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Hypertensive load predicts recovery of renal function for patients undergoing revascularisation for renal artery stenosis
Get PDFRenal ischaemia due to renal artery stenosis produces two differing responses - a juxtaglomerular hypertensive response and cortical renal dysfunction. The reversibility of renal impairment is not predictable, and thus renal revascularisation is controversial. This study aims to test the hypothesis that the hypertensive response to renal ischaemia reflects viable renal parenchyma, and thus could be used to predict the recovery in renal function. A retrospective analysis was performed of all patients who had renal revascularisation for renal impairment in a defined geographical area (West of Scotland, population 2.4 million) between 2008 and 2024. Clinical records were used to determine the pre-intervention blood pressure, anti-hypertensive medication load and renal function, and post-intervention outcomes. The Hypertensive Index (HTi), a combined measure of systolic blood pressure and antihypertensive drug load, was used as a measure of pre-intervention hypertensive response. 75 patients had intervention for renal impairment over 15 years (68 endovascular, 7 open). Mean pre-intervention serum creatinine of 323 µmol/L was reduced to 191 umol/L at discharge and 182 µmol/L at 6-month follow-up. Refractory hypertension (HTi > 120) was associated with a significant benefit from revascularisation with improved renal function (p = 0.003) and reduced risk of future dialysis (p = 0.001). Renal impairment with no hypertensive response was highly predictive of the need for future dialysis. The hypertensive index is a good predictor of the impact of renal revascularisation on improving renal function with good outcomes in selected patients, and the absence of this is an indicator of chronic non-reversible renal dysfunction
Mixed-methods study of first-year physics students: soft barriers to coding
Get PDFDigital proficiency, including coding, is increasingly essential in physics education. However, disparities in coding skills among students are influenced by demographic factors and prior educational exposure. This study examines barriers to pre-university coding exposure for first-year physics students across five UK institutions, proposing a fourth level of the digital divide that emphasizes technical and production knowledge in coding. A survey of 199 first-year physics students reveals significant gender and ethnicity differences in coding experience. Males were more than twice as likely to have prior coding experience than females. Students with no prior coding experience viewed it as more challenging, requiring advanced math and powerful computing resources. Despite these challenges, both groups strongly disagreed that gender affects coding ability. Qualitative data pointed to technical difficulties, a lack of role models, and insufficient pre-university exposure as major obstacles. Black, Asian, and Minority Ethnicity (BAME) students reported less teacher encouragement and faced structural barriers similar to those found in literature. The study identifies a fourth level of the digital divide in coding knowledge, stressing the need for targeted interventions to enhance diversity and inclusivity in physics coding education. Recommendations include improving pre-university coding exposure, using gender-sensitive teaching methods, providing consistent encouragement to students, and deeply integrating coding into physics curricula. These steps are vital for preparing students for the digital demands of their academic and professional futures, ensuring equitable access to essential digital competencies
Characterisation of RNA guanine-7 methyltransferase (RNMT) using a small molecule approach
Get PDFThe maturation of the RNA cap involving guanosine N-7 methylation, catalyzed by the HsRNMT (RNA guanine-7 methyltransferase)-RAM (RNA guanine-N7 methyltransferase activating subunit) complex, is currently under investigation as a novel strategy to combat PIK3CA mutant breast cancer. However, the development of effective drugs is hindered by a limited understanding of the enzyme's mechanism and a lack of small molecule inhibitors. Following the elucidation of the HsRNMT-RAM molecular mechanism, we report the biophysical characterization of two small molecule hits. Biophysics, biochemistry and structural biology confirm that both compounds bind competitively with cap and bind effectively to HsRNMT-RAM in the presence of the co-product SAM, with a binding affinity (KD) of approximately 1 μM. This stabilisation of the enzyme-product complex results in uncompetitive inhibition. Finally, we describe the properties of the cap pocket and provided suggestions for further development of the tool compounds
The relationship between tumour necrosis, systemic inflammation, body composition and survival in patients with colon cancer
Get PDFBackground:
In cancer cachexia the relationship between the tumour, its environment and the systemic inflammatory response is not clear. This study aims to examine this relationship in greater detail.
Methods:
Host characteristics included the presence of a Systemic Inflammatory Response (SIR) as measured by Systemic Inflammatory Grade (SIG), sarcopenia (SMI) and myosteatosis (SMD) were measured. Categorical variables were analysed using χ2 test for linear-by-linear association, or χ2 test for 2 by 2 tables. Survival analysis was carried out using univariate and multivariate Cox regression.
Results:
A total of 473 patients were included. Of these, 70.4% were over 65 years of age, 54.8% were male and 49.8% had an ASA grade of 1 or 2. Pathological examination showed that the majority of patients had a T3 (53.7%) or a T4 (34.0%) cancer and 73.0% had evidence of necrosis. A SIG score of 0 or 1 was present in 57.7% of patients. Tumour necrosis was associated with age (p < 0.01), tumour location (p < 0.01), T-stage (p < 0.001), margin involvement (p < 0.05), SIG (p < 0.001), SMI (p < 0.01), SMD (p < 0.05) and 5-year survival (p < 0.001). On multivariate survival analysis in patients with T3 cancers age (HR: 1.45 95% CI 1.13–1.86 p < 0.01), ASA grade (HR: 1.50 95% CI 1.15–1.95 p < 0.01) and SIG (HR: 1.28 95% CI 1.11–1.48 p < 0.001) remained independently associated with survival.
Conclusion:
These results suggest that tumour necrosis and the subsequent SIR could result in profound changes in body composition and survival. Further pre-clinical and clinical work is required to prove causation
Solar radiation drives the plant species distribution in urban built-up areas
Get PDFUrban areas serve as critical habitats for numerous plant species. Existing studies suggest that, due to human-mediated introductions, urban environments often harbor a greater variety of plant species compared to suburban areas, potentially becoming focal points for biodiversity. Consequently, investigating the driving forces and complex mechanisms by which urban environmental factors influence plant species distribution is essential for establishing the theoretical foundation for urban biodiversity conservation and future urban planning and management. Solar radiation, among these factors, is a critical determinant of plant growth, development, and reproduction. However, there is a notable lack of research on how this factor affects the distribution of urban plant species and influences species’ richness and composition within plant communities. We present for the first time an analysis of how solar radiation drives the spatial distribution of plant species within the built-up areas of Nanchang City, China. Based on three years of monitoring and survey data from experimental sites, this study employs three evaluation models—Species Richness Index (R), Simpson’s Diversity Index (D), and Shannon–Wiener Index (H)—to analyze and validate the survey results. Additionally, MATLAB and ArcGIS Pro software are utilized for the numerical simulation and visualization of spatial data. Our study shows that areas with low solar radiation exhibit higher plant species richness, while plots with high plant diversity are primarily concentrated in regions with strong solar radiation. Moreover, the Diversity Index D proves to be more sensitive than the Shannon–Wiener Index (H) in evaluating the spatial distribution of plant species, making it a more suitable metric for studying urban plant diversity in our study area. Among the 18 plant species analyzed, Mulberry and Dandelion are predominantly dispersed by birds and wind, showing no significant correlation with solar radiation. This finding indicates that the spatial distribution of urban plant species is influenced by multiple interacting factors beyond solar radiation, highlighting the critical need for long-term observation, monitoring, and analysis. This study also suggests that shaded urban areas may serve as hubs of high species richness, while regions with relatively strong solar radiation can sustain greater plant diversity. These findings underscore the practical significance of this research, offering essential insights to guide urban planning and management strategies. Additionally, this study offers valuable insights for the future predictions of plant species distribution and potential areas of high plant diversity in various urban settings by integrating computational models, building data, Digital Elevation Models (DEMs), and land cover data
Phenotypic evolution of SARS-CoV-2 spike during the COVID-19 pandemic
Get PDFSARS-CoV-2 variants are mainly defined by mutations in their spike. It is therefore critical to understand how the evolutionary trajectories of spike affect virus phenotypes. So far, it has been challenging to comprehensively compare the many spikes that emerged during the pandemic in a single experimental platform. Here we generated a panel of recombinant viruses carrying different spike proteins from 27 variants circulating between 2020 and 2024 in the same genomic background. We then assessed several of their phenotypic traits both in vitro and in vivo. We found distinct phenotypic trajectories of spike among and between variants circulating before and after the emergence of Omicron variants. Spike of post-Omicron variants maintained enhanced tropism for the nasal epithelium and large airways but displayed, over time, several phenotypic traits typical of the pre-Omicron variants. Hence, spike with phenotypic features of both pre- and post-Omicron variants may continue to emerge in the future
Field vaccination of locally-owned cattle against malignant catarrhal fever under environmentally challenging conditions in Tanzania
Get PDFMalignant catarrhal fever (MCF), caused by alcelaphine herpesvirus-1 (AIHV-1) transmitted from wildebeest, is a lethal cattle disease with significant impacts on East African pastoralists. Development of a live attenuated MCF vaccine has prompted research into its use in communities at risk. This study reports results from the first utilisation of the MCF vaccine in locally-owned cattle under field conditions. The study involved a primary two-dose course vaccination of 1634 cattle, followed a year later, by boost vaccination of 385 of these cattle. It aimed to: (a) evaluate the antibody response to a two-dose AlHV-1 primary vaccination course, including initial response, antibody levels after one year, and clinical events post-vaccination; (b) assess how factors like age, reproductive status, body condition, and breed influence the initial response; and (c) compare antibody responses to single- and two-dose booster protocols one year after primary vaccination. Analyses were carried out using linear mixed-effects models and paired t-tests.
Clinical incidents were reported in 11/1634 cattle vaccinated during the primary course and in 0/385 cattle during the boost regimens. The primary vaccination resulted in a 9-fold increase in comparison to pre-vaccination antibody levels and the response was consistent across animals of different ages, reproductive statuses and body conditions. While antibody levels declined 11 months after primary vaccination, they remained high, and a single-dose booster vaccination was sufficient to elicit a strong immune response, with only marginal increases after a second booster.
The study provides evidence of high immunogenicity and low incidences of clinical events of the vaccine in cattle across individual host factors and immunologically vulnerable groups, under prevailing environmental conditions. It also indicates the utility of a single-dose booster regimen. These findings will support progress towards commercial production and larger-scale adoption which could generate important benefits for the livelihoods, and sustainability of pastoral livestock systems
High‐nuclearity polyoxometalate‐based metal–organic frameworks for photocatalytic oxidative cleavage of C−C bond
No full textHigh‐nuclearity polyoxometalate (POM) clusters are attractive building blocks (BBs) for the synthesis of metal–organic frameworks (MOFs) due to their high connectivity and inherently multiple metal centers as functional sites. This work demonstrates a strategy of step‐wise growth on ring‐shaped [P8W48O184]40− precursor, which produced two new high‐nuclearity polyoxotungstates, a half‐closed [H16P8W58O218]32− {W58} and a fully‐closed [H16P8W64O236]32− {W64}. By in situ synthesis, unique MOFs of copper triazole‐benzoic acid (HL) complexes incorporating the negatively‐charged {W58} and {W64} as nodes, {Cu11(HL)9W58} HNPOMOF‐1 and {Cu9(HL)9W64} HNPOMOF‐2, were constructed by delicately tuning the reaction conditions, mainly solution pH, which controls the formation of {W58} and {W64}, and at the same time the protonation of triazole‐benzoic acid ligand thus its coordination mode to copper ion that creates the highest nuclearity POM‐derived MOFs reported to date. HNPOMOF‐1 features 3D framework possessing cage‐like cavities filled with exposed carboxyl groups, while the inherent 2D layer‐like HNPOMOF‐2 allows for facile exfoliation into ultrathin nanosheets, and the resulted HNPOMOF‐2NS exhibits superior activity towards photocatalytic oxidative cleavage of C−C bond for a series of lignin models. This work not only provides a strategy to build high‐nuclearity POM cluster‐based frameworks, but also demonstrates their great potential as functional materials for green catalysis
Low-temperature aqueous alteration of chondrites
Get PDFChondritic meteorites (chondrites) contain evidence for the interaction of liquid water with the interiors of small bodies early in Solar System history. Here we review the processes, products and timings of the low-temperature aqueous alteration reactions in CR, CM, CI and ungrouped carbonaceous chondrites, the asteroids Ryugu and Bennu, and hydrated dark clasts in different types of meteorites. We first consider the nature of chondritic lithologies and the insights that they provide into alteration conditions, subdivided by the mineralogy and petrology of hydrated chondrites, the mineralogy of hydrated dark clasts, the effects of alteration on presolar grains, and the evolution of organic matter. We then describe the properties of the aqueous fluids and how they reacted with accreted material as revealed by physicochemical modelling and hydrothermal experiments, the analysis of fluid inclusions in aqueously formed minerals, and isotope tracers. Lastly, we outline the chronology of aqueous alteration reactions as determined using the 53Mn-53Cr and 129I-129Xe systems
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