The nuclear isoforms of the Fragile X mental retardation RNA-binding protein associate with genomic DNA bridges.

The fragile-X mental retardation protein (FMRP) is a canonical RNA-binding protein whose absence in humans leads to the development of the fragile-X syndrome, characterized by multiple phenotypes including neurodevelopmental disorders, intellectual disability, autism, and macroorchidism. The primary transcripts of the FMR1 gene undergo extensive alternative splicing processes, and multiple protein isoforms are produced. The predominantly cytoplasmic isoforms are translational regulators, while the roles of the nuclear ones have been neglected. In this study, we discovered that nuclear FMRP isoforms specifically associate with DNA bridges, aberrant genomic structures that form during mitosis and whose accumulation can drive genome instability by inducing DNA damage. Further localization studies showed that a subset of FMRP-positive bridges contain proteins that have been shown to associate with specific DNA bridges known as ultrafine DNA bridges (UFBs) and surprisingly are RNA positive. Significantly, the depletion of nuclear FMRP isoforms promotes the accumulation of DNA bridges, correlating with the accumulation of DNA damages and cell death, unveiling an important function of these neglected isoforms.

Intraluminal immunoreactive caseinomacropeptide after milk protein ingestion in humans.

Caseinomacropeptide (CMP)is a 64 amino acids peptide which is the first product released after kappa-casein hydrolysis. The present work investigates the kinetics delivery of CMP in human jejunal lumen during the digestion of intrinsically [15N]-labelled casein, whey protein, yoghurt and pea flour meal. Effluents were collected through a nasointestinal tube and analysed for the enrichment in [15N] to evaluate the dietary nitrogen fraction. Detection and quantification of CMP was performed by an inhibition Elisa procedure. No trace of CMP was detected in the ileum of volunteers after the ingestion of the casein meal. The results showed that CMP appears in the jejunal effluents within the first 20 min after meal ingestion at a level varying from meal to meal. During digestion of whey protein, CMP appeared rapidly as a single peak and in high amounts, whereas it is discharged slowly in moderate proportions with the casein meal. These results demonstrate that CMP is emptied from the stomach in significant amounts during milk products digestion and support the hypothesis that food-born peptides could exert a physiological function. Moreover, in the present study a relation could be assumed between the amount of CMP in the meal and the stimulation of luminal endogenous nitrogen secretion. However, the specific physiological activity of CMP in humans, particularly on the digestion process, requires further studies.

Alcohol consumption by young actively growing rats: a study of cortical bone histomorphometry and mechanical properties.

Alcohol consumption by young actively growing rats has been previously demonstrated to decrease cortical and cancellous bone density, to reduce trabecular bone volume, and to inhibit bone growth at the epiphyseal growth plate. This study addresses the action of alcohol on cortical bone growth using histomorphometric techniques and on mechanical properties by three-point bending. Four-week-old, female Sprague-Dawley rats were divided into three groups. Alcohol-treated animals were fed a modified Lieber-DeCarli diet ad libitum containing 35% ethanol-derived calories, whereas the pair-fed animals (weight-matched to ethanol rats) received an isocaloric liquid diet in which maltose-dextrin-substituted calories were supplied by ethanol. Chow animals were fed a standard rat chow ad libitum. Femora were removed for analysis after 2, 4, 6, or 8 weeks on the diets. Cortical bone area, bone formation rates, and mineral apposition rates were reduced in the alcohol-fed animals. Bone stiffness, strength, and energy absorbed to fracture were significantly lower in the alcohol-fed animals. This distinctive alcohol effect was revealed to be caused by lower quality bone tissue as reflected by lower elastic moduli and yield strengths.