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Abstract Global warming is a major challenge to the sustainable and humane production of food because of the increased risk of livestock to heat stress. Here, the example of the prolactin receptor (PRLR) gene is used to demonstrate how gene editing can increase the resistance of cattle to heat stress by the introduction of mutations conferring thermotolerance. Several cattle populations in South and Central America possess natural mutations in PRLR that result in affected animals having short hair and being thermotolerant. CRISPR/Cas9 technology was used to introduce variants of PRLR in two thermosensitive breeds of cattle – Angus and Jersey. Gene‐edited animals exhibited superior ability to regulate vaginal temperature (heifers) and rectal temperature (bulls) compared to animals that were not gene‐edited. Moreover, gene‐edited animals exhibited superior growth characteristics and had larger scrotal circumference. There was no evidence for deleterious effects of the mutation on carcass characteristics or male reproductive function. These results indicate the potential for reducing heat stress in relevant environments to enhance cattle productivity.

Abstract Nanophase mixtures, leveraging the complementary strengths of each component, are vital for composites to overcome limitations posed by single elemental materials. Among these, metal-elastomer nanophases are particularly important, holding various practical applications for stretchable electronics. However, the methodology and understanding of nanophase mixing metals and elastomers are limited due to difficulties in blending caused by thermodynamic incompatibility. Here, we present a controlled method using kinetics to mix metal atoms with elastomeric chains on the nanoscale. We find that the chain migration flux and metal deposition rate are key factors, allowing the formation of reticular nanophases when kinetically in-phase. Moreover, we observe spontaneous structural evolution, resulting in gyrified structures akin to the human brain. The hybridized gyrified reticular nanophases exhibit strain-invariant metallic electrical conductivity up to 156% areal strain, unparalleled durability in organic solvents and aqueous environments with pH 2–13, and high mechanical robustness, a prerequisite for environmentally resilient devices.

BackgroundGiven its putative roles in mediating prosocial behavior, attachment bonds, and stress physiology, oxytocin modulation has been hypothesized to be a biological correlate of the salubrious effects of meditation practice. Here we investigated the effects of a month-long silent meditation retreat on changes in oxytocin, and the related hormone and vasopressin, in relation to psychosocial changes in attachment style, anxiety, personality measures, and feelings of social connectedness with fellow meditators.MethodsPlasma oxytocin and vasopressin and self-report questionnaires were measured in retreat participants (n = 28) at the beginning of, and 3 weeks into, a residential meditation retreat. Control participants (n = 34), who were similar in age, gender, and meditation experience, were also assessed across a 3-week interval. Linear mixed effects models were used to assess outcomes.ResultsThe retreat group showed a small but significant decrease in oxytocin compared to controls who showed no change. In the retreat group, higher openness to experience at Time 1 predicted greater reductions in oxytocin during the retreat, and lower oxytocin at Time 2 was related to stronger feelings of personal connection with fellow meditators. The changes in oxytocin were not related to attachment style or anxiety. Vasopressin decreased over time across both groups, suggesting no specific effect of retreat.ConclusionThese preliminary findings suggest that meditation training in the context of a silent residential retreat may reduce circulating levels of oxytocin. We interpret this finding from multiple theoretical perspectives, discussing key measurement limitations and proposing future study designs that may help to differentiate the effects of different meditation practices and contexts on oxytocin signaling.

Abstract Background In beef cattle, more than 50% of the energy input to produce a unit of beef is consumed by the female that produced the calf. Development of genomic tools to identify females with high genetic merit for reproductive function could increase the profitability and sustainability of beef production. Results Genome-wide association studies (GWAS) were performed using a single-step genomic best linear unbiased prediction approach on pregnancy outcome traits from a population of Angus–Brahman crossbred heifers. Furthermore, a validation GWAS was performed using data from another farm. Heifers were genotyped with the Bovine GGP F250 array that contains 221,077 SNPs. In the discovery population, heifers were bred in winter breeding seasons involving a single round of timed artificial insemination (AI) followed by natural mating for 3 months. Two phenotypes were analyzed: pregnancy outcome to first-service AI (PAI; n = 1,481) and pregnancy status at the end of the breeding season (PEBS; n = 1,725). The heritability was estimated as 0.149 and 0.122 for PAI and PEBS, respectively. In the PAI model, one quantitative trait locus (QTL), located between 52.3 and 52.5 Mb on BTA7, explained about 3% of the genetic variation, in a region containing a cluster of γ-protocadherin genes and SLC25A2. Other QTLs explaining between 0.5% and 1% of the genetic variation were found on BTA12 and 25. In the PEBS model, a large QTL on BTA7 was synonymous with the QTL for PAI, with minor QTLs located on BTA5, 9, 10, 11, 19, and 20. The validation population for pregnancy status at the end of the breeding season were Angus–Brahman crossbred heifers bred by natural mating. In concordance with the discovery population, the large QTL on BTA7 and QTLs on BTA10 and 12 were identified. Conclusions In summary, QTLs and candidate SNPs identified were associated with pregnancy outcomes in beef heifers, including a large QTL associated with a group of protocadherin genes. Confirmation of these associations with larger populations could lead to the development of genomic predictions of reproductive function in beef cattle. Moreover, additional research is warranted to study the function of candidate genes associated with QTLs.

The field of climate justice has been growing in relevance since its conception in 1997. This paper presents a comprehensive bibliometric and topic modelling analyses to examine the evolution and trajectory of the climate justice literature. We analyse 1,683 publications covering the period from 1997 to 2021, highlighting foundational works, influential authors, leading nations and institutions, and prevailing research topics within this field. We employ Latent Dirichlet Allocation to uncover latent research trends in the literature providing a crucial baseline for future scholarly endeavours and policy development in the realm of climate justice.Our results show that the field of climate justice has grown exponentially from less than 5 papers annually between 1997 and 2005, to around 200 papers annually in recent years. This growth has seen a diversification of research themes with an increase in papers around the topics of health, vulnerability and adaptation, and policy and activism. There has been a consistent backdrop of publications around the topics of sustainable development and policy, and international relations and carbon emissions. Other prominent topics in the literature include education and food security, and human rights and Indigenous people. The field has moved from theoretical research to examining actual examples of climate injustices, with an increased diversification of topics.Future research could usefully focus on exploring future generations and more-than-human entities; the integration of climate justice and climate activism with broader struggles for justice; re-thinking climate adaptation “success” and “effectiveness” through the lens of climate justice, and the ramifications of the Global Goal on Adaptation on climate justice led-approaches that are inclusive, build on human rights approaches, and extend the scale of adaptation analysis beyond the local. It is imperative to prioritise addressing the climate justice needs of those most affected by climate change, transcending national borders, generational gaps, cultural differences, and even the well-being of various species. Such a holistic approach will help inform and refine global climate policy and action.

Abstract A spatial view of macroscopic polymer material properties, in terms of nanostructure and irregularities, can help to better understand engineering processes such as when materials may fail. However, bridging the gap between the molecular‐scale arrangement of polymer chains and the spatially resolved macroscopic properties of a material poses numerous difficulties. Herein, an integrated messenger material that can report on the material micro‐ to nanostructure and its processes is introduced. It is based on polymer chains labeled with fluorescent dyes that feature Förster resonance energy transfer (FRET) dependent on chain conformation and concentration within a host polymer material. These FRET materials are integrated within electrospun polystyrene microfibers, and the FRET is analyzed by confocal laser scanning microscopy (CLSM). Importantly, the use of CLSM allows a spatial view of material nanostructure and irregularities within the microfibers, where changes in FRET are significant when differences in fiber geometries and regularities exist. Furthermore, changes in FRET observed in damaged regions of the fibers indicate changes in polymer conformation and/or concentration as the material changes during compression. The system promises high utility for applications where nano‐to‐macro communication is needed for a better understanding of material processes.

R-loops (RNA–DNA hybrids with displaced single-stranded DNA) have emerged as a potent source of DNA damage and genomic instability. The termination of defective RNA polymerase II (RNAPII) is one of the major sources of R-loop formation. 5′-3′-exoribonuclease 2 (XRN2) promotes genome-wide efficient RNAPII termination, and XRN2-deficient cells exhibit increased DNA damage emanating from elevated R-loops. Recently, we showed that DNA damage instigated by XRN2 depletion in human fibroblast cells resulted in enhanced poly(ADP-ribose) polymerase 1 (PARP1) activity. Additionally, we established a synthetic lethal relationship between XRN2 and PARP1. However, the underlying cellular stress response promoting this synthetic lethality remains elusive. Here, we delineate the molecular consequences leading to the synthetic lethality of XRN2-deficient cancer cells induced by PARP inhibition. We found that XRN2-deficient lung and breast cancer cells display sensitivity to two clinically relevant PARP inhibitors, Rucaparib and Olaparib. At a mechanistic level, PARP inhibition combined with XRN2 deficiency exacerbates R-loop and DNA double-strand break formation in cancer cells. Consistent with our previous findings using several different siRNAs, we also show that XRN2 deficiency in cancer cells hyperactivates PARP1. Furthermore, we observed enhanced replication stress in XRN2-deficient cancer cells treated with PARP inhibitors. Finally, the enhanced stress response instigated by compromised PARP1 catalytic function in XRN2-deficient cells activates caspase-3 to initiate cell death. Collectively, these findings provide mechanistic insights into the sensitivity of XRN2-deficient cancer cells to PARP inhibition and strengthen the underlying translational implications for targeted therapy.

The experiences of autistic college students have become an increasing focus of research over the past 10 years. As a part of a larger research project, 40 successful autistic college students were interviewed about their experiences transitioning from high school to college. Participants reported being active participants in selecting colleges, but not receiving robust transition services during high school. They reported wanting additional opportunities in high school to develop executive function skills and to have more social opportunities. Further, they stressed the importance of developing greater independence while in high school.

Alternaria is often one on the most abundant fungal genera recovered from a wide array of plant hosts and environmental substrates. Many species within the sub-generic Alternaria section Alternaria are common plant pathogens that cause pre-harvest losses due to reduced productivity and post-harvest losses due to spoilage and contamination with mycotoxins. As certain species of Alternaria may have distinct mycotoxin profiles, and very broad host ranges, understanding the distribution of species by geography and host is critical for disease prediction, toxicological risk assessment, and guiding regulatory decisions. In two previous reports, we performed phylogenomic analyses to identify highly informative molecular markers for Alternaria section Alternaria, and validated their diagnostic ability. Here, we perform molecular characterization of 558 section Alternaria strains, collected from 64 host genera in 12 countries, using two of these section-specific loci (ASA-10 and ASA-19) along with the RNA polymerase II second largest subunit (rpb2) gene. The majority of strains (57.4%) originated from various cereal crops in Canada, which formed the main focus of our study. Phylogenetic analyses were used to classify strains into section Alternaria species/lineages, demonstrating that the most common species on Canadian cereal crops are Alternaria alternata and A. arborescens. Further population genetic analyses were consistent with A. alternata being a widely distributed species with relatively low levels of geographic isolation (i.e., Canadian isolates did not form distinct clades when compared to other regions). Our expanded sampling of A. arborescens has greatly increased the known diversity of this group, with A. arborescens isolates forming at least three distinct phylogenetic lineages. Proportionally, A. arborescens is more prevalent in Eastern Canada than in Western Canada. Sequence analyses, putative hybrids, and mating-type distributions provided some evidence for recombination events, both within and between species. There was little evidence for associations between hosts and genetic haplotypes of A. alternata or A. arborescens.

Abstract Ionic liquids (ILs) are a widely investigated class of solvents for scientific and industrial applications due to their desirable and “tunable” properties. The IL–solid interface is a complex entity, and despite intensive investigation, its true nature remains elusive. The understanding of the IL–solid interface has evolved over the last decade from a simple 1D double layer, to a 2D ordered interface, and finally a liquid‐specific, complex 3D ordered liquid interface. However, most studies depend solely on one technique, which often only examine one aspect of the interfacial nanostructure. Here, a holistic study of the protic IL–solid interface is presented, which provides a more detailed picture of IL interfacial solvation. The 3D nanostructure of the ethylammonium nitrate (EAN)–mica interface is investigated using a combination of 1D, 2D, and 3D amplitude modulated‐atomic force microscopy and molecular dynamics simulations. Importantly, it is found that the EAN–mica interface is more complex than previously reported, possessing surface‐adsorbed, near‐surface, surface‐normal, and lateral heterogeneity, which propagates at relatively large distances from the solid substrate. The work presented in this study meaningfully enhances the understanding of the IL–solid interface.

Abstract Background The school is a key setting for the provision of mental health services to children, particularly those underserved through traditional service delivery systems. School-wide Positive Behavioral Interventions and Supports (PBIS) is a tiered approach to service delivery based on the public health model that schools use to implement universal (Tier 1) supports to improve school climate and safety. As our prior research has demonstrated, PBIS is a useful vehicle for implementing mental and behavioral health evidence-based practices (EBPs) at Tier 2 for children with, or at risk for, mental health disorders. Very little research has been conducted regarding the use of mental health EBPs at Tier 2 or how to sustain implementation in schools. Methods/design The main aim of the study is to compare fidelity, penetration, cost-effectiveness, and student outcomes of Tier 2 mental health interventions across 2 sustainment approaches for school implementers in 12 K-8 schools. The study uses a 2-arm, cluster randomized controlled trial design. The two arms are: (a) Preparing for Sustainment (PS)—a consultation strategy implemented by school district coaches who receive support from external consultants, and (b) Sustainment as Usual (SAU)—a consultation strategy implemented by school district coaches alone. Participants will be 60 implementers and 360 students at risk for externalizing and anxiety disorders. The interventions implemented by school personnel are: Coping Power Program (CPP) for externalizing disorders, CBT for Anxiety Treatment in Schools (CATS) for anxiety disorders, and Check-in/Check-out (CICO) for externalizing and internalizing disorders. The Interactive Systems Framework (ISF) for Dissemination and Implementation guides the training and support procedures for implementers. Discussion We expect that this study will result in a feasible, effective, and cost-effective strategy for sustaining mental health EBPs that is embedded within a multi-tiered system of support. Results from this study conducted in a large urban school district would likely generalize to other large, urban districts and have an impact on population-level child mental health. Trial registration ClinicalTrials.gov identifier number NCT04869657. Registered May 3, 2021.

Background: Meditation retreats are characterized by intensive or concentrated periods of meditation practice, commonly undertaken in a residential setting. Although research indicates that meditation training can positively influence physical and mental health outcomes, the biological consequences of meditation retreat interventions are relatively understudied. In this study, we examined the influence of a month-long, silent meditation retreat on the expression of genes involved in epigenetic modulation and immune processes. Method: We assessed gene expression changes in experienced meditators attending a month-long Insight meditation retreat (n = 28), as compared to a community control group (n = 34) of experienced practitioners living their everyday lives. Blood samples were collected on day two of the retreat (Time 1) and again 3 weeks later (Time 2). Control participants were also assessed across a 3-week interval, during which they maintained their regular daily routines. Results: As compared to controls, retreat participants showed differential changes in the expression of several genes involved in chromatin modulation and inflammation. The most substantive finding was downregulation of the TNF pathway in retreat participants, which was not observed in controls. Conclusions: These findings indicate that meditation retreat participation may influence some of the inflammatory mechanisms involved in the development of chronic diseases, and that this style of psychosocial intervention may have therapeutic potential, particularly in experienced practitioners.

Abstract Increasingly, land managers have attempted to use extreme prescribed fire as a method to address woody plant encroachment in savanna ecosystems. The effect that these fires have on herbaceous vegetation is poorly understood. We experimentally examined immediate (

This paper focuses on data from a study of middle- to upper-middle class Scottish S2 ([approximately]seventh grade) students who participated in Inspiring Purpose, a school-based character development program, during the 2016 to 2017 school year. Directed by their teachers, participating youth reflected on values and future aspirations and researched and wrote about an inspiring person. We examine the hypotheses that youth who select a more proximal inspiring figure and/or make a personal connection with that person will demonstrate higher developmental outcomes in the areas of confidence, contribution, self-reflection, goal development, and self-concept. We connected 230 student posters of inspirational figures, 34 youth interviews, and 462 student surveys. Mixed-method analysis revealed students were more likely to describe proximal figures as inspiring and make explicit personal connections over the course of their engagement with the Inspiring Purpose program. Moreover, youth who made personal connections were more likely to score higher on confidence, general self-concept, and contribution. These results suggest that when youth see themselves in inspiring figures and firmly articulate this connection, this can spur beneficial developmental outcomes.

Although vaccine behaviors differ greatly by gender and age, few studies have examined vaccination at the intersection of gender and age within the Black community. We examined COVID-19 vaccination by gender and age using a survey of over 500 Black adults in Chicago, Illinois, fielded from September 2021 to March 2022. Although 54% had received at least one COVID-19 vaccine, the proportion vaccinated was considerably lower for Black men (28%) and women (37%) under 40 years old than Black men (92%) and women (86%) over 40 years (p < 0.001). Concern about vaccine side effects was the most reported barrier for unvaccinated women (56%) and men (38%) under 40 years. Our results suggest that targeted efforts to improve COVID-19 vaccine uptake in the Black community in Chicago after the initial rollout should have focused on young adults, particularly young Black men, with emphasis on addressing concern about vaccine side effects.

Positive behavior support (PBS) is an evidence-based framework for improving quality of life and preventing challenging behavior that is often implemented in combination with person-centered practices in the intellectual and developmental disability (IDD) field. Recently, state agencies and organizations supporting people with IDD have adopted a system-wide approach to PBS, much like multi-tiered school-wide PBS for youth in educational settings (e.g., SW-PBIS). Fidelity tools for guiding team implementation and action planning are essential throughout every phase of implementation in any innovation. Although such tools exist for SW-PBIS, no widely used measure currently exists for assessing the implementation of organization-wide PBS in the adult IDD field. This article describes the initial development of a fidelity of implementation tool used to evaluate organization-wide implementation of PBS and person-centered practices in community settings. A Midwestern state Department of Human Services and a university Center on Developmental Disabilities (UCEDD) in the United States partnered to complete this project. The authors discuss the exploratory and descriptive evaluation process involved in the initial development of the tool and share data for 10 provider organizations over a 6-year period of implementation. A descriptive case study using mixed measures is used to provide more details about the implementation of PBS in one agency to show the types of changes captured by the fidelity tool.

Background: School-based health centers (SBHCs) have the capability to overcome youth barriers to care. Virtual care programs (VCP) facilitate connection between school nurse and off-site SBHC providers and can increase the reach of SBHCs. This project aimed to examine Denver Public School nurses' perspectives of a pilot VCP. Methods: Thirteen semi-structured qualitative interviews were conducted and coded using an inductive approach to identify key themes. Results: Four major themes emerged: (1) obtaining consent, finding space, and capacity are challenges and nurses have suggestions; (2) nurses enjoy feeling like a valued member of a health care team, and providing additional resources to students; (3) nurses perceive benefits in providing free, efficient, higher level of care; (4) adopting novel technology is a facilitator and challenge; limitations included space and privacy. Conclusions: Key findings can be utilized to further inform practice.

This study explores the experiences of NBGQ youth with microaggressions. It investigates the types of microaggressions they face and their subsequent needs and coping mechanisms and the impacts on their lives. Semi-structured interviews with ten NBGQ youth in Belgium were conducted and analyzed using a thematic approach. The results showed that experiences of microaggressions were centered around denial. The most common ways to cope were finding acceptance from (queer) friends and therapists, engaging in a conversation with the aggressor, and rationalizing and empathizing with the aggressor, leading to self-blame and normalization of the experiences. Microaggressions were experienced as exhausting, which influenced the extent to which the NBGQ individuals wanted to explain themselves to others. Furthermore, the study shows an interaction between microaggressions and gender expression, in which gender expression is seen as a motive for microaggressions and microaggressions have an impact on the gender expression of NBGQ youth.

Supervised personal training is most effective in improving the health effects of exercise in older adults. Yet, low frequency (60 min, 1–3 sessions/week) of trainer contact limits influence on behavior change outside sessions. Strategies to extend the effect of trainer contact outside of supervision and that integrate meaningful and intelligent two-way communication to provide complex and interactive problem solving may motivate older adults to “move more and sit less” and sustain positive behaviors to further improve health. This paper describes the experimental protocol of a 16-week pilot RCT (N = 46) that tests the impact of supplementing supervised exercise (i.e., control) with a technology-based behavior-aware text-based virtual “Companion” that integrates a human-in-the-loop approach with wirelessly transmitted sensor-based activity measurement to deliver behavior change strategies using socially engaging, contextually salient, and tailored text message conversations in near-real-time. Primary outcomes are total-daily and patterns of habitual physical behaviors after 16 and 24 weeks. Exploratory analyses aim to understand Companion’s longitudinal behavior effects, its user engagement and relationship to behavior, and changes in cardiometabolic and cognitive outcomes. Our findings may allow the development of a more scalable hybrid AI Companion to impact the ever-growing public health epidemic of sedentariness contributing to poor health outcomes, reduced quality of life, and early death.

Abstract: School climate surveys are frequently used to collect information about student experiences in school. Less is known about how educators use survey data after survey administration. This paper explores one school district’s critical use of evidence to promote equitable change. We conducted eight semi-structured interviews with district and school leaders to investigate their uses of evidence. Through our qualitative, reflexive thematic analysis, we generated six themes: (1) using evidence to provide a common language; (2) bringing attention to trends to shift staff understanding of problems, (3) making structural changes, (4) planning for professional learning, (5) following up directly with students, and (6) engaging with the community. Findings illustrate how education leaders can apply a critical lens to their generation and use of evidence. We explore how the strategic use of evidence is needed to advance the broader goal of fostering school change and improving school climate for all students.

Variants in seven genes (LRRK2, GBA1, PRKN, SNCA, PINK1, PARK7 and VPS35) have been formally adjudicated as causal contributors to Parkinsons disease; however, individuals with Parkinsons disease are often unaware of their genetic status since clinical testing is infrequently offered. As a result, genetic information is not incorporated into clinical care, and variant-targeted precision medicine trials struggle to enrol people with Parkinsons disease. Understanding the yield of genetic testing using an established gene panel in a large, geographically diverse North American population would help patients, clinicians, clinical researchers, laboratories and insurers better understand the importance of genetics in approaching Parkinsons disease. PD GENEration is an ongoing multi-centre, observational study (NCT04057794, NCT04994015) offering genetic testing with results disclosure and genetic counselling to those in the US (including Puerto Rico), Canada and the Dominican Republic, through local clinical sites or remotely through self-enrolment. DNA samples are analysed by next-generation sequencing including deletion/duplication analysis (Fulgent Genetics) with targeted testing of seven major Parkinsons disease-related genes. Variants classified as pathogenic/likely pathogenic/risk variants are disclosed to all tested participants by either neurologists or genetic counsellors. Demographic and clinical features are collected at baseline visits. Between September 2019 and June 2023, the study enrolled 10 510 participants across >85 centres, with 8301 having received results. Participants were: 59% male; 86% White, 2% Asian, 4% Black/African American, 9% Hispanic/Latino; mean age 67.4 ± 10.8 years. Reportable genetic variants were observed in 13% of all participants, including 18% of participants with one or more high risk factors for a genetic aetiology: early onset (

The incidence of inflammatory bowel disease (IBD) is increasing annually. Children with IBD often suffer significant morbidity due to physical and emotional effects of the disease and treatment. Corticosteroids, often a component of therapy, carry undesirable side effects with long term use. Steroid-free remission has become a standard for care-quality improvement. Anticipating therapeutic outcomes is difficult, with treatments often leveraged in a trial-and-error fashion. Artificial intelligence (AI) has demonstrated success in medical imaging classification tasks. Predicting patients who will attain remission will help inform treatment decisions. The provided dataset comprises 951 tissue section scans (167 whole-slides) obtained from 18 pediatric IBD patients. Patient level structured data include IBD diagnosis, 12- and 52-week steroid use and name, and remission status. Each slide is labelled with biopsy site and normal or abnormal classification per the surgical pathology report. Each tissue section scan from an abnormal slide is further classified by an experienced pathologist. Researchers utilizing this dataset may select from the provided outcomes or add labels and annotations from their own institutions.