Analysis of Gene, Environment, and Sex Interaction in the Development of Autistic-like Phenotype in Mice

International Journal of Molecular Sciences · 2026-03-11

Autism Spectrum Disorder (ASD) is a developmental disorder that manifests a broad variability of phenotypes. The underlying factors contributing to the diverse presentation of autistic phenotypes remain poorly understood. Studies have shown that environmental and genetic factors could contribute to ASD. Additionally, there is a sex bias in the disorder, where the prevalence in males is higher than in females. But it is still unknown how exposure to similar risk factors can lead to different phenotypes. The three-hit theory states that the vulnerability of an individual to develop ASD is modulated by the interplay between genetic predisposition, sex, and environmental insults. To better understand this phenomenon, we investigated whether an environmental insult, via maternal immune activation (MIA) during pregnancy could influence the development of the autistic-like phenotype in a genetically predisposed mouse strain, contactin-associated protein-like 2 (CNTNAP2) knockout. CNTNAP2 knockout, sex, and maternal immune activation had significantly additive effects on repetitive/stereotyped and social behavior in the offspring, while working memory and sensory gating were not affected by hits. These results indicate that genetics, sex, and environment interact to influence autistic-like phenotypes in a behavior-specific manner.

P-1295. Meningococcal Disease in Children in Argentina: A 4-year Active Sentinel Hospital Surveillance Study during the Post-Meningococcal Vaccination Era: A Difficult Impact Analysis

Open Forum Infectious Diseases · 2025-01-29

Abstract Background In 2017, MenACWY-CRM197 vaccine was introduced in the national immunization program (NIP) in Argentina (2+1 schedule, +1 dose at 11 years). In the pre-vaccination period (preVp, 2012-2015), the meningococcal disease (MD) burden had been assessed. The objectives of this study were: to evaluate the impact of the intervention on the burden of MD in ≤15 years during a post-vaccination period (postVp, January 2020 to December 2023) and to describe the clinical-epidemiological-bacteriological pattern of all confirmed MD cases of postVp versus preVp. Methods Active hospital surveillance in 6 pediatric sentinel units in Argentina. MD discharge rates per 10,000 hospital discharges between preVp and postVp was compared. Results In postVp, of 186,257 hospitalized patients, 1047 (0.6 %) had suspected meningitis or MD, of which 9.1 % (95/1047) had acute bacterial meningitis (ABM) and 1.1 % (11/1047) meningococcemia; 79 % (75/95) of ABM cases were confirmed by culture, corresponding 8.0 % (6/75) to Neisseria meningitidis (Nm). In addition, in 2 out of 11 meningococcemia cases a Nm was confirmed by culture. 41.4 % (12/29) of MD culture-negative cases were confirmed by PCR. Thus, there were a total of 20 MD cases, a discharge rate of 1.1 (0.7-1.7) and a reduction of 78.9 % compared to the preVp. Of the 20 MD cases in the postVp, median age was 38 months (IQR 26-95), 13 had MenACWY-CRM197. Microbiological/molecular diagnosis was made in blood/serum (9; 40.9 %) and CSF (13; 59.1 %). Capsular group was identified in 14 samples (B:13; C:1). Conclusion After the MenACWY-CRM197 vaccine introduction in the NIP, the burden of MD in ≤15 years was reduced almost 80%. The predominant serogroup was B. These findings could be interpreted as an effect of the vaccine, but it is necessary to also take into account the biases inherent in vaccine impact studies (COVID-19 pandemic, lockdown measures, natural fluctuations in the incidence of MD, among others). Disclosures All Authors: No reported disclosures

Extending Thioflavin T Fluorescence Probe to 2-Ethenyl-benzothiazole Derivatives: Drug-like Quadruplex Ligands with Potent Antitrypanosomatid Activity

ACS Infectious Diseases · 2025-11-04 · 1 citations

Thioflavin T (ThT) is a well-established fluorescence probe with selectivity for G-quadruplex (G4) structures. Over the past few years, G4 ligands have emerged as promising candidates for the development of antiparasitic agents. Building on this concept, we explored extending ThT’s benzothiazole scaffold by introducing various 2-ethenyl aromatic and heteroaromatic moieties, aiming to enhance G4 binding affinity and potential therapeutic effect. A series of benzothiazolium derivatives were synthesized and evaluated for their antiproliferative and antiparasitic activity. Several 2-ethenyl benzothiazole derivatives showed submicromolar activity against Leishmania spp. and Trypanosoma brucei parasites, with up to 200-fold selectivity over MRC-5 human lung fibroblasts. Notably, compound 2b demonstrated remarkable potency, with an IC50 of 0.48 nM and a selectivity index of 46,151 against Leishmania major amastigotes, and an IC50 of 0.019 nM and a selectivity index of 79,206 against T. brucei. In fact, compound 2b demonstrated superior efficacy and selectivity in comparison to the clinically used drugs suramin, fexinidazole, miltefosine, and amphotericin B. Biophysical studies revealed that all tested derivatives exhibited significant G4 stabilization, surpassing ThT. Location of compound 2b inside the nucleus and the kinetoplast, as well as partially in the mitochondria, opens up the possibility of 2b acting against the parasite through binding to G4.

The mass of the exo-Venus Gliese 12 b, as revealed by HARPS-N, ESPRESSO, and CARMENES

ArXiv.org · 2025-06-25 · 2 citations

Small temperate planets are prime targets for exoplanet studies due to their possible similarities with the rocky planets in the Solar System. M dwarfs are promising hosts since the planetary signals are within our current detection capabilities. Gliese 12 b is a Venus-sized temperate planet orbiting a quiet M dwarf. We present here the first precise mass measurement of this small exoplanet. We performed a detailed analysis using HARPS-N, ESPRESSO, and CARMENES radial velocities, along with new and archival \tess, \cheops, and MuSCAT2/3 photometry data. From fitting the available data, we find that the planet has a radius of $R_\mathrm{p} = 0.93\pm0.06 \,\mathrm{R_\oplus}$ and a mass of $M_\mathrm{p} = 0.95^{+0.29}_{-0.30} \,\mathrm{M_\oplus}$ (a $3.2σ$ measurement of the semi-amplitude $K=0.67\pm0.21\,\mathrm{m\,s^{-1}}$), and is on an orbit with a period of $12.761418^{+0.000060}_{-0.000055}\,\mathrm{d}$. A variety of techniques were utilised to attenuate stellar activity signals. Gliese 12 b has an equilibrium temperature of $T_\mathrm{eq}=317 \pm 8\,\mathrm{K}$, assuming an albedo of zero, and a density consistent with that of Earth and Venus ($ρ_\mathrm{p}=6.4\pm2.4\,\mathrm{g\,cm^{-3}}$). We find that Gliese 12 b has a predominantly rocky interior and simulations indicate that it is unlikely to have retained any of its primordial gaseous envelope. The bulk properties of Gliese 12 b place it in an extremely sparsely populated region of both mass--radius and density--$T_\mathrm{eq}$ parameter space, making it a prime target for follow-up observations, including Lyman-$α$ studies.

Coronal and chromospheric activity of Teegarden's star

ArXiv.org · 2025-04-03

Teegarden's star is a late-type M-dwarf planet host, typically showing only rather low levels of activity. In this paper we present an extensive characterisation of this activity at photospheric, chromospheric, and coronal levels. We specifically investigated TESS observations of Teegarden's star, which showed two very large flares with an estimated flare fluence between 10$^{29}$ and 10$^{32}$\,erg comparable to the largest solar flares. We furthermore analysed nearly 300 CARMENES spectra and 11 ESPRESSO spectra covering all the usually used chromospheric lines in the optical from the \ion{Ca}{ii} H \& K lines at 3930\,Å\, to the \ion{He}{i} infrared triplet at 10830\,Å. These lines show different behaviour: The \ion{He}{i} infrared triplet is the only one absent in all spectra, some lines show up only during flares, and others are always present and highly variable. Specifically, the H$α$ line is more or less filled in during quiescence; however, the higher Balmer lines are still observed in emission. Many chromospheric lines show a correlation with H$α$ variability, which, in addition to stochastic behaviour, also shows systematic behaviour on different timescales including the rotation period. Moreover, we found several flares and also report hints of an erupting prominence, which may have led to a coronal mass ejection. Finally, we present X-ray observations of Teegarden's star (i.e. a discovery pointing obtained with the \emph{Chandra} observatory) and an extensive study with the \emph{XMM-Newton} observatory; when these two large flares were observed, one of them showed clear signatures of the Neupert effect, suggesting the production of hard X-rays in the system.

Microwave-assisted synthesis of new triangulenium dyes for lifetime imaging microscopy (FLIM)

Scientific Reports · 2025-12-21

We introduce a novel microwave-assisted method for the rapid and efficient synthesis of triangulenium dyes, enabling the creation of a broader range of these fluorophores, which are characterized by very long fluorescence lifetimes. We prepared different azadioxatriangulenium (ADOTA) and diazaoxatriangulenium (DAOTA) derivatives and thoroughly characterized their photophysical properties. We investigated their solvatochromic properties and the effects of the solvent, aided by computational chemistry results. The new ADOTA and DAOTA dyes were applied in multiple in cellulo microscopy modalities, including confocal, fluorescence lifetime imaging microscopy (FLIM), and super-resolution imaging. ADOTA derivatives predominantly accumulated in mitochondria, while DAOTAs showed pronounced nuclear staining and participation in endocytic pathways. Notably, these dyes enable clear discrimination of subcellular compartments via lifetime contrast in FLIM: mitochondria, where ADOTAs undergo electron transfer-driven quenching and display short lifetimes; nuclei and DNA, where lifetimes remain long; and endocytic vesicles, where partial dye aggregation leads to lifetime reduction.

The CARMENES search for exoplanets around M dwarfs

Astronomy and Astrophysics · 2025-04-11 · 2 citations

Context. A multitude of spectral activity indicators are routinely computed nowadays from the spectra generated as part of planet-hunting radial velocity surveys. Searching for shared periods among them can help to robustly identify astrophysical quantities of interest, such as the stellar rotation period. However, this identification can be complicated due to the fact that many different peaks occur in the periodograms. This is especially true in the presence of aliasing and spurious signals caused by environmental influences affecting the instrument. Aims. Our goal is to test a clustering algorithm to find signals with the same periodicity, (i.e. with the stellar rotation period) in the periodograms of a large number of activity indicators. On this basis, we have looked to evaluate the correlations between activity indicators and fundamental stellar parameters. Methods. We used generalised Lomb–Scargle periodograms to find periodic signals in 24 activity indicators, spanning the VIS and NIR channels of the CARMENES spectrograph. Common periods were subsequently determined by a machine learning algorithm for density-based spatial clustering of applications with noise ( DBSCAN ). Results. The clustering analysis of the signals apparent in the spectral activity indicators is a powerful tool for the detection of stellar rotation periods. It is straightforward to implement and can be easily automated, so that large data sets can be analysed. For a sample of 136 stars, we were able to recover the stellar rotation period in a total of 59 cases, including 3 with a previously unknown rotation period. In addition, we analysed spurious signals frequently occurring at the period of one year and its integer fractions, concluding that they are likely aliases of one underlying signal. Furthermore, we reproduced the results of several previous studies on the relationships between activity indicators and the stellar characteristics.

Beyond antiparasitic activity: elucidating the antibacterial potency of pyrvinium pamoate

Microbiology Spectrum · 2025-09-30

ABSTRACT Antimicrobial resistance represents a critical global health threat, demanding innovative therapeutic strategies. In this study, we investigate the repurposing potential of pyrvinium pamoate (PP)—a long-established anthelmintic agent—for antibacterial applications. Comprehensive in vitro analyses revealed that while gram-negative bacteria exhibited inherent resistance due to limited drug uptake, gram-positive pathogens, particularly within the orders Actinomycetales and Bacillales , were markedly susceptible at low micromolar concentrations. Enhanced antibacterial efficacy was observed when PP was combined with outer membrane-permeabilizing agents, such as the peptide D11 or pentamidine, which facilitated increased intracellular accumulation. Additionally, the role of efflux pump activity was explored; its inhibition in Staphylococcus aureus resulted in significant drug retention and a concomitant reduction in minimum inhibitory concentrations, while disruption of the proton motive force attenuated uptake. The compound demonstrated bactericidal effects against S. aureus and a bacteriostatic profile against Pseudomonas aeruginosa when sensitized with outer membrane permeabilizing agents. Furthermore, synergistic studies with several antibiotics revealed the potential of PP as a valuable addition to the antimicrobial arsenal against multidrug-resistant pathogens. These findings motivate further mechanistic studies and clinical evaluation of PP in antimicrobial therapy. PP shows promise as a repurposed antibacterial agent, particularly against gram-positive pathogens, with enhanced activity against gram-negative pathogens when combined with membrane-permeabilizing agents or in the presence of efflux pump inhibitors. IMPORTANCE Antimicrobial resistance is a growing global crisis that threatens the effectiveness of current treatments. Developing new antibiotics is challenging and time-consuming, so repurposing existing drugs offers a faster alternative. Pyrvinium pamoate (PP) is a well-known antiparasitic drug that has also been studied for cancer treatment, but its antibacterial potential has received little attention. In this study, we show that PP is effective in killing several gram-positive bacteria, including Staphylococcus aureus , at low doses. Although gram-negative bacteria are more resistant, we found that combining PP with agents that open up bacterial membranes makes these bacteria more vulnerable. Our research also explains how bacteria take in and remove PP, which can affect how well it works. These findings support the idea of repurposing PP as an antibiotic, especially in combination therapies, to help combat multidrug-resistant infections.

The mass of the exo-Venus Gliese 12 b, as revealed by HARPS-N, ESPRESSO, and CARMENES

Monthly Notices of the Royal Astronomical Society · 2025-10-06 · 1 citations

ABSTRACT Small temperate planets are prime targets for exoplanet studies due to their possible similarities with the rocky planets in the Solar system. M dwarfs are promising hosts since the planetary signals are within our current detection capabilities. Gliese 12 b is a Venus-sized temperate planet orbiting a quiet M dwarf. We present here the first precise mass measurement of this small exoplanet. We performed a detailed analysis using HARPS-N (High Accuracy Radial velocity Planet Searcher for the Northern Hemisphere), ESPRESSO (Echelle Spectrograph for Rocky Exoplanets and Stable Spectroscopic Observations), and CARMENES (Calar Alto high-Resolution search for M dwarfs with Exoearths with Near-infrared and optical Echelle Spectrographs) radial velocities, along with new and archival TESS (Transiting Exoplanet Survey Satellite), CHEOPS (CHaracterising ExOPlanet Satellite), and MuSCAT2/3 (Multicolor Simultaneous Camera for studying Atmospheres of Transiting exoplanets) photometry data. From fitting the available data, we find that the planet has a radius of $R_\mathrm{p} = 0.93\pm 0.06 \, \mathrm{R_{\rm{\oplus }}}$ and a mass of $M_\mathrm{p} = 0.95^{+0.29}_{-0.30} \, \mathrm{M_{\rm{\oplus }}}$ (a $3.2\sigma$ measurement of the semi-amplitude $K=0.67\pm 0.21\, \mathrm{m\, s^{-1}}$), and is on an orbit with a period of $12.761418^{+0.000060}_{-0.000055}\, \mathrm{d}$. A variety of techniques were utilized to attenuate stellar activity signals. Gliese 12 b has an equilibrium temperature of $T_\mathrm{eq}=317 \pm 8\, \mathrm{K}$, assuming an albedo of zero, and a density consistent with that of Earth and Venus ($\rho _\mathrm{p}=6.4\pm 2.4\, \mathrm{g\, cm^{-3}}$). We find that Gliese 12 b has a predominantly rocky interior and simulations indicate that it is unlikely to have retained any of its primordial gaseous envelope. The bulk properties of Gliese 12 b place it in an extremely sparsely populated region of both mass–radius and density–$T_\mathrm{eq}$ parameter space, making it a prime target for follow-up observations, including Lyman-$\alpha$ studies.

Hydroxytyrosyl punicate: A first overview of a novel phenolipid with antiproliferative and antitrypanosomal activity

Journal of Functional Foods · 2024-05-21

• Phenolipid has been created by esterifying punicic acid with hydroxytyrosol (HT-PA) • HT-PA was more active than HT or PA against cell lung carcinoma A549 cells. • The phenolipid displayed positive activity against Trypanosoma brucei parasites. • HT-PA showed > 100-fold selectivity for T. brucei over healthy MRC-5 cells. Polyunsaturated fatty acids and phenolic compounds are two families of natural products that have been widely investigated for their health benefits. The aim of this study was to prepare the novel phenolipid hydroxytyrosyl punicate (HT-PA) and evaluate its antiproliferative and antiparasitic properties. HT-PA was synthesized from hydroxytyrosol (HT) and punicic acid (PA) in a two-step chemical synthesis. HT-PA had an EC 50 of 8.93 µM against non–small cell lung carcinoma A549 cells and was more active than HT or PA. It achieved a selectivity index of 11.20 for tumor cell line A549 over non-tumor cell line MCR-5. HT-PA displayed 80-fold and 60-fold greater activity against Trypanosoma brucei parasites (EC 50 of 0.95 µM) compared with HT and PA, respectively, and > 100-fold selectivity for T. brucei over healthy MRC-5 cells.