HIV chronicity as a predictor of hippocampal memory deficits in daily cannabis users living with HIV.

Background: Antiretroviral medications have increased the lifespan of persons living with HIV (PLWH) thereby unmasking memory decline that may be attributed to chronological age, HIV symptomatology, HIV disease chronicity, and/or substance use (especially cannabis use which is common among PLWH). To date, few studies have attempted to disentangle these effects. In a sample of daily cannabis-using PLWH, we investigated whether hippocampal memory function, assessed via an object-location associative learning task, was associated with age, HIV chronicity and symptom severity, or substance use. Methods: 48 PLWH (12.9 ± 9.6 years since HIV diagnosis), who were 44 years old on average (range: 24-64 years; 58 % male) and reported daily cannabis use (recent use confirmed by urinalysis) completed the study. We assessed each participant's demographics, substance use, medical history, current HIV symptoms, and hippocampal memory function via a well-validated object-location associative learning task. Results: Multiple regression analyses found that living more years since HIV+ diagnosis predicted significantly worse associative learning total score (r=-0.40) and learning rate (r=-0.34) whereas chronological age, cannabis-use characteristics, and recent HIV symptom severity were not significantly related to hippocampal memory function. Conclusions: In daily cannabis-using PLWH, HIV chronicity was related to worse hippocampal memory function independent from cannabis use, age, and HIV symptomatology. Object-location associative learning performance could serve as an 'early-warning' metric of cognitive decline among PLWH. Future research should examine longitudinal changes in associative learning proficiency and evaluate interventions to prevent hippocampal memory decline among PLWH. ClinicalTrials.gov: NCT01536899.

Cannabis and complementary/alternative self-treatment approaches for symptom management among African American persons living with HIV.

Persons living with HIV (PLWH) experience symptoms from disease progression and side effects of antiretroviral treatment. This study examines in African American PLWH (N = 259) commonly-endorsed symptoms, types and self-rated efficacy of therapies for symptom alleviation. Analyses were stratified by gender (n = 178 males, n = 81 females) and cannabis use typology: non-users (n = 90), mostly recreational use (n = 46), mixed recreational/therapeutic use (n = 51), or mostly therapeutic use (n = 72). Females reported greater severity for pain, fatigue, depression, weight change and tingling in extremities, but there were no gender differences for ratings of poor sleep, anxiety, poor appetite, or headache. Both marijuana (used therapeutically by females more than males) and medication(s) were among the 3 top methods for managing pain, poor sleep, anxiety, and headache. Marijuana was most often used for poor appetite, and medications for depression. Perceived efficacy of self-treatment approaches was moderately good. Among African American PLWH, symptom severity was higher for females and for therapeutic users of cannabis. Marijuana and medicine were often used to self-treat symptoms, but many participants did nothing. These results highlight the need for careful evaluation and management of symptoms in this underserved population.

Characterization of Cytochrome P450s with Key Roles in Determining Herbicide Selectivity in Maize.

Safeners such as metcamifen and benoxacor are widely used in maize to enhance the selectivity of herbicides through the induction of key detoxifying enzymes, notably cytochrome P450 monooxygenases (CYPs). Using a combination of transcriptomics, proteomics, and functional assays, the safener-inducible CYPs responsible for herbicide metabolism in this globally important crop have been identified. A total of 18 CYPs belonging to clans 71, 72, 74, and 86 were safener-induced, with the respective enzymes expressed in yeast and screened for activity toward thiadiazine (bentazon), sulfonylurea (nicosulfuron), and triketone (mesotrione and tembotrione) chemistries. Herbicide metabolism was largely restricted to family CYP81A members from clan 71, notably CYP81A9, CYP81A16, and CYP81A2. Quantitative transcriptomics and proteomics showed that CYP81A9/CYP81A16 were dominant enzymes in safener-treated field maize, whereas only CYP81A9 was determined in sweet corn. The relationship between CYP81A sequence and activities were investigated by splicing CYP81A2 and CP81A9 together as a series of recombinant chimeras. CYP81A9 showed wide ranging activities toward the three herbicide chemistries, while CYP81A2 uniquely hydroxylated bentazon in multiple positions. The plasticity in substrate specificity of CYP81A9 toward multiple herbicides resided in the second quartile of its N terminal half. Further phylogenetic analysis of CYP81A9 showed that the maize enzyme was related to other CYP81As linked to agrochemical metabolism in cereals and wild grasses, suggesting this clan 71 CYP has a unique function in determining herbicide selectivity in arable crops.

The Phytotoxin Myrigalone A Triggers a Phased Detoxification Programme and Inhibits Lepidium sativum Seed Germination via Multiple Mechanisms including Interference with Auxin Homeostasis.

Molecular responses of plants to natural phytotoxins comprise more general and compound-specific mechanisms. How phytotoxic chalcones and other flavonoids inhibit seedling growth was widely studied, but how they interfere with seed germination is largely unknown. The dihydrochalcone and putative allelochemical myrigalone A (MyA) inhibits seed germination and seedling growth. Transcriptome (RNAseq) and hormone analyses of Lepidium sativum seed responses to MyA were compared to other bioactive and inactive compounds. MyA treatment of imbibed seeds triggered the phased induction of a detoxification programme, altered gibberellin, cis-(+)-12-oxophytodienoic acid and jasmonate metabolism, and affected the expression of hormone transporter genes. The MyA-mediated inhibition involved interference with the antioxidant system, oxidative signalling, aquaporins and water uptake, but not uncoupling of oxidative phosphorylation or p-hydroxyphenylpyruvate dioxygenase expression/activity. MyA specifically affected the expression of auxin-related signalling genes, and various transporter genes, including for auxin transport (PIN7, ABCG37, ABCG4, WAT1). Responses to auxin-specific inhibitors further supported the conclusion that MyA interferes with auxin homeostasis during seed germination. Comparative analysis of MyA and other phytotoxins revealed differences in the specific regulatory mechanisms and auxin transporter genes targeted to interfere with auxin homestasis. We conclude that MyA exerts its phytotoxic activity by multiple auxin-dependent and independent molecular mechanisms.

Momentary assessment of aberrant salience, anomalous self-experiences, and psychotic-like experiences.

To improve understanding of emerging psychosis, researchers have identified potential precursory mechanisms that may momentarily precede psychotic-like experiences, including aberrant salience and anomalous self-experiences. Aberrant salience is the misattribution of significance to neutral stimuli and may be linked to atypical dopamine transmission. Anomalous self-experiences include changes in the experience of the self, which may alter top-down cognitive processes. The present study extends previous research on these phenomena by examining the momentary dynamics of aberrant salience, anomalous self-experiences, and psychotic-like experiences in daily life. Participants were 246 young adults who were prompted to complete 6 smartphone surveys daily for 7 days. Baseline measures of aberrant salience and anomalous self-experiences each predicted occurrence of the same phenomena in daily life, supporting the use of these measures to examine within-subject changes. Dynamic structural equation modeling was used to examine lagged effects. Both aberrant salience and anomalous self-experiences exhibited carryover effects across timepoints. Furthermore, aberrant salience and anomalous self-experiences were each associated with psychotic-like experiences at subsequent timepoints, above and beyond the carryover effects of psychotic-like experiences. These temporal relationships provide preliminary support consistent with social-cognitive models of psychosis and support further examination of the within-subject dynamics of aberrant salience and anomalous self-experiences at the momentary scale. (PsycInfo Database Record (c) 2022 APA, all rights reserved).

Rice RS2-9, which is bound by transcription factor OSH1, blocks enhancer-promoter interactions in plants.

Insulators characterized in Drosophila and mammals have been shown to play a key role in the restriction of promiscuous enhancer-promoter interactions, as well as reshaping the topological landscape of chromosomes. Yet the role of insulators in plants remains poorly understood, in large part because of a lack of well-characterized insulators and binding factor(s). In this study, we isolated a 1.2-kb RS2-9 insulator from the Oryza sativa (rice) genome that can, when interposed between an enhancer and promoter, efficiently block the activation function of both constitutive and floral organ-specific enhancers in transgenic Arabidopsis and Nicotiana tabacum (tobacco). In the rice genome, the genes flanking RS2-9 exhibit an absence of mutual transcriptional interactions, as well as a lack of histone modification spread. We further determined that O. sativa Homeobox 1 (OSH1) bound two regions of RS2-9, as well as over 50 000 additional sites in the rice genome, the majority of which resided in intergenic regions. Mutation of one of the two OSH1-binding sites in RS2-9 impaired insulation activity by up to 60%, whereas the mutation of both binding sites virtually abolished insulator function. We also demonstrated that OSH1 binding sites were associated with 72% of the boundaries of topologically associated domains (TADs) identified in the rice genome, which is comparable to the 77% of TAD boundaries bound by the insulator CCCTC-binding factor (CTCF) in mammals. Taken together, our findings indicate that OSH1-RS2-9 acts as a true insulator in plants, and highlight a potential role for OSH1 in gene insulation and topological organization in plant genomes.

Anomalous self-experiences in cognition are negatively associated with neurocognitive functioning in schizophrenia.

INTRODUCTION: Anomalous self-experiences (ASEs) are disturbances in the subjective experience of the self and are common in people with schizophrenia. Theorists have suggested that ASEs may underlie the neurocognitive deficits that are also common in people with schizophrenia; however, few studies have empirically investigated the relationship between these variables. Thus, the current study aimed to determine whether self-reported ASEs, particularly disturbances in cognitive or mental experiences, are meaningfully related to neurocognitive performance in individuals with schizophrenia. METHODS: 48 individuals with schizophrenia and 34 healthy comparison participants completed the Inventory of Psychotic-Like Anomalous Experiences (IPASE), which is composed of five subscales including disturbances in cognition, and the MATRICS Consensus Cognitive Battery (MCCB). RESULTS: Participants with schizophrenia performed worse than controls on each MCCB domain and had higher ASE scores on the total IPASE and all five subscales. Only the IPASE-Cognition subscale was associated with cognitive performance. Specifically, IPASE-Cognition was negatively correlated with scores in attention, visual learning, reasoning, and working memory. CONCLUSIONS: These results suggest that self-reported subjective disturbances in cognition may be meaningfully associated with several objectively-measured domains of neurocognition. Severity of ASEs may therefore be an important consideration when analysing the extent of cognitive deficits in schizophrenia.

Demand curve analysis of marijuana use among persons living with HIV.

BACKGROUND: Despite medicalization and legalization of marijuana use, factors influencing demand for marijuana among persons living with HIV (PLWH) are incompletely understood. This knowledge gap undermines effective clinical management and policies. This study used demand curve simulation methods to address these issues. METHODS: Marijuana-using PLWH (N = 119) completed experimental tasks to simulate amount of marijuana purchasing/use across different costs (money or time), and likelihood of reselling marijuana or marijuana therapeutic-use registration card in relation to profits. Additional simulations assessed purchasing of marijuana relative to other drug and non-drug goods. RESULTS: Simulated marijuana use decreased as money and time costs increased. Consumption was greater for participants with more severe Cannabis Use Disorder (CUD) and anxiety, intermediate pain levels, and past 90-day opioid use. Whereas few participants chose to sell their registration card, marijuana resale (diversion) steeply increased with profit. Likelihood of seeking marijuana therapeutic-use certification decreased in relation to registration card money cost, having to visit more physicians to get a signature, and delay to receiving the card, and increased with duration of certification. Participants who reported recent opioid use were more likely to seek certification. Consumption of several commodities assessed was independent of marijuana. CONCLUSIONS: Simulated marijuana use was related to participants' clinical profile (CUD, anxiety and pain symptoms, recent opioid use), and unrelated to purchasing other goods. Likelihood of seeking marijuana therapeutic-use registration was affected by several types of costs and recent opioid use. Participants were unlikely to divert registration cards. We discuss clinical and policy implications of these findings.

Major latex protein-like encoding genes contribute to Rhizoctonia solani defense responses in sugar beet.

Sugar beets are attacked by several pathogens that cause root damages. Rhizoctonia (Greek for "root killer") is one of them. Rhizoctonia root rot has become an increasing problem for sugar beet production and to decrease yield losses agronomical measures are adopted. Here, two partially resistant and two susceptible sugar beet genotypes were used for transcriptome analysis to discover new defense genes to this fungal disease, information to be implemented in molecular resistance breeding. Among 217 transcripts with increased expression at 2 days post-infection (dpi), three resistance-like genes were found. These genes were not significantly elevated at 5 dpi, a time point when increased expression of three Bet v I/Major latex protein (MLP) homologous genes BvMLP1, BvMLP2 and BvML3 was observed in the partially resistant genotypes. Quantitative RT-PCR analysis on diseased sugar beet seedlings validated the activity of BvMLP1 and BvMLP3 observed in the transcriptome during challenge by R. solani. The three BvMLP genes were cloned and overexpressed in Arabidopsis thaliana to further dissect their individual contribution. Transgenic plants were also compared to T-DNA mutants of orthologous MLP genes. Plants overexpressing BvMLP1 and BvMLP3 showed significantly less infection whereas additive effects were seen on Atmlp1/Atmlp3 double mutants. The data suggest that BvMLP1 and BvMLP3 may contribute to the reduction of the Rhizoctonia root rot disease in sugar beet. Impact on the defense reaction from other differential expressed genes observed in the study is discussed.

Form and content of attenuated psychotic symptoms in psychometrically assessed positive and negative schizotypy.

AIM: Greater attention is being paid to early detection and identification of individuals who are at high risk of developing psychosis. One area of interest is the particular content types of psychotic-like experiences (PLEs), which can be thought of as attenuated, non-clinical positive symptoms (eg, feeling perplexed by reality). Previous research has examined content of PLEs in clinical high-risk samples. The current study aimed to build upon these findings by analysing content in a psychometrically determined high-risk sample. METHODS: One hundred fifty-three undergraduates with scores greater than 1.96 SDs above the mean on a measure of schizotypy symptoms participated in a semi-structured interview for the assessment of prodromal syndromes. Each interview was transcribed verbatim and content of PLEs was rated according to the Content of Attenuated Positive Symptoms scale. RESULTS: Frequencies of content items in the psychometric high-risk sample were similar to those found in a clinical high-risk sample. Multiple regression analyses revealed that certain content items were more predictive of decreased global functioning and increased positive symptom severity. CONCLUSIONS: Content items that were associated with worse outcomes may be cause for greater concern if endorsed by individuals presenting for treatment. Future research should examine content of PLEs in a longitudinal design to determine whether particular items could predict subsequent conversion to a schizophrenia-spectrum disorder.

Chemically induced herbicide tolerance in rice by the safener metcamifen is associated with a phased stress response.

The closely related sulphonamide safeners, metcamifen and cyprosulfamide, were tested for their ability to protect rice from clodinafop-propargyl, a herbicide normally used in wheat. While demonstrating that both compounds were equally bioavailable in planta, only metcamifen prevented clodinafop from damaging seedlings, and this was associated with the enhanced detoxification of the herbicide. Transcriptome studies in rice cultures demonstrated that whereas cyprosulfamide had a negligible effect on gene expression over a 4 h exposure, metcamifen perturbed the abundance of 590 transcripts. Changes in gene expression with metcamifen could be divided into three phases, corresponding to inductions occurring over 30 min, 1.5 h and 4 h. The first phase of gene induction was dominated by transcription factors and proteins of unknown function, the second by genes involved in herbicide detoxification, while the third was linked to cellular homeostasis. Analysis of the inducible genes suggested that safening elicited similar gene families to those associated with specific biotic and abiotic stresses, notably those elicited by abscisic acid, salicylic acid, and methyl jasmonate. Subsequent experiments with safener biomarker genes induced in phase 1 and 2 in rice cell cultures provided further evidence of similarities in signalling processes elicited by metcamifen and salicylic acid.

Associations among domains of self-disturbance in schizophrenia.

Self-disturbances are increasingly recognized as important, possibly even central, features of schizophrenia. However, little is known about the associations among different manifestations of self-disturbances. The aims of the current study were threefold. We aimed to (1) replicate previous findings of increased self-disturbances in schizophrenia, (2) correlate manifestations of self-disturbances in schizophrenia across three domains, and (3) correlate self-disturbances with five symptoms domains of schizophrenia, including positive, negative, disorganized symptoms, excitement, and emotional distress. We examined three domains of self-experience, including somatosensation, anomalous self-experiences, and self-concept clarity. Participants included 48 individuals with schizophrenia and 36 non-psychiatric controls. The results of this study replicate previous findings of significantly higher levels of self-disturbances in people with schizophrenia. The results also indicate positive correlations between the domains of anomalous self-experiences and self-concept clarity, but not somatosensation, in individuals with schizophrenia. As well, anomalous self-experiences were positively correlated with positive symptoms, disorganized symptoms, and emotional distress and self-concept clarity was negatively correlated with disorganized symptoms and emotional distress.

Where are the drought tolerant crops? An assessment of more than two decades of plant biotechnology effort in crop improvement.

Since the dawn of modern biotechnology public and private enterprise have pursued the development of a new breed of drought tolerant crop products. After more than 20 years of research and investment only a few such products have reached the market. This is due to several technical and market constraints. The technical challenges include the difficulty in defining tractable single-gene trait development strategies, the logistics of moving traits from initial to commercial genetic backgrounds, and the disconnect between conditions in farmer's fields and controlled environments. Market constraints include the significant difficulty, and associated costs, in obtaining access to markets around the world. Advances in the biology of plant water management, including response to water deficit reveal new opportunities to improve crop response to water deficit and new genome-based tools promise to usher in the next era of crop improvement. As biotechnology looks to improve crop productivity under drought conditions, the environmental and food security advantages will influence public perception and shift the debate toward benefits rather than risks.

Trehalose 6-Phosphate Regulates Photosynthesis and Assimilate Partitioning in Reproductive Tissue.

Transgenic maize (Zea mays) that expresses rice (Oryza sativa) TREHALOSE PHOSPHATE PHOSPHATASE1 (TPP1) from the rice MADS6 promoter, which is active over the flowering period, produces higher yields than wild type. This yield increase occurs with or without drought conditions during flowering. To understand the mechanistic basis of the increased yield, we characterized gene expression and metabolite profiles in leaves and developing female reproductive tissue, comprising florets, node, pith, and shank, over the flowering period with and without drought. The MADS6 promoter was most active in the vasculature, particularly phloem companion cells in florets and pith, consistent with the largest decreases in trehalose 6-phosphate (T6P) levels (2- to 3-fold) being found in pith and florets. Low T6P led to decreased gene expression for primary metabolism and increased gene expression for secondary metabolism, particularly lipid-related pathways. Despite similar changes in gene expression, the pith and floret displayed opposing assimilate profiles: sugars, sugar phosphates, amino acids, and lipids increased in florets, but decreased in pith. Possibly explaining this assimilate distribution, seven SWEET genes were found to be up-regulated in the transgenic plants. SnRK1 activity and the expression of the gene for the SnRK1 beta subunit, expression of SnRK1 marker genes, and endogenous trehalose pathway genes were also altered. Furthermore, leaves of the transgenic maize maintained a higher photosynthetic rate for a longer period compared to wild type. In conclusion, we found that decreasing T6P in reproductive tissues down-regulates primary metabolism and up-regulates secondary metabolism, resulting in different metabolite profiles in component tissues. Our data implicate T6P/ SnRK1 as a major regulator of whole-plant resource allocation for crop yield improvement.

The role of ethnic identity, self-concept, and aberrant salience in psychotic-like experiences.

OBJECTIVES: Social-cognitive models of psychosis suggest that aberrant salience and self-concept clarity are related to the development and maintenance of psychoticlike experiences (PLEs). People with high aberrant salience but low self-concept clarity tend to have the highest levels of PLEs. Ethnic identity may also be related to PLEs. The current research aimed to (a) replicate the interaction between aberrant salience and self-concept clarity in their association with PLEs in an ethnically diverse sample, (b) examine whether ethnic identity and aberrant salience interact in their association with PLEs, and (c) determine if self-concept clarity and ethnic identity independently interact with aberrant salience in their association with PLEs. METHOD: An ethnically diverse group of undergraduates (n = 663) completed self-report measures of aberrant salience, self-concept clarity, ethnic identity, and PLEs. RESULTS: There was an interaction between aberrant salience and self-concept clarity such that people with high levels of aberrant salience and low levels of self-concept clarity had the highest levels of PLEs. Similarly, there was an interaction between aberrant salience and ethnic identity such that people with high aberrant salience but low ethnic identity had the highest PLEs. These interactions independently contributed to explaining variance in PLEs. This interaction was present for the Exploration but not Commitment subscales of ethnic identity. CONCLUSION: These results suggest that, in addition to low self-concept clarity, low ethnic identity may be a risk factor for the development of psychosis. (PsycINFO Database Record

Strategies and tools to improve crop productivity by targeting photosynthesis.

Crop productivity needs to substantially increase to meet global food and feed demand for a rapidly growing world population. Agricultural technology developers are pursuing a variety of approaches based on both traditional technologies such as genetic improvement, pest control and mechanization as well as new technologies such as genomics, gene manipulation and environmental modelling to develop crops that are capable of meeting growing demand. Photosynthesis is a key biochemical process that, many suggest, is not yet optimized for industrial agriculture or the modern global environment. We are interested in identifying control points in maize photoassimilation that are amenable to gene manipulation to improve overall productivity. Our approach encompasses: developing and using novel gene discovery techniques, translating our discoveries into traits and evaluating each trait in a stepwise manner that reflects a modern production environment. Our aim is to provide step change advancement in overall crop productivity and deliver this new technology into the hands of growers.This article is part of the themed issue 'Enhancing photosynthesis in crop plants: targets for improvement'.

How does decision complexity affect shared decision making? An analysis of patient-provider antiretroviral initiation dialogue.

OBJECTIVES: This study analyzed patient-provider dialogue regarding anti-retroviral therapy (ART) initiation, assessing the degree to which shared decision making (SDM) occurred. METHODS: We analyzed 24 audio-recorded dialogues between 14 HIV providers and their patients regarding ART initiation. We coded transcribed dialogues for seven SDM elements. We stratified dialogues into three levels of decision complexity (basic, intermediate, complex) based on patient CD4 counts and evaluated SDM criteria fulfillment at each level of decision complexity. RESULTS: There were five basic, twelve intermediate, and seven complex decisions in our sample. While only two met the defined criteria for SDM, the mean number of SDM elements present increased with each level of decision complexity. Discussion of the clinical issue requiring the decision occurred most frequently (88%), while discussion of pros/cons (13%), patient's understanding (21%), and decision alternatives (29%) occurred least frequently. CONCLUSION/PRACTICE IMPLICATIONS: While few dialogues met the defined SDM criteria, providers are having conversations that respond to decision complexity. Clinicians should be aware that discussion of pros/cons, alternatives, and uncertainties are frequently skipped, even when these elements are clearly relevant, as in complex decisions. In addition, rhetorical questions to assess patient preferences and understanding are insufficient to fully engage patients in SDM.