Constitutive Promoter Occupancy by the MBF-1 Activator and Chromatin Modification of the Developmental Regulated Sea Urchin alpha-H2A Histone Gene

The tandemly repeated sea urchin α-histone genes are developmentally regulated. These genes are transcribed up to the early blastula stage and permanently silenced as the embryos approach gastrulation. As previously described, expression of the α-H2A gene depends on the binding of the MBF-1 activator to the 5′ enhancer, while down-regulation relies on the functional interaction between the 3′ sns 5 insulator and the GA repeats located upstream of the enhancer. As persistent MBF-1 binding and enhancer activity are detected in gastrula embryos, we have studied the molecular mechanisms that prevent the bound MBF-1 from trans-activating the H2A promoter at this stage of development. Here we used chromatin immunoprecipitation to demonstrate that MBF-1 occupies its site regardless of the transcriptional state of the H2A gene. In addition, we have mapped two nucleosomes specifically positioned on the enhancer and promoter regions of the repressed H2A gene. Interestingly, insertion of a 26 bp oligonucleotide between the enhancer and the TATA box, led to upregulation of the H2A gene at gastrula stage, possibly by changing the position of the TATA nucleosome. Finally, we found association of histone de-acetylase and de-acetylation and methylation of K9 of histone H3 on the promoter and insulator of the repressed H2A chromatin. These data argue for a role of a defined positioned nucleosome in the promoter and histone tail post-translational modifications, in the 3′ insulator and 5′ regulatory regions, in the repression of the α-H2A gene despite the presence of the MBF-1 activator bound to the enhance

Down regulation of early sea urchin histone H2A gene relies on cis regulative sequences located in the 5’ and 3’ regions and including the enhancer blocker sns

The tandem repeated sea urchin α-histone genes are developmentally regulated by gene-specific promoter elements. Coordinate transcription of the five genes begins after meiotic maturation of the oocyte, continues through cleavage, and reaches its maximum at morula stage, after which these genes are shut off and maintained in a silenced state for the life cycle of the animal. Although cis regulative sequences affecting the timing and the level of expression of these genes have been characterized, much less is known about the mechanism of their repression. Here we report the results of a functional analysis that allowed the identification of the sequence elements needed for the silencing of the α-H2A gene at gastrula stage. We found that important negative regulative sequences are located in the 462 bp sns 5 fragment located in the 3′ region. Remarkably, sns 5 contains the sns enhancer blocking element and the most 3′ H2A codons. In addition, we made the striking observation that inhibition of the anti-enhancer activity of sns, by titration of the binding proteins in microinjected embryos, also affected the capability of sns 5 to down-regulate transgene expression at gastrula stage. A further sequence element essential for repression of the H2A gene was identified upstream of the enhancer, in the 5′ region, and contains four GAGA repeats. Altogether these findings suggest that down-regulation of the α-H2A gene occurs by the functional interaction of the 5′ and 3′ cis sequence elements. These results demonstrate the involvement of a genomic insulator in the silencing of gene expression

Transcriptomic Profile Reveals Deregulation of Hearing-Loss Related Genes in Vestibular Schwannoma Cells Following Electromagnetic Field Exposure

From MDPI via Jisc Publications RouterHistory: accepted 2021-07-18, pub-electronic 2021-07-20Publication status: PublishedFunder: Capita Foundation; Grant(s): grant 2019 to V.M.Funder: Università degli Studi di Milano; Grant(s): grant PSR_VMAGN_2019 to V.MFunder: MIUR Italian Ministry of Research; Grant(s): Progetto di EccellenzaHearing loss (HL) is the most common sensory disorder in the world population. One common cause of HL is the presence of vestibular schwannoma (VS), a benign tumor of the VIII cranial nerve, arising from Schwann cell (SC) transformation. In the last decade, the increasing incidence of VS has been correlated to electromagnetic field (EMF) exposure, which might be considered a pathogenic cause of VS development and HL. Here, we explore the molecular mechanisms underlying the biologic changes of human SCs and/or their oncogenic transformation following EMF exposure. Through NGS technology and RNA-Seq transcriptomic analysis, we investigated the genomic profile and the differential display of HL-related genes after chronic EMF. We found that chronic EMF exposure modified the cell proliferation, in parallel with intracellular signaling and metabolic pathways changes, mostly related to translation and mitochondrial activities. Importantly, the expression of HL-related genes such as NEFL, TPRN, OTOGL, GJB2, and REST appeared to be deregulated in chronic EMF exposure. In conclusion, we suggest that, at a preclinical stage, EMF exposure might promote the transformation of VS cells and contribute to HL

Sensory substitution increases robotic surgical performance and sets the ground for a mediating role of the sense of embodiment: a systematic review

Sensory Substitution (SS) allows the elaboration of information via non preferential sensory modalities. This phenomenon occurs in robotic-assisted surgery (RAS), in which haptic feedback is lacking. It has been suggested that SS could sustain surgeons' proficiency by means of visual clues for inferring tactile information, that also promotes the feeling of haptic phantom sensations. A critical role in reaching a good performance in procedural tasks is also sustained by the Sense of Embodiment (SE), that is, the capacity to integrate objects into subjective bodily self representation. As SE is enhanced by haptic sensations, we hypothesize a role of SS in promoting SE in RAS. Accordingly, the goal of this systematic review is to summarize the evidence pertaining the study of SS in RAS in order to highlight the impact on the performance, and to identify a mediating role of the SE in increasing dexterity in RAS.Eight studies selected from the MEDLINE and Scopus (R) databases met inclusion criteria for a qualitative synthesis. Results indicated that haptic to other modalities SS enhanced force consistency and accuracy, and decreased surgeon fatigue. Expert surgeons, as compared to novices, showed a better natural SS processing, testified by a proficient performance with and without SS aids. No studies investigated the mediating role of SE. These findings indicate that SS is subjected to learning and memory processes that help surgeons to rapidly derive haptic-correlates from visual clues, which are highly required for a good performance. Also, the higher ability of doing SS and the associated perception of haptic sensations might increase multisensory integration, which might sustain performance

Hearing loss and vestibular schwannoma: new insights into Schwann cells implication

Abstract Hearing loss (HL) is the most common and heterogeneous disorder of the sensory system, with a large morbidity in the worldwide population. Among cells of the acoustic nerve (VIII cranial nerve), in the cochlea are present the hair cells, the spiral ganglion neurons, the glia-like supporting cells, and the Schwann cells (SCs), which alterations have been considered cause of HL. Notably, a benign SC-derived tumor of the acoustic nerve, named vestibular schwannoma (VS), has been indicated as cause of HL. Importantly, SCs are the main glial cells ensheathing axons and forming myelin in the peripheral nerves. Following an injury, the SCs reprogram, expressing some stemness features. Despite the mechanisms and factors controlling their biological processes (i.e., proliferation, migration, differentiation, and myelination) have been largely unveiled, their role in VS and HL was poorly investigated. In this review, we enlighten some of the mechanisms at the base of SCs transformation, VS development, and progression, likely leading to HL, and we pose great attention on the environmental factors that, in principle, could contribute to HL onset or progression. Combining the biomolecular bench-side approach to the clinical bedside practice may be helpful for the diagnosis, prediction, and therapeutic approach in otology

Sense of Agency and Skills Learning in Virtual-Mediated Environment: A Systematic Review

: Agency is central to remote actions, and it may enhance skills learning due to a partial overlap between brain structures and networks, the promotion of confidence towards a telemanipulator, and the feeling of congruence of the motor choice to the motor plan. We systematically reviewed studies aiming to verify the role of agency in improving learning. Fifteen studies were selected from MEDLINE and Scopus®. When a mismatch is introduced between observed and performed actions, the decrease in agency and learning is proportional to the intensity of the mismatch, which is due to greater interference with the motor programming. Thanks to multisensory integration, agency and learning benefit both from sensory and performance feedback and from the timing of feedback based on control at the goal level or the perceptual-motor level. This work constitutes a bedrock for professional teleoperation settings (e.g., robotic surgery), with particular reference to the role of agency in performing complex tasks with remote control