optical conductivity. The results presented here are relevant to a wide range of strongly correlated metals, including transition metal oxides, strontium ruthenates, and organic metals.Comment: 19 pages, 9 eps figure

Infectious Offspring: How Birds Acquire and Transmit an Avian Polyomavirus in the Wild

Detailed patterns of primary virus acquisition and subsequent dispersal in wild vertebrate populations are virtually absent. We show that nestlings of a songbird acquire polyomavirus infections from larval blowflies, common nest ectoparasites of cavity-nesting birds, while breeding adults acquire and renew the same viral infections via cloacal shedding from their offspring. Infections by these DNA viruses, known potential pathogens producing disease in some bird species, therefore follow an ‘upwards vertical’ route of an environmental nature mimicking horizontal transmission within families, as evidenced by patterns of viral infection in adults and young of experimental, cross-fostered offspring. This previously undescribed route of viral transmission from ectoparasites to offspring to parent hosts may be a common mechanism of virus dispersal in many taxa that display parental care

Superconductivity mediated by charge fluctuations in layered molecular crystals

We consider the competition between superconducting, charge ordered, and metallic phases in layered molecular crystals with the theta and beta" structures. Applying slave-boson theory to the relevant extended Hubbard model, we show that the superconductivity is mediated by charge fluctuations and the Cooper pairs have d(xy) symmetry. This is in contrast to the kappa-(BEDT-TTF)(2)X family, for which theoretical calculations give superconductivity mediated by spin fluctuations and with d(x)2(-y)2 symmetry. We predict several materials that should become superconducting under pressure

Mice deficient in CD38 develop an attenuated form of collagen type II-induced arthritis

CD38, a type II transmembrane glycoprotein expressed in many cells of the immune system, is involved in cell signaling, migration and differentiation. Studies in CD38 deficient mice (CD38 KO mice) indicate that this molecule controls inflammatory immune responses, although its involvement in these responses depends on the disease model analyzed. Here, we explored the role of CD38 in the control of autoimmune responses using chicken collagen type II (col II) immunized C57BL/6-CD38 KO mice as a model of collagen-induced arthritis (CIA). We demonstrate that CD38 KO mice develop an attenuated CIA that is accompanied by a limited joint induction of IL-1β and IL-6 expression, by the lack of induction of IFNγ expression in the joints and by a reduction in the percentages of invariant NKT (iNKT) cells in the spleen. Immunized CD38 KO mice produce high levels of circulating IgG1 and low of IgG2a anti-col II antibodies in association with reduced percentages of Th1 cells in the draining lymph nodes. Altogether, our results show that CD38 participates in the pathogenesis of CIA controlling the number of iNKT cells and promoting Th1 inflammatory responses

Design of a WSN for smart irrigation in citrus plots with fault-tolerance and energy-saving algorithms

[EN] Wireless sensor networks are widely used for monitoring different processes, including agriculture, in order to reach sustainability. One of the keys to sustainable crops is water saving. In particular, saving water is extremely important in arid and semiarid regions. In those regions, citrus trees are cultivated, and drip irrigation is used to save water. In this paper, we propose a smart irrigation system for citrus trees using a WSN. We describe the employed sensors and nodes for this proposal. Next, we present the proposed architecture and the operational algorithms for the nodes. Moreover, we designed different algorithms for fault tolerance and energy saving functionalities. The energy saving algorithm is based on the relevance of the gathered data, which is analyzed in order to consider whether the information should be forwarded or not. A TPC-based protocol is proposed to perform the communication among the nodes of our system. In addition, we present different simulations of the proposed system. Particularly, we show the consumed bandwidth and the remaining energy in the different nodes. Finally, we test different energy configurations to evaluate the network lifetime and the remaining energy when the first node depletes its energy.This work has been partially supported by the “Conselleria d' Educació, Investigació, Cultura i Esport” through the “Subvenciones para la contratación de personal investigator de carácter predoctoral (Convocatoria 2017)” Grant number ACIF/2017/069, by the “Ministerio de Educación, Cultura y Deporte”, through the “Ayudas para contratacion predoctoral de Formación del Profesorado Universitario FPU (Convocatoria 2014)”. Grant number FPU14/02953 and finally, the research leading to these results has received funding from “la Caixa” Foundation and Triptolemos Foundation. This work has also been partially supported by European Union through the ERANETMED (Euromediterranean Cooperation through ERANET joint activities and beyond) project ERANETMED3-227 SMARTWATIR.Parra-Boronat, L.; Rocher-Morant, J.; García-García, L.; Lloret, J.; Tomás Gironés, J.; Romero Martínez, JO.; Rodilla, M.... (2018). Design of a WSN for smart irrigation in citrus plots with fault-tolerance and energy-saving algorithms. Network Protocols and Algorithms. 10(2):95-115. https://doi.org/10.5296/npa.v10i2.13205S9511510