Mindreading beliefs in same- and cross-neurotype interactions.

LAY ABSTRACT: Autistic people are often characterised as having problems with mindreading, which refers to understanding other people's thoughts, beliefs and feelings. However, it has recently been suggested that mindreading difficulties may be a two-way issue between autistic and non-autistic people. This would imply that autistic people may not have difficulty reading the minds of other autistic people, whereas non-autistic people may struggle to read autistic people effectively. In this study, we created a survey in which we asked a relatively large sample of autistic and non-autistic people to rate their own and others' mindreading abilities in relation to autistic and non-autistic others, respectively. Both groups believed that they were better at reading others in their own group than the other group. The autistic respondents reported levels of mindreading skill at least commensurate with the non-autistic respondents when the mind to be read was specified as autistic. Thus, both groups of participants' responses were consistent with the notion that mindreading abilities are relational. Although self-reports are subjective, such beliefs could have important consequences for well-being and intergroup relations.

Plant-Environment Response Pathway Regulation Uncovered by Investigating Non-Typical Legume Symbiosis and Nodulation.

Nitrogen is an essential element needed for plants to survive, and legumes are well known to recruit rhizobia to fix atmospheric nitrogen. In this widely studied symbiosis, legumes develop specific structures on the roots to host specific symbionts. This review explores alternate nodule structures and their functions outside of the more widely studied legume-rhizobial symbiosis, as well as discussing other unusual aspects of nodulation. This includes actinorhizal-Frankia, cycad-cyanobacteria, and the non-legume Parasponia andersonii-rhizobia symbioses. Nodules are also not restricted to the roots, either, with examples found within stems and leaves. Recent research has shown that legume-rhizobia nodulation brings a great many other benefits, some direct and some indirect. Rhizobial symbiosis can lead to modifications in other pathways, including the priming of defence responses, and to modulated or enhanced resistance to biotic and abiotic stress. With so many avenues to explore, this review discusses recent discoveries and highlights future directions in the study of nodulation.

Environmental surveillance of antimicrobial resistance (AMR), perspectives from a national environmental regulator in 2023.

The development, and in some cases increasing prevalence, of resistance to antimicrobials used in clinical and veterinary settings has long been recognised. In recent years, the concept of 'One Health' has added recognition of the role that the environment plays in health protection along with the need for protection of the health of the environment itself. Organisations including the World Health Organization, United Nations Environment Programme, and national governments have identified a need for surveillance of antimicrobial resistance in the environment to sit alongside the surveillance carried out in clinical, veterinary and food sectors. However, having recognised the need for environmental surveillance there are multiple challenges in deciding what this should entail. For example, what pathogens or genes to monitor, who or what we wish to protect and what measures we wish to enable to decrease infection risks. That might include sampling near a source of resistant organisms entering the environment or conversely sampling where the exposure actually occurs. Choices need to be made at both policy and technical levels based on the detailed purposes of surveillance. This paper discusses these issues from the perspective of a national environmental regulator.

Proportional contributions to organic chemical mixture effects in groundwater and surface water.

Semi-quantitative GC-MS and LC-MS measurements of organic chemicals in groundwater and surface waters were used to assess the overall magnitude and contribution of the most important substances to calculated mixture hazard. Here we use GC-MS and LC-MS measurements taken from two separate national monitoring programs for groundwater and surface water in England, in combination with chronic species sensitivity distribution (SSD) HC50 values published by Posthuma et al. (2019, Environ. Toxicol. Chem, 38, 905-917) to calculate individual substance hazard quotients and mixture effects using a concentration addition approach. The mixture analysis indicated that, as anticipated, there was an increased hazard from the presence of a cocktail of substances at sites compared to the hazard for any single chemical. The magnitude of the difference between the hazard attributed to the most important chemical and the overall mixture effect, however, was not large. Thus, the most toxic chemical contributed ≥ 20% of the calculated mixture effect in >99% of all measured groundwater and surface water samples. On the basis of this analysis, a 5 fold assessment factor placed on the risk identified for any single chemical would offer a high degree of in cases where implementation of a full mixture analysis was not possible. This finding is consistent with previous work that has assessed chemical mixture effects within field monitoring programs and as such provides essential underpinning for future policy and management decisions on how to effectively and proportionately manage mixture risks.

Worst-case ranking of organic chemicals detected in groundwaters and surface waters in England.

The Environment Agency has been using Gas Chromatography-Mass Spectrometry (GC-MS) and Accurate-mass Quadrupole Time-of-Flight (Q-TOF) / Liquid Chromatography-Mass Spectrometry (LC-MS) target screen analysis to semi-quantitatively measure organic substances in groundwater and surface water since 2009 for GC-MS and 2014 for LC-MS. Here we use this data to generate a worst-case "risk" ranking of the detected substances. Three sets of hazard values relating to effects on aquatic organisms, namely Water Framework Directive EQSs, NORMAN Network PNECs (hereafter NORMAN PNEC) and chronic Species Sensitivity Distribution (SSD) HC50s from Posthuma et al., (2019) were used for the assessment. These hazard values were compared to the highest measured concentration for each chemical to generate a worst-case hazard quotient (HQ). Calculated HQs for each metric were ranked, averaged and multiplied by rank for detection frequency to generate an overall ordering based on HQ and occurrence. This worst-case approach was then used to generate ranking lists for GC-MS and LC-MS detected substances in groundwater and surface water. Pesticides in the top 30 overall ranked list included more legacy pesticides in groundwater and more current use actives in surface water. Specific uses were linked to some high rankings (e.g. rotenone for invasive species control). A number of industrial and plastics associated chemicals were ranked highly in the groundwater dataset, while more personal care products and pharmaceuticals were highly ranked in surface waters. Perfluoroalkyl and Polyfluoroalkyl Substances (PFAS) compounds were commonly highly ranked in both environmental compartments. The approach confirmed high rankings for some substance (e.g. selected pesticides) from previous prioritization exercises, but also identified novel substance for consideration (e.g. some PFAS compounds and pharmaceuticals). Overall our approach provided a simple approach using readily accessible data to identify substances for further and more detailed assessment.

Elucidating connections between the strigolactone biosynthesis pathway, flavonoid production and root system architecture in Arabidopsis thaliana.

Strigolactones (SLs) are the most recently discovered phytohormones, and their roles in root architecture and metabolism are not fully understood. Here, we investigated four MORE AXILLARY GROWTH (MAX) SL mutants in Arabidopsis thaliana, max3-9, max4-1, max1-1 and max2-1, as well as the SL receptor mutant d14-1 and karrikin receptor mutant kai2-2. By characterising max2-1 and max4-1, we found that variation in SL biosynthesis modified multiple metabolic pathways in root tissue, including that of xyloglucan, triterpenoids, fatty acids and flavonoids. The transcription of key flavonoid biosynthetic genes, including TRANSPARENT TESTA4 (TT4) and TRANSPARENT TESTA5 (TT5) was downregulated in max2 roots and seedlings, indicating that the proposed MAX2 regulation of flavonoid biosynthesis has a widespread effect. We found an enrichment of BRI1-EMS-SUPPRESSOR 1 (BES1) targets amongst genes specifically altered in the max2 mutant, reflecting that the regulation of flavonoid biosynthesis likely occurs through the MAX2 degradation of BES1, a key brassinosteroid-related transcription factor. Finally, flavonoid accumulation decreased in max2-1 roots, supporting a role for MAX2 in regulating both SL and flavonoid biosynthesis.

Antifungal Exposure and Resistance Development: Defining Minimal Selective Antifungal Concentrations and Testing Methodologies.

This scoping review aims to summarise the current understanding of selection for antifungal resistance (AFR) and to compare and contrast this with selection for antibacterial resistance, which has received more research attention. AFR is an emerging global threat to human health, associated with high mortality rates, absence of effective surveillance systems and with few alternative treatment options available. Clinical AFR is well documented, with additional settings increasingly being recognised to play a role in the evolution and spread of AFR. The environment, for example, harbours diverse fungal communities that are regularly exposed to antifungal micropollutants, potentially increasing AFR selection risk. The direct application of effect concentrations of azole fungicides to agricultural crops and the incomplete removal of pharmaceutical antifungals in wastewater treatment systems are of particular concern. Currently, environmental risk assessment (ERA) guidelines do not require assessment of antifungal agents in terms of their ability to drive AFR development, and there are no established experimental tools to determine antifungal selective concentrations. Without data to interpret the selective risk of antifungals, our ability to effectively inform safe environmental thresholds is severely limited. In this review, potential methods to generate antifungal selective concentration data are proposed, informed by approaches used to determine antibacterial minimal selective concentrations. Such data can be considered in the development of regulatory guidelines that aim to reduce selection for AFR.

Comparative Genomics across Three Ensifer Species Using a New Complete Genome Sequence of the Medicago Symbiont Sinorhizobium (Ensifer) meliloti WSM1022.

Here, we report an improved and complete genome sequence of Sinorhizobium (Ensifer) meliloti strain WSM1022, a microsymbiont of Medicago species, revealing its tripartite structure. This improved genome sequence was generated combining Illumina and Oxford nanopore sequencing technologies to better understand the symbiotic properties of the bacterium. The 6.75 Mb WSM1022 genome consists of three scaffolds, corresponding to a chromosome (3.70 Mb) and the pSymA (1.38 Mb) and pSymB (1.66 Mb) megaplasmids. The assembly has an average GC content of 62.2% and a mean coverage of 77X. Genome annotation of WSM1022 predicted 6058 protein coding sequences (CDSs), 202 pseudogenes, 9 rRNAs (3 each of 5S, 16S, and 23S), 55 tRNAs, and 4 ncRNAs. We compared the genome of WSM1022 to two other rhizobial strains, closely related Sinorhizobium (Ensifer) meliloti Sm1021 and Sinorhizobium (Ensifer) medicae WSM419. Both WSM1022 and WSM419 species are high-efficiency rhizobial strains when in symbiosis with Medicago truncatula, whereas Sm1021 is ineffective. Our findings report significant genomic differences across the three strains with some similarities between the meliloti strains and some others between the high efficiency strains WSM1022 and WSM419. The addition of this high-quality rhizobial genome sequence in conjunction with comparative analyses will help to unravel the features that make a rhizobial symbiont highly efficient for nitrogen fixation.

Symbiotic Outcome Modified by the Diversification from 7 to over 700 Nodule-Specific Cysteine-Rich Peptides.

Legume-rhizobium symbiosis represents one of the most successfully co-evolved mutualisms. Within nodules, the bacterial cells undergo distinct metabolic and morphological changes and differentiate into nitrogen-fixing bacteroids. Legumes in the inverted repeat lacking clade (IRLC) employ an array of defensin-like small secreted peptides (SSPs), known as nodule-specific cysteine-rich (NCR) peptides, to regulate bacteroid differentiation and activity. While most NCRs exhibit bactericidal effects in vitro, studies confirm that inside nodules they target the bacterial cell cycle and other cellular pathways to control and extend rhizobial differentiation into an irreversible (or terminal) state where the host gains control over bacteroids. While NCRs are well established as positive regulators of effective symbiosis, more recent findings also suggest that NCRs affect partner compatibility. The extent of bacterial differentiation has been linked to species-specific size and complexity of the NCR gene family that varies even among closely related species, suggesting a more recent origin of NCRs followed by rapid expansion in certain species. NCRs have diversified functionally, as well as in their expression patterns and responsiveness, likely driving further functional specialisation. In this review, we evaluate the functions of NCR peptides and their role as a driving force underlying the outcome of rhizobial symbiosis, where the plant is able to determine the outcome of rhizobial interaction in a temporal and spatial manner.

Examining the relationship between burnout and empathy in healthcare professionals: A systematic review.

OBJECTIVE: Empathy and burnout are two related yet distinct constructs that are relevant to clinical healthcare staff. The nature of their relationship is uncertain and this review aimed to complete a rigorous, systematic exploration of the literature investigating the relationship between burnout and empathy in healthcare staff. DESIGN: A systematic review was conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidance. DATA SOURCES: Search terms (Burnout OR Burn-out OR "Burn out") AND (Empathy OR Empath*) enabled identification of studies investigating burnout and empathy in healthcare staff, using five electronic data bases (MEDLINE, PsycINFO, CINAHL Plus, PubMed, and SCOPUS). Manual searching amongst reference lists of eligible articles was also completed. REVIEW METHODS: Databases were searched for studies published in the English language, from inception to February 2017. Key inclusion criteria were: 1) participants who were nurses or medical professionals, 2) full written manuscript in English, 3) use of the Maslach Burnout Inventory to assess burnout and a standardized outcome measure for empathy, 4) quantitative methodology exclusively. RESULTS: Ten eligible studies were reviewed. Of those, seven were conducted in countries where English was not the first language. Eight of the studies provided empirical support for a negative relationship between empathy and burnout. One study provided support for a positive relationship between burnout and empathy. One study reported contradictory evidence with positive and negative correlations between different subscales of the empathy and burnout measures. In general, the quality of the studies was assessed to be good. However, some of the studies failed to provide information pertaining to sample size, with the reporting of data less than adequate from one study. CONCLUSIONS: There was consistent evidence for a negative association between burnout and empathy. This review avoided a common English-speaking country bias of some areas of the literature. Given that all of the studies reviewed were cross sectional, further research is necessary to establish causality.

A Framework for Developing a Curriculum Regarding Autism Spectrum Disorders for Primary Care Providers.

INTRODUCTION: The prevalence of Autism Spectrum Disorders (ASDs) has increased and varies across age groups. Thus there is an increasing need for educational opportunities for General Practitioners (GPs) and other Primary Care providers to help in early identification and referral to specialist services. An earlier survey of GPs in New South Wales (Australia) demonstrated two broad domains for educational activities: (1) a general knowledge (important for early identification and referral) and (2) surveillance (important for ongoing management). AIM: To seek further evidence to these domains and synthesize the important contents for educational programs for GPs. MATERIALS AND METHODS: We conducted a (1) Confirmatory Factor Analysis (CFA) on our original survey data and (2) systematic review of the literature to identify important educational topics, using a life cycle approach. RESULTS: CFA and literature review support theoretical framework of two domains. Alerts and red flags for ASDs, knowledge of simple surveillance tools, communication of diagnosis with parents, referral pathways particularly to speech pathologists before a formal diagnosis is confirmed, and appreciation of vulnerabilities for identifying supports were important in the general knowledge domain, while supporting the families through transition points such as from pre-school to school entry, secondary school and adolescence, role of psychopharmacology such as medications for sleep issues, and for common co-morbidities of anxiety were important in the surveillance dimension. CONCLUSION: GP supervisors and medical and nursing educators can use findings from this paper for developing structured learning activities for training primary health care workforce regarding ASD's.

Homing pigeons respond to time-compensated solar cues even in sight of the loft.

The sun has long been thought to guide bird navigation as the second step in a two-stage process, in which determining position using a map is followed by course setting using a compass, both over unfamiliar and familiar terrain. The animal's endogenous clock time-compensates the solar compass for the sun's apparent movement throughout the day, and this allows predictable deflections in orientation to test for the compass' influence using clock-shift manipulations. To examine the influence of the solar compass during a highly familiar navigational task, 24 clock-shifted homing pigeons were precision-tracked from a release site close to and in sight of their final goal, the colony loft. The resulting trajectories displayed significant partial deflection from the loft direction as predicted by either fast or slow clock-shift treatments. The partial deflection was also found to be stable along the entire trajectory indicating regular updating of orientation via input from the solar compass throughout the final approach flight to the loft. Our results demonstrate that time-compensated solar cues are deeply embedded in the way birds orient during homing flight, are accessed throughout the journey and on a remarkably fine-grained scale, and may be combined effectively simultaneously with direct guidance from familiar landmarks, even when birds are flying towards a directly visible goal.

A model-based prioritisation exercise for the European water framework directive.

A model-based prioritisation exercise has been carried out for the Water Framework Directive (WFD) implementation. The approach considers two aspects: the hazard of a certain chemical and its exposure levels, and focuses on aquatic ecosystems, but also takes into account hazards due to secondary poisoning, bioaccumulation through the food chain and potential human health effects. A list provided by EU Member States, Stakeholders and Non-Governmental Organizations comprising 2,034 substances was evaluated according to hazard and exposure criteria. Then 78 substances classified as "of high concern" where analysed and ranked in terms of risk ratio (Predicted Environmental Concentration/Predicted No-Effect Concentration). This exercise has been complemented by a monitoring-based prioritization exercise using data provided by Member States. The proposed approach constitutes the first step in setting the basis for an open modular screening tool that could be used for the next prioritization exercises foreseen by the WFD.

Comparison of the Arylamine N-acetyltransferase from Mycobacterium marinum and Mycobacterium tuberculosis.

Arylamine N-acetyltansferase (NAT) from Mycobacterium tuberculosis (TBNAT) is a potential drug target for anti-tubercular therapy. Recombinant TBNAT is much less soluble and is produced in lower yields than the closely related NAT from Mycobacterium marinum (MMNAT). In order to explore MMNAT as a model for TBNAT in drug discovery, we compare the two mycobacterial NAT enzymes. Two site-directed mutants of MMNAT have been prepared and characterised: MMNAT71, Tyr --> Phe and MMNAT209, Met --> Thr, in which residues within 6 A of the active-site cysteine have been replaced with the corresponding residue from TBNAT. Two chimeric proteins have also been produced in which the third domain of MMNAT has been replaced by the third domain of TBNAT and vice versa. The activity profile of the chimeric proteins suggests a role for the third domain in the evolutionary divergence of NAT between these closely related mycobacterial species.

Inhibition of proteasomal degradation of Mcl-1 by cobalt chloride suppresses cobalt chloride-induced apoptosis in HCT116 colorectal cancer cells.

Cobalt promotes apoptosis in multiple cell systems, however, the molecular mechanisms that influence cobalt-induced apoptosis are not fully understood. We investigated mechanisms of cobalt chloride induced apoptosis in HCT116 colorectal cancer cells. Cobalt chloride induced dose dependent apoptosis in HCT116 cells (250-750 muM) which, at higher concentrations (500-750 muM), was associated with an increase in the expression of the Bcl-2-related Mcl-1 survival protein. Cobalt chloride caused the accumulation of higher molecular weight ubiquitin-conjugates of Mcl-1 in intact HCT116 cells and inhibited the activity of the trypsin-like site of the 20S proteasome in an in vitro assay. Although siRNA-mediated knockdown of Mcl-1 increased apoptosis in HCT116 cells, the combination of Mcl-1 siRNA and cobalt chloride induced very high levels of cell killing. Therefore, inhibition of the proteasome by cobalt chloride leads to the accumulation of Mcl-1 which acts to limit cobalt chloride induced apoptosis.

Identification, molecular cloning, and characterization of a novel GABAA receptor-associated protein, GRIF-1.

A novel 913-amino acid protein, gamma-aminobutyric acid type A (GABA(A)) receptor interacting factor-1 (GRIF-1), has been cloned and identified as a GABA(A) receptor-associated protein by virtue of its specific interaction with the GABA(A) receptor beta 2 subunit intracellular loop in a yeast two-hybrid assay. GRIF-1 has no homology with proteins of known function, but it is the rat orthologue of the human ALS2CR3/KIAA0549 gene. GRIF-1 is expressed as two alternative splice forms, GRIF-1a and a C-terminally truncated form, GRIF-1b. GRIF-1 mRNA has a wide distribution with a major transcript size of 6.2 kb. GRIF-1a protein is only expressed in excitable tissues, i.e. brain, heart, and skeletal muscle major immunoreactive bands of M(r) approximately 115 and 106 kDa and, in muscle and heart only, an additional 88-kDa species. When expressed in human embryonic kidney 293 cells, GRIF-1a yielded three immunoreactive bands with M(r) approximately 115, 106, and 98 kDa. Co-expression of GRIF-1a and alpha 1 beta 2 gamma 2 GABA(A) receptors in mammalian cells revealed some co-localization in the cell cytoplasm. Anti-FLAG-agarose specifically precipitated GRIF-1(FLAG) and GABA(A) receptor beta 2 subunits from human embryonic kidney 293 cells co-transfected with GRIF-1a(FLAG) and beta 2 subunit clones. Further, immobilized GRIF-1-(8-633) specifically precipitated in vitro GABA(A) receptor alpha 1 and beta 2 subunit immunoreactivities from detergent extracts of adult rat brain. The respective GABA(A) receptor beta 2 subunit/GRIF-1 binding domains were mapped using the yeast two-hybrid reporter gene assays. A possible role for GRIF-1 as a GABA(A) receptor beta 2 subunit trafficking factor is proposed.