The long noncoding RNA RNCR2 directs mouse retinal cell specification

<p>Abstract</p> <p>Background</p> <p>Recent work has identified that many long mRNA-like noncoding RNAs (lncRNAs) are expressed in the developing nervous system. Despite their abundance, the function of these ncRNAs has remained largely unexplored. We have investigated the highly abundant lncRNA RNCR2 in regulation of mouse retinal cell differentiation.</p> <p>Results</p> <p>We find that the RNCR2 is selectively expressed in a subset of both mitotic progenitors and postmitotic retinal precursor cells. ShRNA-mediated knockdown of RNCR2 results in an increase of both amacrine cells and Müller glia, indicating a role for this lncRNA in regulating retinal cell fate specification. We further report that RNCR2 RNA, which is normally nuclear-retained, can be exported from the nucleus when fused to an IRES-GFP sequence. Overexpression of RNCR2-IRES-GFP phenocopies the effects of shRNA-mediated knockdown of RNCR2, implying that forced mislocalization of RNCR2 induces a dominant-negative phenotype. Finally, we use the IRES-GFP fusion approach to identify specific domains of RNCR2 that are required for repressing both amacrine and Müller glial differentiation.</p> <p>Conclusion</p> <p>These data demonstrate that the lncRNA RNCR2 plays a critical role in regulating mammalian retinal cell fate specification. Furthermore, we present a novel approach for generating dominant-negative constructs of lncRNAs, which may be generally useful in the functional analysis of this class of molecules.</p

Interprofessional Communication Team for Caregivers of Patients Hospitalized in the COVID-19 Wards: Results From an Italian Experience

Background: During the COVID-19 pandemic, emergency restrictions did not allow clinician family meetings and relatives' visits. In Molinette Hospital, a new communication model between healthcare providers and families of COVID-19 affected patients was developed by a team of physicians and psychologists. The study's aims were to investigate caregivers' distress and to analyse their satisfaction with the communications provided. Methods: A cross-sectional study was conducted among caregivers of patients of Molinette Hospital COVID wards. Between April and June 2020, all caregivers were contacted 2 weeks after the patient's discharge/death to assess their satisfaction with the communications received through an online survey. Results: A total of 155 caregivers completed the survey. Caregivers' distress level was found to be higher in women than men (p = 0.048) and in caregivers whose relative died compared to the caregivers whose relative was discharged (p < 0.001). More than 85% of caregivers defined communication “excellent”/“very good”; being male was associated with higher satisfaction levels than women (β = −0.165, p = 0.046). Besides daily communication, 63 caregivers (40.6%) received additional support from a psychologist of the team. Conclusions: To our knowledge, this is the first study presenting, in an emergency, a new model of communication provided by a team of physicians and psychologists, and analyzing satisfaction with it. This model was highly appreciated by caregivers and it limited the discomfort caused by the restrictions on relatives' visits. It would be interesting to further evaluate the possibility of extending a communication model that includes doctors and psychologists in routine clinical practice

NETME: on-the-fly knowledge network construction from biomedical literature

Background: The rapidly increasing biological literature is a key resource to automatically extract and gain knowledge concerning biological elements and their relations. Knowledge Networks are helpful tools in the context of biological knowledge discovery and modeling. Results: We introduce a novel system called NETME, which, starting from a set of full-texts obtained from PubMed, through an easy-to-use web interface, interactively extracts biological elements from ontological databases and then synthesizes a network inferring relations among such elements. The results clearly show that our tool is capable of inferring comprehensive and reliable biological networks

Simulation of the Out-of-Plane Behaviour of URM Walls by Means of Discrete Macro-Element Method

The seismic response of masonry structures without box-type behaviour is given by a complex interaction between in-plane and out-of-plane behaviours. Previous earthquakes demonstrated that out-of-plane failure mechanisms represent the main cause of structural collapses of UnReinforced Masonry (URM) and historical structures. Previous experimental and analytical studies, investigating the out-of-plane behaviour of URM structures, mostly considered the effects of one-way bending moment. In this regard, recent experimental campaigns and numerical simulations have been conducted in order to investigate the out-ofplane behaviour of masonry walls subjected to two-way bending. These investigations have demonstrated the complexity of this mechanism and stressed the need for accurate numerical tools capable of providing reliable predictions in terms of ultimate strength and failure mechanisms. This paper focuses on the assessment of the dynamic behaviour of a U-shape URM prototype, subjected to shaking table tests, by means of a simplified computational strategy denoted as Discrete Macro-Element Method (DMEM). In this investigation, a comparison between experimental and numerical results was conducted in order to validate the capabilities of the proposed modelling approach. Subsequently, a parametric analysis was carried aiming at determining the influence that masonry mechanical properties, and additional model parameters, have on the out-of-plane nonlinear dynamic response of URM masonry structures

Numerical Modelling of Masonry Arches Strengthened with SFRM

The adoption of effective strengthening techniques of historical constructions is one of the most widely debated aspects in structural engineering. Within this topic, the application of steel fiber reinforced mortar (SFRM) has been recently proposed as a low invasive and effective way to obtain a considerable structural benefit in the safety of existing masonry structure. To this purpose, in this paper the experimental results obtained on a circular masonry arches are presented. The considered specimens, subjected to a vertical increasing static load, is tested in the unstrengthened and strengthened configurations, and is part of a wider experimental campaign. After presenting and discussing the experimental results, they are compared with those relative to numerical simulations conducted by means of a discrete macro-element (DME) strategy, based on a simple mechanical scheme, able to model the nonlinear behavior of masonry structures with a limited computational effort. Such an approach is here extended to model the SFRM strengthening technique accounting for the main failure mechanisms associated to the combined presence existing masonry and the additional strengthening layer applied at the intrados of the arch. Numerical and experimental results demonstrate the efficacy of the proposed retrofitting strategy both in terms of bearing capacity and increase of ductility

Status and perspectives of the 4 pi charged particles multidetector CHIMERA

The construction of the multidetector CHIMERA designed to detect and identify charged particles and fragments emitted in heavy ion reactions at intermediate energy is in progress and is coming to an end. The construction of this multidetector is presented in this paper as well as the status of the project

Dynamic Chromatin Localization of Sirt6 Shapes Stress- and Aging-Related Transcriptional Networks

The sirtuin Sirt6 is a NAD-dependent histone deacetylase that is implicated in gene regulation and lifespan control. Sirt6 can interact with the stress-responsive transcription factor NF-κB and regulate some NF-κB target genes, but the full scope of Sirt6 target genes as well as dynamics of Sirt6 occupancy on chromatin are not known. Here we map Sirt6 occupancy on mouse promoters genome-wide and show that Sirt6 occupancy is highly dynamic in response to TNF-α. More than half of Sirt6 target genes are only revealed upon stress-signaling. The majority of genes bound by NF-κB subunit RelA recruit Sirt6, and dynamic Sirt6 relocalization is largely driven in a RelA-dependent manner. Integrative analysis with global gene expression patterns in wild-type, Sirt6−/−, and double Sirt6−/− RelA−/− cells reveals the epistatic relationships between Sirt6 and RelA in shaping diverse temporal patterns of gene expression. Genes under the direct joint control of Sirt6 and RelA include several with prominent roles in cell senescence and organismal aging. These data suggest dynamic chromatin relocalization of Sirt6 as a key output of NF-κB signaling in stress response and aging

Non-Coding RNAs in Retinal Development

Retinal development is dependent on an accurately functioning network of transcriptional and translational regulators. Among the diverse classes of molecules involved, non-coding RNAs (ncRNAs) play a significant role. Members of this family are present in the cell as transcripts, but are not translated into proteins. MicroRNAs (miRNAs) are small ncRNAs that act as post-transcriptional regulators. During the last decade, they have been implicated in a variety of biological processes, including the development of the nervous system. On the other hand, long-ncRNAs (lncRNAs) represent a different class of ncRNAs that act mainly through processes involving chromatin remodeling and epigenetic mechanisms. The visual system is a prominent model to investigate the molecular mechanisms underlying neurogenesis or circuit formation and function, including the differentiation of retinal progenitor cells to generate the seven principal cell classes in the retina, pathfinding decisions of retinal ganglion cell axons in order to establish the correct connectivity from the eye to the brain proper, and activity-dependent mechanisms for the functionality of visual circuits. Recent findings have associated ncRNAs in several of these processes and uncovered a new level of complexity for the existing regulatory mechanisms. This review summarizes and highlights the impact of ncRNAs during the development of the vertebrate visual system, with a specific focus on the role of miRNAs and a synopsis regarding recent findings on lncRNAs in the retina