Short-chain lipid peroxidation products form covalent adducts with pyruvate kinase and inhibit its activity in vitro and in breast cancer cells

Pyruvate kinase catalyses the last step in glycolysis and has been suggested to contribute to the regulation of aerobic glycolysis in cancer cells. It can be inhibited by oxidation of cysteine residues in vitro and in vivo, which is relevant to the more pro-oxidant state in cancer and proliferating tissues. These conditions also favour lipid peroxidation and the formation of electrophilic fragmentation products, including short-chain aldehydes that can covalently modify proteins. However, as yet few studies have investigated their interactions with pyruvate kinase, so we investigated the effects of three different aldehydes, acrolein, malondialdehyde and 4-hydroxy-2(E)-hexenal (HHE), on the structure and activity of the enzyme. Analysis by LC-MS/MS showed unique modification profiles for each aldehyde, but Cys152, Cys423 and Cys474 were the residues most susceptible to electrophilic modification. Analysis of enzymatic activity under these conditions showed that acrolein was the strongest inhibitor, and at incubation times longer than 2 h, pathophysiological concentrations induced significant effects. Treatment of MCF-7 cells with the aldehydes caused similar losses of pyruvate kinase activity to those observed in vitro, and at lower concentrations than those required to cause cell death, with time and dose-dependent effects; acrolein adducts on Cys152 and Cys358 were detected. Cys358 and Cys474 are located at or near the allosteric or active sites, and formation of adducts on these residues probably contributes to loss of activity at low treatment concentrations. This study provides the first detailed analysis of the structure-activity relationship of C3 and C6 aldehydes with pyruvate kinase, and suggests that reactive short-chain aldehydes generated in diseases with an oxidative aetiology or from environmental exposure such as smoking could be involved in the metabolic alterations observed in cancer cells, through alteration of pyruvate kinase activity

The Globular Cluster System in the Inner Region of M87

1057 globular cluster candidates have been identified in a WFPC2 image of the inner region of M87. The Globular Cluster Luminosity Function (GCLF) can be well fit by a Gaussian profile with a mean value of m_V^0=23.67 +/- 0.07 mag and sigma=1.39 +/- 0.06 mag (compared to m_V^0=23.74 mag and sigma=1.44 mag from an earlier study using the same data by Whitmore it et al. 1995). The GCLF in five radial bins is found to be statistically the same at all points, showing no clear evidence of dynamical destruction processes based on the luminosity function (LF), in contradiction to the claim by Gnedin (1997). Similarly, there is no obvious correlation between the half light radius of the clusters and the galactocentric distance. The core radius of the globular cluster density distribution is R_c=56'', considerably larger than the core of the stellar component (R_c=6.8''). The mean color of the cluster candidates is V-I=1.09 mag which corresponds to an average metallicity of Fe/H = -0.74 dex. The color distribution is bimodal everywhere, with a blue peak at V-I=0.95 mag and a red peak at V-I=1.20 mag. The red population is only 0.1 magnitude bluer than the underlying galaxy, indicating that these clusters formed late in the metal enrichment history of the galaxy and were possibly created in a burst of star/cluster formation 3-6 Gyr after the blue population. We also find that both the red and the blue cluster distributions have a more elliptical shape (Hubble type E3.5) than the nearly spherical galaxy. The average half light radius of the clusters is ~2.5 pc which is comparable to the 3 pc average effective radius of the Milky Way clusters, though the red candidates are ~20% smaller than the blue ones.Comment: 40 pages, 17 figures, 4 tables, latex, accepted for publication in the Ap

Benchmarking a foundation LLM on its ability to re-label structure names in accordance with the AAPM TG-263 report

Purpose: To introduce the concept of using large language models (LLMs) to re-label structure names in accordance with the American Association of Physicists in Medicine (AAPM) Task Group (TG)-263 standard, and to establish a benchmark for future studies to reference. Methods and Materials: The Generative Pre-trained Transformer (GPT)-4 application programming interface (API) was implemented as a Digital Imaging and Communications in Medicine (DICOM) storage server, which upon receiving a structure set DICOM file, prompts GPT-4 to re-label the structure names of both target volumes and normal tissues according to the AAPM TG-263. Three disease sites, prostate, head and neck, and thorax were selected for evaluation. For each disease site category, 150 patients were randomly selected for manually tuning the instructions prompt (in batches of 50) and 50 patients were randomly selected for evaluation. Structure names that were considered were those that were most likely to be relevant for studies utilizing structure contours for many patients. Results: The overall re-labeling accuracy of both target volumes and normal tissues for prostate, head and neck, and thorax cases was 96.0%, 98.5%, and 96.9% respectively. Re-labeling of target volumes was less accurate on average except for prostate - 100%, 93.1%, and 91.1% respectively. Conclusions: Given the accuracy of GPT-4 in re-labeling structure names of both target volumes and normal tissues as presented in this work, LLMs are poised to be the preferred method for standardizing structure names in radiation oncology, especially considering the rapid advancements in LLM capabilities that are likely to continue.Comment: 20 pages, 5 figures, 1 tabl

The impact of aluminosilicate-based additives upon the sintering and melting behaviour of biomass ash

The composition of ash arising from biomass combustion can cause significant slagging and fouling issues in pulverised-fuel boilers, particularly if high concentrations of alkalis are present. Al–Si additives have shown promise in improving the ash deposition characteristics of troublesome biomass, converting volatile potassium to potassium aluminosilicates. This article presents results of lab-scale testing for two high-potassium biomass ashes, olive-cake (OCA) and white-wood (WWA), combined with two promising additives, coal pulverised fuel ash (PFA) and kaolin powder, at 5% mass fraction. Ash fusion testing results show that the use of these additives consistently increases flow temperatures. For WWA, kaolin was observed to reduce deformation temperatures and increase flow temperatures to far above combustion temperatures. Sinter strength testing showed that additive use significantly improves the deposition properties of OCA, preventing the precipitation of KCl and formation of deposits that are highly undesirable for removal via sootblower. Sintering was eliminated at all temperatures measured with the use of kaolin. Both additives had negative effects upon the sintering of WWA, indicating that Al–Si additive use should be restricted to high K, high Cl biomass. High temperature viscometry of OCA, combined with thermodynamic modelling, showed that viscosities at combustion temperatures were far below ideal values due high Mg concentration and silicate formation. Kaolin at 5% mass fraction was predicted to significantly improve this behaviour, with aluminosilicate formation producing favourable viscosities. Results indicate that kaolin addition to high K, high Cl biomass such as OCA shows promise in making the ash compositions viable for pulverised-fuel combustion

Progress in upscaling Miscanthus biomass production for the European bio-economy with seed-based hybrids

Funded by UK's Biotechnology and Biological Sciences Research Council (BBSRC) Department for Environment, Food and Rural Affairs (DEFRA). Grant Number: LK0863 BBSRC strategic programme Grant on Energy Grasses & Bio-refining. Grant Number: BBS/E/W/10963A01 OPTIMISC. Grant Number: FP7-289159 WATBIO. Grant Number: FP7-311929 Innovate UK/BBSRC ‘MUST’. Grant Number: BB/N016149/1Peer reviewedPublisher PD

Breeding progress and preparedness for mass‐scale deployment of perennial lignocellulosic biomass crops switchgrass, miscanthus, willow and poplar

UK: The UK‐led miscanthus research and breeding was mainly supported by the Biotechnology and Biological Sciences Research Council (BBSRC), Department for Environment, Food and Rural Affairs (Defra), the BBSRC CSP strategic funding grant BB/CSP1730/1, Innovate UK/BBSRC “MUST” BB/N016149/1, CERES Inc. and Terravesta Ltd. through the GIANT‐LINK project (LK0863). Genomic selection and genomewide association study activities were supported by BBSRC grant BB/K01711X/1, the BBSRC strategic programme grant on Energy Grasses & Bio‐refining BBS/E/W/10963A01. The UK‐led willow R&D work reported here was supported by BBSRC (BBS/E/C/00005199, BBS/E/C/00005201, BB/G016216/1, BB/E006833/1, BB/G00580X/1 and BBS/E/C/000I0410), Defra (NF0424) and the Department of Trade and Industry (DTI) (B/W6/00599/00/00). IT: The Brain Gain Program (Rientro dei cervelli) of the Italian Ministry of Education, University, and Research supports Antoine Harfouche. US: Contributions by Gerald Tuskan to this manuscript were supported by the Center for Bioenergy Innovation, a US Department of Energy Bioenergy Research Center supported by the Office of Biological and Environmental Research in the DOE Office of Science, under contract number DE‐AC05‐00OR22725. Willow breeding efforts at Cornell University have been supported by grants from the US Department of Agriculture National Institute of Food and Agriculture. Contributions by the University of Illinois were supported primarily by the DOE Office of Science; Office of Biological and Environmental Research (BER); grant nos. DE‐SC0006634, DE‐SC0012379 and DE‐SC0018420 (Center for Advanced Bioenergy and Bioproducts Innovation); and the Energy Biosciences Institute. EU: We would like to further acknowledge contributions from the EU projects “OPTIMISC” FP7‐289159 on miscanthus and “WATBIO” FP7‐311929 on poplar and miscanthus as well as “GRACE” H2020‐EU.3.2.6. Bio‐based Industries Joint Technology Initiative (BBI‐JTI) Project ID 745012 on miscanthus.Peer reviewedPostprintPublisher PD

Missense mutation of Brain Derived Neurotrophic Factor (BDNF) alters neurocognitive performance in patients with mild traumatic brain injury: a longitudinal study

The predictability of neurocognitive outcomes in patients with traumatic brain injury is not straightforward. The extent and nature of recovery in patients with mild traumatic brain injury (mTBI) are usually heterogeneous and not substantially explained by the commonly known demographic and injury-related prognostic factors despite having sustained similar injuries or injury severity. Hence, this study evaluated the effects and association of the Brain Derived Neurotrophic Factor (BDNF) missense mutations in relation to neurocognitive performance among patients with mTBI. 48 patients with mTBI were prospectively recruited and MRI scans of the brain were performed within an average 10.1 (SD 4.2) hours post trauma with assessment of their neuropsychological performance post full Glasgow Coma Scale (GCS) recovery. Neurocognitive assessments were repeated again at 6 months follow-up. The paired t-test, Cohen’s d effect size and repeated measure ANOVA were performed to delineate statistically significant differences between the groups [wildtype G allele (Val homozygotes) vs. minor A allele (Met carriers)] and their neuropsychological performance across the time point (T1 = baseline/ admission vs. T2 = 6th month follow-up). Minor A allele carriers in this study generally performed more poorly on neuropsychological testing in comparison wildtype G allele group at both time points. Significant mean differences were observed among the wildtype group in the domains of memory (M = -11.44, SD = 10.0, p = .01, d = 1.22), executive function (M = -11.56, SD = 11.7, p = .02, d = 1.05) and overall performance (M = -6.89 SD = 5.3, p = .00, d = 1.39), while the minor A allele carriers showed significant mean differences in the domains of attention (M = -11.0, SD = 13.1, p = .00, d = .86) and overall cognitive performance (M = -5.25, SD = 8.1, p = .01, d = .66).The minor A allele carriers in comparison to the wildtype G allele group, showed considerably lower scores at admission and remained impaired in most domains across the timepoints, although delayed signs of recovery were noted to be significant in the domains attention and overall cognition. In conclusion, the current study has demonstrated the role of the BDNF rs6265 Val66Met polymorphism in influencing specific neurocognitive outcomes in patients with mTBI. Findings were more detrimentally profound among Met allele carriers

TRY plant trait database – enhanced coverage and open access

Plant traits - the morphological, anatomical, physiological, biochemical and phenological characteristics of plants - determine how plants respond to environmental factors, affect other trophic levels, and influence ecosystem properties and their benefits and detriments to people. Plant trait data thus represent the basis for a vast area of research spanning from evolutionary biology, community and functional ecology, to biodiversity conservation, ecosystem and landscape management, restoration, biogeography and earth system modelling. Since its foundation in 2007, the TRY database of plant traits has grown continuously. It now provides unprecedented data coverage under an open access data policy and is the main plant trait database used by the research community worldwide. Increasingly, the TRY database also supports new frontiers of trait‐based plant research, including the identification of data gaps and the subsequent mobilization or measurement of new data. To support this development, in this article we evaluate the extent of the trait data compiled in TRY and analyse emerging patterns of data coverage and representativeness. Best species coverage is achieved for categorical traits - almost complete coverage for ‘plant growth form’. However, most traits relevant for ecology and vegetation modelling are characterized by continuous intraspecific variation and trait–environmental relationships. These traits have to be measured on individual plants in their respective environment. Despite unprecedented data coverage, we observe a humbling lack of completeness and representativeness of these continuous traits in many aspects. We, therefore, conclude that reducing data gaps and biases in the TRY database remains a key challenge and requires a coordinated approach to data mobilization and trait measurements. This can only be achieved in collaboration with other initiatives

Building the Policy Ecosystem in Europe for Cultivation and Use of Perennial Biomass Crops

Perennial biomass crops (PBCs) can potentially contribute to all ten Common Agricultural Policy (2023-27) objectives and up to eleven of the seventeen UN Sustainable Development Goals. This paper discusses interlinked issues that must be considered in the expansion of PBC production: i) available land; ii) yield potential; iii) integration into farming systems; iv) research and development requirements; v) utilisation options; and vi) market systems and the socio-economic environment. The challenge to create development pathways that are acceptable for all actors, relies on measurement, reporting and verification of greenhouse gas emissions reduction in combination with other environmental, economic and social aspects. This paper makes the following policy recommendations to enable greater PBC deployment: 1) incentivise farmers and land managers through specific policy measures, including carbon pricing, to allocate their less productive and less profitable land for uses which deliver demonstrable greenhouse gas reductions; 2) enable greenhouse gas mitigation markets to develop and offer secure contracts for commercial developers of verifiable low carbon bioenergy and bio-products; 3) support innovation in biomass utilisation value chains; and 4) continue long-term, strategic research and development and education for positive environmental, economic and social sustainability impacts. © 2023 ETA-Florence Renewable Energies