Live-cell imaging of circular and long non-coding RNAs associated to FUS pathological aggregates by Pepper fluorescent RNA.

Lately, important advancements in visualizing RNAs in fixed and live cells have been achieved. While mRNA imaging techniques are well-established, the development of effective methods for studying non-coding RNAs (ncRNAs) in living cells are still challenging but necessary, as they show a variety of functions and intracellular localizations, including participation in highly dynamic processes like phase-transition, which is still poorly studied in vivo. Addressing this issue, we tagged two exemplary ncRNAs with the fluorescent RNA (fRNA) Pepper.

ALS-associated FUS mutation reshapes the RNA and protein composition of stress granules.

Stress granules (SG) are part of a cellular protection mechanism where untranslated messenger RNAs and RNA-binding proteins are stored upon conditions of cellular stress. Compositional variations due to qualitative or quantitative protein changes can disrupt their functionality and alter their structure. This is the case of different forms of amyotrophic lateral sclerosis (ALS) where a causative link has been proposed between the cytoplasmic de-localization of mutant proteins, such as FUS (Fused in Sarcoma), and the formation of cytotoxic inclusions.

Integrating system biology and intratumor gene therapy by trans-complementing the appropriate co-stimulatory molecule as payload in oncolytic herpes virus.

Systems biology has been applied at the multi-scale level within the cancer field, improving cancer prevention, diagnosis and enabling precision medicine approaches. While systems biology can expand the knowledge and skills for oncological treatment, it also represents a challenging expedition due to cancer complexity, heterogeneity and diversity not only between different cancer indications, but also in its evolution process through space and time. Here, by characterizing the transcriptional perturbations of the tumor microenvironment induced by oncolytic, we aimed to rationally design a novel armed oncolytic herpes virus.

A Curriculum on Digital Psychiatry for a US-Based Psychiatry Residency Training Program: Pilot Implementation Study.

Background: Digital psychiatry, defined as the application of health technologies to the prevention, assessment, and treatment of mental health illnesses, is a growing field. Interest in the clinical use of these technologies continues to grow. However, psychiatric trainees receive limited or no formal education on the topic.

Extracellular vesicles as human therapeutics: A scoping review of the literature.

Extracellular vesicles (EVs) are released by all cells and contribute to cell-to-cell communication. The capacity of EVs to target specific cells and to efficiently deliver a composite profile of functional molecules have led researchers around the world to hypothesize their potential as therapeutics. While studies of EV treatment in animal models are numerous, their actual clinical benefit in humans has more slowly started to be tested.

In Situ Hybridization of circRNAs in Cells and Tissues through BaseScope™ Strategy.

Imaging-based approaches are powerful strategies that nowadays have been largely used to gain insight into the function of different types of macromolecules. As for RNA, it is becoming clear how important is its intracellular localization for the control of proper cell differentiation and development and how its perturbation can be linked to several pathological states. This aspect is even more important if one thinks of highly polarized cells such as neurons.

Single-photon microscopy to study biomolecular condensates.

Biomolecular condensates serve as membrane-less compartments within cells, concentrating proteins and nucleic acids to facilitate precise spatial and temporal orchestration of various biological processes. The diversity of these processes and the substantial variability in condensate characteristics present a formidable challenge for quantifying their molecular dynamics, surpassing the capabilities of conventional microscopy. Here, we show that our single-photon microscope provides a comprehensive live-cell spectroscopy and imaging framework for investigating biomolecular condensation.

The long noncoding RNA nHOTAIRM1 is necessary for differentiation and activity of iPSC-derived spinal motor neurons.

The mammalian nervous system is made up of an extraordinary array of diverse cells that form intricate functional connections. The programs underlying cell lineage specification, identity and function of the neuronal subtypes are managed by regulatory proteins and RNAs, which coordinate the succession of steps in a stereotyped temporal order. In the central nervous system (CNS), motor neurons (MNs) are responsible for controlling essential functions such as movement, breathing, and swallowing by integrating signal transmission from the cortex, brainstem, and spinal cord (SC) towards peripheral muscles.

Proteomic profiling of centrosomes across multiple mammalian cell and tissue types by an affinity capture method.

Centrosomes are the major microtubule-organizing centers in animals and play fundamental roles in many cellular processes. Understanding how their composition varies across diverse cell types and how it is altered in disease are major unresolved questions, yet currently available centrosome isolation protocols are cumbersome and time-consuming, and they lack scalability. Here, we report the development of centrosome affinity capture (CAPture)-mass spectrometry (MS), a powerful one-step purification method to obtain high-resolution centrosome proteomes from mammalian cells.

The Impact of Covid-19 Pandemic on Mental Health Services: A Comparison Between First Psychiatric Consultations Before and After the Pandemic.

Objective: A high rate of onset or exacerbation of several mental disorders has been observed during the COVID-19 pandemic. However, the risk contributing to mental distress during the pandemic remains unclear. The study aims to evaluate the risk of the onset of mental disorders by comparing the number of requests for the first psychiatric consultation before and after the COVID-19 pandemic at the psychiatric outpatient services of Varese, a small town in Northern Italy.

Balancing the Roles of Clinicians and Police in Separating Firearms from People in a Dangerous Mental Health Crisis: Legal Rules, Policy Tools, and Ethical Considerations.

In COVID's immediate wake, the 2020 death toll from a different enemy of the public's health - gun violence - ticked up by 15 percent in the United States from the previous year. Meanwhile, the U.S.

Microtubule detyrosination drives symmetry breaking to polarize cells for directed cell migration.

To initiate directed movement, cells must become polarized, establishing a protrusive leading edge and a contractile trailing edge. This symmetry-breaking process involves reorganization of cytoskeleton and asymmetric distribution of regulatory molecules. However, what triggers and maintains this asymmetry during cell migration remains largely elusive.

A KO mouse model for the lncRNA Lhx1os produces motor neuron alterations and locomotor impairment.

Here, we describe a conserved motor neuron-specific long non-coding RNA, Lhx1os, whose knockout in mice produces motor impairment and postnatal reduction of mature motor neurons (MNs). The ER stress-response pathway result specifically altered with the downregulation of factors involved in the unfolded protein response (UPR). Lhx1os was found to bind the ER-associated PDIA3 disulfide isomerase and to affect the expression of the same set of genes controlled by this protein, indicating that the two factors act in conjunction to modulate the UPR.

SUN2 regulates mitotic duration in response to extracellular matrix rigidity.

How cells adjust their growth to the spatial and mechanical constraints of their surrounding environment is central to many aspects of biology. Here, we examined how extracellular matrix (ECM) rigidity affects cell division. We found that cells divide more rapidly when cultured on rigid substrates.

Strain Relaxation of InAs Quantum Dots on Misoriented InAlAs(111) Metamorphic Substrates.

We investigate in detail the role of strain relaxation and capping overgrowth in the self-assembly of InAs quantum dots by droplet epitaxy. InAs quantum dots were realized on an In0.6Al0.

Optineurin links Hace1-dependent Rac ubiquitylation to integrin-mediated mechanotransduction to control bacterial invasion and cell division.

Extracellular matrix (ECM) elasticity is perceived by cells via focal adhesion structures, which transduce mechanical cues into chemical signalling to conform cell behavior. Although the contribution of ECM compliance to the control of cell migration or division is extensively studied, little is reported regarding infectious processes. We study this phenomenon with the extraintestinal Escherichia coli pathogen UTI89.

Socially Distanced Emergencies: Clinicians' Experience with Tele-behavioral Health Safety Planning.

Psychiatry has experienced a rapid expansion in providing behavioral health services using virtual means; however, little is known regarding clinicians' experience in managing patient emergencies during virtual encounters. We present survey data from a large academic psychiatry department designed to better understand safety planning while delivering ambulatory tele-behavioral health services during the COVID-19 pandemic. Clinical faculty in the department were sent an anonymous electronic survey developed and distributed using the Qualtrics™ software.

Band-Gap Tuning Induced by Germanium Introduction in Solution-Processed Kesterite Thin Films.

In the last few decades, the attention of scientific community has been driven toward the research on renewable energies. In particular, the photovoltaic (PV) thin-film technology has been widely explored to provide suitable candidates as top cells for tandem architectures, with the purpose of enhancing current PV efficiencies. One of the most studied absorbers, made of earth-abundant elements, is kesterite CuZnSnS (CZTS), showing a high absorption coefficient and a band gap around 1.

Circ-Hdgfrp3 shuttles along neurites and is trapped in aggregates formed by ALS-associated mutant FUS.

CircRNAs belong to a family of RNA molecules which are conserved in evolution, have tissue-specific expression, and are abundant in neuronal cells. Here, we define several features of circ-Hdgfrp3 and describe interesting alterations occurring in motor neurons (MNs) carrying ALS-associated FUS mutations. Through a highly sensitive approach we describe that circ-Hdgfrp3 traffics along neurites, while upon oxidative stress it is retained in the perinuclear region.

Videoconferencing of Involuntary Commitment Hearings in the COVID Era.

Involuntary commitment hearings have been conducted utilizing videoconferencing technology for several years. There is limited information available in the published psychiatric literature pertaining to the use of this technology for commitment proceedings. The University of North Carolina Hospitals adopted a remote videoconferencing (tele-hearing) format for its civil commitment proceedings in response to the COVID-19 pandemic, and this provided us with the opportunity to investigate the use of such an arrangement.

Navigating Care From Afar: Ethical Considerations for Police Welfare Checks.

The clinical practice of contacting law enforcement to perform safety welfare checks for persons who have missed psychiatry appointments is commonly regarded as benign. However, in nonemergency situations, these interventions may carry greater risk than is usually assumed, especially if the person whose welfare is being checked belongs to a racial-ethnic minority group, and there is little evidence on the safety and effectiveness of these interventions. This Open Forum presents a case analysis to examine the central ethical considerations for these situations.