2,517 research outputs found

    A Meiotic Checkpoint Alters Repair Partner Bias to Permit Inter-sister Repair of Persistent DSBs

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    Accurate meiotic chromosome segregation critically depends on the formation of inter-homolog crossovers initiated by double-strand breaks (DSBs). Inaccuracies in this process can drive aneuploidy and developmental defects, but how meiotic cells are protected from unscheduled DNA breaks remains unexplored. Here we define a checkpoint response to persistent meiotic DSBs in C. elegans that phosphorylates the synaptonemal complex (SC) to switch repair partner from the homolog to the sister chromatid. A key target of this response is the core SC component SYP-1, which is phosphorylated in response to ionizing radiation (IR) or unrepaired meiotic DSBs. Failure to phosphorylate (syp-16A) or dephosphorylate (syp-16D) SYP-1 in response to DNA damage results in chromosome non-dysjunction, hyper-sensitivity to IR-induced DSBs, and synthetic lethality with loss of brc-1BRCA1. Since BRC-1 is required for inter-sister repair, these observations reveal that checkpoint-dependent SYP-1 phosphorylation safeguards the germline against persistent meiotic DSBs by channelling repair to the sister chromatid.Cancer Research UK FC0010048UK Medical Research Council FC0010048Wellcome Trust FC0010048Ministerio de EconomĂ­a y Competitividad BFU2016-75058-PEuropean Research Council ERC2014 AdG669898 TARLOO

    A prototype reactor to compost agricultural wastes of Fusagasuga Municipality. Colombia

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    Crop and animal production generate a high level of organic waste that causes negative effects on the environment and communities. The use of composting processes can improve the quality of these biowastes. Additionally, the application of technologies such as telemetry and remote sensors, allows optimizing the transformation of organic matter in a more controlled and efficient way. The city of Fusagasugá is well known in agriculture. However, it lacks sustainable management of the organic waste system. In this study, after a three-dimensional electromechanical design, a prototype reactor to compost agricultural wastes of Fusagasuga municipality will provide. The capacity of this prototype reactor is considered to be 20 litres. In order to control temperature and humidity of biowastes in different working conditions, it is used A PI controller with 3 temperature and a humidity sensors. With these sensors the compost materials temperature and humidity will remain at 65 °C and 55–60%. By using a special form of temperature sensor placement, the time to oxygenate the compost materials will be found. Furthermore, this system is integrated by a Human-Machine Interface (HMI), which allows the supervision and manipulation from a remote access user

    Proyecto de ordenación territorial y plan general de desarrollo del municipio San José de Cusmapa en el contexto del proyecto "Aldeas del Milenio"

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    Proyecto de ordenación territorial y plan general de desarrollo del municipio San José de Cusmapa en el contexto del proyecto "Aldeas del Milenio

    The ROCK inhibitor Fasudil prevents chronic restraint stress-induced depressive-like behaviors and dendritic spine loss in rat hippocampus

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    IndexaciĂłn: Web of Science; Scopus.Background: Dendritic arbor simplification and dendritic spine loss in the hippocampus, a limbic structure implicated in mood disorders, are assumed to contribute to symptoms of depression. These morphological changes imply modifications in dendritic cytoskeleton. Rho GTPases are regulators of actin dynamics through their effector Rho kinase. We have reported that chronic stress promotes depressive-like behaviors in rats along with dendritic spine loss in apical dendrites of hippocampal pyramidal neurons, changes associated with Rho kinase activation. The present study proposes that the Rho kinase inhibitor Fasudil may prevent the stress-induced behavior and dendritic spine loss. Methods: Adult male Sprague-Dawley rats were injected with saline or Fasudil (i.p., 10 mg/kg) starting 4 days prior to and maintained during the restraint stress procedure (2.5 h/d for 14 days). Nonstressed control animals were injected with saline or Fasudil for 18 days. At 24 hours after treatment, forced swimming test, Golgi-staining, and immuno-western blot were performed. Results: Fasudil prevented stress-induced immobility observed in the forced swimming test. On the other hand, Fasudiltreated control animals showed behavioral patterns similar to those of saline-treated controls. Furthermore, we observed that stress induced an increase in the phosphorylation of MYPT1 in the hippocampus, an exclusive target of Rho kinase. This change was accompanied by dendritic spine loss of apical dendrites of pyramidal hippocampal neurons. Interestingly, increased pMYPT1 levels and spine loss were both prevented by Fasudil administration. Conclusion: Our findings suggest that Fasudil may prevent the development of abnormal behavior and spine loss induced by chronic stress by blocking Rho kinase activity.https://academic.oup.com/ijnp/article/20/4/336/263217

    Magnetic field production during preheating at the electroweak scale

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    We study the generation of magnetic fields during preheating within an scenario of hybrid inflation at the electroweak (EW) scale. We find that the non-perturbative and strongly out-of-equilibrium process of magnetic field production occurs along the lines predicted by Vachaspati many years ago. The system starts in the false vacuum at the end of inflation, and very quickly the initial quantum fluctuations of the Higgs field get amplified via long wavelength spinodal instabilities. The subsequent nucleation of the random Gaussian Higgs field bubbles (lumps) leads to EW symmetry breaking, and to the creation of ZZ-strings, which soon decay, along with longwave magnetic flux tubes with nontrivial helicity. The intensity and scales in these helical magnetic fields are consistent with their later development into the microgauss fields observed in galaxies and clusters of galaxies.Comment: 4 pages, 6 figures, uses revtex

    The shape of our gut: Dissecting its impact on drug absorption in a 3D bioprinted intestinal model

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    The small intestine is a complex organ with a characteristic architecture and a major site for drug and nutrient absorption. The three-dimensional (3D) topography organized in finger-like protrusions called villi increases surface area remarkably, granting a more efficient absorption process. The intestinal mucosa, where this process occurs, is a multilayered and multicell-type tissue barrier. In vitro intestinal models are routinely used to study different physiological and pathological processes in the gut, including compound absorption. Still, standard models are typically two-dimensional (2D) and represent only the epithelial barrier, lacking the cues offered by the 3D architecture and the stromal components present in vivo, often leading to inaccurate results. In this work, we studied the impact of the 3D architecture of the gut on drug transport using a bioprinted 3D model of the intestinal mucosa containing both the epithelial and the stromal compartments. Human intestinal fibroblasts were embedded in a previously optimized hydrogel bioink, and enterocytes and goblet cells were seeded on top to mimic the intestinal mucosa. The embedded fibroblasts thrived inside the hydrogel, remodeling the surrounding extracellular matrix. The epithelial cells fully covered the hydrogel scaffolds and formed a uniform cell layer with barrier properties close to in vivo. In particular, the villus-like model revealed overall increased permeability compared to a flat counterpart composed by the same hydrogel and cells. In addition, the efflux activity of the P-glycoprotein (P-gp) transporter was significantly reduced in the villus-like scaffold compared to a flat model, and the genetic expression of other drugs transporters was, in general, more relevant in the villus-like model. Globally, this study corroborates that the presence of the 3D architecture promotes a more physiological differentiation of the epithelial barrier, providing more accurate data on drug absorbance measurements.Copyright © 2023. Published by Elsevier B.V

    Generalized plane-fronted gravitational waves in any dimension

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    We study the gravitational waves in spacetimes of arbitrary dimension. They generalize the pp-waves and the Kundt waves, obtained earlier in four dimensions. Explicit solutions of the Einstein and Einstein-Maxwell equations are derived for an arbitrary cosmological constant.Comment: Revtex, 18 pages, no figure

    The nuclear and extended infrared emission of the Seyfert galaxy NGC 2992 and the interacting system Arp 245

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    We present subarcsecond resolution infrared (IR) imaging and mid-IR spectroscopic observations of the Seyfert 1.9 galaxy NGC 2992, obtained with the Gemini North Telescope and the Gran Telescopio CANARIAS (GTC). The N-band image reveals faint extended emission out to ~3 kpc, and the PAH features detected in the GTC/CanariCam 7.5-13 micron spectrum indicate that the bulk of this extended emission is dust heated by star formation. We also report arcsecond resolution MIR and far-IR imaging of the interacting system Arp 245, taken with the Spitzer Space Telescope and the Herschel Space Observatory. Using these data, we obtain nuclear fluxes using different methods and find that we can only recover the nuclear fluxes obtained from the subarcsecond data at 20-25 micron, where the AGN emission dominates. We fitted the nuclear IR spectral energy distribution of NGC 2992, including the GTC/CanariCam nuclear spectrum (~50 pc), with clumpy torus models. We then used the best-fitting torus model to decompose the Spitzer/IRS 5-30 spectrum (~630 pc) in AGN and starburst components, using different starburst templates. We find that, whereas at shorter mid-IR wavelengths the starburst component dominates (64% at 6 micron), the AGN component reaches 90% at 20 micron. We finally obtained dust masses, temperatures and star formation rates for the different components of the Arp 245 system and find similar values for NGC 2992 and NGC 2993. These measurements are within those reported for other interacting systems in the first stages of the interaction.Comment: 20 pages, 12 figures, accepted by MNRA
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