Search

Up to 85% of shellfish reefs have been lost worldwide, resulting in declining ecosystem services, and increasing restoration demand. However, more information regarding the conditions which maximise oyster settlement and growth is required to optimise restoration. We deployed oyster settlement tiles at 21 intertidal sites throughout Moreton Bay, Australia; a region where > 96% of rock oyster reefs are lost and demand for restoration is high. We quantified effects of variables describing the spatial (from GIS), local habitat (using quadrats and water quality measures), and oyster predator (using underwater videography) characteristics of sites on oyster density and size on tiles. Oyster density was highest at sites with intermediate predator abundance and temperature, highest nearby invertebrate cover, and low and high values of turbidity and nearby rock and algae cover. Conversely, oyster size was highest at sites with intermediate predator density, higher fish species richness and turbidity, and lowest temperatures. Together, this showed that optimal restoration requires sites with 22 to 23 °C average water temperatures, between 10 and 15 oyster predators, and either low (< 2 NTU) or high (> 6 NTU) turbidity levels. Notably, we observed multiple peaks for several variables, suggesting the potential presence of multiple cryptic oyster species on settlement tiles. We found that oysters shared preferred environmental conditions with polychaetes, coralline algae, and tunicates, and were more prevalent and abundant at sites with lower turf algae, barnacle, and mussel cover. Identifying environmental variables influencing oyster population distribution, settlement, and growth can guide the selection and approach of oyster restoration sites. [ABSTRACT FROM AUTHOR]

Identifying environmental variables that affect the distribution of pest and/or nuisance species promotes effective management strategies by improving urban planning and the targeted application of direct interventions like population control. Australian white ibis Threskiornis moluccus are considered a nuisance species throughout Australia, having increased significantly in abundance in coastal urban landscapes following declines in their native inland habitats over the past three decades. Few management interventions thus far have successfully reduced conflicts between ibis and humans, necessitating a better understanding of conditions driving ibis distribution and abundance. We surveyed 26 ibis colonies throughout the Moreton Bay region in central eastern Australia and quantified the effects of a range of spatial (e.g. connectivity with waste management facilities, urban land and wetlands) and habitat (e.g. nesting tree species, density and size) variables on ibis and nest abundance. Ibis and their nests were most abundant at sites within 10 km of waste management facilities, and < 60 m from residential or industrial estates. Ibis were also more abundant at sites with tree canopy height < 10 m and lower tree species richness. Nests were most abundant on water bound islands with tree density > 0.5 trees/m2. Urbanisation had contrasting effects, with nest numbers increasing with higher connectivity (i.e. closer proximity) to urban land, while ibis numbers decreased (relative to waste management facilities). Multifaceted approaches are required for controlling ibis populations, including restricting access to anthropogenic food resources, managing the condition of remnant habitats, and considering population control at sites with high connectivity to foraging grounds. [ABSTRACT FROM AUTHOR]

Rationale: Alcohol exposure during adolescence has been linked to long-lasting behavioral consequences, contributing to the development of alcohol use disorder. Negative affect and chronic pain during alcohol withdrawal are critical factors influencing problematic alcohol use and relapse. Our previous research demonstrated that adolescent intermittent ethanol (AIE) vapor exposure elicits sex-specific negative affect-like behavior in adult mice following stress exposure. Additionally, AIE induces persistent mechanical hypersensitivity, which is accompanied by increased activation of corticotropin-releasing factor receptor type 1 (CRFR1) neurons in the dorsolateral bed nucleus of the stria terminalis (dlBNST). Objectives: This study extends previous work by investigating plasma corticosterone levels and CRFR1 protein expression in the dlBNST following restraint stress exposure in adult mice with an AIE history. We also aim to explore the role of dlBNST CRFR1 signaling in mediating negative affect-like behavior and mechanical hypersensitivity. Results: Female mice exhibited elevated plasma corticosterone levels compared to males following restraint stress. Moreover, females with AIE history showed higher expression of CRFR1 protein in the dlBNST compared to air controls. Antagonism of CRFR1 in the dlBNST blocked AIE-induced mechanical hypersensitivity in adult females but did not affect stress-induced negative affect-like behavior. In alcohol-naïve females, intra-dlBNST administration of a CRFR1 agonist induced mechanical hypersensitivity. Conclusions: These findings provide new insights into the neurobiological mechanisms underlying stress-induced negative affect and pain-related behavior, both influenced by a history of adolescent alcohol exposure. The results suggest that CRFR1 antagonists warrant further investigation for their potential in addressing alcohol-related chronic pain. [ABSTRACT FROM AUTHOR]

Purpose: Vagus nerve stimulation (VNS) is emerging as a unique and potent intervention, particularly within neurology and psychiatry. The clinical value of VNS continues to grow, while the development of noninvasive options promises to change a landscape that is already quickly evolving. In this review, we highlight recent progress in the field and offer readers a glimpse of the future for this bright and promising modality. Methods: We compiled a narrative review of VNS literature using PubMed and organized the discussion by disease states with approved indications (epilepsy, depression, obesity, post-stroke motor rehabilitation, headache), followed by a section highlighting novel, exploratory areas of VNS research. In each section, we summarized the current role, recent advancements, and future directions of VNS in the treatment of each disease. Results: The field continues to gain appreciation for the clinical potential of this modality. VNS was initially developed for treatment-resistant epilepsy, with the first depression studies following shortly thereafter. Overall, VNS has gained approval or clearance in the treatment of medication-refractory epilepsy, treatment-resistant depression, obesity, migraine/cluster headache, and post-stroke motor rehabilitation. Conclusion: Noninvasive VNS represents an opportunity to bridge the translational gap between preclinical and clinical paradigms and may offer the same therapeutic potential as invasive VNS. Further investigation into how VNS parameters modulate behavior and biology, as well as how to translate noninvasive options into the clinical arena, are crucial next steps for researchers and clinicians studying VNS. [ABSTRACT FROM AUTHOR]

In this paper, we prove a lower bound on the soundness of quantum locally testable codes under the distance balancing construction of Evra et al. Our technical contribution is that the soundness of the quantum code after this procedure is at least its soundness before the procedure divided by the length of the classical code used to perform distance balancing. This allows us to use any classical code when distance balancing, where previously only the repetition code had been considered for these codes. By using a good classical low-density parity check (LDPC) code, we are able to grow the dimension of the hypersphere product codes and the hemicubic codes while maintaining their distance and locality, but at the expense of soundness. From this, and also by distance balancing a chain complex of Cross et al., we obtain quantum locally testable codes of new parameters. [ABSTRACT FROM AUTHOR]

Platinum and ruthenium nanoparticles stabilised by an amine modified polymer immobilised ionic liquid (MNP@NH2-PEGPIILS, M = Pt, Ru) catalyse the hydrolytic liberation of hydrogen from dimethylamine borane (DMAB), ammonia borane (AB) and NaBH4 under mild conditions. While RuNP@NH2-PEGPIILS and PtNP@NH2-PEGPIILS catalyse the hydrolytic evolution of hydrogen from NaBH4 with comparable initial TOFs of 6,250 molesH2.molcat−1.h−1 and 5,900 molesH2.molcat−1.h−1, respectively, based on the total metal content, RuNP@NH2-PEGPIILS is a markedly more efficient catalyst for the dehydrogenation of DMAB and AB than its platinum counterpart, as RuNP@NH2-PEGPIILS gave initial TOFs of 8,300 molesH2.molcat−1.h−1 and 21,200 molesH2.molcat−1.h−1, respectively, compared with 3,050 molesH2.molcat−1.h−1 and 8,500 molesH2.molcat−1.h−1, respectively, for PtNP@NH2-PEGPIILS. Gratifyingly, for each substrate tested RuNP@NH2-PEGPIILS and PtNP@NH2-PEGPIILS were markedly more active than commercial 5wt % Ru/C and 5wt% Pt/C, respectively. The apparent activation energies of 55.7 kJ mol−1 and 27.9 kJ mol−1 for the catalytic hydrolysis of DMAB and AB, respectively, with RuNP@NH2-PEGPIILS are significantly lower than the respective activation energies of 74.6 kJ mol−1 and 35.7 kJ mol−1 for its platinum counterpart, commensurate with the markedly higher initial rates obtained with the RuNPs. In comparison, the apparent activation energies of 44.1 kJ mol−1 and 46.5 kJ mol−1, for the hydrolysis NaBH4 reflect the similar initial TOFs obtained for both catalysts. The difference in apparent activation energies for the hydrolysis of DMAB compared with AB also reflect the higher rates of hydrolysis for the latter. Stability and reuse studies revealed that RuNP@NH2-PEGPIILS recycled efficiently as high conversions for the hydrolysis of DMAB were maintained across five runs with the catalyst retaining 97% of its activity. [ABSTRACT FROM AUTHOR]

The method of Feynman–Kac perturbation of quantum stochastic processes has a long pedigree, with the theory usually developed within the framework of processes on von Neumann algebras. In this work, the theory of operator spaces is exploited to enable a broadening of the scope to flows on C ∗ algebras. Although the hypotheses that need to be verified in this general setting may seem numerous, we provide auxiliary results that enable this to be simplified in many of the cases which arise in practice. A wide variety of examples is provided by way of illustration. [ABSTRACT FROM AUTHOR]

Genetic toxicity testing assesses the potential of compounds to cause DNA damage. There are many genetic toxicology screening assays designed to assess the DNA damaging potential of chemicals in early drug development aiding the identification of promising drugs that have low-risk potential for causing genetic damage contributing to cancer risk in humans. Despite this, in vitro tests generate a high number of misleading positives, the consequences of which can lead to unnecessary animal testing and/or the abandonment of promising drug candidates. Understanding chemical Mode of Action (MoA) is vital to identifying the true genotoxic potential of substances and, therefore, the risk translation into the clinic. Here we demonstrate a simple, robust protocol for staining fixed, human-lymphoblast p53 proficient TK6 cells with antibodies against ɣH2AX, p53 and pH3S28 along with DRAQ5™ DNA staining that enables analysis of un-lysed cells via microscopy approaches such as imaging flow cytometry. Here, we used the Cytek® Amnis® ImageStream®X Mk II which provides a high-throughput acquisition platform with the sensitivity of flow cytometry and spatial morphological information associated with microscopy. Using the ImageStream manufacturer's software (IDEAS® 6.2), a masking strategy was developed to automatically detect and quantify micronucleus events (MN) and characterise biomarker populations. The gating strategy developed enables the generation of a template capable of automatically batch processing data files quantifying cell-cycle, MN, ɣH2AX, p53 and pH3 populations simultaneously. In this way, we demonstrate how a multiplex system enables DNA damage assessment alongside MN identification using un-lysed cells on the imaging flow cytometry platform. As a proof-of-concept, we use the tool chemicals carbendazim and methyl methanesulphonate (MMS) to demonstrate the assay's ability to correctly identify clastogenic or aneugenic MoAs using the biomarker profiles established. [ABSTRACT FROM AUTHOR]

Background: The increasing burden of cancer has economic implications for the healthcare system in England. However, there is limited evidence on the cost of cancer treatment. We calculated the costs of initial cancer treatment (resection, radiotherapy, systemic anti-cancer therapy [SACT]) based on stage at diagnosis. Methods: Data from England's National Cancer Registration Dataset were matched to English Hospital, Radiotherapy and SACT data for breast, lung, prostate, colon and rectal cancers diagnosed between 2016 and 2018. Treatment data were matched to National Schedule of Reference Costs data to calculate the cost of each treatment event. Results: Breast, colon and rectal cancers treated with resection, radiotherapy or SACT had increasing costs with later stage at diagnosis; costs for lung and prostate cancers were lower at stages 1 and 4 compared to stages 2 and 3. In general, surgery and SACT were the most expensive treatments. Radiotherapy and SACT costs showed little change across stages 1–3; radiotherapy costs decreased in stage 4, while SACT costs increased. Conclusions: This analysis estimates initial treatment costs by stage based on observed data. Future research can build on this to provide more comprehensive costings associated with cancer; this is important for future planning of cancer services. [ABSTRACT FROM AUTHOR]

Hikitia te Ora (Certificate in Health Sciences) is a 1 year Indigenous bridging foundation programme at the University of Auckland, Aotearoa New Zealand. The programme aims to increase Māori and Pacific health workforce representation. This qualitative study applied a Kaupapa Māori positioning to elucidate the strengths, challenges, and opportunities of the programme. Data were collected through two workshops and seven focus groups with a total of 67 participants who were students of Hikitia te Ora from past and present cohorts, or their family members. Using a general inductive thematic analysis, the primary themes identified were that programme successes encompassed whanaungatanga (process of establishing relationships), academic and pastoral support, programme structure and the teaching content. Challenges included social cliques and divisive social groupings, timetabling of courses and high workloads. The three areas that emerged for further development include extending Pacific content, increasing the number of students in the programme, and maintaining a programme-specific study space for students. Implementing the findings from this study into Hikitia te Ora is expected to improve educational outcomes for Māori and Pacific students and may have the potential to benefit other bridging foundation courses aiming to promote Indigenous health workforce development. [ABSTRACT FROM AUTHOR]

Signal transducers and activators of transcription (STAT) proteins regulate mammary development. Here we investigate the expression of phosphorylated STAT3 (pSTAT3) in the mouse and cow around the day of birth. We present localised colocation analysis, applicable to other mammary studies requiring identification of spatially congregated events. We demonstrate that pSTAT3-positive events are multifocally clustered in a non-random and statistically significant fashion. Arginase-1 expressing cells, consistent with macrophages, exhibit distinct clustering within the periparturient mammary gland. These findings represent a new facet of mammary STAT3 biology, and point to the presence of mammary sub-microenvironments. [ABSTRACT FROM AUTHOR]

Anterior cruciate ligament (ACL) reconstruction (ACLR) is used to treat clinical instability post ACL rupture, however, there is a high rate of incomplete return to sport and rerupture. There is increasing interest in posterior tibial slope as an intrinsic risk factor for ACLR failure and persistent instability. Zoobiquity describes the collaboration between the human and veterinary professions in order to advance the scientific understanding of both fields. Given the cranial cruciate ligament (CCL) in dogs is synonymous with the anterior cruciate ligament in humans, functioning to control internal rotation and anterior translation, but osteotomies, rather than ligament reconstruction, are the mainstay of treatment for CCL rupture, this editorial sort to gain insights into this form of treatment from the veterinary world. Level of Evidence: Level V, evidence. [ABSTRACT FROM AUTHOR]

Primary human hepatocytes (PHHs) are used extensively for in vitro liver cultures to study hepatic functions. However, limited availability and invasive retrieval prevent their widespread use. Induced pluripotent stem cells exhibit significant potential since they can be obtained non-invasively and differentiated into hepatic lineages, such as hepatocyte-like cells (iHLCs). However, there are concerns about their fetal phenotypic characteristics and their hepatic functions compared to PHHs in culture. Therefore, we performed an RNA-sequencing (RNA-seq) analysis to understand pathways that are either up- or downregulated in each cell type. Analysis of the RNA-seq data showed an upregulation in the bile secretion pathway where genes such as AQP9 and UGT1A1 were higher expressed in PHHs compared to iHLCs by 455- and 15-fold, respectively. Upon immunostaining, bile canaliculi were shown to be present in PHHs. The TCA cycle in PHHs was upregulated compared to iHLCs. Cellular analysis showed a 2–2.5-fold increase in normalized urea production in PHHs compared to iHLCs. In addition, drug metabolism pathways, including cytochrome P450 (CYP450) and UDP-glucuronosyltransferase enzymes, were upregulated in PHHs compared to iHLCs. Of note, CYP2E1 gene expression was significantly higher (21,810-fold) in PHHs. Acetaminophen and ethanol were administered to PHH and iHLC cultures to investigate differences in biotransformation. CYP450 activity of baseline and toxicant-treated samples was significantly higher in PHHs compared to iHLCs. Our analysis revealed that iHLCs have substantial differences from PHHs in critical hepatic functions. These results have highlighted the differences in gene expression and hepatic functions between PHHs and iHLCs to motivate future investigation. Characterizing the transcriptomic differences between primary human hepatocytes (PHHs) and induced pluripotent stem cell hepatocyte-like cells (iHLCs) using RNA-sequencing and phenotypic measurements [ABSTRACT FROM AUTHOR]

Appropriate interaction between pantograph and catenary is imperative for smooth operation of electric trains. Changing heights of overhead lines to accommodate level crossings, overbridges, and tunnels pose significant challenges in maintaining consistent current collection performance as the pantograph aerodynamic profile, and thus aerodynamic load changes significantly with operational height. This research aims to analyse the global flow characteristics and aerodynamic forces acting on individual components of an HSX pantograph operating in different configurations and orientations, such that the results can be combined with multibody simulations to obtain accurate dynamic insight into contact forces. Specifically, computational fluid dynamics simulations are used to investigate the pantograph component loads in a representative setting, such as that of the recessed cavity on a Class 800 train. From an aerodynamic perspective, this study indicates that the total drag force acting on non-fixed components of the pantograph is larger for the knuckle-leading orientation rather than the knuckle-trailing, although the difference between the two is found to reduce with increasing pantograph extension. Combining the aerodynamic loads acting on individual components with multibody tools allows for realistic dynamic insight into the pantograph behaviour. The results obtained show how considering aerodynamic forces enhance the realism of the models, leading to behaviour of the pantograph–catenary contact forces closely matching that seen in experimental tests. [ABSTRACT FROM AUTHOR]

Boundaries to movement form a specific class of landmark information used for navigation: Boundary Vector Cells (BVCs) are neurons which encode an animal's location as a vector displacement from boundaries. Here we characterise the prevalence and spatial tuning of subiculum BVCs in adult and developing male rats, and investigate the relationship between BVC spatial firing and boundary geometry. BVC directional tunings align with environment walls in squares, but are uniformly distributed in circles, demonstrating that environmental geometry alters BVC receptive fields. Inserted barriers uncover both excitatory and inhibitory components to BVC receptive fields, demonstrating that inhibitory inputs contribute to BVC field formation. During post-natal development, subiculum BVCs mature slowly, contrasting with the earlier maturation of boundary-responsive cells in upstream Entorhinal Cortex. However, Subiculum and Entorhinal BVC receptive fields are altered by boundary geometry as early as tested, suggesting this is an inherent feature of the hippocampal representation of space. How neural responses to boundaries develop in the subiculum remains unknown. Here authors show that the receptive fields of Boundary Vector Cells (neurons signalling vector displacement to boundaries) are altered by environment geometry, with directional tunings aligning with square arena walls, including during development. [ABSTRACT FROM AUTHOR]

The St. Clair-Detroit River System (SCDRS) connects Lake Huron to Lake Erie and provides important habitats for many fishes of economic and ecological importance. Portions of the SCDRS are designated as Great Lakes Areas of Concern and fish production and conservation may be compromised. Efforts to address beneficial use impairments have focused on restoring habitat for native fishes and improving aquatic ecosystem health. Considerable site-specific research and long-term, annual fish surveys have examined responses to habitat improvements. However, there is uncertainty surrounding whether individual studies and surveys can assess (1) population-level benefits of habitat enhancements and (2) whether management objectives are being met. To identify monitoring gaps and inform long-term monitoring program development, we compared outputs from SCDRS fish monitoring surveys (based on discussions with regional agencies) with performance measures specified in management plans (obtained through gray literature searches). Performance measures for harvested species aligned well with outputs of existing surveys. In contrast, at-risk fishes often had objectives and performance measures that reflected knowledge gaps and study needs. Although harvested species were well-monitored relative to specified performance measures, at-risk fishes were less reliably collected by existing surveys, except for lake sturgeon Acipenser fulvescens. Effective evaluation of restoration efforts for at-risk fishes may require additional survey efforts that target species-specific habitat use and life history characteristics. [ABSTRACT FROM AUTHOR]

Purpose: Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a chronic condition with a constellation of symptoms presenting as severe and profound fatigue of ≥ 6 months not relieved by rest. ME/CFS affects health-related quality of life (HRQoL), which can be measured using multi-attribute health state utility (HSU) instruments. The aims of this study were to quantify HSUs for people living with ME/CFS, and to identify an instrument that is preferentially sensitive for ME/CFS. Methods: Cross-sectional national survey of people with ME/CFS using the AQoL-8D and EQ-5D-5L. Additional questions from the AQoL-8D were used as 'bolt-ons' to the EQ-5D-5L (i.e., EQ-5D-5L-Psychosocial). Disability and fatigue severity were assessed using the De Paul Symptom Questionnaire-Short Form (DSQ-SF). HSUs were generated using Australian tariffs. Mean HSUs were stratified for sociodemographic and clinical factors. Bland–Altman plots were used to compare the three HSU instruments. Results: For the 198 participants, mean HSUs (95% confidence intervals) were EQ-5D-5L: 0.46 (0.42–0.50); AQoL-8D: 0.43 (0.41–0.45); EQ-5D-5L-Psychosocial: 0.44 (0.42–0.46). HSUs were substantially lower than population norms: EQ-5D-5L: 0.89; AQoL-8D: 0.77. As disability and fatigue severity increased, HSUs decreased in all three instruments. Bland–Altman plots revealed interchangeability between the AQoL-8D and EQ-5D-5LPsychosocial. Floor and ceiling effects of 13.5% and 2.5% respectively were observed for the EQ-5D-5L instrument only. Conclusions: ME/CFS has a profound impact on HRQoL. The AQoL-8D and EQ-5D-5L-Psychosocial can be used interchangeably: the latter represents a reduced participant burden. [ABSTRACT FROM AUTHOR]

Exercise-based cardiac rehabilitation (CR) is an evidence-based recommendation for patients with stable heart failure (HF). Less clear is how effective exercise-based CR is for women with HF. The aim of this review was to synthesize the evidence for the effects of exercise-based CR on mortality, hospitalizations, exercise capacity, and quality of life (QOL) among women with HF. We identified 18 studies comprising 4917 patients, of which 1714 were women. The interventions evaluated consisted of various combinations of supervised in-hospital and out-patient sessions as well as home-based programs that included aerobic (walking, treadmill, bicycle) and resistance training. The interventions ranged from 12 to 54 weeks, with a frequency of 2–7 sessions per week, lasting from 30 to 105 min per session. Because of a paucity of sex-specific analyses of the outcomes, it was not possible to draw conclusions for women. There was limited evidence for mortality benefit for men or women participating in exercise-based CR. There was more substantial evidence for reductions in hospitalizations for the participants. Generally, exercise training improved exercise capacity. The effects of exercise-based CR on QOL were mixed with most studies favoring CR at 3 months but not at 4, 5, and 12 months. Moreover, generally, the physical dimension of QOL but not the mental dimensions improved. Recommendations for future research to reduce the gap in knowledge about the effects of exercise-based CR for women are offered. [ABSTRACT FROM AUTHOR]

Abstract Cancer genome sequencing projects have identified hundreds of genetic alterations, often at low frequencies, raising questions as to their functional relevance. One exemplar gene is HUWE1, which has been found to be mutated in numerous studies. However, due to the large size of this gene and a lack of functional analysis of identified mutations, their significance to carcinogenesis is unclear. To determine the importance of HUWE1, we chose to examine its function in colorectal cancer, where it is mutated in up to 15 per cent of tumours. Modelling of identified mutations showed that they inactivate the E3 ubiquitin ligase activity of HUWE1. Genetic deletion of Huwe1 rapidly accelerated tumourigenic in mice carrying loss of the intestinal tumour suppressor gene Apc, with a dramatic increase in tumour initiation. Mechanistically, this phenotype was driven by increased MYC and rapid DNA damage accumulation leading to loss of the second copy of Apc. The increased levels of DNA damage sensitised Huwe1‐deficient tumours to DNA‐damaging agents and to deletion of the anti‐apoptotic protein MCL1. Taken together, these data identify HUWE1 as a bona fide tumour suppressor gene in the intestinal epithelium and suggest a potential vulnerability of HUWE1‐mutated tumours to DNA‐damaging agents and inhibitors of anti‐apoptotic proteins.

Species richness is strikingly uneven across taxonomic groups at all hierarchical levels, but the reasons for this heterogeneity are poorly understood. It is well established that morphological diversity (disparity) is decoupled from taxonomic diversity, both between clades and across geological time. Morphological complexity has been much less studied, but there is theory linking complexity with differential diversity across groups. Here we devise an index of complexity from the differentiation of the fore and hind limb pairs for a sample of 983 species of extant birds. We test the null hypothesis that this index of morphological complexity is uncorrelated with clade diversity, revealing a significant and negative correlation between the species richness of clades and the mean morphological complexity of those clades. Further, we find that more complex clades tend to occupy a smaller number of dietary and habitat niches, and that this proxy for greater ecological specialisation correlates with lower species richness. Greater morphological complexity in the appendicular skeleton therefore appears to hinder the generation and maintenance of species diversity. This may result from entrenchment into morphologies and ecologies that are less capable of yielding further diversity. Biodiversity is unevenly distributed across the tree of life, and theoretical work suggests that biological complexity may be influential in forming these patterns. Here, Brinkworth et al. have shown that bird clades with more complex appendicular skeletons tend to have lower extant species richness. [ABSTRACT FROM AUTHOR]

Copyright of Plant Ecology is the property of Springer Nature and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

ABCG2 is a medically important ATP-binding cassette transporter with crucial roles in the absorption and distribution of chemically-diverse toxins and drugs, reducing the cellular accumulation of chemotherapeutic drugs to facilitate multidrug resistance in cancer. ABCG2's capacity to transport both hydrophilic and hydrophobic compounds is not well understood. Here we assess the molecular basis for substrate discrimination by the binding pocket. Substitution of a phylogenetically-conserved polar residue, N436, to alanine in the binding pocket of human ABCG2 permits only hydrophobic substrate transport, revealing the unique role of N436 as a discriminator. Molecular dynamics simulations show that this alanine substitution alters the electrostatic potential of the binding pocket favoring hydration of the transport pore. This change affects the contact with substrates and inhibitors, abrogating hydrophilic compound transport while retaining the transport of hydrophobic compounds. The N436 residue is also required for optimal transport inhibition of ABCG2, as many inhibitors are functionally impaired by this ABCG2 mutation. Overall, these findings have biomedical implications, broadly extending our understanding of substrate and inhibitor interactions. ABCG2, an ATP-binding cassette transporter, extrudes hundreds of hydrophilic and hydrophobic compounds from cells, playing roles in xenobiotic clearance or multidrug resistance in cancer. Gose et al provide key insights into ABCG2 substrate selection. [ABSTRACT FROM AUTHOR]

Rationale: Psychotic disorders such as schizophrenia are often accompanied by high rates of cigarette smoking, reduced quit success, and high relapse rates, negatively affecting patient outcomes. However, the mechanisms underlying altered relapse-like behaviors in psychosis are poorly understood. Objectives: The present study analyzed changes in extinction and reinstatement of nicotine conditioned place preference (CPP) and resulting changes in brain-derived neurotrophic factor (BDNF) in a novel heritable rodent model of psychosis, demonstrating increased dopamine D2 receptor sensitivity, to explore mechanisms contributing to changes in relapse-like behaviors. Methods: Male and female offspring of two neonatal quinpirole-treated (1 mg/kg quinpirole from postnatal day (P)1–21; QQ) and two neonatal saline-treated (SS) Sprague–Dawley rats (F1 generation) were tested on an extended CPP paradigm to analyze extinction and nicotine-primed reinstatement. Brain tissue was analyzed 60 min after the last nicotine injection for BDNF response in the ventral tegmental area (VTA), the infralimbic (IfL) and prelimbic (PrL) cortices. Results: F1 generation QQ offspring demonstrated delayed extinction and more robust reinstatement compared to SS control animals. In addition, QQ animals demonstrated an enhanced BDNF response to nicotine in the VTA, IfL and Prl cortices compared to SS offspring. Conclusions: This study is the first to demonstrate altered relapse-like behavior in a heritable rodent model with relevance to comorbid drug abuse and psychosis. This altered pattern of behavior is hypothesized to be related to elevated activity-dependent BDNF in brain areas associated with drug reinforcement during conditioning that persists through the extinction phase, rendering aberrantly salient drug associations resistant to extinction and enhancing relapse vulnerability. [ABSTRACT FROM AUTHOR]

The MYC oncogene is a potent driver of growth and proliferation but also sensitises cells to apoptosis, which limits its oncogenic potential. MYC induces several biosynthetic programmes and primary cells overexpressing MYC are highly sensitive to glutamine withdrawal suggesting that MYC-induced sensitisation to apoptosis may be due to imbalance of metabolic/energetic supply and demand. Here we show that MYC elevates global transcription and translation, even in the absence of glutamine, revealing metabolic demand without corresponding supply. Glutamine withdrawal from MRC-5 fibroblasts depletes key tricarboxylic acid (TCA) cycle metabolites and, in combination with MYC activation, leads to AMP accumulation and nucleotide catabolism indicative of energetic stress. Further analyses reveal that glutamine supports viability through TCA cycle energetics rather than asparagine biosynthesis and that TCA cycle inhibition confers tumour suppression on MYC-driven lymphoma in vivo. In summary, glutamine supports the viability of MYC-overexpressing cells through an energetic rather than a biosynthetic mechanism. MYC activation can sensitise cells to apoptosis upon glutamine withdrawal. Here the authors show that MYC activation enhances global transcription and translation that creates a metabolic demand, while glutamine limitation causes a metabolic demand and supply imbalance through loss of TCA energetics and thus, sensitises cells to apoptosis. [ABSTRACT FROM AUTHOR]

Middle school is a cornerstone for success in high school. However, cognitive, emotional, and behavioral engagement of adolescents often decline as they transition from elementary to middle school, resulting in lower school grades and more challenging behaviors, especially for adolescents with or at risk for emotional and behavioral disorders (EBD). Class-wide function-related intervention teams (CW-FIT), a classroom management program based on school-wide positive behavior support, has been found to be effective in elementary general and special education classrooms. The present study, a randomized control trial of CW-FIT for middle schools (CW-FIT MS), evaluated the effects on class-wide on-task behavior, as well as the on-task and disruptive behaviors of students identified as at risk for EBD. Participants included 629 students (70 identified as at risk) enrolled in 28 middle school classrooms across five Title I schools representing diverse geographic, ethnic, and socioeconomic areas. The study also addressed research questions regarding effects of the intervention on teacher praise and reprimands, as well as teacher and student social validity. Results suggested that CW-FIT MS was associated with improvements in class-wide and at-risk student on-task behavior, student disruptions, teacher praise, and teacher reprimand rates. Both teachers and students reported the intervention to be socially valid. Study limitations and areas for future research are addressed. [ABSTRACT FROM AUTHOR]

Effective Global Citizenship Education (GCED) and Education for Sustainable Development (ESD) benefit from three interrelated dimensions of learning identified by UNESCO: cognitive, social-emotional and behavioural. The latter two of these are especially relevant to mindful compassion pedagogies, and the purpose of the literature review presented here was to ascertain how well such pedagogies could cultivate GCED and ESD social and emotional behavioural competencies in preschool to secondary-level education, tertiary-level education and professional development programmes for educators. The research team analysed 37 relevant peer-reviewed research articles and reports published between 1956 and 2021. Their findings point to many possibilities for how mindful compassion practices could serve as building blocks for desired GCED and ESD competencies. However, this requires a great deal of intentionality on the part of those responsible for the design, implementation and evaluation of mindful compassion-based programmes seeking to cultivate GCED- and ESD-related behavioural competencies. In essence, curriculum designers need to provide opportunities for students to practise mindful compassion as a microskill that leads to the attainment of behavioural competencies conducive to global citizenship and sustainable development. This article summarises the researchers' findings and posits guiding questions for educators and researchers to consider as they design and evaluate social-emotional competencies of the kind needed for GCED and ESD to be effective. [ABSTRACT FROM AUTHOR]

The risk-based access control model is one of the dynamic models that use the security risk as a criterion to decide the access decision for each access request. This model permits or denies access requests dynamically based on the estimated risk value. The essential stage of implementing this model is the risk estimation process. This process is based on estimating the possibility of information leakage and the value of that information. Several researchers utilized different methods for risk estimation but most of these methods were based on qualitative measures, which cannot suit the access control context that needs numeric and precise risk values to decide either granting or denying access. Therefore, this paper presents a novel Adaptive Neuro-Fuzzy Inference System (ANFIS) model for risk estimation in the risk-based access control model for the Internet of Things (IoT). The proposed ANFIS model was implemented and evaluated against access control scenarios of smart homes. The results demonstrated that the proposed ANFIS model provides an efficient and accurate risk estimation technique that can adapt to the changing conditions of the IoT environment. To validate the applicability and effectiveness of the proposed ANFIS model in smart homes, ten IoT security experts were interviewed. The results of the interviews illustrated that all experts confirmed that the proposed ANFIS model provides accurate and realistic results with a 0.713 in Cronbach's alpha coefficient which indicates that the results are consistent and reliable. Compared to existing work, the proposed ANFIS model provides an efficient processing time as it reduces the processing time from 57.385 to 10.875 Sec per 1000 access requests, which demonstrates that the proposed model provides effective and accurate risk evaluation in a timely manner. [ABSTRACT FROM AUTHOR]

The human skin barrier, a biological imperative, is impaired in inflammatory skin diseases such as atopic dermatitis (AD). Staphylococcus aureus is associated with AD lesions and contributes to pathological inflammation and further barrier impairment. S. aureus secretes extracellular proteases, such as V8 (or 'SspA'), which cleave extracellular proteins to reduce skin barrier. Previous studies demonstrated that the host defence peptide human beta-defensin 2 (HBD2) prevented V8-mediated damage. Here, the mechanism of HBD2-mediated barrier protection in vitro is examined. Application of exogenous HBD2 provided protection against V8, irrespective of timeline of application or native peptide folding, raising the prospect of simple peptide analogues as therapeutics. HBD2 treatment, in context of V8-mediated damage, modulated the proteomic/secretomic profiles of HaCaT cells, altering levels of specific extracellular matrix proteins, potentially recovering V8 damage. However, HBD2 alone did not substantially modulate cellular proteomic/secretomics profiles in the absence of damage, suggesting possible therapeutic targeting of lesion damage sites only. HBD2 did not show any direct protease inhibition or induce expression of known antiproteases, did not alter keratinocyte migration or proliferation, or form protective nanonet structures. These data validate the barrier-protective properties of HBD2 in vitro and establish key protein datasets for further targeted mechanistic analyses. [ABSTRACT FROM AUTHOR]

Acidic deposition has been well studied for its impacts on forest soils and plants and is thought to detrimentally affect sugar maple (Acer saccharum) in northeastern North America. The physiological mechanism driving reduced tree growth on acid impaired sites is not well understood, but has been suggested to involve increased autotrophic respiration rates. We measured foliar respiration and leaf elemental composition on two species with contrasting acid tolerances (sugar maple and American beech, Fagus grandifolia) across a naturally occurring soil base saturation (BS) gradient in the Adirondack Mountains of New York. Foliar chemistry varied strongly as anticipated across the BS gradient, with decreases in base cations and increases in phytotoxic metals (e.g., Mn) on sites with highly acidified soils. However, foliar respiration rates were not correlated with most measures of acidity (e.g., BS, foliar concentrations of Ca, Mg, Al content). Respiration rates did correlate with other leaf traits (N content, leaf mass per unit area) reflective of leaf morphological variation in response to variable light availability. After accounting for multivariate trait covariation, mass-based respiration rates were associated with foliar Mn content, suggesting a positive relationship between the concentration of this phytotoxic metal and foliar respiration rates. Soluble foliar Ca, Mg, and Mn were closely correlated with total foliar concentrations of these elements. Overall these results demonstrate that soil acidification and loss of base cations is largely unrelated to foliar respiration rates, although the accumulation of foliar Mn on acidified soils may contribute to the metabolic burden of both sugar maple and American beech trees. [ABSTRACT FROM AUTHOR]

A current debate in addiction research concerns the linkage between behavioral addictions (e.g., smartphone and Internet) and chemical addictions (e.g., smoking and drinking). In this study, we investigated associations between smoking and smartphone addiction by examining correlation with motives for smoking as mediators. Participants were high school and university students (N = 295; aged between 15 and 30 years). Using cluster analysis, we identified four clusters. Cluster 1 was not susceptible to either smoking or smartphone addiction. In Cluster 2, smoking frequency was high but these youth were not addicted to smartphone use. Cluster 3 was characterized by a high susceptibility to smartphone addiction but low levels of smoking motives and low rate of smoking. In Cluster 4, smartphone addiction occurred together with a high smoking rate. High school students and university students showed different cluster categorizations. Based on these results, we can conclude that youth's susceptibility to addiction may be influenced by motivations. [ABSTRACT FROM AUTHOR]

Bonefish are members of one of the oldest extant teleost superorders, Elopomorpha, which also includes eels, tarpons, and ladyfish. All share a common larval stage called the leptocephalus or "glass eel" stage. Though bonefish serve an important role in Caribbean ecosystems and fisheries, little is known about their life history and reproductive process. In order to observe and better describe bonefish spawning characteristics, wild bonefish (Albula goreensis) were collected off of Stuart, FL, USA. The group was transported to Harbor Branch Oceanographic Institute and acclimated to captive habitats where they underwent monthly hormonal manipulation to induce spawning. Spawning events occurred on October 4 and 6, 2020. For both spawns, eggs were collected in an egg collector and transferred to Kreisel tanks to hatch. Samples of eggs were collected prior to hatching to determine biometrics such as size, fertilization success, and hatching success. Leptocephalus larvae were collected daily for up to 3 days post-hatch, and biometric data was recorded for a subsample of larvae. Total fatty acids were extracted from egg and larvae samples and analyzed using GC–MS detection methods. Larvae samples showed a general decrease in polyunsaturated fatty acids (PUFAs) coinciding with growth after hatching, supporting the notion that PUFAs are utilized for growth and metabolic processes. This project is part of a multi-year effort to successfully spawn bonefish in captivity and can be utilized as a baseline in future studies intended to inform conservation methods for wild populations. [ABSTRACT FROM AUTHOR]

Background: Outcomes-based agreements (OBAs) have the potential to provide more timely patient access to novel therapies, although they are not suitable for every new medication or reimbursement scenario. The authors of this paper studied how to operationalize an OBA in oncology by leveraging existing real-world data (RWD) infrastructure in the province of Alberta. Objective: The main objectives were to (1) evaluate which health outcomes in oncology are suitable for OBAs and whether they can be tracked with existing infrastructure, and (2) determine how RWD in oncology can be used to implement an OBA and the expected timing for delivery. Methods: Using the Oncology Outcomes (O2) Group infrastructure and Alberta administrative data, a review of five key oncology outcomes was performed to determine suitability to support an OBA. Results: Overall survival and time-to-next-treatment were determined as potentially suitable oncology outcomes for OBAs; progression-free survival, patient-reported outcomes, and return to work were deemed inadequate for OBAs at the current time due to data limitations. Conclusions: Results indicate that it is feasible to leverage RWD to support OBAs in oncology in Alberta, with minimal additional data, resources, and infrastructure. The operational processes and steps to collect and analyze RWD for OBAs were identified, starting with performing an RWD feasibility study. The expected timeframe to fulfill the real-world evidence (RWE) requirements for an OBA is approximately 3 years for cancers with short trajectories. [ABSTRACT FROM AUTHOR]

The correction notice published in Nature Communications addresses an error in the author name Megan L. O'Mara, which was incorrectly written as Megan L. O'Mara. The original article has been corrected to reflect the accurate name. The article is licensed under a Creative Commons Attribution 4.0 International License, allowing for sharing, adaptation, and distribution with appropriate credit to the original author(s) and source. [Extracted from the article]

A seasonal comparison of the nutritional profile of sea lettuce (Ulva lactuca) produced in a land-based integrated multi-trophic aquaculture (IMTA) system in Florida was conducted quarterly (March, June, September, December) over the course of an annual production cycle. Nutritional parameters evaluated included proximate analysis, mineral and total carotenoid content, and amino acid profile. Water quality parameters evaluated included temperature, salinity, pH, light availability, and nitrogenous compounds. No significant differences with respect to seasonality were seen with regard to proximate analysis. In contrast, significant differences were noted in mineral concentrations for potassium (highest spring, lowest fall), copper (highest spring, lowest winter), and iron (highest fall, lowest summer). Levels of arsenic, cadmium, and lead were below European Union (EU) recommended threshold levels, and no mercury was detected. Seasonal variation was seen in arsenic (highest in fall) and cadmium (highest in spring). The percent of non-essential amino acids was higher than that of essential amino acids, with high concentrations of aspartic acid, glutamic acid, and alanine noted in all seasons. Carotene concentrations ranged from 114 to 229 mg/kg. In general, the nutritional profile of U. lactuca produced in a sub-tropical IMTA system is seasonally consistent, allowing harvested product to be utilized year-round without concern for nutritional loss. [ABSTRACT FROM AUTHOR]

To determine perceptions of climate change among millennials and Gen-Z, eighty respondents participated in one of four focus groups to discuss perceptions of climate change messages. The objective of this exploratory conversation with the participants was to determine climate change perceptions and understand more completely how attitudes of climate change are developed, to what strategic narratives these participants have been exposed, and how participants both consume messages and engage in message generation. The findings from this research will support or negate the findings of previous research on strategic climate change narrative themes, expand the number of themes of strategic narratives, and provide direction for developing climate change narratives that more effectively move future generations to action. [ABSTRACT FROM AUTHOR]

A genomic and bioactivity informed analysis of the metabolome of the extremophile Amycolatopsis sp. DEM30355 has allowed for the discovery and isolation of the polyketide antibiotic tatiomicin. Identification of the biosynthetic gene cluster was confirmed by heterologous expression in Streptomyces coelicolor M1152. Structural elucidation, including absolute stereochemical assignment, was performed using complementary crystallographic, spectroscopic and computational methods. Tatiomicin shows antibiotic activity against Gram-positive bacteria, including methicillin-resistant Staphylococcus aureus (MRSA). Cytological profiling experiments suggest a putative antibiotic mode-of-action, involving membrane depolarisation and chromosomal decondensation of the target bacteria. [ABSTRACT FROM AUTHOR]

Analytical characterization efforts carried out in support of the conservation treatment of Mark Rothko's painting 'Black on Maroon' 1958 (Tate T01170), involving the removal of graffiti (tag) ink, are summarized. The proprietary ink product, of unfamiliar and unknown composition, was investigated using a suite of analytical techniques (IR spectroscopy, GC–MS, ICP-MS, pyrolysis GC–MS, thin layer chromatography, SEC, MALDI-TOF–MS, and UHPLC-MS) to identify key colorants and other components. The ink solubility properties proved vital to informing the solvent selection process for the ink removal procedure, which helped enable the re-display of the painting at Tate Modern in 2014. The possible impact of ink residues remaining within the cotton duck canvas support of the conserved painting was also explored using mockup canvas mechanical strength data, measured before and after 'soiling' at two ink levels to assess whether the ink residues had any immediate and possible longer-term effects on canvas properties. These findings, elucidated using a range of complementary analytical techniques, provide information on this hitherto-unknown graffiti product, contribute to a growing body of knowledge in this area, and offer analytical approaches which may be useful for the characterization of similar unknown materials, whether used to damage, augment, or create works of art. [ABSTRACT FROM AUTHOR]

Sodium nitrite (NaNO2) is a compound with broad practical applications in food preservation, automotive maintenance, and animal control. Sodium nitrite is also potentially fatal when ingested, as it interferes with the ability of red blood cells to transport oxygen. While incidents of accidental consumption have been reported in the literature, case reports of sodium nitrite being used as a pharmacological suicide agent are becoming more frequent. Therefore, a study was undertaken to evaluate trends in sodium nitrite deaths in South Australia between 2000 and 2019. All cases of fatal sodium nitrite ingestion were identified in the Toxicology database and autopsy reports at Forensic Science SA (FSSA). Ten cases of fatal sodium nitrite ingestion were identified, with the rate of cases increasing significantly over the study period (p >.001). Of the ten deaths attributed to sodium nitrite toxicity, eight were male, and two were female. The age range of decedents was 22–74 years (mean 51.9, SD 21.1), 22–74 years for males (mean 58.4, SD 18.2) and 23–29 years for females (mean 26.0, SD 4.2). Males (80%) and those with a history of depression and/or suicidal ideation (70%) were over-represented within the study population. While autopsy findings were generally consistent with the literature, scene findings emphasized the accessibility of sodium nitrite to the general public. This study highlights both a significant increasing trend in the use of sodium nitrite in suicides and important analytical limitations in the evaluation of suspected cases. [ABSTRACT FROM AUTHOR]

Risk assessments are increasingly reliant on information from in vitro assays. The in vitro micronucleus test (MNvit) is a genotoxicity test that detects chromosomal abnormalities, including chromosome breakage (clastogenicity) and/or whole chromosome loss (aneugenicity). In this study, MNvit datasets for 292 chemicals, generated by the US EPA's ToxCast program, were evaluated using a decision tree-based pipeline for hazard identification. Chemicals were tested with 19 concentrations (n = 1) up to 200 µM, in the presence and absence of Aroclor 1254-induced rat liver S9. To identify clastogenic chemicals, %MN values at each concentration were compared to a distribution of batch-specific solvent controls; this was followed by cytotoxicity assessment and benchmark concentration (BMC) analyses. The approach classified 157 substances as positives, 25 as negatives, and 110 as inconclusive. Using the approach described in Bryce et al. (Environ Mol Mutagen 52:280–286, 2011), we identified 15 (5%) aneugens. IVIVE (in vitro to in vivo extrapolation) was employed to convert BMCs into administered equivalent doses (AEDs). Where possible, AEDs were compared to points of departure (PODs) for traditional genotoxicity endpoints; AEDs were generally lower than PODs based on in vivo endpoints. To facilitate interpretation of in vitro MN assay concentration–response data for risk assessment, exposure estimates were utilized to calculate bioactivity exposure ratio (BER) values. BERs for 50 clastogens and two aneugens had AEDs that approached exposure estimates (i.e., BER < 100); these chemicals might be considered priorities for additional testing. This work provides a framework for the use of high-throughput in vitro genotoxicity testing for priority setting and chemical risk assessment. [ABSTRACT FROM AUTHOR]

Phylogenetic relationships are inferred principally from two classes of data: morphological and molecular. Currently, most phylogenies of extant taxa are inferred from molecules and when morphological and molecular trees conflict the latter are often preferred. Although supported by simulations, the superiority of molecular trees has rarely been assessed empirically. Here we test phylogenetic accuracy using two independent data sources: biogeographic distributions and fossil first occurrences. For 48 pairs of morphological and molecular trees we show that, on average, molecular trees provide a better fit to biogeographic data than their morphological counterparts and that biogeographic congruence increases over research time. We find no significant differences in stratigraphic congruence between morphological and molecular trees. These results have implications for understanding the distribution of homoplasy in morphological data sets, the utility of morphology as a test of molecular hypotheses and the implications of analysing fossil groups for which molecular data are unavailable. Using biogeographical and phylogenetic data, it is shown that molecular trees fit species geographical data better than trees inferred from morphology, and that these differences are not simply due to better tree resolution. [ABSTRACT FROM AUTHOR]

RNA-binding proteins play key roles in controlling gene expression in many organisms, but relatively few have been identified and characterised in detail in Gram-positive bacteria. Here, we globally analyse RNA-binding proteins in methicillin-resistant Staphylococcus aureus (MRSA) using two complementary biochemical approaches. We identify hundreds of putative RNA-binding proteins, many containing unconventional RNA-binding domains such as Rossmann-fold domains. Remarkably, more than half of the proteins containing helix-turn-helix (HTH) domains, which are frequently found in prokaryotic transcription factors, bind RNA in vivo. In particular, the CcpA transcription factor, a master regulator of carbon metabolism, uses its HTH domain to bind hundreds of RNAs near intrinsic transcription terminators in vivo. We propose that CcpA, besides acting as a transcription factor, post-transcriptionally regulates the stability of many RNAs. RNA-binding proteins play key roles in controlling gene expression in many organisms. Here, Chu et al. identify hundreds of RNA-binding proteins in methicillin-resistant Staphylococcus aureus, and show that a major transcription factor uses its helix-turn-helix domain to bind RNAs near intrinsic transcription terminators. [ABSTRACT FROM AUTHOR]

The most common host entry point of human adapted coronaviruses (CoV) including SARS-CoV-2 is through the initial colonization in the nostril and mouth region which is responsible for spread of the infection. Most recent studies suggest that the commercially available oral and nasal rinse products are effective in inhibiting the viral replication. However, the anti-viral mechanism of the active ingredients present in the oral rinses have not been studied. In the present study, we have assessed in vitro enzymatic inhibitory activity of active ingredients in the oral mouth rinse products: aloin A and B, chlorhexidine, eucalyptol, hexetidine, menthol, triclosan, methyl salicylate, sodium fluoride and povidone, against two important proteases of SARS-CoV-2 PLpro and 3CLpro. Our results indicate only aloin A and B effectively inhibited proteolytic activity of PLpro with an IC50 of 13.16 and 16.08 μM. Interestingly, neither of the aloin isoforms inhibited 3CLpro enzymatic activity. Computational structural modelling of aloin A and B interaction with PLpro revealed that, both aloin isoforms form hydrogen bond with Tyr268 of PLpro, which is critical for their proteolytic activity. Furthermore, 100 ns molecular dynamics (MD) simulation studies predicted that both aloin isoforms have strong interaction with Glu167, which is required for PLpro deubiquitination activity. Our results from the in vitro deubiquitinase inhibition assay show that aloin A and B isomers exhibit deubiquitination inhibitory activity with an IC50 value of 15.68 and 17.51 µM, respectively. In conclusion, the isoforms of aloin inhibit both proteolytic and the deubiquitinating activity of SARS-CoV-2 PLpro, suggesting potential in inhibiting the replication of SARS-CoV-2 virus. [ABSTRACT FROM AUTHOR]

Relative to studying alone, guessing the meanings of unknown words can improve later recognition of their meanings, even if those guesses were incorrect – the pretesting effect (PTE). The error-correction hypothesis suggests that incorrect guesses produce error signals that promote memory for the meanings when they are revealed. The current research sought to test the error-correction explanation of the PTE. In three experiments, participants studied unfamiliar Finnish-English word pairs by either studying each complete pair or by guessing the English translation before its presentation. In the latter case, the participants also guessed which of two categories the word belonged to. Hence, guesses from the correct category were semantically closer to the true translation than guesses from the incorrect category. In Experiment 1, guessing increased subsequent recognition of the English translations, especially for translations that were presented on trials in which the participants' guesses were from the correct category. Experiment 2 replicated these target recognition effects while also demonstrating that they do not extend to associative recognition performance. Experiment 3 again replicated the target recognition pattern, while also examining participants' metacognitive recognition judgments. Participants correctly judged that their memory would be better after small than after large errors, but incorrectly believed that making any errors would be detrimental, relative to study-only. Overall, the data are inconsistent with the error-correction hypothesis; small, within-category errors produced better recognition than large, cross-category errors. Alternative theories, based on elaborative encoding and motivated learning, are considered. [ABSTRACT FROM AUTHOR]

Purpose: There is scarce literature regarding genitourinary symptoms in COVID-19, especially post-acute disease otherwise known as Long COVID. We identified recovered COVID-19 patients presenting with new or worsening overactive bladder symptoms, known as COVID-19-associated cystitis (CAC). Methods: We used the American Urological Association Urology Care Foundation Overactive Bladder (OAB) Assessment Tool to screen COVID-19 recovered patients presenting with urological complaints at our urban-located institution from 5/22/2020 to 12/31/2020. Patients 10–14 weeks post-discharge responded to 5 symptom and 4 quality-of-life (QoL) questions. We reported median symptom scores, as well as QoL scores, based on new or worsening urinary symptoms, and by sex. Results: We identified 350 patients with de novo or worsening OAB symptoms 10–14 weeks after hospitalization with COVID-19. The median total OAB symptom score in both men and women was 18. The median total QoL score for both men and women was 19. Patients with worsening OAB symptoms had a median pre-COVID-19 symptom score of 8 (4–10) compared to post-COVID-19 median symptom score of 19 (17–21). Median age was 64.5 (range 47–82). Median hospital length-of-stay was 10 days (range 5–30). Conclusion: We report survey-based results of patients suffering from new or worsening OAB symptoms months after their hospitalization from COVID-19. Future studies with larger sample sizes and more extensive testing will hopefully elucidate the specific pathophysiology of OAB symptoms in the context of long COVID so urologists can timely and appropriately treat their patients. [ABSTRACT FROM AUTHOR]

Background: Twenty percent of women referred to colposcopy have a type 3 transformation zone-where colposcopic assessment for high-grade dysplasia (CIN2+) is not possible. This study examines the effectiveness of HPV biomarkers and genotyping in combination with techniques that sample an endocervical TZ.Methods: A prospective diagnostic accuracy study. Women booked for large-loop excision (LLETZ) with squamous dyskaryosis, high-risk HPV and a TZ3 were recruited. Immediately prior to LLETZ samples were collected for p16/Ki-67 dual-stained cytology, HPV genotyping and H&E, p16- and Ki-67-stained endocervical curettings.Results: In women with low-grade screening (n = 64), 35.9% had CIN2+; dual-stained cytology had the greatest effect on the PPV of routine screening (76.1% vs 35.9%) and perfectly predicted the absence of CIN2+. In women with a high-grade screening result (n = 37); 75.6% had CIN2+ and dual-stained curettings improved the PPV (96.5 vs 75.6%).Conclusions: With high-grade screening and a TZ3, LLETZ appears safest as three quarters have CIN2+ . Women with low-grade screening and a TZ3 have a twofold increased risk of CIN2+ when compared to women where the TZ is visible. The use of dual-stained cytology may help identify those women who can be safely offered surveillance and those who require treatment. [ABSTRACT FROM AUTHOR]