Evolutionary rate covariation is a reliable predictor of co-functional interactions but not necessarily physical interactions.

Co-functional proteins tend to have rates of evolution that covary over time. This correlation between evolutionary rates can be measured over the branches of a phylogenetic tree through methods such as evolutionary rate covariation (ERC), and then used to construct gene networks by the identification of proteins with functional interactions. The cause of this correlation has been hypothesized to result from both compensatory coevolution at physical interfaces and nonphysical forces such as shared changes in selective pressure. This study explores whether coevolution due to compensatory mutations has a measurable effect on the ERC signal. We examined the difference in ERC signal between physically interacting protein domains within complexes compared to domains of the same proteins that do not physically interact. We found no generalizable relationship between physical interaction and high ERC, although a few complexes ranked physical interactions higher than nonphysical interactions. Therefore, we conclude that coevolution due to physical interaction is weak, but present in the signal captured by ERC, and we hypothesize that the stronger signal instead comes from selective pressures on the protein as a whole and maintenance of the general function.

Integrating a virtual reality relaxation clinic within acute psychiatric services: A pilot study.

People with acute psychiatric conditions experience heightened stress, which is associated with worsened symptoms and increased violence on psychiatric wards. Traditional stress management techniques can be challenging for patients. Virtual reality (VR) relaxation appears promising to reduce stress; however, research on VR for psychiatric wards is limited. This mixed-methods study investigated feasibility and acceptability of integrating a VR relaxation clinic within acute psychiatric services. The study evaluated a VR relaxation session for inpatients and outpatients with acute psychiatric conditions (N = 42) and therapists' (N = 6) experience facilitating VR sessions for patients. Self-report assessments of psychological wellbeing were completed by patients pre- and post-VR. Patients and therapists provided qualitative feedback. The number of violent incidents and restrictive practices on the wards in the 12 weeks before VR implementation was compared to the first 12 weeks of VR. Post-VR, there were statistically significant increases in patients' relaxation, happiness, and connectedness to nature, and decreases in stress, anxiety, and sadness. Qualitative findings indicate patients found sessions enjoyable, relaxing, and helpful. Therapists provided positive feedback but highlighted practical challenges. Violent incidents and restrictive practices halved during VR implementation. VR relaxation appears feasible and acceptable in acute services. Larger studies should evaluate potential impact on psychiatric wards.

Gadusol is a maternally provided sunscreen that protects fish embryos from DNA damage.

Exposure to ultraviolet radiation (UVR) is harmful to living cells, leading organisms to evolve protective mechanisms against UVR-induced cellular damage and stress.1,2 UVR, particularly UVB (280-320 nm), can damage proteins and DNA, leading to errors during DNA repair and replication. Excessive UVR can induce cellular death. Aquatic organisms face risk of UV exposure as biologically harmful levels of UVB can penetrate >10 m in clear water.3 While melanin is the only known sunscreen in vertebrates, it often emerges late in embryonic development, rendering embryos of many species vulnerable during the earlier stages. Algae and microbes produce a class of sunscreening compounds known as mycosporine-like amino acids (MAAs).4 Fish eggs contain a similar compound called gadusol, whose role as a sunscreen has yet to be tested despite its discovery over 40 years ago.5 The recent finding that many vertebrate genomes contain a biosynthetic pathway for gadusol suggests that many fish may produce and use this molecule as a sunscreen.6 We generated a gadusol-deficient mutant zebrafish to investigate the role of gadusol in protecting fish embryos and larvae from UVR. Our results demonstrate that maternally provided gadusol is the primary sunscreen in embryonic and larval development, while melanin provides modest secondary protection. The gadusol biosynthetic pathway is retained in the vast majority of teleost genomes but is repeatedly lost in species whose young are no longer exposed to UVR. Our data demonstrate that gadusol is a maternally provided sunscreen that is critical for early-life survival in the most species-rich branch of the vertebrate phylogeny.

Gadusol is a maternally provided sunscreen that protects fish embryos from DNA damage.

Ultraviolet radiation (UVR) and its deleterious effects on living cells selects for UVR-protective mechanisms. Organisms across the tree of life evolved a variety of natural sunscreens to prevent UVR-induced cellular damage and stress. However, in vertebrates, only melanin is known to act as a sunscreen. Here we demonstrate that gadusol, a transparent compound discovered over 40 years ago in fish eggs, is a maternally provided sunscreen required for survival of embryonic and larval zebrafish exposed to UVR. Mutating an enzyme involved in gadusol biosynthesis increases the formation of cyclobutane pyrimidine dimers, a hallmark of UVB-induced DNA damage. Compared to the contributions of melanin and the chorion, gadusol is the primary sunscreening mechanism in embryonic and larval fish. The gadusol biosynthetic pathway is retained in the vast majority of teleost genomes but is repeatedly lost in species whose young are no longer exposed to UVR. Our data demonstrate that gadusol is a maternally provided sunscreen that is critical for early-life survival in the most species-rich branch of the vertebrate phylogeny.

Virtual reality relaxation for people with mental health conditions: a systematic review.

PURPOSE: Vulnerability to stress is linked to poor mental health. Stress management interventions for people with mental health conditions are numerous but they are difficult to implement and have limited effectiveness in this population. Virtual reality (VR) relaxation is an innovative intervention that aims to reduce stress. This review aimed to synthesize evidence of VR relaxation for people with mental health conditions (PROSPERO 269405). METHODS: Embase, Medline, PsycInfo, and Web of Science were searched until 17th September 2021. The review was carried out according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses. The Effective Public Health Practice Project (EPHPP) tool assessed methodological quality of studies. RESULTS: Searching identified 4550 studies. Eighteen studies (N = 848) were included in the review. Studies were published between 2008 and 2021. Eleven were conducted in Europe. Thirteen studies were controlled trials. Participants were mostly working-age adult outpatients experiencing anxiety or stress-related conditions. Other conditions included eating disorders, depression, bipolar disorder, and psychosis. Five studies tested inpatients. All studies used a range of nature-based virtual environments, such as forests, islands, mountains, lakes, waterfalls, and most commonly, beaches to promote relaxation. Studies provided evidence of the feasibility, acceptability, and short-term effectiveness of VR relaxation to increase relaxation and reduce stress. EPHPP ratings were 'strong' (N = 11), 'moderate' (N = 4), and 'weak' (N = 3). CONCLUSIONS: VR relaxation has potential as a low-intensity intervention to promote relaxation and reduce stress for adults with mental health conditions, especially anxiety and stress-related problems. Further research is warranted on this promising intervention.

Methods and feasibility study for exome sequencing as a universal second-tier test in newborn screening.

PURPOSE: Newborn screening disorders increasingly require genetic variant analysis as part of second-tier or confirmatory testing. Sanger sequencing and gene-specific next-generation sequencing (NGS)-based tests, the current methods of choice, are costly and lack scalability when expanding to new conditions. We describe a scalable, exome sequencing-based NGS pipeline with a priori analysis restriction that can be universally applied to any NBS disorder. METHODS: De-identified abnormal newborn screening specimens representing severe combined immune deficiency (SCID), cystic fibrosis (CF), VLCAD deficiency, metachromatic leukodystrophy (MLD), and in silico sequence read data sets were used to validate the pipeline. To support interpretation and clinical decision-making within the bioinformatics pipeline, variants from multiple databases were curated and validated. RESULTS: CFTR variant panel analysis correctly identified all variants. Concordance compared with diagnostic testing results for targeted gene analysis was between 78.6% and 100%. Validation of the bioinformatics pipeline with in silico data sets revealed a 100% detection rate. Varying degrees of overlap were observed between ClinVar and other databases ranging from 3% to 65%. Data normalization revealed that 11% of variants across the databases required manual curation. CONCLUSION: This pipeline allows for restriction of analysis to variants within a single gene or multiple genes, and can be readily expanded to full exome analysis if clinically indicated and parental consent is granted.