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Targeting Glutaminase Isoforms GLS and GLS2 in Luminal Breast Cancer
No full textUpregulation of glutaminase enzymatic activity promotes tumour cell proliferation. Its overexpression correlates with poor disease outcome in patients, including those with breast cancer. A selective glutaminase inhibitor, CB-839, which targets cancer cells through blocking of glutamine conversion to glutamate, has shown promising preclinical results as a therapeutic target in triple-negative breast cancer treatment. The current study aimed to determine the importance of glutaminase in Oestrogen Receptor positive/lu-minal breast cancer to potentially identify therapeutic targets to treat this subtype. In vitro studies using luminal breast cancer cells were performed to investigate the effects of siRNA knockdown of glutaminase isoforms (GLS and GLS2) and inhibition using CB-839 on functional assays. Silencing GLS in luminal breast cancer cells significantly reduced cell proliferation whilst inducing apoptosis. Similar impact on cell proliferation was ob-served when silencing GLS2 in luminal B cells, but there was no observed effect on cell apoptosis and cell cycle. There was little effect of GLS inhibition using CB-839 in luminal breast cancer. This study demonstrates that glutaminase is necessary for luminal breast cancer growth and survival. Co-targeting GLS and GLS2 might be a novel approach for the treatment of this subclass. Further functional studies to evaluate the underlying mo-lecular mechanisms of this process are warranted
Assessing peat surface motion using Interferometric Synthetic Aperture Radar (InSAR) in the Great Fen area of Cambridgeshire, UK
Get PDFPeatland degradation is a critical global climate issue, releasing millions of tonnes of CO2 annually due to drainage and changes in land use. As countries strive to meet net-zero targets, restoring degraded peatlands has become a priority for carbon sequestration and biodiversity conservation. However, monitoring peatland recovery remains a challenge, especially for large-scale restoration projects. This research is driven by the need for low-cost validation of peatland re-wetting schemes, enabling robust monitoring of peat physical condition and hydrological recovery, with implications for carbon accounting and agriculture's contribution to net-zero targets. This paper addresses this gap by applying satellite remote sensing data from Interferometric Synthetic Aperture Radar (InSAR) to track peat surface motion in Cambridgeshire's Great Fen, one of the UK's largest lowland peatland restoration initiatives. Sentinel-1 InSAR data (2015–2025) were used to quantify ground motion and derive deformation-based proxies for peat carbon flux. Our analysis revealed distinct subsidence patterns for undrained, early-restored, and later-restored farms, enabling first-order, deformation-based carbon flux estimation under common parameter assumptions. Early-restored farms experienced subsidence rates of up to 1.17 cm/year and deformation-associated carbon flux proxies of 14.50 tons CO2/ha/year, compared to 1.40 cm/year and 17.37 tons CO2/ha/year in later-restored sites. National Nature Reserves (Holme Fen and Woodwalton), under long-term conservation management, recorded the lowest subsidence (∼0.48 cm/year) and lowest deformation-associated carbon loss proxy (5.98 tons CO2/ha/year), consistent with higher peat moisture conditions relative to restored farmland. These estimates, interpreted as relative indicators rather than direct measurements of net ecosystem carbon balance, demonstrate InSAR's utility for tracking peatland condition and relative peat carbon vulnerability across restoration timelines. Seasonal fluctuations aligned with soil moisture and precipitation anomalies, indicating a strong hydrological control on peat surface motion. Together, these findings show that InSAR provides a high-resolution, cost-effective tool for continuous monitoring of peatland physical dynamics, supporting comparative assessment of restoration outcomes and climate-relevant land management decisions
Re-positioning Mental Health Experiences from Deficit to Asset. A Qualitative Study Exploring When the Idea of Becoming a Mental Health Peer Support Worker Takes Shape
Get PDFmental health conditions engage in supporting others experiencing similar challenges. Becoming a peer support worker (PSW) includes a transition from being a service user to becoming a provider of care and personal roles and identity are challenged when adjusting to the new role. Through individual interviews, this study explored eight PSWs’ personal stories of mental illness, recovery, and when the possibility of becoming a peer support worker emerged during this process. Thematic analysis led to four themes: 1) Struggles in everyday life, 2) Landmark events, 3) Turning points, and 4) Finding your way. The PSWs told deeply personal stories of how mental illness had impacted their lives. The themes display when the initial idea and then the ambition to become a PSW emerged during the process of recovery. This study provides insight into how the PSWs at different times—and in different ways—became aware of the possibility of using their personal experience to support others. At an overall level, these findings represent descriptions of individual processes in which the PSWs moved towards re-positioning their lived experiences with mental health challenges from deficit to asset
The application of bacteriophage to veterinary and One-Health medicine—a road map
Get PDFThe STAR-IDAZ international research consortium established a working group on Alternatives to Antimicrobials to explore various approaches for reducing our reliance on antimicrobials. These included bacteriophages, activating the immune system and manipulating the microbiome. The sub-group investigating bacteriophages have developed a road map for the application of phages in a One Health context. We present this roadmap here, in review format, along with a discussion of how phages may be combined with other therapies
Sucrose transport to the root and shoot in the seedling phloem
Get PDFIn the seedling, sucrose synthesised within the leaves is transported via the phloem throughout the plant for growth and maintenance. Sucrose allocation between the root and shoot thus determines their relative growth; however, our understanding of how phloem characteristics affects sucrose allocation remains incomplete. In this paper, we develop and analyse a mathematical model that describes phloem sucrose transport in the Arabidopsis thaliana seedling, from a source region in a leaf to a sink region in either the root or shoot. Motivated by experimental observations in Arabidopsis seedlings, we assume sucrose unloading occurs via both bulk flow and diffusion. Moreover, we extend previous models by assuming that the phloem water and sucrose are unloaded via two different microscopic channels traversing the phloem boundary (plasmodesmata and aquaporins), the density of which vary along the phloem. Numerical solutions of our mathematical model predict that differences between the plasmodesmatal fluxes in the root or shoot (which are controlled by plasmodesmatal number and aperture) are the dominant mechanism controlling root-shoot sucrose allocation. We predict that while the sucrose concentration external to the phloem affects the relative diffusive and advective unloading, it has limited affect on sucrose allocation. Furthermore, we predict that negative pressure gradients external to the phloem (due to the xylem, for example) can inhibit sucrose allocation to the root. However, the model predicts that the Arabidopsis thaliana seedling modelled here can alleviate this effect by increasing the plasmodesmatal conductivity within the root
The Midas touch: Recombinant antibodies transforming diagnostic platforms
Get PDFAntibodies, crucial for diagnostics due to their specific antigen-binding, can be identified using in vitro display technologies. Recombinant antibodies are a new generation of antibodies devoid of immunization thus eliminating the need for a host animal. However, the application of recombinant antibodies in diagnostics is still lagging in comparison to animal derived antibodies. This review will focus on the antibodies derived from phage display, a technology that presents antibodies on filamentous phage for selection. We explore its application and discuss derivative display systems, such as ribosome, yeast, bacterial, and mammalian cell display in recombinant antibody development. This review showcases the exciting potential of recombinant antibodies for diagnostic innovation
The relationship between food insecurity and tobacco or alcohol use in Great Britain: A representative population-based survey
Get PDFIntroductionTobacco and alcohol use are linked to health disparities. In recent years, food insecurity, an indicator of disparities, has increased in Great Britain. This study examined the associations between food insecurity and tobacco or alcohol use.MethodsData were drawn from a representative cross-sectional study of people aged ≥16 years in Great Britain (N = 4,056), conducted in January‒February 2025. Food insecurity was measured with the 6-item Household Food Security Scale, divided into high/marginal, low, or very low food security. Logistic regression models with food insecurity (combining low and very low food insecurity) as the outcome and adjusted for age, gender, nation of residence, socioeconomic position, financial hardship and smoking or alcohol consumption (measured using AUDIT-C score), were used to derive odds ratios (ORadj).ResultsOverall, 7.9 % (95 % CI: 6.9, 8.9) reported low and 9.6 % (8.6, 10.7) very low food security. Smoking was associated with food insecurity (ORadj = 1.75; 95 % CI: 1.32, 2.31). People who abstained from alcohol were more likely to be food insecure compared with those who drank at increasing (AUDIT-C 5: ORadj = 0.62; 0.41, 0.93) or higher risks of harm (AUDIT-C 8: ORadj = 0.63; 0.40, 0.97); however, this relationship was moderated by psychological distress.ConclusionFood insecurity was associated with higher smoking prevalence. Among people experiencing distress, those abstaining from alcohol and at risk of dependence appeared more likely to experience food insecurity than those drinking at other levels. These findings suggest the need for interventions that offer support for smoking, alcohol and which address underlying stressors of food insecurity
Yield of the Four-Carbon Stabilized Criegee Intermediates from Isoprene Ozonolysis
Get PDFIsoprene is the single most abundant nonmethane hydrocarbon emitted into the atmosphere. Despite this, uncertainties in the oxidation chemistry remain. Here, we investigate the yields of Criegee intermediates that are produced from the ozonolysis reaction, where we conduct a series of atmospheric simulation chamber experiments in which the transient stabilized Criegee intermediates (sCIs) are titrated in the gas phase using either biacetyl or acetylpropionyl. This reaction yields a stable ketone-substituted secondary ozonide (SOZ), which was observed directly in the gas phase using a proton-transfer-reaction time-of-flight mass spectrometer operated in NH4+ mode. Both C1 and C4 sCIs were observed in this way, with the mass of the NH4+ adduct shifting according to the mass of the sCI and its diketone titrant. The relative abundance of the C4 sCI was constrained against C1 assuming a similar sensitivity for the two SOZ derivatives. This was supported by quantum chemical calculations that demonstrated very similar binding energies between NH4+ and the C1 and C4 SOZ adducts. Our results demonstrate an overall yield of ∼11% for the long-lived C4 sCIs, which may survive long enough to participate in various bimolecular reactions in the atmosphere
Blastocystis infection enhances vitamins B and K2 biosynthesis in the Tibetan antelope (Pantholops hodgsonii) gut microbiota
Get PDFThe gut microbiota of the Tibetan antelope (Pantholops hodgsonii) plays a vital role in host nutrition, particularly by contributing to the biosynthesis of essential micronutrients such as vitamins B and K 2. In this study, we integrated existing P. hodgsonii gut metagenome-assembled genomes with healthy and Blastocystis-infected gut metagenomic samples to investigate microbial strategies for vitamins B and K 2 production, as well as the potential modulation of these biosynthetic pathways in the gut of P. hodgsonii. From a total of 33,925 metagenome-assembled genomes, we identified 14,549 non-redundant genomes encoding 182 KEGG orthologs linked to vitamin biosynthesis. Among these, 2,115 high-quality genomes were predicted to synthesize at least one vitamin de novo, yet only 2.9% could produce four or more vitamins. Comparative analyses across multiple host species, including humans, chickens, cats, and mice, revealed that members of the phyla Bacillota_A and Bacteroidetes consistently serve as primary contributors to microbial vitamin biosynthesis. Blastocystis infection was associated with a significant increase in the abundance and diversity of vitamin biosynthesis genes, reflecting adaptive shifts in microbial metabolism. Detailed genomic analyses of the thiamine biosynthesis pathway highlighted the core contributions of Bacillota_A, Bacteroidota, Verrucomicrobiota, and Methanobacteriota, underscoring complex taxonomic cooperation. These results provide novel insights into the functional specialization and taxonomic composition of the P. hodgsonii gut microbiota, offering novel insights into microbial adaptation and metabolic cooperation that support host nutritional homeostasis and resilience in extreme environments
Colour Algebras over Rings
Get PDFColour algebras are noncommutative Jordan algebras and closely Colour algebras are noncommutative Jordan algebras and closely related to octonion algebras. They initially emerged in physics since the multiplication of a colour algebra over the real or complex numbers describes the colour symmetry of the Gell–Mann quark model. Over fields of characteristic not equal to two, their structure is now well-known. We initiate the study of colour algebras over a unital commutative base ring R where two is an invertible element, and show when colour algebras can be constructed canonically by employing nondegenerate ternary hermitian forms with trivial determinant. We investigate their structure, their automorphism group and their derivations. We show that there is again a close connection between the colour algebras obtained from hermitian forms and certain types of octonion algebras
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