Crosstalk between alternatively spliced UGT1A isoforms and colon cancer cell metabolism

Alternative splicing at the human glucuronosyltransferase 1 gene locus (UGT1) produces alternate isoforms UGT1A_i2s that control glucuronidation activity through protein-protein interactions. Here, we hypothesized that UGT1A_i2s function into a complex protein network connecting other metabolic pathways with influence on cancer cell metabolism. This is based on a pathway enrichment analysis of proteomic data that identified several high-confidence candidate interaction proteins of UGT1A_i2 proteins in human tissues, namely the rate-limiting enzyme of glycolysis pyruvate kinase (PKM), which plays a critical role in cancer cell metabolism and tumor growth. The partnership of UGT1A_i2 and PKM2 was confirmed by co-immunoprecipitation in the HT115 colon cancer cells and was supported by a partial co-localization of these two proteins. In support of a functional role for this partnership, depletion of UGT1A_i2 proteins in HT115 cells enforced the Warburg effect with higher glycolytic rate at the expense of mitochondrial respiration, and led to lactate accumulation. Untargeted metabolomics further revealed a significantly altered cellular content of 58 metabolites including many intermediates derived from the glycolysis and TCA cycle pathways. These metabolic changes were associated with a greater migration potential. The potential relevance of our observations is supported by the down-regulation of UGT1A_i2s mRNA in colon tumors compared to normal tissues. Alternate UGT1A variants may thus be part of the expanding compendium of metabolic pathways involved in cancer biology directly contributing to the oncogenic phenotype of colon cancer cells. Findings uncover new aspects of UGT functions diverging from their transferase activity

Myopericarditis complicated by pulmonary embolism in an immunocompetent patient with acute cytomegalovirus infection: a case report

Background Primary acute cytomegalovirus infection in immunocompetent patients is common worldwide. Infection is most often asymptomatic or occurs sub-clinically with a self-limited mononucleosis-like syndrome. More rarely, the infection may lead to severe organ complications with pneumonia, myocarditis, pericarditis, colitis and hemolytic anemia. Recent cases of cytomegalovirus-associated thrombosis have also been reported sporadically in the medical literature. Case presentation We report here a case of simultaneous myopericarditis and pulmonary embolism in a 30-year-old man with no medical history. The patient was not immunocompromised. We discuss the possible role of acute cytomegalovirus infection in the induction of vascular damage and review relevant cases in the literature. Conclusion Thrombosis in patients with acute cytomegalovirus infection may be more frequent than is generally thought. Physicians need to be aware of the possible association between acute cytomegalovirus and thrombosis in immunocompetent patients, especially in the presence of severe systemic infection, as our case illustrates

Nanocomposite MFI-alumina and FAU-alumina Membranes: Synthesis, Characterization and Application to Paraffin Separation and CO2 Capture

Rouleau, L. Pirngruber, G. Guillou, F. Barrere-Tricca, C. Omegna, A. Valtchev, V. Pera-Titus, M. Miachon, S. Dalmon, J. A.International audienceIn this work, we report the preparation of thermally and mechanically resistant high-surface (24-cm2) nanocomposite MFI-alumina and FAUalumina membranes by pore-plugging synthesis inside the macropores of α-alumina multilayered tubular supports. The MFI membranes were prepared from a clear solution precursor mixture being able to easily penetrate into the pores of the support. The MFI membranes were evaluated in the separation of n-/i-butane mixtures. The synthesis reliability was improved by mild stirring. The most selective MFI membranes were obtained for supports with mean pore sizes of 0.2 and 0.8 μm. The MFI effective thickness could be reduced to less than 10 μm by impregnating the support with water prior to synthesis and by diluting the synthesis mixture. The best MFI membrane offered an excellent tradeoff between selectivity and permeance at 448 K, with separation factors for equimolar n-butane/i-butane mixtures up to 18 and n-butane mixture permeances as high as 0.7 μmol$\cdot$s-1$\cdot$m-2$\cdot$Pa-1.Furthermore, a novel nanocomposite FAU membrane architecture has been obtained by an original synthesis route including in situ seeding using a cold gel-like precursor mixture, followed by growth of the FAU material by hydrothermal synthesis in two steps using a clear solution of low viscosity. This new membrane showed interesting performance in the separation of an equimolar CO2/N2 mixture at 323 K, with CO2/N2 separation factors and mixture CO2 permeances up to 12 and 0.4 μmol$\cdot$s-1$\cdot$m-2$\cdot$Pa-1,respectively

The CC-Bio Project: Studying the Effects of Climate Change on Quebec Biodiversity

Anticipating the effects of climate change on biodiversity is now critical for managing wild species and ecosystems. Climate change is a global driver and thus affects biodiversity globally. However, land-use planners and natural resource managers need regional or even local predictions. This provides scientists with formidable challenges given the poor documentation of biodiversity and its complex relationships with climate. We are approaching this problem in Quebec, Canada, through the CC-Bio Project (http://cc‑bio.uqar.ca/), using a boundary organization as a catalyst for team work involving climate modelers, biologists, naturalists, and biodiversity managers. In this paper we present the CC-Bio Project and its general approach, some preliminary results, the emerging hypothesis of the northern biodiversity paradox (a potential increase of biodiversity in northern ecosystems due to climate change), and an early assessment of the conservation implications generated by our team work

Discordance between testosterone measurement methods in castrated prostate cancer patients

Failure to suppress testosterone below 0.7 nM in castrated prostate cancer patients is associated with poor clinical outcomes. Testosterone levels in castrated patients are therefore routinely measured. Although mass spectrometry is the gold standard used to measure testosterone, most hospitals use an immunoassay method. In this study, we sought to evaluate the accuracy of an immunoassay method to measure castrate testosterone levels, with mass spectrometry as the reference standard. We retrospectively evaluated a cohort of 435 serum samples retrieved from castrated prostate cancer patients from April to September 2017. No follow-up of clinical outcomes was performed. Serum testosterone levels were measured in the same sample using liquid chromatography coupled with tandem mass spectrometry and electrochemiluminescent immunoassay methods. The mean testosterone levels were significantly higher with immunoassay than with mass spectrometry (0.672 ± 0.359 vs 0.461 ± 0.541 nM; P 0.7 nM was significantly higher with immunoassay (22.1%) than with mass spectrometry (13.1%; P 0.7 nM by immunoassay can result in an inaccurately identified castration status. Suboptimal testosterone levels in castrated patients should be confirmed by either mass spectrometry or an immunoassay method validated at low testosterone levels and interpreted with caution before any changes are made to treatment management

How do things become strategic? ‘Strategifying’ corporate social responsibility

How do things become ‘strategic’? Despite the development of strategy-as-practice studies and the recognized institutional importance of strategy as a social practice, little is known about how strategy boundaries change within organizations. This article focuses on this gap by conceptualizing ‘strategifying’ – or making something strategic – as a type of institutional work that builds on the institution of strategy to change the boundaries of what is regarded as strategy within organizations. We empirically investigate how corporate social responsibility has been turned into strategy at a UK electricity company, EnergyCorp. Our findings reveal the practices that constitute three types of strategifying work – cognitive coupling, relational coupling and material coupling – and show how, together and over time, these types of work changed the boundaries of strategy so that corporate social responsibility became included in EnergyCorp’s official strategy, became explicitly attended to by strategists and corporate executives and became inscribed within strategy devices. By disambiguating the notions of strategifying and strategizing, our study introduces new perspectives for analysing the institutional implications of the practice of strategy

Extracorporeal Membrane Oxygenation for Severe Acute Respiratory Distress Syndrome associated with COVID-19: An Emulated Target Trial Analysis.

RATIONALE: Whether COVID patients may benefit from extracorporeal membrane oxygenation (ECMO) compared with conventional invasive mechanical ventilation (IMV) remains unknown. OBJECTIVES: To estimate the effect of ECMO on 90-Day mortality vs IMV only Methods: Among 4,244 critically ill adult patients with COVID-19 included in a multicenter cohort study, we emulated a target trial comparing the treatment strategies of initiating ECMO vs. no ECMO within 7 days of IMV in patients with severe acute respiratory distress syndrome (PaO2/FiO2 <80 or PaCO2 ≥60 mmHg). We controlled for confounding using a multivariable Cox model based on predefined variables. MAIN RESULTS: 1,235 patients met the full eligibility criteria for the emulated trial, among whom 164 patients initiated ECMO. The ECMO strategy had a higher survival probability at Day-7 from the onset of eligibility criteria (87% vs 83%, risk difference: 4%, 95% CI 0;9%) which decreased during follow-up (survival at Day-90: 63% vs 65%, risk difference: -2%, 95% CI -10;5%). However, ECMO was associated with higher survival when performed in high-volume ECMO centers or in regions where a specific ECMO network organization was set up to handle high demand, and when initiated within the first 4 days of MV and in profoundly hypoxemic patients. CONCLUSIONS: In an emulated trial based on a nationwide COVID-19 cohort, we found differential survival over time of an ECMO compared with a no-ECMO strategy. However, ECMO was consistently associated with better outcomes when performed in high-volume centers and in regions with ECMO capacities specifically organized to handle high demand. This article is open access and distributed under the terms of the Creative Commons Attribution Non-Commercial No Derivatives License 4.0 (http://creativecommons.org/licenses/by-nc-nd/4.0/)

CNG direct injection spark-ignition engine with high turbulence and high compression ratio: numerical and experimental investigations

International audienceThis study carried on within the H2020 GasOn project scope of work showed the interest to improve the turbulence of a CNG direct injection spark ignited engine with high compression by a dedicated cylinder head design. The in-cylinder air motion was optimally configured through 3D-CFD simulation in order to cope with the high performance targets (~240 N.m/L at 1500 rpm, ~80kW/L at 4500 rpm) within the cylinder pressure limit of 160 bar (Pcylmax+2s = 180 bar). To sustain such level of pressure a Diesel engine basis was used. The compression ratio was set to 13.4:1 in line with the knock resistance of the natural gas. This newly design engine was compared to a reference engine developed in a previous study. The flow test bench measurements confirmed the high tumble level of the optimized cylinder head. This new cylinder head was next tested on a single cylinder engine equipped with high mass flow rate gas injector prototype developed by Continental. The results, integrating the boundary conditions of the air path system including LP-EGR, validated the good effect of faster combustion revealed by the lower fuel consumption and the high tolerance to EGR dilution in stoichiometric conditions. Consequently, the results showed a significant improvement compared to the previous engine and a performance attaining Diesel-like break thermal engine efficiencies (~41%)

Perimacular Ganglion Cell Complex Thinning Detected By Spectral-Domain OCT Useful In Detecting Optic Tract Syndrome

"Unilateral lesions to the optic tract lead to optic nerve atrophy (bow-tie atrophy) and concurrent macular ganglion cell complex (GCC) thickness reduction in a reproducible pattern in both eyes. This is called optic tract syndrome and it is reflected clinically as an incongruous homonymous hemianopia and a contralateral relative afferent pupillary defect (RAPD).