Instituto Nacional de Investigaciones Nucleares

BackgroundNETosis is a conserved process that has been maintained throughout evolution in various species. However, in the cattle tick Rhipicephalus microplus, a process similar to NETosis, known as ETosis, has not been previously described.MethodsIn this work, we demonstrate, using fluorometry and confocal and electron microscopy, the chromatin release and the extracellular trap (ET) formation in tick hemocytes in response to various treatments.ResultsThe treatments analysis showed greater chromatin release in zymosan A-, Escherichia coli-, and LPS-treated hemocytes. This was consistent with the expression of the peroxinectin gene (pxn), the myeloperoxidase (mpo) analog gene in vertebrates, which participates in NETosis activation. Furthermore, DNA fibers were observed in tick hemocytes under all treatments, and transmission electron microscopy (TEM) showed that hemocytes treated with zymosan A have a clear nuclear envelope disruption, with a unidirectional release of chromatin.ConclusionsThis work investigates the existence of ETosis in tick hemocytes, representing a significant step toward understanding the tick’s immune response. In addition to this contribution, new areas of research are emerging to understand the molecular mechanisms that govern this process, which we are currently exploring.Graphical

Background: While reperfusion significantly improves acute myocardial infarction (MI) survival rates, the process leads to an inflammatory cascade that upregulates fibrotic pathways and proliferation of cardiac fibroblasts. Targeted SPECT imaging of fibroblast activation protein (FAP) provides a means to non-invasively quantify activated fibroblasts in the remodeling myocardium. We aimed to explore the relation between myocardial strain, regional stress and fibroblast activation with a FAP SPECT radiotracer, 99m Tc-iFAP, in a post-ischemia reperfusion (IR) porcine model using a novel 360° Hybrid SPECT CZT/CT camera along with histological validation. Methods: Transmural IR injury was induced in n=5 swine by a 90-min balloon occlusion of the LAD. Global circumferential strain was assessed by 3D echocardiography at baseline and post-MI with LV hemodynamics. At 7-11 days post-MI, a hybrid SPECT/CT image was acquired 90 min following injection of 99m Tc-iFAP with infarct uptake delineated as the region two standard deviations above blood activity in the aorta. Contrast CT was used to define the myocardial borders, LV diameter and wall thickness for calculation of regional wall stress. Following euthanasia, hearts were quantitatively evaluated histologically for fibrosis, myofibroblasts, and FAP. Results: Global circumferential strain was significantly impaired post-MI (Fig.1A, p<0.01) with a significant increase in LVEDP (Fig.1B, p<0.05). Regional wall stress in the MI region was significantly elevated compared to the contralateral region (Fig.1C, p<0.05). 99m Tc-iFAP uptake in the infarct area was significantly elevated (Fig. 1D, p<0.01) and demonstrated significant correlation with an increase in regional wall stress (Fig.1E, R=0.75). These in vivo imaging findings were associated with an increase in fibrosis (Fig.1F), myofibroblasts (Fig.1G) and FAP (Fig.1H) in the infarcted LV compared to the non-infarcted LV as assessed by histological staining of the tissue postmortem. Conclusion: 99m Tc-iFAP uptake in the infarct region post ischemia/reperfusion had a significant direct correlation with increased regional wall stress and histological findings of active fibrosis in MI region. We have demonstrated that 99m Tc-iFAP uptake accurately defines the area of active cardiac remodeling with fibroblast activation which could be used for guiding and monitoring therapeutic interventions directed at modulating adverse post-MI remodeling.

Background/AimDifluorodeoxycytidine (dFdC) has been reported to increase radiosensitivity, although its mechanism of action is unknown. The objective of this study was to determine the early and late effects of dFdC on mouse cell radiosensitivity in vivo.Materials and MethodsThe early effects of dFdC on bone marrow cell radiosensitivity were evaluated a few minutes after dFdC treatment using single-cell gel electrophoresis. Four groups of mice were set up: non-treated, dFdC-treated, radiation-treated, and dFdC plus radiation-treated. To evaluate the late effects of dFdC, the kinetics of micronucleus production and the inhibition of proliferation were measured in mouse normoblasts in vivo.ResultsThe early radiosensitization index was 1.7 and correlated with the proportion of severely damaged cells, likely in S phase. Late effects of dFdC were additive with radiation in both micronucleus induction and cytotoxicity. The pattern and duration of micronucleus formation suggest a dependency on dFdC incorporation into DNA. Although cytotoxicity increased over time, it did not influence the radiosensitization index.ConclusiondFdC enhances early radiosensitivity in bone marrow cells, likely by inhibiting DNA synthesis and generating reactive oxygen species (ROS)-induced DNA breaks. Late genotoxic effects were additive and kinetically linked to dFdC incorporation. Both dFdC alone and in combination with radiation exerted prolonged cytotoxic effects on normoblast precursors, with slightly greater toxicity observed in the combination group.

Objective.The aim of this study was to evaluate the impact of the nuclear properties of sixβ--emitting radionuclides (47Sc,67Cu,111Ag,161Tb,177Lu, and188Re) on the dosimetric outcomes of two tumour-targeting radiopharmaceuticals (RPs), with distinct pharmacokinetics: the peptide DOTA-folate conjugate cm09 and the monoclonal antibody HuM195. The study specifically focused on assessing the radiation-absorbed doses in organs and tumours, as well as comparing the efficacy and safety of the twelve RPs for targeted radionuclide therapy (TRT).Approach.Murine biodistribution data for both RPs were scaled to adult human models to determine biological residence times and the number of disintegrations in source organs and tumours. Dosimetric estimations were performed using OLINDA and MIRDCell software, considering different tumour sizes and organ-specific radiation exposure for both male and female phantoms.Main results.Significant differences in organ and tumour dosimetry were found across the considered radionuclides and tumour-targeting agents, attributable to the nuclear properties of the radionuclides and the RP pharmacokinetics. PFP-HuM195 labelled with161Tb and111Ag demonstrated efficient dose delivery to tumour from 1-10 mm, but also higher organ-absorbed doses per unit of injected activity than other labelling radionuclides. Cm09 exhibited less variability in tumour absorbed dose as the labelling radionuclide varied, but also produced much higher kidney absorbed doses than PFP-HuM195. Normalising to the same tumour absorbed dose showed that177Lu and161Tb are the safer options for treating small tumours (2.7-12.4 mm) with both RPs. These results demonstrate that the choice of radionuclide has a significant impact on both therapeutic efficacy and organ safety.Significance.This research demonstrates that selecting the appropriate radionuclide for TRT can optimise therapeutic outcomes while minimising radiation exposure to healthy tissues. The findings contribute to advancing personalised TRT approaches by considering RP-specific pharmacokinetics and radionuclide characteristics, paving the way for more effective cancer treatments.

Abstract We investigate the black hole information paradox in the setting of pseudo-complex gravity, a covariant geometric extension of general relativity that introduces a minimal length scale by deforming the spacetime manifold. In this framework, curvature invariants stay finite, and the classical singularity is geometrically regularized via a smooth core. We show that the correction term B/(6r 4) alters the Schwarzschild metric, generating the regularized geometry above, yielding a finite Hawking temperature, and inducing subleading corrections to the Bekenstein–Hawking entropy. Crucially, we demonstrate that the pseudo-complex geometric structure obstructs a clean factorization of the Hilbert space into interior and exterior regions, thereby removing the key assumption behind the standard derivation of the paradox. This structural reinterpretation of entanglement flow offers a new geometric route to unitarity preservation and information recovery. We examine the resulting effects on evaporation dynamics, entropy flow, and thermodynamic behavior. Our predictions are compared with those of generalized uncertainty principles (GUP), loop quantum gravity (LQG), and island-based models, and are summarized in a comparative table. Observable signatures—such as shifts in quasi-normal mode frequencies and the appearance of gravitational wave echoes from the regularized core—suggest that pseudo-complex gravity (pc-Gravity) is a testable, covariant approach to resolving the paradox without invoking firewalls, holography, or exotic quantum states.

Hydrogen generation and the correct simulation of severe accidents have been of utmost importance since the Fukushima Dai-ichi accident. QUENCH experiments are quite useful for validating mathematical models implemented in system codes for early-phase severe accidents, where hydrogen generation, fuel rod temperature, and their deterioration during these conditions are of vital importance. This paper presents a new system code, TLANESY, designed for the simulation of thermal–hydraulic systems with two-phase flow (mainly water) and with application in the analysis of severe accidents during the early phase. The computational implementation consists of fast-running numerical methods and their validation with experimental data from the QUENCH-01 experiment. The results showed an error with respect to the total hydrogen generation of approximately 0.6%. A stand-alone sensitivity analysis was also performed with some parameters related to the cladding, where it was shown that variation in the thermal conductivity by 15% can alter the total hydrogen generation by up to 5%, indicating that impurities in this material can have a significant impact on this Figure of Merit.

The nopal cactus, a plant from the Cactaceae family, holds significant economic and nutritional value for Mexico. This study aimed to enhance the genetic diversity and morphological traits of Opuntia velutina, a species cultivated as a vegetable nopal. A total of 1050 in vitro O. velutina explants were exposed to 15 different doses of gamma radiation from 60Co gamma, ranging from 5 to 125 Gy. The lethal dose was above 50 Gy, with an LD50 of 22.8 Gy for stimulating in vitro shoot growth. Shoots derived from doses between 5 and 50 Gy were subjected to in vitro shoot proliferation across four consecutive generations to stabilize morphological traits. Cluster analysis categorized the 178 irradiated shoots into 13 distinct morphological groups (CG1–CG13). Twenty-seven shoots exhibiting significant morphological improvements, such as a 50–100% increase in cladode length, up to a six-fold increase in shoot number, and up to a seven-fold increase in root number, were selected for molecular analysis of genetic diversity. Six primers were used with the Inter Simple Sequence Repeat (ISSR) molecular markers to examine genetic uniformity, yielding 54.5% polymorphic bands, indicating a high level of genetic variation. Both a UPGMA dendrogram and STRUCTURE-based Bayesian analysis confirmed the genetic divergence among the selected mutant lines. Overall, gamma irradiation effectively enhanced both phenotypic and genotypic diversity in O. velutina. This study corroborates that in vitro mutagenesis through gamma radiation is a viable strategy for generating novel genotypes with breeding potential within the Opuntia genus.