Study of the relationship between photosynthesis, respiration, transpiration, and mineral nutrition in wheat

The growth of wheat (triticum aestivum) was studied in an enclosed controlled environment for a period of 70 days. The exchange of gases (photosynthesis, respiration), water (transpiration) and the consumption of mineral elements (nitrogen, phosphorus, potassium) were continuously measured. The dynamical relations observed in the different physiological functions, under the influence of growth and in response to environment modifications are presented. The influence of carbon dioxide content during growth (normal or double percentage) was made clear

Phase 2 Study of Pomalidomide (CC-4047) Monotherapy for Children and Young Adults With Recurrent or Progressive Primary Brain Tumors

INTRODUCTION: Treatment of recurrent primary pediatric brain tumors remains a major challenge, with most children succumbing to their disease. We conducted a prospective phase 2 study investigating the safety and efficacy of pomalidomide (POM) in children and young adults with recurrent and progressive primary brain tumors. BACKGROUND: METHODS: Patients with recurrent and progressive high-grade glioma (HGG), diffuse intrinsic pontine glioma (DIPG), ependymoma, or medulloblastoma received POM 2.6 mg/m2/day (the recommended phase 2 dose [RP2D]) on days 1-21 of a 28-day cycle. A Simon’s Optimal 2-stage design was used to determine efficacy. Primary endpoints included objective response (OR) and long-term stable disease (LTSD) rates. Secondary endpoints included duration of response, progression-free survival (PFS), overall survival (OS), and safety. RESULTS: 46 patients were evaluable for response (HGG, n = 19; DIPG, ependymoma, and medulloblastoma, n = 9 each). Two patients with HGG achieved OR or LTSD (10.5% [95% CI, 1.3%-33.1%]; 1 partial response and 1 LTSD) and 1 patient with ependymoma had LTSD (11.1% [95% CI, 0.3%-48.2%]). There were no ORs or LTSD in the DIPG or medulloblastoma cohorts. The median PFS for patients with HGG, DIPG, ependymoma, and medulloblastoma was 7.86, 11.29, 8.43, and 8.43 weeks, respectively. Median OS was 5.06, 3.78, 12.02, and 11.60 months, respectively. Neutropenia was the most common grade 3/4 adverse event. CONCLUSIONS: Treatment with POM monotherapy did not meet the primary measure of success in any cohort. Future studies are needed to evaluate if POM would show efficacy in tumors with specific molecular signatures or in combination with other anticancer agents. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov, identifier NCT03257631; EudraCT, identifier 2016-002903-25

Spatially targeted nature-based solutions can mitigate climate change and nature loss but require a systems approach

Funding Information: This study was funded by the Royal Society for the Protection of Birds (RSPB) and Natural England (project code ECM 58632). The Breeding Bird Survey is a Partnership between the BTO, RSPB, and Joint Nature Conservation Committee (on behalf of Natural Resources Wales, Natural England, Council for Nature Conservation and Countryside, and NatureScot) and relies on volunteer surveyors. Simon Gillings provided tetrad-level predictions of relative abundance for wading birds. We are grateful to members of the RSPB steering group, who contributed to the development of our scenarios, and Profs. Tim Benton and Andrew Balmford who commented on an earlier version of this manuscript. Conceptualization, T.F. R.B.B. T.B.-L. G.M.B. W.J.P. and R.H.F.; methodology, T.F. T.B.-L. J.P.C. D.M. P.S. and R.H.F.; software, T.F.; formal analysis, T.F.; resources, D.M.; data curation, T.F.; writing – original draft, T.F.; writing – review & editing, R.B.B. T.B.-L. G.M.B. J.P.C. D.M. P.S. W.J.P. and R.H.F.; visualization, T.F.; supervision, W.J.P. The authors declare no competing interests. Publisher Copyright: © 2023 The AuthorsPeer reviewedPublisher PD

Cherenkov Telescope Array Data Management

Very High Energy gamma-ray astronomy with the Cherenkov Telescope Array (CTA) is evolving towards the model of a public observatory. Handling, processing and archiving the large amount of data generated by the CTA instruments and delivering scientific products are some of the challenges in designing the CTA Data Management. The participation of scientists from within CTA Consortium and from the greater worldwide scientific community necessitates a sophisticated scientific analysis system capable of providing unified and efficient user access to data, software and computing resources. Data Management is designed to respond to three main issues: (i) the treatment and flow of data from remote telescopes; (ii) "big-data" archiving and processing; (iii) and open data access. In this communication the overall technical design of the CTA Data Management, current major developments and prototypes are presented.Comment: 8 pages, 2 figures, In Proceedings of the 34th International Cosmic Ray Conference (ICRC2015), The Hague, The Netherlands. All CTA contributions at arXiv:1508.0589

Genome-wide analyses of platinum-induced ototoxicity in childhood cancer patients: Results of GO-CAT and United Kingdom MAGIC consortia

: Hearing loss (ototoxicity) is a major adverse effect of cisplatin and carboplatin chemotherapy. The aim of this study is to identify novel genetic variants that play a role in platinum-induced ototoxicity. Therefore, a genome-wide association study was performed in the Genetics of Childhood Cancer Treatment (GO-CAT) cohort (n = 261) and the United Kingdom Molecular Genetics of Adverse Drug Reactions in Children Study (United Kingdom MAGIC) cohort (n = 248). Results of both cohorts were combined in a meta-analysis. In primary analysis, patients with SIOP Boston Ototoxicity Scale grade ≥1 were considered cases, and patients with grade 0 were controls. Variants with a p-value <10-5 were replicated in previously published data by the PanCareLIFE cohort (n = 390). No genome-wide significant associations were found, but variants in TSPAN5, RBBP4P5, AC010090.1 and RNU6-38P were suggestively associated with platinum-induced ototoxicity. The lowest p-value was found for rs7671702 in TSPAN5 (odds ratio 2.0 (95% confidence interval 1.5-2.7), p-value 5.0 × 10-7). None of the associations were significant in the replication cohort, although the effect directions were consistent among all cohorts. Validation and functional understanding of these genetic variants could lead to more insights in the development of platinum-induced ototoxicity

Clinical, radiologic, pathologic, and molecular characteristics of long-term survivors of diffuse intrinsic pontine glioma (DIPG): a collaborative report from the International and European Society for Pediatric Oncology DIPG registries

Purpose Diffuse intrinsic pontine glioma (DIPG) is a brainstem malignancy with a median survival of < 1 year. The International and European Society for Pediatric Oncology DIPG Registries collaborated to compare clinical, radiologic, and histomolecular characteristics between short-term survivors (STSs) and long-term survivors (LTSs). Materials and Methods Data abstracted from registry databases included patients from North America, Australia, Germany, Austria, Switzerland, the Netherlands, Italy, France, the United Kingdom, and Croatia. Results Among 1,130 pediatric and young adults with radiographically confirmed DIPG, 122 (11%) were excluded. Of the 1,008 remaining patients, 101 (10%) were LTSs (survival ≥ 2 years). Median survival time was 11 months (interquartile range, 7.5 to 16 months), and 1-, 2-, 3-, 4-, and 5-year survival rates were 42.3% (95% CI, 38.1% to 44.1%), 9.6% (95% CI, 7.8% to 11.3%), 4.3% (95% CI, 3.2% to 5.8%), 3.2% (95% CI, 2.4% to 4.6%), and 2.2% (95% CI, 1.4% to 3.4%), respectively. LTSs, compared with STSs, more commonly presented at age < 3 or > 10 years (11% v 3% and 33% v 23%, respectively; P < .001) and with longer symptom duration ( P < .001). STSs, compared with LTSs, more commonly presented with cranial nerve palsy (83% v 73%, respectively; P = .008), ring enhancement (38% v 23%, respectively; P = .007), necrosis (42% v 26%, respectively; P = .009), and extrapontine extension (92% v 86%, respectively; P = .04). LTSs more commonly received systemic therapy at diagnosis (88% v 75% for STSs; P = .005). Biopsies and autopsies were performed in 299 patients (30%) and 77 patients (10%), respectively; 181 tumors (48%) were molecularly characterized. LTSs were more likely to harbor a HIST1H3B mutation (odds ratio, 1.28; 95% CI, 1.1 to 1.5; P = .002). Conclusion We report clinical, radiologic, and molecular factors that correlate with survival in children and young adults with DIPG, which are important for risk stratification in future clinical trials

A national-scale assessment of climate change impacts on species: assessing the balance of risks and opportunities for multiple taxa

It is important for conservationists to be able to assess the risks that climate change poses to species, in order to inform decision making. Using standardised and repeatable methods, we present a national-scale assessment of the risks of range loss and opportunities for range expansion, that climate change could pose for over 3,000 plants and animals that occur in England. A basic risk assessment that compared projected future changes in potential range with recently observed changes classified 21% of species as being at high risk and 6% at medium risk of range loss under a B1 climate change scenario. A greater number of species were classified as having a medium (16%) or high (38%) opportunity to potentially expand their distribution. A more comprehensive assessment, incorporating additional ecological information, including potentially confounding and exacerbating factors, was applied to 402 species, of which 35 % were at risk of range loss and 42 % may expand their range extent. This study covers a temperate region with a significant proportion of species at their poleward range limit. The balance of risks and opportunities from climate change may be different elsewhere. The outcome of both risk assessments varied between taxonomic groups, with bryophytes and vascular plants containing the greatest proportion of species at risk from climate change. Upland habitats contained more species at risk than other habitats. Whilst the overall pattern was clear, confidence was generally low for individual assessments, with the exception of well-studied taxa such as birds. In response to climate change, nature conservation needs to plan for changing species distributions and increasing uncertainty of the future

Sequestration of free cholesterol in cell membranes by prions correlates with cytoplasmic phospholipase A2 activation

<p>Abstract</p> <p>Background</p> <p>The transmissible spongiform encephalopathies (TSEs), otherwise known as the prion diseases, occur following the conversion of the normal cellular prion protein (PrP^C) to an alternatively folded isoform (PrP^Sc). The accumulation of PrP^Scwithin the brain leads to neurodegeneration through an unidentified mechanism. Since many neurodegenerative disorders including prion, Parkinson's and Alzheimer's diseases may be modified by cholesterol synthesis inhibitors, the effects of prion infection on the cholesterol balance within neuronal cells were examined.</p> <p>Results</p> <p>We report the novel observation that prion infection altered the membrane composition and significantly increased total cholesterol levels in two neuronal cell lines (ScGT1 and ScN2a cells). There was a significant correlation between the concentration of free cholesterol in ScGT1 cells and the amounts of PrP^Sc. This increase was entirely a result of increased amounts of free cholesterol, as prion infection reduced the amounts of cholesterol esters in cells. These effects were reproduced in primary cortical neurons by the addition of partially purified PrP^Sc, but not by PrP^C. Crucially, the effects of prion infection were not a result of increased cholesterol synthesis. Stimulating cholesterol synthesis via the addition of mevalonate, or adding exogenous cholesterol, had the opposite effect to prion infection on the cholesterol balance. It did not affect the amounts of free cholesterol within neurons; rather, it significantly increased the amounts of cholesterol esters. Immunoprecipitation studies have shown that cytoplasmic phospholipase A₂(cPLA₂) co-precipitated with PrP^Scin ScGT1 cells. Furthermore, prion infection greatly increased both the phosphorylation of cPLA₂and prostaglandin E₂production.</p> <p>Conclusion</p> <p>Prion infection, or the addition of PrP^Sc, increased the free cholesterol content of cells, a process that could not be replicated by the stimulation of cholesterol synthesis. The presence of PrP^Scincreased solubilisation of free cholesterol in cell membranes and affected their function. It increased activation of the PLA₂pathway, previously implicated in PrP^Scformation and in PrP^Sc-mediated neurotoxicity. These observations suggest that the neuropathogenesis of prion diseases results from PrP^Scaltering cholesterol-sensitive processes. Furthermore, they raise the possibility that disturbances in membrane cholesterol are major triggering events in neurodegenerative diseases.</p