Photoswitch dissociation from a G protein-coupled receptor resolved by time-resolved serial crystallography.

G protein-coupled receptors (GPCRs) are the largest family of cell surface receptors in humans. The binding and dissociation of ligands tunes the inherent conformational flexibility of these important drug targets towards distinct functional states. Here we show how to trigger and resolve protein-ligand interaction dynamics within the human adenosine A receptor.

Collection and sharing of health information in mental health and related systems in Australia: perspectives of people who access mental health services.

Background: Information sharing and information privacy are important issues in mental health services. Yet the perspectives of Australians who access mental health services about these issues are poorly understood. This article addresses the research question: What are the concerns of people who use mental health services about the collection and use of their health information in mental health and related systems in Australia?

Methods: Participants were 16 people who had accessed mental health services and were involved in a series of co-design workshops as part of a larger study.

Kinetic Basis for the Design of Azobenzene-Based Photoswitchable A Adenosine Receptor Ligands.

Photoisomerization of ligands is a key process in the field of photopharmacology. Thus, the kinetics and efficiency of this initial photoreaction are of great importance but can be influenced by the molecular environment of the binding pocket and the resulting confinement of the reaction pathway. In this study, we investigated the photoisomerization of an azobenzene derivative of the anti-Parkinson's drug istradefylline.

We can do better: Recommendations for mental health crisis care from people with lived experience.

The ED is increasingly the first point of contact for people who have no alternative when they are in a mental health crisis. However, there is mounting evidence of inadequate and negative responses to mental health crises in the ED, which has been identified as a 'human rights flashpoint'. This paper presents the desired crisis support from people who have accessed the ED in a mental health crisis and offers significant opportunities to use lived experience knowledge to reshape crisis care.

Mitochondria and cell death.

Mitochondria are cellular factories for energy production, calcium homeostasis and iron metabolism, but they also have an unequivocal and central role in intrinsic apoptosis through the release of cytochrome c. While the subsequent activation of proteolytic caspases ensures that cell death proceeds in the absence of collateral inflammation, other phlogistic cell death pathways have been implicated in using, or engaging, mitochondria. Here we discuss the emerging complexities of intrinsic apoptosis controlled by the BCL-2 family of proteins.

Our Wished-for Responses: Recommendations for Creating a Lived and Embodied Sense of Safety During Mental Health Crisis.

Background: Medical interventions have a place in crisis support; however, narrow biomedical and risk-driven responses negatively impact people seeking crisis care. With increasing shifts towards involving people with lived experience (service users) in designing services, foregrounding people's desired responses is critical. Accordingly, the aim of the study was to explore the wished-for crisis responses from the perspective of people who have experienced crisis and accessed crisis care.

Sexual Violence and Social Media Discourse: Exploring Campus Climate Through the Lens of Twitter.

Background: Sexual violence is prevalent on college campuses, yet formal disclosure and open dialogue are often muffled. Social media has become a powerful platform for survivors and presents an opportunity for researchers to explore social discourse surrounding sexual violence on campuses. Healthcare providers must be knowledgeable of campus climate surrounding sexual violence to provide patient-centered, trauma-informed care and mitigate the detrimental, long-term effects experienced by survivors.

Microtubule association of TRIM3 revealed by differential extraction proteomics.

The microtubule network is formed from polymerised tubulin subunits and associating proteins, which govern microtubule dynamics and a diverse array of functions. To identify novel microtubule-binding proteins, we have developed an unbiased biochemical assay, which relies on the selective extraction of cytosolic proteins from U2OS cells, while leaving behind the microtubule network. Candidate proteins are linked to microtubules by their sensitivities to the depolymerising drug nocodazole or the microtubule-stabilising drug taxol, which is quantitated by mass spectrometry.

Rapid Improvements in Itch with Tapinarof Cream 1% Once Daily in Two Phase 3 Trials in Adults with Mild to Severe Plaque Psoriasis.

Introduction: Patients with psoriasis report pruritus as their most bothersome symptom. Tapinarof cream 1% once daily demonstrated significant efficacy versus vehicle and was well tolerated in adults with mild to severe plaque psoriasis in two 12-week trials: PSOARING 1 (NCT03956355) and PSOARING 2 (NCT03983980). Here, we present patient-reported pruritus outcomes from these trials.

A multi-reservoir extruder for time-resolved serial protein crystallography and compound screening at X-ray free-electron lasers.

Serial crystallography at X-ray free-electron lasers (XFELs) permits the determination of radiation-damage free static as well as time-resolved protein structures at room temperature. Efficient sample delivery is a key factor for such experiments. Here, we describe a multi-reservoir, high viscosity extruder as a step towards automation of sample delivery at XFELs.

Visualizing the DNA repair process by a photolyase at atomic resolution.

Photolyases, a ubiquitous class of flavoproteins, use blue light to repair DNA photolesions. In this work, we determined the structural mechanism of the photolyase-catalyzed repair of a cyclobutane pyrimidine dimer (CPD) lesion using time-resolved serial femtosecond crystallography (TR-SFX). We obtained 18 snapshots that show time-dependent changes in four reaction loci.

Single-cell genomics reveals region-specific developmental trajectories underlying neuronal diversity in the human hypothalamus.

The development and diversity of neuronal subtypes in the human hypothalamus has been insufficiently characterized. To address this, we integrated transcriptomic data from 241,096 cells (126,840 newly generated) in the prenatal and adult human hypothalamus to reveal a temporal trajectory from proliferative stem cell populations to mature hypothalamic cell types. Iterative clustering of the adult neurons identified 108 robust transcriptionally distinct neuronal subtypes representing 10 hypothalamic nuclei.

Preferences for telehealth: A qualitative study with people accessing a new mental health service.

Objectives: To examine preferences for telehealth versus in-person services for people who sought mental health support from an unfamiliar service during the COVID-19 pandemic and to identify the factors that influenced these preferences.

Methods: Data are drawn from semi-structured interviews with 45 participants (32 people who accessed mental health services, 7 informal support people, and 6 people who accessed services themselves as well as identifying as informal supports). Data relating to experiences of telehealth, comparisons with in-person services and preferences were coded inductively and analysed using qualitative content analysis.

Signalling pathway crosstalk stimulated by L-proline drives mouse embryonic stem cells to primitive-ectoderm-like cells.

The amino acid L-proline exhibits growth factor-like properties during development - from improving blastocyst development to driving neurogenesis in vitro. Addition of 400 μM L-proline to self-renewal medium drives naïve mouse embryonic stem cells (ESCs) to early primitive ectoderm-like (EPL) cells - a transcriptionally distinct primed or partially primed pluripotent state. EPL cells retain expression of pluripotency genes, upregulate primitive ectoderm markers, undergo a morphological change and have increased cell number.

Mothers' and fathers' attitudes toward stuttering in the Middle East compared to Europe and North America.

Background: Parents play a central role in the treatment of childhood stuttering. Addressing parental attitudes toward stuttering is helpful therapeutically. The extent to which differences in attitudes toward stuttering exist on the basis of sex, geographical region and parental status (e.

Justice Denied: A Call to Action for Forensic Nurses.

Sexual violence is a major public health problem that negatively affects millions of Americans. Persons who have experienced sexual violence may choose to undergo a medical forensic examination and complete a sexual assault kit to collect and preserve evidence. DNA evidence is an impactful tool that has the potential to confirm an assailant's identity, reveal previously unknown offenders, connect serial predators to other crime scenes, exonerate the wrongly convicted, and prevent future acts of sexual violence.

Bird tolerance to humans in open tropical ecosystems.

Animal tolerance towards humans can be a key factor facilitating wildlife-human coexistence, yet traits predicting its direction and magnitude across tropical animals are poorly known. Using 10,249 observations for 842 bird species inhabiting open tropical ecosystems in Africa, South America, and Australia, we find that avian tolerance towards humans was lower (i.e.

Ultrafast structural changes direct the first molecular events of vision.

Vision is initiated by the rhodopsin family of light-sensitive G protein-coupled receptors (GPCRs). A photon is absorbed by the 11-cis retinal chromophore of rhodopsin, which isomerizes within 200 femtoseconds to the all-trans conformation, thereby initiating the cellular signal transduction processes that ultimately lead to vision. However, the intramolecular mechanism by which the photoactivated retinal induces the activation events inside rhodopsin remains experimentally unclear.

Watching the release of a photopharmacological drug from tubulin using time-resolved serial crystallography.

The binding and release of ligands from their protein targets is central to fundamental biological processes as well as to drug discovery. Photopharmacology introduces chemical triggers that allow the changing of ligand affinities and thus biological activity by light. Insight into the molecular mechanisms of photopharmacology is largely missing because the relevant transitions during the light-triggered reaction cannot be resolved by conventional structural biology.

How do Mental Health Services Foster Hope? Experience of People Accessing Services.

Hope is essential to mental health recovery, yet little is known about how mental health services can foster hope. This paper addresses the question: How can mental health services influence the sense of hope experienced by people who access their services? Sixty-one people who accessed a new mental health service were interviewed about their experiences, including about how the service had influenced their sense of hope. Interviews were analysed using constant comparative analysis.

Lessons Learned: A Case of Intimate Partner Violence During the COVID-19 Pandemic.

Intimate partner violence (IPV) has been a major public health threat long before COVID-19. However, the pandemic has removed protective measures from victims, while heightening risk factors associated with IPV. Emergency department providers are often the initial point of contact in the health care system for IPV victims; therefore, knowledge of current screening guidelines and best practices in assessment and management of IPV is essential.

L-Proline Supplementation Drives Self-Renewing Mouse Embryonic Stem Cells to a Partially Primed Pluripotent State: The Early Primitive Ectoderm-Like Cell.

Mouse embryonic stem cells (mESCs) can be grown under a variety of culture conditions as discrete cell states along the pluripotency continuum, ranging from the least mature "ground state" to being "primed" to differentiate. Cells along this continuum are demarcated by differences in gene expression, X chromosome inactivation, ability to form chimeras and epigenetic marks. We have developed a protocol to differentiate "naïve" mESCs to a "partially primed" state by adding the amino acid L-proline to self-renewal medium.

Two new species of Pyrgulopsis Call amp; Pilsbry, 1886 (Mollusca: Caenogastropoda: Hydrobiidae) from springs in the Rio Grande watershed in Texas.

Pyrgulopsis Call Pilsbry, 1886 is a genus of small (<5 mm) spring snails, usually endemic to single freshwater springs. Two new populations of Pyrgulopsis found in very small, isolated springs and spring runs in the mainstem Rio Grande watershed of western Texas are distinguished from congeners. Mitochondrial and nuclear sequences, morphometrics, and morphological characteristics support Pyrgulopsis rubra sp.