Concello de Cervo

Introduction: Ca v1.3 L‐type calcium (Ca 2+) channel plays a critical role in cardiac excitation-contraction coupling, regulating heart rate, contractility, and gene expression. The C-terminus of Ca v1.3 has recently been shown to translocate to the n

Myotonic dystrophy type 1 (DM1) is a genetic disorder that causes muscle weakness and myotonia. In DM1 patients, cardiac electrical manifestations include conduction defects and atrial fibrillation. DM1 results in the expansion of a CTG transcribed into CUG-containing transcripts that accumulate in the nucleus as RNA foci and alter the activity of several splicing regulators. The underlying pathological mechanism involves two key RNA-binding proteins (MBNL and CELF) with expanded CUG repeats that sequester MBNL and alter the activity of CELF resulting in spliceopathy and abnormal electrical activity. In the present study, we identified two DM1 patients with heart conduction abnormalities and characterized their hiPSC lines. Two differentiation protocols were used to investigate both the ventricular and the atrial electrophysiological aspects of DM1 and unveil the impact of the mutation on voltage-gated ion channels, electrical activity, and calcium homeostasis in DM1 cardiomyocytes derived from hiPSCs. Our analysis revealed the presence of molecular hallmarks of DM1, including the accumulation of RNA foci and sequestration of MBNL1 in DM1 hiPSC-CMs. We also observed mis-splicing of SCN5A and haploinsufficiency of DMPK. Furthermore, we conducted separate characterizations of atrial and ventricular electrical activity, conduction properties, and calcium homeostasis. Both DM1 cell lines exhibited reduced density of sodium and calcium currents, prolonged action potential duration, slower conduction velocity, and impaired calcium transient propagation in both ventricular and atrial cardiomyocytes. Notably, arrhythmogenic events were recorded, including both ventricular and atrial arrhythmias were observed in the two DM1 cell lines. These findings enhance our comprehension of the molecular mechanisms underlying DM1 and provide valuable insights into the pathophysiology of ventricular and atrial involvement.

Contexte : Le programme STEP est une intervention prénatale de groupe destinée aux femmes enceintes ayant vécu des traumatismes interpersonnels au cours de leur enfance tels que la maltraitance. La présente étude vise à décrire l’expérience des participantes de leur participation au programme.Méthodologie : Des entretiens individuels ont été réalisés auprès de 21 participantes ayant complété le programme afin de sonder leur appréciation de l’intervention, l’adéquation entre le contenu et leurs attentes, les points forts et les points faibles, la sensibilité à leur réalité personnelle, familiale et culturelle ainsi que l’importance qu’elles attribuent aux différents thèmes abordés.Résultats : Les participantes se représentent le programme STEP comme une occasion unique d’exploration de soi à titre d’individu et de mère et considèrent que le programme favorise un sentiment subjectif de mieux-être. Trois dimensions ont été identifiées au coeur de cette expérience : (1) le contenu du programme est perçu comme étant sensible, équilibré, concret et progressif, (2) le collectif/entre-mères favorise la socialisation de la maternité, la prise de recul, les échanges et la validation de soi et (3) le cadre d’animation sécurisant est perçu par le biais de la bienveillance de l’équipe d’animation, sa compétence, sa cohésion et la réciprocité dont elle fait preuve dans sa relation avec les participantes.Discussion : Les résultats soutiennent que les femmes enceintes ayant vécu une forme de traumatisme interpersonnel perçoivent que le programme STEP répond à leurs besoins et que ses composantes favorisent une expérience plus profonde et sereine de leur grossesse ainsi qu’une meilleure disposition à accueillir leur enfant.

The prebiotic effect of the agave plant polysaccharides (agavin) was evaluated to improve enteritis caused by soybean meal (SBM) in juveniles of Totoaba macdonaldi (60.8 ± 2.3 g). Four isoproteic and isolipidic diets were formulated: an FM-based formulation as reference (RD), a blend of FM and PBM (FM-PBM; 1:2 as previously shown better performance than FM), the blend combined with 24% SBM (SBM-B) and, lastly, the latter combination with 2% agavin (SBM-B + A). After 44 days, the SBM-B + A treatment resulted in a definite enteritis improvement, besides a significantly higher final growth (207.1 ± 3.8 vs. 195 ± 3.4) compared to the rest of the treatments. According to the microbiota intestine structure, it can be revealed that agavin resulted in enrichment of the Sinorhizobium genera, characterized by nitrogen fixation. However, at a species level, Clostridium botyricum was the more prominent in PBM-based feeds, known as beneficial for the suppression of inflammatory response. In contrast, Enterococcus cecorum was identified in the gut of fish fed SBM-based feeds, intensified in agavin-supplemented feeds. Higher expression of hsp70 and aqp8 was registered in FM-PBM. It is concluded that agavin provides a clear benefit when added to diets. The implications of FM substitution are discussed.

Abstract Fluorescence fluctuation spectroscopy (FFS) can be used to measure the aggregation of fluorescently labeled molecules and is typically performed using time series data. Spatial intensity distribution analysis (SpIDA) and fluorescence moment image analysis (FMIA) are established tools for measuring molecular brightnesses from single-color images collected with laser scanning microscopes. We have extended these tools for analysis of two-color images to resolve heteromeric interactions between molecules labeled with spectrally distinct chromophores. We call these new methods two-color SpIDA (2c-SpIDA) and two-color spatial cumulant analysis (2c-SpCA). To implement these techniques on a hyperspectral imaging system, we developed a spectral shift filtering (SSF) technique to remove artifacts due to intrinsic crosstalk between detector bins. We determined that 2c-SpCA provides better resolution from samples containing multiple fluorescent species, hence this technique was carried forward to study images of living cells. We used fluorescent heterodimers labeled with EGFP and mApple to quantify the effects of resonance energy transfer and incomplete maturation of mApple on brightness measurements. We show that 2c-SpCA can detect the interaction between two components of trimeric G-protein complexes. Thus 2c-SpCA presents a robust and computationally expedient means of measuring heteromeric interactions in cellular environments.Statement of SignificanceFluorescence fluctuation spectroscopy (FFS) techniques determine biophysical parameters from samples containing fluorescently labeled biomolecules by considering the statistical nature of fluorescent signals measured with photodetectors. The present study introduces two-color spatial cumulant analysis (2c-SpCA) to the canon of FFS techniques. 2c-SpCA analyzes pixel-value data of two-color images collected with laser scanning fluorescence microscopes. We show that 2c-SpCA can determine several biophysical parameters in living cells including Forster resonance energy transfer efficiency, the dark state fraction of fluorescent proteins, and heteromerization between distinctly labeled proteins. In comparison to existing techniques, 2c-SpCA requires very few image frames for analysis, minimal computations, and can be applied to images of fixed tissue samples.