Proximity labeling reveals dynamic changes in the SQSTM1 protein network.

Sequestosome1 (SQSTM1) is an autophagy receptor that mediates the degradation of intracellular cargo, including protein aggregates, through multiple protein interactions. These interactions form the SQSTM1 protein network, and these interactions are mediated by SQSTM1 functional interaction domains, which include LIR, PB1, UBA, and KIR. Technological advances in cell biology continue to expand our knowledge of the SQSTM1 protein network and the relationship between the actions of the SQSTM1 protein network in cellular physiology and disease states.

Attitudes of Forensic Fellowship Psychiatry Directors towards an Applicant Match.

Forensic psychiatry fellowship programs recruit applicants through a nonstandardized process that differs by program. Although there are deadlines, informal guidance, and more recent communication guidelines, perceived differences in recruitment practices persist between geographic regions, small and large programs, and newer and more well-established programs. In the wake of a survey of fellowship applicants that found mixed opinions surrounding the application process, U.

A Systematic Review of Multisystemic Therapy in Adolescent Sex Offenders.

Multisystemic therapy (MST) is an intense, family-focused, community-based treatment designed for youth with criminal behaviors. Literature on its usefulness among juvenile sexual offenders (JSOs) remains limited. We conducted a systematic review of published studies assessing effectiveness of MST among JSOs.

Proximity labeling reveals dynamic changes in the SQSTM1 protein network.

Sequestosome1 (SQSTM1) is an autophagy receptor that mediates degradation of intracellular cargo, including protein aggregates, through multiple protein interactions. These interactions form the SQSTM1 protein network, and these interactions are mediated by SQSTM1 functional interaction domains, which include LIR, PB1, UBA and KIR. Technological advances in cell biology continue to expand our knowledge of the SQSTM1 protein network and of the relationship of the actions of the SQSTM1 protein network in cellular physiology and disease states.

Jail-Based Competency Restoration Services in the United States: The Need, the Controversy, the Impact of COVID-19, and Implications for Future Treatment Delivery.

Jail-based competency restoration largely emerged as a method to address the backlog at forensic hospitals around the United States, as the number of justice-involved persons in need of restoration outgrew available beds. Jail-based competency restoration units (JBCRUs) appear to be highly effective and cost-saving. However, after the COVID-19 outbreak, services at some JBCRUs were stalled, as providers were forced to either quickly initiate or ramp up technology use to maintain services.

Interaction of tau with HNRNPA2B1 and N-methyladenosine RNA mediates the progression of tauopathy.

The microtubule-associated protein tau oligomerizes, but the actions of oligomeric tau (oTau) are unknown. We have used Cry2-based optogenetics to induce tau oligomers (oTau-c). Optical induction of oTau-c elicits tau phosphorylation, aggregation, and a translational stress response that includes stress granules and reduced protein synthesis.

TIA1 potentiates tau phase separation and promotes generation of toxic oligomeric tau.

Tau protein plays an important role in the biology of stress granules and in the stress response of neurons, but the nature of these biochemical interactions is not known. Here we show that the interaction of tau with RNA and the RNA binding protein TIA1 is sufficient to drive phase separation of tau at physiological concentrations, without the requirement for artificial crowding agents such as polyethylene glycol (PEG). We further show that phase separation of tau in the presence of RNA and TIA1 generates abundant tau oligomers.

Protein Interaction Network Biology in Neuroscience.

Mapping the intricate networks of cellular proteins in the human brain has the potential to address unsolved questions in molecular neuroscience, including the molecular basis of cognition, synaptic plasticity, long-term potentiation, learning, and memory. Perturbations to the protein-protein interaction networks (PPIN) present in neurons, glia, and other cell-types have been linked to multifactorial neurological disorders. Yet while knowledge of brain PPINs is steadily improving, the complexity and dynamic nature of the heterogeneous central nervous system in normal and disease contexts poses a formidable experimental challenge.

Actionable Cytopathogenic Host Responses of Human Alveolar Type 2 Cells to SARS-CoV-2.

Human transmission of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), causative pathogen of the COVID-19 pandemic, exerts a massive health and socioeconomic crisis. The virus infects alveolar epithelial type 2 cells (AT2s), leading to lung injury and impaired gas exchange, but the mechanisms driving infection and pathology are unclear. We performed a quantitative phosphoproteomic survey of induced pluripotent stem cell-derived AT2s (iAT2s) infected with SARS-CoV-2 at air-liquid interface (ALI).

Building Capacity in Health Professionals to Conduct Quality Improvement: Evaluation From a Collaborative Interorganizational Program.

Background: The Toronto Academic Health Sciences Network Health Professions Innovation Fellowship Program began in 2014 as a pilot initiative among 4 academic teaching hospitals in Toronto, Ontario. The purpose of the Program was to cultivate applied leadership, interprofessional collaboration, and quality improvement capacity among health professionals.

Purpose: This article reports on the evaluation findings from the initial year as well as an update on current program status and sustainability.

5' UTR variants in the quantitative trait gene Hnrnph1 support reduced 5' UTR usage and hnRNP H protein as a molecular mechanism underlying reduced methamphetamine sensitivity.

We previously identified a 210 kb region on chromosome 11 (50.37-50.58 Mb, mm10) containing two protein-coding genes (Hnrnph1, Rufy1) that was necessary for reduced methamphetamine-induced locomotor activity in C57BL/6J congenic mice harboring DBA/2J polymorphisms.

BraInMap Elucidates the Macromolecular Connectivity Landscape of Mammalian Brain.

Connectivity webs mediate the unique biology of the mammalian brain. Yet, while cell circuit maps are increasingly available, knowledge of their underlying molecular networks remains limited. Here, we applied multi-dimensional biochemical fractionation with mass spectrometry and machine learning to survey endogenous macromolecules across the adult mouse brain.

A Jail-Based Competency Restoration Unit as a Component of a Continuum of Restoration Services.

This study reports on restoration outcomes of a sample of pretrial defendants ( = 877, 69% male) who were found incompetent to stand trial and underwent restoration services in a large urban county. Each male defendant was initially assigned to restoration in one of four settings on a continuum of services of varying intensity (ie, outpatient, jail general population, dedicated jail-based restoration unit, or forensic hospital inpatient unit) based on the defendant's assessed clinical need. Of those who received services on the jail-based restoration unit ( = 398), 40 percent were restored to competency, 31 percent were diverted out of the criminal justice system, and 29 percent were referred for more intensive inpatient services, primarily because of refusal of medication (i.

A Mutation in That Decreases Methamphetamine-Induced Reinforcement, Reward, and Dopamine Release and Increases Synaptosomal hnRNP H and Mitochondrial Proteins.

Individual variation in the addiction liability of amphetamines has a heritable genetic component. We previously identified (heterogeneous nuclear ribonucleoprotein H1) as a quantitative trait gene underlying decreased methamphetamine-induced locomotor activity in mice. Here, we showed that mice (both females and males) with a heterozygous mutation in the first coding exon of (H1) showed reduced methamphetamine reinforcement and intake and dose-dependent changes in methamphetamine reward as measured via conditioned place preference.

TIA1 regulates the generation and response to toxic tau oligomers.

RNA binding proteins (RBPs) are strongly linked to the pathophysiology of motor neuron diseases. Recent studies show that RBPs, such as TIA1, also contribute to the pathophysiology of tauopathy. RBPs co-localize with tau pathology, and reduction of TIA1 protects against tau-mediated neurodegeneration.

Heavy Metal Neurotoxicants Induce ALS-Linked TDP-43 Pathology.

Heavy metals, such as lead, mercury, and selenium, have been epidemiologically linked with a risk of ALS, but a molecular mechanism proving the connection has not been shown. A screen of putative developmental neurotoxins demonstrated that heavy metals (lead, mercury, and tin) trigger accumulation of TDP-43 into nuclear granules with concomitant loss of diffuse nuclear TDP-43. Lead (Pb) and methyl mercury (MeHg) disrupt the homeostasis of TDP-43 in neurons, resulting in increased levels of transcript and increased splicing activity of TDP-43.

AAPL Practice Resource for the Forensic Psychiatric Evaluation of Competence to Stand Trial.

Full Document: Wall BW, Ash P, Keram E, et al: AAPL Practice Resource for the Forensic Psychiatric Evaluation of Competence to Stand Trial Update 2018. Journal of the American Academy of Psychiatry and the Law Online Supplement 2018, 46 (3). Available at: http://www.

RNA binding proteins co-localize with small tau inclusions in tauopathy.

The development of insoluble, intracellular neurofibrillary tangles composed of the microtubule-associated protein tau is a defining feature of tauopathies, including Alzheimer's disease (AD). Accumulating evidence suggests that tau pathology co-localizes with RNA binding proteins (RBPs) that are known markers for stress granules (SGs). Here we used proteomics to determine how the network of tau binding proteins changes with disease in the rTg4510 mouse, and then followed up with immunohistochemistry to identify RNA binding proteins that co-localize with tau pathology.