p53-sensitive epileptic behavior and inflammation in Ft1 hypomorphic mice

Epilepsy is a complex clinical condition characterized by repeated spontaneous seizures. Seizures have been linked to multiple drivers including DNA damage accumulation. Investigation of epilepsy physiopathology in humans imposes ethical and practical limitations, for this reason model systems are mostly preferred. Among animal models, mouse mutants are particularly valuable since they allow conjoint behavioral, organismal, and genetic analyses. Along with this, since aging has been associated with higher frequency of seizures, prematurely aging mice, simulating human progeroid diseases, offer a further useful modeling element as they recapitulate aging over a short time-window. Here we report on a mouse mutant with progeroid traits that displays repeated spontaneous seizures. Mutant mice were produced by reducing the expression of the gene Ft1 (AKTIP in humans). In vitro, AKTIP/Ft1 depletion causes telomere aberrations, DNA damage, and cell senescence. AKTIP/Ft1 interacts with lamins, which control nuclear architecture and DNA function. Premature aging defects of Ft1 mutant mice include skeletal alterations and lipodystrophy. The epileptic behavior of Ft1 mutant animals was age and sex linked. Seizures were observed in 18 mutant mice (23.6% of aged ≥ 21 weeks), at an average frequency of 2.33 events/mouse. Time distribution of seizures indicated non-random enrichment of seizures over the follow-up period, with 75% of seizures happening in consecutive weeks. The analysis of epileptic brains did not reveal overt brain morphological alterations or severe neurodegeneration, however, Ft1 reduction induced expression of the inflammatory markers IL-6 and TGF-β. Importantly, Ft1 mutant mice with concomitant genetic reduction of the guardian of the genome, p53, showed no seizures or inflammatory marker activation, implicating the DNA damage response into these phenotypes. This work adds insights into the connection among DNA damage, brain function, and aging. In addition, it further underscores the importance of model organisms for studying specific phenotypes, along with permitting the analysis of genetic interactions at the organismal level

Implementing BDI Continual Temporal Planning for Robotic Agents

Making autonomous agents effective in real-life applications requires the ability to decide at run-time and a high degree of adaptability to unpredictable and uncontrollable events. Reacting to events is still a fundamental ability for an agent, but it has to be boosted up with proactive behaviors that allow the agent to explore alternatives and decide at run-time for optimal solutions. This calls for a continuous planning as part of the deliberation process that makes an agent able to reconsider plans on the base of temporal constraints and changes of the environment. Online planning literature offers several approaches used to select the next action on the base of a partial exploration of the solution space. In this paper, we propose a BDI continuous temporal planning framework, where interleave planning and execution loop is used to integrate online planning with the BDI control-loop. The framework has been implemented with the ROS2 robotic framework and planning algorithms offered by JavaFF

Effects of an innovative densification process on mechanical and physical properties of beech and Norway spruce veneers

AbstractIncreased wood density is obtained by compressing the wood porous structure under suitable moisture and temperature conditions to improve its physical, mechanical and color properties. A recently proposed wood densification method based on partial removal of lignin and hemicellulose in hot water solution of sodium hydroxide and sodium sulphite has shown promising results on solid wood. However, its applicability and effect on thin wood veneers have not been tested yet. In this study, the timing of the method has been adapted to estimate the densification treatment intensity dependence of wood properties (wood density and modulus of elasticity) and color change of softwood (Norway spruce) and hardwood (beech) veneers. Compared to control, density and rigidity increased, with improved wood properties peaking after only 90 s of treatment intensity. Furthermore, the color became darker after treatment compared to control, with no significant color difference between treatment intensities. In conclusion, densification of veneers, according to the presented adapted method, provides a significant improvement of veneers physical and mechanical properties, and produces color changes perceptible by the human eye. Our results can be further implemented and adapted to application in industrial plants, calling for new application of densified veneers.</jats:p

Survival and divergence in a small group: The extraordinary genomic history of the endangered Apennine brown bear stragglers

About 100 km east of Rome, in the central Apennine Mountains, a critically endangered population of ∼50 brown bears live in complete isolation. Mating outside this population is prevented by several 100 km of bear-free territories. We exploited this natural experiment to better understand the gene and genomic consequences of surviving at extremely small population size. We found that brown bear populations in Europe lost connectivity since Neolithic times, when farming communities expanded and forest burning was used for land clearance. In central Italy, this resulted in a 40-fold population decline. The overall genomic impact of this decline included the complete loss of variation in the mitochondrial genome and along long stretches of the nuclear genome. Several private and deleterious amino acid changes were fixed by random drift; predicted effects include energy deficit, muscle weakness, anomalies in cranial and skeletal development, and reduced aggressiveness. Despite this extreme loss of diversity, Apennine bear genomes show nonrandom peaks of high variation, possibly maintained by balancing selection, at genomic regions significantly enriched for genes associated with immune and olfactory systems. Challenging the paradigm of increased extinction risk in small populations, we suggest that random fixation of deleterious alleles (i) can be an important driver of divergence in isolation, (ii) can be tolerated when balancing selection prevents random loss of variation at important genes, and (iii) is followed by or results directly in favorable behavioral changes

Antibacterial and antibiofilm activity of carvacrol against Salmonella enterica serotype Typhimurium

The present study evaluated the antibacterial and antibiofilm activity of carvacrol against Salmonella Typhimurium. The minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) were determined and the time-kill curve and scanning electron microscopy (SEM) were performed to evaluate antibacterial activity. Antibiofilm activity was evaluated by quantifying total biomass using crystal violet assay, and metabolic activity was determined using MTT [3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide] assay. The action of carvacrol against preformed biofilm on polypropylene and stainless steel was also evaluated by colony counting and SEM. The MIC and MBC was 312 µg mL-1. Carvacrol at MIC and 2 x MIC eliminated cells after 6 and 1 h of treatment, respectively, as exhibited in the time-kill curve. The greatest reduction in biofilm biomass and metabolic activity was 1,719 OD550 and 0,089 OD550 respectively, both at 4 x MIC of carvacrol. In carvacrol treated biofilms of S. Typhimurium on polypropylene, a reduction of 5.12 log was observed with 4 x MIC, while on stainless steel, carvacrol at 4 x MIC reduced bacterial counts by 5 log. The results showed that carvacrol exhibits antibacterial activity and can be used as an alternative for the control of S. Typhimurium biofilms

Survival and divergence in a small group: The extraordinary genomic history of the endangered Apennine brown bear stragglers

About 100 km east of Rome, in the central Apennine Mountains, a critically endangered population of &sim;50 brown bears live in complete isolation. Mating outside this population is prevented by several 100 km of bear-free territories. We exploited this natural experiment to better understand the gene and genomic consequences of surviving at extremely small population size. We found that brown bear populations in Europe lost connectivity since Neolithic times, when farming communities expanded and forest burning was used for land clearance. In central Italy, this resulted in a 40-fold population decline. The overall genomic impact of this decline included the complete loss of variation in the mitochondrial genome and along long stretches of the nuclear genome. Several private and deleterious amino acid changes were fixed by random drift; predicted effects include energy deficit, muscle weakness, anomalies in cranial and skeletal development, and reduced aggressiveness. Despite this extreme loss of diversity, Apennine bear genomes show nonrandom peaks of high variation, possibly maintained by balancing selection, at genomic regions significantly enriched for genes associated with immune and olfactory systems. Challenging the paradigm of increased extinction risk in small populations, we suggest that random fixation of deleterious alleles (i) can be an important driver of divergence in isolation, (ii) can be tolerated when balancing selection prevents random loss of variation at important genes, and (iii) is followed by or results directly in favorable behavioral changes.Additional co-authors: Claudio Groff, Ladislav Paule, Leonardo Gentile, Carles Vilà, Saverio Vicario, Luigi Boitani, Ludovic Orlando, Silvia Fuselli, Cristiano Vernesi, Beth Shapiro, Paolo Ciucci, and Giorgio Bertorell

Simultaneous quantitative assessment of circulating cell-free mitochondrial and nuclear DNA by multiplex real-time PCR

Quantification of circulating nucleic acids in plasma and serum could be used as a non-invasive diagnostic tool for monitoring a wide variety of diseases and conditions. We describe here a rapid, simple and accurate multiplex real-time PCR method for direct synchronized analysis of circulating cell-free (ccf) mitochondrial (mtDNA) and nuclear (nDNA) DNA in plasma and serum samples. The method is based on one-step multiplex real-time PCR using a FAM-labeled MGB probe and primers to amplify the mtDNA sequence of the ATP 8 gene, and a VIC-labeled MGB probe and primers to amplify the nDNA sequence of the glycerinaldehyde-3-phosphate-dehydrogenase (GAPDH) gene, in plasma and serum samples simultaneously. The efficiencies of the multiplex assays were measured in serial dilutions. Based on the simulation of the PCR reaction kinetics, the relative quantities of ccf mtDNA were calculated using a very simple equation. Using our optimised real-time PCR conditions, close to 100% efficiency was obtained from the two assays. The two assays performed in the dilution series showed very good and reproducible correlation to each other. This optimised multiplex real-time PCR protocol can be widely used for synchronized quantification of mtDNA and nDNA in different samples, with a very high rate of efficiency

Tolerância de duas variedades de algodoeiro a herbicidas aplicados em pré-emergência

This work aimed to evaluate the selectivity of herbicides applied pre-emergence, isolated or in tank-mixtures, for two cotton varieties, Delta-Opal and FMT-701. Treatments applied were: alachlor, S-metolachlor, diuron (two rates), prometryn (two rates), oxyfluorfen, alachlor + diuron, alachlor + prometryn (two rates of this mixture), S-metolachlor + diuron, S-metolachlor + prometryn (two rates of this mixture), oxyfluorfen + diuron, oxyfluorfen + prometryn. Evaluations performed were related to the visual plant intoxication, height of plants and crop yield. When rates of diuron and prometryn were increased, symptoms of crop injury were also more evident, in relation to lower rates of the same products. Oxyfluorfen, isolated or in tank mixture with diuron or prometryn propitiated intense symptoms of crop injury, but the only treatment which was considered as non-selective for both cotton varieties was the mixture of oxyfluorfen + prometryn (0.192 + 0.9 kg ha-1).Este trabalho teve por objetivo avaliar a seletividade de herbicidas aplicados em pré-emergência, isolados ou em misturas, para as variedades Delta-Opal e FMT-701. Os tratamentos avaliados foram: alachlor, S-metolachlor, diuron (em duas doses), prometryn (em duas doses), oxyfluorfen, alachlor + diuron, alachlor + prometryn (em duas doses da mistura), S-metolachlor + diuron, S-metolachlor + prometryn (em duas doses da mistura), oxyfluorfen + diuron, oxyfluorfen + prometryn. Foram realizadas avaliações relacionadas à fitointoxicação visual, altura de plantas e produtividade da cultura. Quando houve incremento na dose de diuron e prometryn, os sintomas de fitointoxicação foram intensificados em relação às menores doses. O herbicida oxyfluorfen quando aplicado isolado e em mistura com diuron ou prometryn proporcionou sintomas intensos de fitointoxicação à cultura do algodoeiro. No entanto, o único tratamento que não foi seletivo para ambas variedades de algodoeiro foi a mistura oxyfluorfen + prometryn (0,192 + 0,900 kg ha-1)

Country-level gender inequality is associated with structural differences in the brains of women and men

男女間の不平等と脳の性差 --男女間の不平等は脳構造の性差と関連する--. 京都大学プレスリリース. 2023-05-10.Gender inequality across the world has been associated with a higher risk to mental health problems and lower academic achievement in women compared to men. We also know that the brain is shaped by nurturing and adverse socio-environmental experiences. Therefore, unequal exposure to harsher conditions for women compared to men in gender-unequal countries might be reflected in differences in their brain structure, and this could be the neural mechanism partly explaining women’s worse outcomes in gender-unequal countries. We examined this through a random-effects meta-analysis on cortical thickness and surface area differences between adult healthy men and women, including a meta-regression in which country-level gender inequality acted as an explanatory variable for the observed differences. A total of 139 samples from 29 different countries, totaling 7, 876 MRI scans, were included. Thickness of the right hemisphere, and particularly the right caudal anterior cingulate, right medial orbitofrontal, and left lateral occipital cortex, presented no differences or even thicker regional cortices in women compared to men in gender-equal countries, reversing to thinner cortices in countries with greater gender inequality. These results point to the potentially hazardous effect of gender inequality on women’s brains and provide initial evidence for neuroscience-informed policies for gender equality