Search

Genetic syndromes have been studied by extensive research allowing a better definition of their clinical manifestations, natural history, and etiopathogenetic mechanisms. Nevertheless, some relevant, but still unexplored aspects of these multisystemic conditions need to be clarified. One of these aspects is the characterization of the vocal production, especially in some genetic syndromes in which the distinctive voice is the hallmark of the syndrome (e.g., Cri du chat syndrome, CdCS). The aim of this study is to provide a detailed description of phonotype of patients affected by CdCS. We prospectively recorded and analysed acoustical features of three corner vowels [a], [i], and [u] and number listing from 1 to 10 of 29 patients with molecularly confirmed CdCS (age range 4-21 years; mean 11 ± 6; median 10 years). For perceptual analysis, the GIRBAS scale was completed. The acoustical analysis was performed through BioVoice software. When stratified by age and gender, in the older men subgroup the grade, roughness, and asthenia mean values are the highest for each vowel, when compared with values of the same parameters obtained in the other subgroups. Statistical analysis highlighted 26 significant differences: 38% (10) concern the sustained phonation of /a/, 27% (7) are related to /i/ whereas 19% (5) to /u/. Ratio1, Ratio2, VSA, and FCR were also significant. Conclusion: The voice production not only conveys linguistic and paralinguistic information but also can give information regarding the speaker's biological and clinical characteristics., Competing Interests: Declarations. Ethics approval: This study was performed in line with the principles of the Declaration of Helsinki and approved by the Research Ethical Committee of the Catholic University of Sacred Heart, Rome. Consent to participate: Informed consent was obtained from parents of all participants included in the study. Competing interests: The authors declare no competing interests., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Nuclear factors rapidly scan the genome for their targets, but the role of nuclear organization in such search is uncharted. Here we analyzed how multiple factors explore chromatin, combining live-cell single-molecule tracking with multifocal structured illumination of DNA density. We find that factors displaying higher bound fractions sample DNA-dense regions more exhaustively. Focusing on the tumor-suppressor p53, we demonstrate that it searches for targets by alternating between rapid diffusion in the interchromatin compartment and compact sampling of chromatin dense regions. Efficient targeting requires balanced interactions with chromatin: fusing p53 with an exogenous intrinsically disordered region potentiates p53-mediated target gene activation at low concentrations, but leads to condensates at higher levels, derailing its search and downregulating transcription. Our findings highlight the role of disordered regions on factors search and showcase a powerful method to generate traffic maps of the eukaryotic nucleus to dissect how its organization guides nuclear factors action., (© 2023. Springer Nature Limited.)

In eukaryotes, transcription is a discontinuous process with mRNA being generated in bursts, after the binding of transcription factors (TFs) to regulatory elements on the genome. Live-cell single-molecule microscopy has highlighted that transcriptional bursting can be controlled by tuning TF/DNA binding kinetics. Yet the timescales of these two processes seem disconnected with TF/DNA interactions typically lasting orders of magnitude shorter than transcriptional bursts. To test models that could reconcile these discrepancies, reliable measurements of TF binding kinetics are needed, also accounting for the current limitations in performing these single-molecule measurements at specific regulatory elements. Here, we review the recent studies linking TF binding kinetics to transcriptional bursting and outline some current and future challenges that need to be addressed to provide a microscopic description of transcriptional regulation kinetics., Competing Interests: Conflict of interest statement Nothing declared., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Transcription factors (TFs) regulate transcription of their target genes by identifying and binding to regulatory regions of the genome among billions of potential non-specific decoy sites, a task that is often presented as a 'needle in the haystack' challenge. The TF search process is now well understood in bacteria, but its characterization in eukaryotes needs to account for the complex organization of the nuclear environment. Here we review how live-cell single molecule tracking is starting to shed light on the TF search mechanism in the eukaryotic cell and we outline the future challenges to tackle in order to understand how nuclear organization modulates the TF search process in physiological and pathological conditions., (© 2021 The Author(s).)

The "M. L. Marenzi" Centre of Infantile Otophoniatrics, in collaboration with the Department of Neonatal Pathology of the Fatebenefratelli Hospital in Milan, performed longitudinal controls of an audiological and phoniatric type in 252 children. In the present study attention is focused in particular on audiological evaluations made in a group of 71 infants aged from 6-9 months old. During audiological tests the evaluation of auditory capacity and the type of response to acoustic stimulus were taken into account. The behavioural observation of selective attention to sound is a very important index of the maturity of sensorial patterns. The retarded development of response to an acoustic stimulus may indicate future communication disorders. The type of response to acoustic stimulus obtained in 71 infants were compared with those in a further two groups of children: the first comprised 3822 children with no audiological risk, and the second 3755 children at audiological risk according to Feinmeser and Telly's expanded list. This comparison highlighted a significant persistence of an archaic-type response in the group of infants from the Department of Neonatal Pathology. It is therefore essential that these children are examined further from a phoniatric point of view.