An ethics analysis of antipsychotic dose reduction and discontinuation: Principles for supporting recovery from psychosis.

Objective: To examine the evidence and practice of antipsychotic dose reduction from the lens of biomedical ethics (specifically principlism) to support evidence-based practice and patient choice and self-determination.

Methods: An overview of the evidence from randomized controlled trials of antipsychotic dose reduction versus maintenance is presented. This is followed by a theoretical examination of the four key biomedical ethical principles of autonomy, nonmaleficence, beneficence, and justice and how they apply in the case of antipsychotic dose reduction.

Toward AI-driven neuroepigenetic imaging biomarker for alcohol use disorder: A proof-of-concept study.

Alcohol use disorder (AUD) is a disorder of clinical and public health significance requiring novel and improved therapeutic solutions. Both environmental and genetic factors play a significant role in its pathophysiology. However, the underlying epigenetic molecular mechanisms that link the gene-environment interaction in AUD remain largely unknown.

Validating cognitive screening in young people with first-episode psychosis: The CogScreen protocol.

Aim: Cognitive impairments are a core feature of first-episode psychosis (FEP) and one of the strongest predictors of long-term psychosocial functioning. Cognition should be assessed and treated as part of routine clinical care for FEP. Cognitive screening offers the opportunity to rapidly identify and triage those in most need of cognitive support.

Remote submerged banks and mesophotic ecosystems can provide key habitat for endangered marine megafauna.

The importance of some ecosystems remains poorly understood. We showed that mesophotic ecosystems (30 to 150 m) are a key habitat for a critically endangered species, with strong evidence that a globally important population of adult hawksbill turtles () almost exclusively foraged at these depths on remote submerged banks. This discovery highlights the need for such areas to be included in conservation planning, for example, as part of the United Nations High Seas Treaty.

The fidelity of transcription in human cells.

To determine the error rate of transcription in human cells, we analyzed the transcriptome of H1 human embryonic stem cells with a circle-sequencing approach that allows for high-fidelity sequencing of the transcriptome. These experiments identified approximately 100,000 errors distributed over every major RNA species in human cells. Our results indicate that different RNA species display different error rates, suggesting that human cells prioritize the fidelity of some RNAs over others.

Feasibility of wearable technology for 'real-world' gait analysis in children with Prader-Willi and Angelman syndromes.

Background: Prader-Willi syndrome (PWS) and Angelman syndrome (AS) are neurodevelopmental disorders in need of innovative 'real-world' outcome measures to evaluate treatment effects. Instrumented gait analysis (IGA) using wearable technology offers a potentially feasible solution to measure "real-world' neurological and motor dysfunction in these groups.

Methods: Children (50% female; 6-16 years) diagnosed with PWS (n = 9) and AS (n = 5) completed 'real-world' IGA assessments using the Physilog®5 wearable.

Travel routes to remote ocean targets reveal the map sense resolution for a marine migrant.

How animals navigate across the ocean to isolated targets remains perplexing greater than 150 years since this question was considered by Charles Darwin. To help solve this long-standing enigma, we considered the likely resolution of any map sense used in migration, based on the navigational performance across different scales (tens to thousands of kilometres). We assessed navigational performance using a unique high-resolution Fastloc-GPS tracking dataset for post-breeding hawksbill turtles () migrating relatively short distances to remote, isolated targets on submerged banks in the Indian Ocean.

Synthesis and characterization of a new Positron emission tomography probe for orexin 2 receptors neuroimaging.

The orexin receptors (OXRs) have been involved in multiple physiological and neuropsychiatric functions. Identification of PET imaging probes specifically targeting OXRs enables us to better understand the OX system. Seltorexant (JNJ-42847922) is a potent OXR antagonist with the potential to be an OXR PET imaging probe.

Visualization of Receptor-Interacting Protein Kinase 1 (RIPK1) by Brain Imaging with Positron Emission Tomography.

We report the development of the first positron emission tomography (PET) radiotracer, [F]CNY-07, based on a highly specific and potent RIPK1 inhibitor, Nec-1s, for RIPK1/necroptosis brain imaging in rodents. [F]CNY-07 was synthesized through copper-mediated F-radiolabeling from an aryl boronic ester precursor and studied PET imaging in rodents. PET imaging results showed that [F]CNY-07 can penetrate the blood-brain barrier with a maximum percent injected dose per unit volume of 3 at 10 min postinjection in the brain .

A family study implicates GBE1 in the etiology of autism spectrum disorder.

Autism spectrum disorders (ASD) are neurodevelopmental disorders with an estimated heritability of >60%. Family-based genetic studies of ASD have generally focused on multiple small kindreds, searching for de novo variants of major effect. We hypothesized that molecular genetic analysis of large multiplex families would enable the identification of variants of milder effects.

High accuracy tracking reveals how small conservation areas can protect marine megafauna.

Space use estimates can inform conservation management but relaying high-accuracy locations is often not straightforward. We used Fastloc-GPS Argos satellite tags with the innovation of additional data relay via a ground station (termed a "Mote") to record high volumes (typically >20 locations per individual per day) of high accuracy tracking data. Tags were attached in the Chagos Archipelago (Indian Ocean) in 2018-2019 to 23 immature turtles of two species for which there have been long-standing conservation concerns: 21 hawksbill turtles (Eretmochelys imbricata) and two green turtles (Chelonia mydas).

Why do Argos satellite tags stop relaying data?

Satellite tracking of animals is very widespread across a range of marine, freshwater, and terrestrial taxa. Despite the high cost of tags and the advantages of long deployments, the reasons why tracking data from tags stop being received are rarely considered, but possibilities include shedding of the tag, damage to the tag (e.g.

Certification of a Pilot with Charcot-Marie-Tooth Disease.

Charcot-Marie-Tooth disease (CMT) is a rare hereditary motor and sensory neuropathy. This is a report of a pilot with this condition with a discussion of the challenges for the regulator in the assessment for medical certification of pilots with a neurological disability. A pilot with CMTX1 declared his condition to the United Kingdom Civil Aviation Authority when his brother was diagnosed with the same condition.

Deletions in CWH43 cause idiopathic normal pressure hydrocephalus.

Idiopathic normal pressure hydrocephalus (iNPH) is a neurological disorder that occurs in about 1% of individuals over age 60 and is characterized by enlarged cerebral ventricles, gait difficulty, incontinence, and cognitive decline. The cause and pathophysiology of iNPH are largely unknown. We performed whole exome sequencing of DNA obtained from 53 unrelated iNPH patients.

λ Recombineering Used to Engineer the Genome of Phage T7.

Bacteriophage T7 and T7-like bacteriophages are valuable genetic models for lytic phage biology that have heretofore been intractable with in vivo genetic engineering methods. This manuscript describes that the presence of λ Red recombination proteins makes in vivo recombineering of T7 possible, so that single base changes and whole gene replacements on the T7 genome can be made. Red recombination functions also increase the efficiency of T7 genome DNA transfection of cells by ~100-fold.

Open Ocean Reorientation and Challenges of Island Finding by Sea Turtles during Long-Distance Migration.

In 1873, Charles Darwin marveled at the ability of sea turtles to find isolated island breeding sites [1], but the details of how sea turtles and other taxa navigate during these migrations remains an open question [2]. Exploring this question using free-living individuals is difficult because, despite thousands of sea turtles being satellite tracked across hundreds of studies [3], most are tracked to mainland coasts where the navigational challenges are easiest. We overcame this problem by recording unique tracks of green turtles (Chelonia mydas) migrating long distances in the Indian Ocean to small oceanic islands.

Local and regional scale habitat heterogeneity contribute to genetic adaptation in a commercially important marine mollusc (Haliotis rubra) from southeastern Australia.

Characterising adaptive genetic divergence among conspecific populations is often achieved by studying genetic variation across defined environmental gradients. In marine systems this is challenging due to a paucity of information on habitat heterogeneity at local and regional scales and a dependency on sampling regimes that are typically limited to broad longitudinal and latitudinal environmental gradients. As a result, the spatial scales at which selection processes operate and the environmental factors that contribute to genetic adaptation in marine systems are likely to be unclear.

Applications of unmanned aerial vehicles in intertidal reef monitoring.

Monitoring of intertidal reefs is traditionally undertaken by on-ground survey methods which have assisted in understanding these complex habitats; however, often only a small spatial footprint of the reef is observed. Recent developments in unmanned aerial vehicles (UAVs) provide new opportunities for monitoring broad scale coastal ecosystems through the ability to capture centimetre resolution imagery and topographic data not possible with conventional approaches. This study compares UAV remote sensing of intertidal reefs to traditional on-ground monitoring surveys, and investigates the role of UAV derived geomorphological variables in explaining observed intertidal algal and invertebrate assemblages.

A Transcription Fidelity Reporter Identifies GreA as a Major RNA Proofreading Factor in .

We made a coupled genetic reporter that detects rare transcription misincorporation errors to measure RNA polymerase transcription fidelity in Using this reporter, we demonstrated that the transcript cleavage factor GreA, but not GreB, is essential for proofreading of a transcription error where a riboA has been misincorporated instead of a riboG. A mutant strain had more than a 100-fold increase in transcription errors relative to wild-type or a mutant. However, overexpression of GreB in Δ cells reduced the misincorporation errors to wild-type levels, demonstrating that GreB at high concentration could substitute for GreA in RNA proofreading activity .

The effects of an invasive seaweed on native communities vary along a gradient of land-based human impacts.

The difficulty in teasing apart the effects of biological invasions from those of other anthropogenic perturbations has hampered our understanding of the mechanisms underpinning the global biodiversity crisis. The recent elaboration of global-scale maps of cumulative human impacts provides a unique opportunity to assess how the impact of invaders varies among areas exposed to different anthropogenic activities. A recent meta-analysis has shown that the effects of invasive seaweeds on native biota tend to be more negative in relatively pristine than in human-impacted environments.

Exploring Spatiotemporal Trends in Commercial Fishing Effort of an Abalone Fishing Zone: A GIS-Based Hotspot Model.

Assessing patterns of fisheries activity at a scale related to resource exploitation has received particular attention in recent times. However, acquiring data about the distribution and spatiotemporal allocation of catch and fishing effort in small scale benthic fisheries remains challenging. Here, we used GIS-based spatio-statistical models to investigate the footprint of commercial diving events on blacklip abalone (Haliotis rubra) stocks along the south-west coast of Victoria, Australia from 2008 to 2011.

Elevated mutation rate during meiosis in Saccharomyces cerevisiae.

Mutations accumulate during all stages of growth, but only germ line mutations contribute to evolution. While meiosis contributes to evolution by reassortment of parental alleles, we show here that the process itself is inherently mutagenic. We have previously shown that the DNA synthesis associated with repair of a double-strand break is about 1000-fold less accurate than S-phase synthesis.

GAP-Seq: a method for identification of DNA palindromes.

Background: Closely spaced long inverted repeats, also known as DNA palindromes, can undergo intrastrand annealing to form DNA hairpins. The ability to form these hairpins results in genome instability, difficulties in maintaining clones in Escherichia coli and major problems for most DNA sequencing approaches. Because of their role in genomic instability and gene amplification in some human cancers, it is important to develop systematic approaches to detect and characterize DNA palindromes.

Replication stress-induced alternative mRNA splicing alters properties of the histone RNA-binding protein HBP/SLBP: a key factor in the control of histone gene expression.

Animal replication-dependent histone genes produce histone proteins for the packaging of newly replicated genomic DNA. The expression of these histone genes occurs during S phase and is linked to DNA replication via S-phase checkpoints. The histone RNA-binding protein HBP/SLBP (hairpin-binding protein/stem-loop binding protein), an essential regulator of histone gene expression, binds to the conserved hairpin structure located in the 3'UTR (untranslated region) of histone mRNA and participates in histone pre-mRNA processing, translation and histone mRNA degradation.