Gene duplication and rate variation in the evolution of plastid ACCase and Clp genes in angiosperms.

While the chloroplast (plastid) is known for its role in photosynthesis, it is also involved in many other metabolic pathways essential for plant survival. As such, plastids contain an extensive suite of enzymes required for non-photosynthetic processes. The evolution of the associated genes has been especially dynamic in flowering plants (angiosperms), including examples of gene duplication and extensive rate variation. We examined the role of ongoing gene duplication in two key plastid enzymes, the acetyl-CoA carboxylase (ACCase) and the caseinolytic protease (Clp), responsible for fatty acid biosynthesis and protein turnover, respectively. In plants, there are two ACCase complexes-a homomeric version present in the cytosol and a heteromeric version present in the plastid. Duplications of the nuclear-encoded homomeric ACCase gene and retargeting of one resultant protein to the plastid have been previously reported in multiple species. We find that these retargeted homomeric ACCase proteins exhibit elevated rates of sequence evolution, consistent with neofunctionalization and/or relaxation of selection. The plastid Clp complex catalytic core is composed of nine paralogous proteins that arose via ancient gene duplication in the cyanobacterial/plastid lineage. We show that further gene duplication occurred more recently in the nuclear-encoded core subunits of this complex, yielding additional paralogs in many species of angiosperms. Moreover, in six of eight cases, subunits that have undergone recent duplication display increased rates of sequence evolution relative to those that have remained single copy. We also compared substitution patterns between pairs of Clp core paralogs to gain insight into post-duplication evolutionary routes. These results show that gene duplication and rate variation continue to shape the plastid proteome.

Clinical differences between patients with psychogenic nonepileptic seizures and functional motor disorder.

OBJECTIVES: Why a patient might present with psychogenic nonepileptic seizures (PNES) as opposed to another functional neurological symptom is unknown. A recent review suggested that patients with PNES and functional motor disorders (FMD) differ on demographic and clinical factors of potential aetiological and mechanistic significance, arguing they might represent different disorders, though direct comparisons are limited. We sought to determine whether these factors differed in patients presenting with FMD and PNES at our clinic, as well as whether preceding medical complaints would differ between the two, particularly those affecting the limbs or head. METHODS: A retrospective chart review of all presentations with FMD or PNES patients to a functional neurology clinic, collecting demographic and clinical data, including medical and surgical history. RESULTS: Fifty-six patients with FMD and 52 with PNES were included. Significantly more patients with FMD had functional somatic syndromes (46% vs 27%, p = 0.036) and preceding medical events that affected their limbs than patients with PNES (34% vs 14%, p = 0.013); significantly more patients with PNES had dissociative symptoms (31% vs 4%, p < 0.001) and lifetime suicidal ideation (56% vs 32%, p = 0.013). SIGNIFICANCE: These results highlight the substantial comorbidities affecting FMD and PNES, but find clinical differences between the two groups that may be of aetiological or mechanistic significance.

Medicinal psychedelics for mental health and addiction: Advancing research of an emerging paradigm.

The medical use of psychedelic substances (e.g. psilocybin, ayahuasca, lysergic acid diethylamide and 3,4-methylenedioxymethamphetamine) is attracting renewed interest, driven by a pressing need for research and development of novel therapies for psychiatric disorders, as well as promising results of contemporary studies. In this Viewpoint, we reflect upon the 'Clinical Memorandum on Psychedelics' recently released by the Royal Australian and New Zealand College of Psychiatrists and note subsequent developments including the application for down-scheduling of psilocybin and 3,4-methylenedioxymethamphetamine presently being considered by the Therapeutic Goods Administration and approvals for access via the Special Access Scheme. We suggest that this field is worthy of rigorous research to assess potential benefits, address safety parameters and clarify therapeutic mechanisms. To this end, we outline recent research findings, provide an overview of current knowledge relating to mechanisms of action and discuss salient aspects of the psychedelic-assisted psychotherapy treatment model. The sum of this research points towards medicinal psychedelics as a potential new class of psychiatric treatments when used within a medically supervised framework with integrated psychotherapeutic support. However, before widespread translation into clinical use can occur, appropriately designed and sufficiently powered trials are required to detect both potential positive and negative outcomes. Unique safety and regulatory challenges also need to be addressed. As for any new medical therapy, psychedelic research needs to be conducted in a rigorous manner, through the dispassionate lens of scientific enquiry. Carte blanche availability to practitioners, without specific protocols and appropriate training, would be potentially harmful to individuals and detrimental to the field.

Exercise alone impacts short-term adult visual neuroplasticity in a monocular deprivation paradigm.

Adult homeostatic visual plasticity can be induced by short-term patching, heralded by a shift in ocular dominance in favor of the deprived eye after monocular occlusion. The potential to boost visual neuroplasticity with environmental enrichment such as exercise has also been explored; however, the results are inconsistent, with some studies finding no additive effect of exercise. Studies to date have only considered the effect of patching alone or in combination with exercise. Whether exercise alone affects typical outcome measures of experimental estimates of short-term visual neuroplasticity is unknown. We therefore measured binocular rivalry in 20 healthy young adults (20-34 years old) at baseline and after three 2-hour interventions: patching (of the dominant eye) only, patching with exercise, and exercise only. Consistent with previous work, the patching interventions produced a shift in ocular dominance toward the deprived (dominant) eye. Mild- to moderate-intensity exercise in the absence of patching had several effects on binocular rivalry metrics, including a reduction in the dominant eye percept. The proportion of mixed percept and the time to first switch (onset rivalry) did not change from baseline across all interventions. Thus, we demonstrate that exercise alone can impact binocular rivalry outcomes measures. We did not observe a synergistic effect between patching and exercise in our data.

Efficacy of a brief group intervention for carers of individuals with eating disorders: A randomized control trial.

OBJECTIVE: Interventions for carers of individuals with eating disorders are often time and resource intensive, which may be a barrier for service providers or attendees. This study aimed to evaluate the efficacy of a very brief, two-session psychoeducation and communication skills-based intervention for carers of individuals with eating disorders. METHOD: Carers (N = 44) were randomized to attend two 2.5 hr sessions delivered 1 week apart or waitlist control. Carer burden, self-efficacy, skills, knowledge, expressed emotion (emotional overinvolvement and critical comments), distress (anxiety and depression), and accommodating and enabling behaviors were assessed at preintervention and postintervention and 1-month follow-up. RESULTS: Carer burden, self-efficacy, skills, knowledge, and one component of expressed emotion (critical comments) improved significantly more in the treatment group compared to the waitlist. Changes in anxiety, depression, and accommodating and enabling behaviors did not significantly differ between groups. DISCUSSION: These results demonstrated that substantial improvements can be made from a very brief carers' intervention. More intensive and targeted interventions might be required to address carers' emotional symptoms and to reduce accommodating and enabling behaviors.

5-HT2A Agonists: A Novel Therapy for Functional Neurological Disorders?

Functional neurological disorders are frequently encountered in clinical practice. They have a poor prognosis and treatment options are limited. Their etiology is unknown, but leading theories propose a disturbance of somatic self-representation: the mind perceives dysfunction of a body region despite intact motor and sensory pathways. Central to this model is the concept of an abnormal top-down cognitive influence upon sensorimotor function. There is growing interest in the use of 5-HT2A agonists in the management of neuropsychiatric conditions. Recent studies have shown that these agents induce changes in neural activity that disrupt hierarchical brain dynamics and modulate networks subserving self-related processing. Converging evidence suggests they may hold unique therapeutic potential in functional neurological disorders. This is of importance given the considerable personal and societal burden of this condition and we argue a clinical trial to test this hypothesis is warranted.

Effects of a common transcranial direct current stimulation (tDCS) protocol on motor evoked potentials found to be highly variable within individuals over 9 testing sessions.

Transcranial direct current stimulation (tDCS) uses a weak electric current to modulate neuronal activity. A neurophysiologic outcome measure to demonstrate reliable tDCS modulation at the group level is transcranial magnetic stimulation engendered motor evoked potentials (MEPs). Here, we conduct a study testing the reliability of individual MEP response patterns following a common tDCS protocol. Fourteen participants (7m/7f) each underwent nine randomized sessions of 1 mA, 10 min tDCS (3 anode; 3 cathode; 3 sham) delivered using an M1/orbito-frontal electrode montage (sessions separated by an average of ~5.5 days). Fifteen MEPs were obtained prior to, immediately following and in 5 min intervals for 30 min following tDCS. TMS was delivered at 130 % resting motor threshold using neuronavigation to ensure consistent coil localization. A number of non-experimental variables were collected during each session. At the individual level, considerable variability was seen among different testing sessions. No participant demonstrated an excitatory response ≥20 % to all three anodal sessions, and no participant demonstrated an inhibitory response ≥20 % to all three cathodal sessions. Intra-class correlation revealed poor anodal and cathodal test-retest reliability [anode: ICC(2,1) = 0.062; cathode: ICC(2,1) = 0.055] and moderate sham test-retest reliability [ICC(2,1) = 0.433]. Results also revealed no significant effect of tDCS at the group level. Using this common protocol, we found the effects of tDCS on MEP amplitudes to be highly variable at the individual level. In addition, no significant effects of tDCS on MEP amplitude were found at the group level. Future studies should consider utilizing a more strict experimental protocol to potentially account for intra-individual response variations.

Hallucinations and mental imagery demonstrate top-down effects on visual perception.

In this commentary, we present two examples where perception is not only influenced by, but also in fact driven by, top-down effects: hallucinations and mental imagery. Crucially, both examples avoid all six of the potential confounds that Firestone & Scholl (F&S) raised as arguments against previous studies claiming to demonstrate the influence of top-down effects on perception.

Behavioral sensitivity to reward is reduced for far objects.

Many studies have demonstrated that people will adjust their behavioral response to a reward on the basis of the time taken to receive the reward. Yet despite growing evidence that time and space are not mentally independent, there has been no examination of whether spatial distance may also affect the way people respond to rewarding objects. We examined speeded binary decisions about objects associated with high, low, or no reward for correct responses. Using a 3-D display, we varied perceived spatial distance so that objects appeared at distances near to or far from participants. Both the speed and the accuracy of responses were better for high-reward objects compared with low- and no-reward objects, but this difference occurred only when the objects appeared at near distance to participants. These results demonstrate that when people respond to rewarding objects, they show sensitivity to spatial-distance information even if the information is irrelevant to the task.

Development of a real-time PCR assay for detection of hemp russet mite (Aculops cannabicola).

Of the many arthropod species affecting hemp (Cannabis sativa L.) cultivation in the United States, one species of particular importance is the hemp russet mite (Aculops cannabicola, HRM). Hemp russet mite is a microscopic arthropod which feeds on all parts of hemp plants. Due to its minute size, HRM can proliferate undetected for a long time, complicating management efforts and causing serious economic losses. DNA sequencing and PCR assays can facilitate accurate identification and early detection of HRM in infested-plants. Therefore, a real-time SYBR Green based species-specific PCR assay (quantitative PCR, qPCR) was developed for the identification of HRM DNA by amplification of a 104 bp Internal Transcribed Spacer 1 (ITS1) sequence. The detection limit was estimated to be approximately 48 copies of the HRM marker gene sequence. The real-time-PCR assay is rapid, detects all life stages of mite under 2 hours. A 10-fold serial dilution of the plasmid DNA containing the ITS1 insert were used as standards in the real-time PCR assay. The quantification cycle (Cq) value of the assay showed a strong linear relationship with HRM DNA with R2 of 0.96. The assay was tested against several commonly found hemp pests including two-spotted spider mite and western flower thrips to determine specificity of the assay and to show that no non-target species DNA was amplified. The outcomes of this research will have important applications for agricultural biosecurity through accurate identification of HRM, early detection and timely deployment of management tactics to manage and prevent pest outbreaks.

Side-effects of mdma-assisted psychotherapy: a systematic review and meta-analysis.

Evidence suggests that MDMA-assisted psychotherapy (MDMA-AP) has therapeutic potential for treatment of psychiatric illness. We conducted the first comprehensive systematic review and meta-analysis of the side effects of MDMA-AP across indications. We also assessed the quality of side effects-reporting in published trials of MDMA-AP. PubMed, EMBASE, PsycINFO, MEDLINE and Cochrane Central Register of Controlled Trials (CENTRAL) were systematically searched. Phase 2 and 3 MDMA-AP studies were included; Phase 1 studies, which assessed MDMA without psychotherapy, were not. Quality of side effects-reporting was assessed against the CONSORT Harms 2022 guidelines. We also compared numbers of adverse events reported in publications to those recorded in ClinicalTrial.gov registers. Thirteen studies were included, with eight contributing to the meta-analysis. In Phase 2 studies, MDMA-AP was associated with increased odds of any side effect during medication sessions (OR = 1.67, 95%CI (1.12, 2.49)) and in the 7 days following (OR = 1.59, 95%CI (1.12, 2.24)) relative to control conditions. In Phase 3 studies, MDMA-AP was associated with increased odds of any adverse event during the treatment period relative to placebo-assisted psychotherapy (OR = 3.51, 95%CI (2.76, 4.46)). The majority of RCTs were rated as having high risk of bias. Certainty of the evidence was rated as very low to moderate according to the GRADE framework. No included RCT had adequate adherence to the CONSORT Harms 2022 recommendations and reporting rates were also low. Compared to placebo, MDMA-AP was associated with increased odds of side effects, which were largely transient and mild or moderate in severity. However, identified limitations in existing evidence indicate that further investigation is needed to better characterize the safety profile of MDMA-AP and guide implementation.

Self-motion induced environmental kinetopsia and pop-out illusion - Insight from a single case phenomenology.

Stable visual perception, while we are moving, depends on complex interactions between multiple brain regions. We report a patient with damage to the right occipital and temporal lobes who presented with a visual disturbance of inward movement of roadside buildings towards the centre of his visual field, that occurred only when he moved forward on his motorbike. We describe this phenomenon as "self-motion induced environmental kinetopsia". Additionally, he was identified to have another illusion, in which objects displayed on the screen, appeared to pop out of the background. Here, we describe the clinical phenomena and the behavioural tasks specifically designed to document and measure this altered visual experience. Using the methods of lesion mapping and lesion network mapping we were able to demonstrate disrupted functional connectivity in the areas that process flow-parsing such as V3A and V6 that may underpin self-motion induced environmental kinetopsia. Moreover, we suggest that altered connectivity to the regions that process environmental frames of reference such as retrosplenial cortex (RSC) might explain the pop-out illusion. Our case adds novel and convergent lesion-based evidence to the role of these brain regions in visual processing.

Agency in schizophrenia and autism: a systematic review.

Introduction: Previous research suggests that altered experiences of agency are an underlying vulnerability in both schizophrenia and autism. Here, we explore agency as a potential transdiagnostic factor by conducting a systematic review of existing literature investigating agency in autism and schizophrenia individually and together. Methods: Following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, we conducted three systematic searches on PsycINFO, Embase, Medline, PubMed and Web of Science to identify studies that investigated (1) agency in schizophrenia, (2) agency in autism, and (3) agency in both schizophrenia and autism. Results: A total of 31 articles met eligibility criteria for inclusion and data extraction, with 24 measuring agency in schizophrenia, 7 investigating agency in autism, and no articles comparing the two. Results show that, compared to control populations, agency is significantly different in every identified schizophrenia study and generally not significantly different in autism. Discussion: Importantly, we identified a lack of studies using common tasks and a disproportionate number of studies investigating different dimensions of agency across the two conditions, resulting in limited grounds for valid comparison. Systematic review registration: Prospero, CRD42021273373.

Biology and management of hemp russet mite (Acari: Eriophyidae).

Hemp is rapidly becoming a crop of global agricultural importance, and one of the more serious pests of this crop is hemp russet mite (HRM) Aculops cannabicola (Acari: Eriophyidae). Significant knowledge gaps presently exist regarding critical aspects of pest biology, quantification of crop damage, and efficacy of pesticides. Here we assessed the role of cannabidiol (CBD) on HRM performance, efficacy of sulfur treatments in field trials, and effect of hot water immersion with and without surfactants in reducing HRM counts on hemp cuttings. We found that HRM fecundity was reduced on a high-CBD cultivar compared with a low-CBD cultivar in detached leaf assays. In contrast, HRM fecundity and survival were not impacted when reared on high-CBD diet in artificial feeding assays. This suggests that cannabinoids other than CBD may aid in reduction of mite populations on the high-CBD cultivar. Sulfur sprays reduced HRM populations by up to 98% with the greatest effects seen in plants receiving dual applications, one during the vegetative period in July and the second at the initiation of flowering in August. Yields of plants treated with sulfur increased by up to 33%, and there was a further increase in cannabinoid production by up to 45% relative to untreated plants. Hot water immersion treatments with and without surfactant solution reduced HRM on infested hemp cuttings, and no phytotoxicity was observed. This study provides novel approaches to mitigating HRM at multiple stages in hemp production.

Meta-analysis of dichotomous and ordinal tests with an imperfect gold standard.

Standard methods for the meta-analysis of medical tests, without assuming a gold standard, are limited to dichotomous data. Multivariate probit models are used to analyse correlated dichotomous data, and can be extended to model ordinal data. Within the context of an imperfect gold standard, they have previously been used for the analysis of dichotomous and ordinal test data from a single study, and for the meta-analysis of dichotomous tests. However, they have not previously been used for the meta-analysis of ordinal tests. In this article, we developed a Bayesian multivariate probit latent class model for the simultaneous meta-analysis of ordinal and dichotomous tests without assuming a gold standard, which also allows one to obtain summary estimates of joint test accuracy. We fitted the models using the software Stan, which uses a state-of-the-art Hamiltonian Monte Carlo algorithm, and we applied the models to a dataset in which studies evaluated the accuracy of tests, and test combinations, for deep vein thrombosis. We demonstrate the issues with dichotomising ordinal test accuracy data in the presence of an imperfect gold standard, before applying and comparing several variations of our proposed model which do not require the data to be dichotomised. The models proposed will allow researchers to more appropriately meta-analyse ordinal and dichotomous tests without a gold standard, potentially leading to less biased estimates of test accuracy. This may lead to a better understanding of which tests, and test combinations, should be used for any given medical condition.

Cognitive and perceptual impairments in schizophrenia extend to other psychotic disorders but not schizotypy.

Well characterised cognitive and perceptual impairments in schizophrenia may not be diagnostically specific with some studies suggesting no significant differences between psychotic disorders. This transdiagnostic ambiguity is paralleled in the boundary distinctions between psychotic disorders and the sub-threshold symptomatology of schizotypy. The current study used the CNTRACS test battery to explore if performance deficits in visual integration, relational memory and goal maintenance were specific to schizophrenia or extend to other psychotic disorders; and if task performance varied between individuals with schizophrenia and schizotypy in healthy adults. The sample consisted of healthy controls, and patients who met DSM-IV criteria for schizophrenia, other psychotic disorders and non-psychotic disorders who were tested in person; and an online sample of self-assessed healthy adults. No significant differences were found in performance between patients with schizophrenia and other psychotic disorders in contrast to non-psychotic disorders and healthy controls. The high schizotypy group performed better on the tasks compared to the other psychoses and schizophrenia groups. There were no differences in the healthy control group between individuals with high versus low schizotypy or between in-person and online task performance. These findings support the notion that cognitive and perceptual impairments in schizophrenia extend to other psychotic disorders but are discontinuous with schizotypy. This study provides insights into similarities between schizophrenia and other psychotic disorders with regards to the potential neural substrates underpinning these functions and supports the use of online tools for assessing domains of cognition and perception.

Tactile rivalry demonstrated with an ambiguous apparent-motion quartet.

When observers view ambiguous visual stimuli, their perception will often alternate between the possible interpretations, a phenomenon termed perceptual rivalry [1]. To induce perceptual rivalry in the tactile domain, we developed a new tactile illusion, based on the visual apparent-motion quartet [2]. Pairs of 200 ms vibrotactile stimuli were applied to the finger pad at intervals separated by 300 ms. The location of each successive stimulus pair alternated between the opposing diagonal corners of the approximately 1 cm(2) stimulation array. This stimulation sequence led all participants to report switches between the perception of motion traveling either up and down or left and right across their fingertip. Adaptation to tactile stimulation biased toward one direction caused subsequent ambiguous stimulation to be experienced in the opposing direction. In contrast, when consecutive trials of ambiguous stimulation were presented, motion was generally perceived in the direction consistent with the motion reported in the previous trial. Voluntary eye movements induced shifts in the tactile perception toward a motion axis aligned along a world-centered coordinate frame. Because the tactile quartet results in switching perceptual states despite unvaried sensory input, it is ideally suited to future studies of the neural processes associated with conscious tactile perception.