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Diffuse midline gliomas (DMG), including diffuse intrinsic pontine gliomas (DIPGs), are the most lethal of childhood cancers. Palliative radiotherapy is the only established treatment, with median patient survival of 9-11 months. ONC201 is a DRD2 antagonist and ClpP agonist that has shown preclinical and emerging clinical efficacy in DMG. However, further work is needed to identify the mechanisms of response of DIPGs to ONC201 treatment and to determine whether recurring genomic features influence response. Using a systems-biological approach, we showed that ONC201 elicits potent agonism of the mitochondrial protease ClpP to drive proteolysis of electron transport chain and tricarboxylic acid cycle proteins. DIPGs harboring PIK3CA-mutations showed increased sensitivity to ONC201, while those harboring TP53-mutations were more resistant. Metabolic adaptation and reduced sensitivity to ONC201 was promoted by redox-activated PI3K/Akt signaling, which could be counteracted using the brain penetrant PI3K/Akt inhibitor, paxalisib. Together, these discoveries coupled with the powerful anti-DIPG/DMG pharmacokinetic and pharmacodynamic properties of ONC201 and paxalisib have provided the rationale for the ongoing DIPG/DMG phase II combination clinical trial NCT05009992.

Over the last number of years, there has been an increased move towards attending to the social and emotional wellbeing of students in Irish post-primary schools. Several studies have indicated that educators' positive attitudes toward health and wellbeing education are crucial to achieving whole-school implementation in terms of the promotion of student wellbeing. However, as of yet, no test instrument exists that is designed to quantify the attitudes of educators in this regard. This study aimed to develop a test instrument that could be used to assess educators' attitudes with regard to the promotion of student wellbeing in Irish post-primary schools. The study was conducted in three stages: Content validity, involving seven experts and 14 educators; exploratory factor analysis (n = 129), and; confirmatory factor analysis (n = 99). Analyses indicated the viability of a 10-item two-factor model, which was named the 'Attitudes Toward Wellbeing Promotion' (ATWP) scale.

Understanding the systemic biochemistry of early pregnancy in the mare is essential for developing new diagnostics and identifying causes for pregnancy loss. This study aimed to elucidate the dynamic lipidomic changes occurring during the initial stages of equine pregnancy, with a specific focus on days 7 and 14 post-ovulation. By analysing and comparing the plasma lipid profiles of pregnant and non-pregnant mares, the objective of this study was to identify potential biomarkers for pregnancy and gain insights into the biochemical adaptations essential for supporting maternal recognition of pregnancy and early embryonic development. Employing discovery lipidomics, we analysed plasma samples from pregnant and non-pregnant mares on days 7 and 14 post-conception using the SCIEX ZenoTOF 7600 system. This high-resolution mass spectrometry approach enabled us to comprehensively profile and compare the lipidomes across these critical early gestational timepoints. Our analysis revealed significant lipidomic alterations between pregnant and non-pregnant mares and between days 7 and 14 of pregnancy. Key findings include the upregulation of bile acids, sphingomyelins, phosphatidylinositols, and triglycerides in pregnant mares. These changes suggest enhanced lipid synthesis and mobilization, likely associated with the embryo's nutritional requirements and the establishment of embryo–maternal interactions. There were significant differences in lipid metabolism between pregnant and non-pregnant mares, with a notable increase in the sterol lipid BA 24:1;O5 in pregnant mares as early as day 7 of gestation, suggesting it as a sensitive biomarker for early pregnancy detection. Notably, the transition from day 7 to day 14 in pregnant mares is characterized by a shift towards lipids indicative of membrane biosynthesis, signalling activity, and preparation for implantation. The study demonstrates the profound lipidomic shifts that occur in early equine pregnancy, highlighting the critical role of lipid metabolism in supporting embryonic development. These findings provide valuable insights into the metabolic adaptations during these period and potential biomarkers for early pregnancy detection in mares. [ABSTRACT FROM AUTHOR]

Introduction: Prickles are often deemed undesirable traits in many crops, including roses (Rosa sp.), and there is demand for rose cultivars with no or very few prickles. This study aims to identify new and/or validate reported quantitative trait loci (QTLs) associated with stem and leaf rachis prickle density, characterize the effects of functional haplotypes for major QTLs, and identify the sources of QTL-alleles associated with increased/decreased prickle density in roses. Methods: QTL mapping using pedigree-based analysis (PBA), and haplotype analysis were conducted on two multi-parental diploid rose populations (TX2WOB and TX2WSE). Results and discussion: Twelve QTLs were identified on linkage groups (LGs) 2, 3, 4, and 6. The major QTLs for the stem prickle density were located between 42.25 and 45.66 Mbp on chromosome 3 of the Rosa chinensis genome assembly, with individual QTLs explaining 18 to 49% of phenotypic variance (PVE). The remaining mapped QTLs were minor. As for the rachis prickle density, several QTLs were detected on LG3, 4, and 6 with PVE 8 to 17%. Also, this study identified that ancestors R. wichurana 'Basye's Thornless', 'Old Blush', and the pollen parent of M4-4 were common sources of favorable alleles (q) associated with decreased prickle density, whereas 'Little Chief' and 'Srche Europy' were the source of unfavorable alleles (Q) in the TX2WOB and TX2WSE populations, respectively. The outcomes of this work complement other studies to locate factors that affect prickle density. These results can also be utilized to develop high-throughput DNA tests and apply parental selection to develop prickle-free rose cultivars. [ABSTRACT FROM AUTHOR]

Context: Integrated omics studies hold a crucial role in improving our understanding of reproductive biology. However, the complex datasets so generated are often only accessible via supplementary data files, which lack the capacity for interactive features to allow users to readily interrogate and visualise data of interest. Aims: The intent of this technical note was to develop an interactive web-based application that enables detailed interrogation of a representative sperm proteome, facilitating a deeper understanding of the proteins identified, their relative abundance, classifications, functions, and associated phenotypes. Methods: We developed a Shiny web application, ShinySperm (), utilising R and several complementary libraries for data manipulation (dplyr), interactive tables (DT), and visualisation (ggplot2, plotly). ShinySperm features a responsive user interface, dynamic filtering options, interactive charts, and data export capabilities. Key results: ShinySperm allows users to interactively search, filter, and visualise sperm proteomics data based on key features (e.g. protein classification, sperm cell domain, presence, or absence at different maturation stages). This application responds live to filtering options and enables the generation of interactive plots and tables, thus enhancing user engagement and understanding of the data. Conclusions: ShinySperm provides a robust platform for the dynamic exploration of epididymal sperm proteome data. It significantly improves accessibility and interpretability of complex datasets, allowing for effective data-driven insights. Implications: This technical note highlights the potential of interactive web applications in reproductive biology and provides a plug and play script for the field to produce applications for meaningful researcher interaction with complex omic datasets. Understanding complex biological data is crucial for advancements in reproductive biology. Our study developed ShinySperm, a web application that allows researchers to easily explore, interrogate, and visualise intricate sperm proteomic data. This tool sets out a blueprint for future research, enabling researchers to bring their intricate datasets to life, allowing others to interact with and interpret more effectively, ultimately driving innovation in reproductive biology. Image by David Skerrett-Byrne. This article belongs to the Collection Frontiers in Reproduction Science – Rising Stars at the Society for Reproductive Biology 2023. [ABSTRACT FROM AUTHOR]

Copyright of Equine Veterinary Journal is the property of Wiley-Blackwell 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.)

Copyright of Equine Veterinary Journal is the property of Wiley-Blackwell 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.)

In 2017, the National Council for Curriculum and Assessment (NCCA) in the Republic of Ireland introduced a universal social and emotional learning (SEL) intervention in the form of the NCCA wellbeing guidelines. These guidelines are aimed at facilitating the promotion of student wellbeing during the first three years of post-primary education. This paper will provide an overview of the NCCA wellbeing guidelines, while also establishing the educational context within which these guidelines have become necessary. While the introduction of these guidelines is arguably timely, little is known of the attitudes and perspectives that are held by the principal stakeholders, namely the educators, regarding these guidelines and the promotion of student wellbeing in general. This constitutes a significant gap in knowledge as the success (or otherwise) of the new wellbeing guidelines in Ireland may be in some way contingent upon teachers' attitudes toward both the guidelines themselves, and their ability to deliver them. It will be proposed that research, which is currently being conducted, is necessary to further understand educators' perspectives in this area in order to secure 'whole-school' implementation of the wellbeing guidelines and curricula.