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

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 Economía y Competitividad BFU2016-75058-PEuropean Research Council ERC2014 AdG669898 TARLOO

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

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"

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

Indexación: 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

Tunable Magnetocaloric Effect Towards Cryogenic Range by Varying Mn:Ni Ratio in All-d-metal Ni(Co)-Mn-Ti Heusler Alloys

Cryogenic magnetic refrigeration is a highly efficient and environmentally friendly technique for gas liquefaction. However, refrigerant materials undergoing large magnetocaloric response at the interesting cryogenic range are dominated by critical elements (mainly rare-earth elements) which impedes practical applicability of such refrigeration systems. Therefore, there is a need for dedicated investigations on optimization of magnetocaloric response at cryogenic range by utilizing compositions that are rare-earth free. In this work, we synthesize the mechanically stable and rare-earth free, all-d-metal Ni35Co15Mn35Ti15 Heusler alloys and investigate the role of varying Mn:Ni ratio on the magnetostructural and magnetocaloric properties of the alloy system. The results of the microstructural characterization indicate homogenous composition for the investigated alloy series. As the Mn:Ni ratio increases from 1.01 to 1.10, the martensitic transition shifts from near-room temperature down to cryogenic region (120–140 K) while the magnetization of the austenitic phase remains unaltered. Isothermal entropy change as high as ∼ 13 J kg−1 K−1 at 1.5 T is achieved for the sample with the highest Mn:Ni ratio at the temperature region for natural gas liquefaction, which significantly surpasses the values previously reported in the literature for similar alloys. In addition to large magnetocaloric response, the martensitic transformation falls in an interesting temperature of the cryogenic region, paving the way for various low-temperature magnetocaloric applications.Air Force Office of Scientific Research FA8655–21-1–7044HyLICAL 101101461Junta de Andalucía EMC21_0041

All-d-metal Ni(Co)-Mn(X)-Ti (X = Fe or Cr) Heusler Alloys: Enhanced Magnetocaloric Effect for Moderate Magnetic Fields

All-d-metal Ni(Co)-Mn-Ti Heusler alloys show high magnetocaloric/barocaloric effects ascribed to the occurrence of a martensitic transformation together with excellent mechanical properties. However, high magnetic fields are needed to fully drive the transformation and to obtain their maximum responses. To further tune the martensitic transition and the associated magnetocaloric response, we systematically investigate the role of partial Mn substitution by Fe or Cr on the parent composition Ni36Co14Mn35Ti15. On the one hand, Cr doping increases the entropy change of the transformation but causes a tighter overlap of both martensitic and Curie transitions. This significantly reduces the magnetization difference between austenite and martensite and, consequently, strongly decreases the magnetocaloric response. On the other hand, Fe doping reduces the entropy change of the transformation and separates both martensitic and Curie transitions while keeping the magnetization difference among both phases. These two combined features reduce the magnetic field needed to completely drive the martensitic transformation and leads to higher and broader isothermal entropy change peaks for moderate magnetic field changes, reaching up to 25% enhancement for 2 T when compared to the undoped alloy.Ministerio de Ciencia e Innovación PID2019-105720RB-I00Junta de Andalucía P18-RT-746Air Force Office of Scientific Research FA8655-21-1-704

Magnetic field production during preheating at the electroweak scale

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 $Z$-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

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