38332 research outputs found
Sort by
Helix pomatia agglutinin bound to surface glycans of small extracellular vesicles in-vitro and in-vivo increases in early and late stage breast cancer
Get PDFBackground: Breast cancer is the most frequently diagnosed cancer and a leading cause of cancer-related mortality in women globally. Small extracellular vesicles (sEVs) play a crucial role in cell communication and cancer progression. This study aimed to investigate the glycosylation patterns of sEVs derived from breast epithelial cells and plasma samples from breast cancer patients, focusing on the presence of truncated O-linked glycans, such as the Tn antigen, using Helix pomatia agglutinin (HPA).
Methods: Breast cancer cell lines were investigated for HPA lectin surface binding by confocal microscopy and flow cytometry. The sEVs of these were tested for surface HPA and tetraspanin binding using nano-flow cytometry, single particle interferometry, and direct stochastical optical reconstruction microscopy. Plasma from healthy and stage II-IV breast cancer patients were tested by nano-flow cytometry for HPA binding and analysed for the source of HPA+ EVs using 37 colocalised markers by multiplex flow cytometry (MACSPlex).
Results: Quantitative analysis revealed elevated HPA binding in sEVs from metastatic MCF-7 cells compared to that in non-metastatic BT-474 and immortalised healthy normal hTERT-HME1 cells, suggesting a correlation between HPA binding and metastatic potential. Analysis of sEVs revealed differential glycan presentation with CD81-positive sEVs from MCF-7 cells compared to CD63. In patient-derived plasma sEVs, HPA binding was significantly higher in patients with breast cancer than in healthy individuals, highlighting its potential as a biomarker for cancer detection.
Conclusions: These findings highlight the complex glycosylation of sEVs and their potential early diagnostic utility in breast cancer for HPA positive sEVs
Screening for malnutrition in people living with cancer and overweight or obesity : a scoping review
No full textBackground: Current approaches to malnutrition screening in cancer pathways may not identify malnutrition in people living with overweight or obesity. The review aims to identify current screening techniques and their potential validity in people living overweight or obesity and cancer.
Methods: PubMed, Medline and CINAHL were searched for English-language publications reporting data from malnutrition screening tools in adults with cancer living with overweight or obesity. These included 1) diagnostic accuracy studies with validity analysis against a reference, 2) comparative studies, without validity analysis, and 3) monomethod studies of single malnutrition screening tools. Registered in Open Science Framework. (https://doi.org/10.17605/OSF.IO/ZWFBM).
Results: 3705 records were identified with 16 full-text papers included. Eleven tools and measures were used to screen for malnutrition in people living with overweight or obesity and cancer. These included questionnaires (Malnutrition Universal Screening Tool; Malnutrition Screening Tool; Patient Generated Subjective Global Assessment (original/Short Form); Nutrition Risk Screening-2002; Short Nutritional Assessment Questionnaire and its variations; Mini Nutrition Assessment-Short Form), an algorithm-based tool (Nutrition Risk Index), and handgrip strength measures.
Discussion: There is a lack of consensus on the most appropriate tool, though combining subjective and objective measures may improve malnutrition screening in people with cancer and overweight or obesity
A balanced inversion polymorphism exhibits a dominance reversal at the gene expression level that depends on developmental context
Get PDFHow genetic variance for fitness is maintained is incompletely understood. Mutation-selection balance and single-locus overdominance cannot account for the large variance observed. Recent work suggests that antagonistic balancing selection, favoring different alleles in different contexts and involving beneficial dominance reversals, might contribute to maintaining fitness variance. However, while this mechanism is plausible, evidence for dominance reversals remains scarce. Here, we study how In(3R)Payne, a balanced inversion polymorphism in D. melanogaster, affects gene expression and chromatin accessibility by using RNA-seq and ATAC-seq. We find that, in embryos, the inverted (INV) arrangement tends to have dominant effects, while the standard (STD) arrangement behaves like a recessive Mendelian allele. Yet, in wing discs, this pattern is reversed: STD has mostly dominant effects, whereas INV behaves recessively. Since this shift in the dominance of the INV "allele" between developmental contexts affects the expression of suites of genes in a concerted manner, it might be mediated by a dominance modifier, for example a transcription factor. In favor of this idea, 25% of the differentially expressed genes between INV and STD encode transcription factors. Interestingly, while only four differentially expressed genes are shared between embryos and wing discs, one of them is HP1c, a chromatin binding protein and major transcriptional regulator, and thus a promising candidate for mediating the context-dependent change in dominance. Although the relationship between these patterns and fitness is presently unknown, our observations are consistent with a potential role of reversals (or, more generally, shifts) of dominance in maintaining inversion polymorphism
The Nuffield Early Language Intervention (NELI) programme is associated with lasting improvements in children’s language and reading skills
Get PDFBackground
Oral language skills are a critical foundation for education and psychosocial development. Learning to read, in particular, depends heavily on oral language skills. The Nuffield Early Language Intervention (NELI) has been shown to improve the language of 4–5-year-old children entering school with language weaknesses in four robust trials. To date, however, there is limited evidence on the durability of the gains produced by the intervention, and some have argued that the effects of such educational interventions typically fade-out quite rapidly.
Methods
A large-scale effectiveness trial of the NELI intervention implemented under real-world conditions produced educationally meaningful improvements in children's language and reading abilities. Here, we report follow-up testing of children from this study conducted approximately 2 years after the completion of the intervention.
Results
At 2-year follow-up, children who had received NELI had better oral language (d = 0.22 or d = 0.33 for children with lower language ability), reading comprehension (d = 0.16 or d = 0.24 for children with lower language ability) and single-word reading skills (d = 0.16 or d = 0.22 for children with lower language ability) than the control group.
Conclusions
Our data show that, although fade-out effects are common in educational research, a widely used language intervention produces durable improvements in language and reading skills, with educationally important effect sizes. These findings have important theoretical and practical implications
Modulation of the ubiquitin-proteasome system by circulating (poly)phenol-derived metabolites : implications for chronic diseases
Get PDFThe ubiquitin–proteasome system (UPS) is a key cellular mechanism responsible for protein turnover, with essential roles in cell cycle regulation, gene expression, and responses to oxidative and inflammatory stress. UPS dysregulation is implicated in the pathogenesis of multiple chronic diseases, including neurodegenerative, cardiovascular, and oncological disorders. This review examines the emerging role of circulating polyphenol-derived metabolites, such as valerolactones (from flavan-3-ols), benzoic acid derivatives, urolithins (from ellagitannins), and hydroxycinnamic acids (e.g., ferulic and caffeic acids), as modulators of UPS activity. We summarize experimental evidence demonstrating their ability to affect proteasome function through diverse mechanisms, including autophagy induction, modulation of ubiquitination-related enzymes, and attenuation of oxidative or inflammatory signals. While bioavailability studies have described the absorption and metabolism of dietary polyphenols, less is known about which specific metabolites reach target tissues at biologically active concentrations capable of modulating the UPS. In addition, current knowledge is primarily based on cellular models (e.g., endothelial cells, myotubes, macrophages, cancer cell lines) and in vivo studies in rodents, often using supraphysiological doses or isolated compounds. To translate these findings into therapeutic applications, further research is needed to integrate mechanistic insights from preclinical models with data from human clinical studies, taking into account physiologically relevant concentrations, chronic exposure patterns, and tissue-specific distribution. Such approaches could help unlock the potential of (poly)phenol-derived metabolites as regulators of proteostasis in chronic disease
Habitat Composition and Preference by the Malabar Slender Loris (Loris lydekkerianus malabaricus) in the Western Ghats, India
Get PDFHabitat degradation poses a critical threat to the Malabar slender loris (Loris lydekkerianus malabaricus), yet little is known about its microhabitat requirements in intact forest. In Aralam Wildlife Sanctuary, we combined nocturnal trail surveys (337 loris sightings) with plotless sampling of 2830 trees (86 species from 35 families) to characterize both vegetation structure and loris presence. Our results show that lorises occur almost exclusively in mildly degraded wet evergreen and secondary moist deciduous subcanopies, where understory trees and climber networks provide continuous pathways. Individuals are most often encountered at heights of 5–15 m—ascending into higher strata as the night progresses—reflecting a balance between foraging access and predator avoidance. Substrate analysis revealed strong preferences for twigs ≤ 1 cm (36.98%) and small branches 2–5 cm in diameter, oriented obliquely to minimize energetic costs and maintain stability during slow, deliberate arboreal locomotion. Day-sleeping sites were overwhelmingly located within dense tangles of lianas on large-girth trees, where intertwined stems and thorny undergrowth offer concealment from both mammalian and avian predators. Vegetation surveys documented a near-equal mix of evergreen (50.6%) and deciduous (49.4%) species—including 26 endemics (18 restricted to the Western Ghats)—with Aporosa cardiosperma emerging as the most abundant riparian pioneer, suggesting both ecological resilience and potential simplification in fragmented patches. Complementing field observations, our recent habitat-suitability modeling in Aralam indicates that broad-scale climatic and anthropogenic factors—precipitation patterns, elevation, and proximity to roads—are the strongest predictors of loris occupancy, underscoring the interplay between landscape-level processes and microhabitat structure. Together, these findings highlight the imperative of multi-strata forest restoration—planting insect-hosting native trees, maintaining continuous canopy and climber networks, and integrating small “mini-forest” modules—to recreate the structural complexity vital for slender loris conservation and the broader resilience of Western Ghats biodiversity
The Extended Project Qualification : an opportunity for all?
No full textAccess to research-based learning remains a privilege, not a right, in post-16 education. The Extended Project Qualification (EPQ) — a unique, mentored, student-led qualification — is proven to support higher education progression, independent learning, and student engagement. Yet current access is geographically and socially uneven.
This project aimed to provide an understanding of access, uptake and attainment of the EPQ as an opportunity for all; explore barriers to access, participation and completion; and gain narratives of effective practices by providers where the EPQ is offered widely to achieve successful outcomes. The research employed a mixed methods design including a literature review, analysis of administrative datasets, a novel spatial mapping approach using geographical information systems (GIS) to identify deprived areas for interviews and focus groups with EPQ teachers and students.
This research shows that taking the EPQ does not undermine attainment in other subjects, can reduce gender gaps in attainment and is academically enriching. However, significant barriers to access and retention exist in deprived areas. The study identifies practices that enable the EPQ to be offered inclusively, including targeted support. Findings suggest the qualification has untapped potential to support policy ambitions on opportunities for all, curriculum reform, widening
participation in HE and employability. An emphasis on strategic value is recommended. The GIS Web app can be used to target areas of geographical deprivation that currently do not have access to the award and may be helpful for higher education institutions making contextual offers.
Further research is needed on the associations between the EPQ and HE outcomes. Advanced spatial analysis could explore the impact of student travel time on EPQ opportunity and access. EPQ centres that have chosen to close provision, or centres who do not offer the qualification, would provide further perspectives on barriers to access
