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Expression profile of human cytomegalovirus UL111A cmvIL-10 and LAcmvIL-10 transcripts in primary cells and cells from renal transplant recipients
Get PDFFunding: This study was supported by Fundação de Amparo à Pesquisa do Estado de São Paulo, Brazil (FAPESP) (Grant number: 2020/08527-1) awarded to MCCS and by the UKRI MRC grant (grant Grant number: MR/Z504361/1) awarded to E.P.Human cytomegalovirus (HCMV) is a high-risk pathogen in immunocompromised individuals, especially in transplant recipients. HCMV viremia must be monitored, and frequently, patients are treated with antiviral agents. HCMV has a variety of strategies to modulate host antiviral responses, and one important player is a viral homolog of the cellular interleukin-10 (cIL-10). The viral UL111A gene produces several HCMV IL-10 transcripts and protein isoforms through alternative splicing. The cmvIL-10 (isoform A) has similar properties to cIL-10, while LAcmvIL-10 (isoform B) has more restricted biological properties. Other isoforms are produced (C to H) but have unknown functions. Here, we investigated the expression of the most abundant transcripts, cmvIL-10 and LAcmvIL-10, in productively and latently infected cells and in peripheral blood mononuclear cells from renal transplant recipients up to 60 days post-transplantation. This study investigated HCMV cmvIL-10 and LAcmvIL-10 transcription profiles in vitro, in productive and latent infection, and in vivo, in peripheral blood mononuclear cells (PBMCs) of renal transplant patients. In vitro, both cmvIL-10 and LAcmvIL-10 transcripts were detected in both types at high levels and low levels in MRC-5 and latent infected (CD14+). When PBMCs from transplant patients were analyzed, LAcmvIL-10 was detected mostly sporadically and in only a few patients, while cmvIL-10 was found in all patients at all time points. Furthermore, it was observed in PBMCs that expression of cmvIL-10 was positively associated with an increase in viral DNA detection in the subsequently collected sample, indicating that expression of cmvIL-10 might precede viral DNA replication. These results contribute to the understanding of HCMV biology in different phases of infection. In addition, our initial analysis suggests that monitoring cmvIL-10, along with viral DNA, could improve early detection of HCMV reactivation in transplant recipients.Peer reviewe
Affect, video games, and postdigital technogenesis in contemporary literary fiction
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Thinking with images : An interview with Thomas E. Wartenberg
Get PDFIn his most recent book, Thoughtful Images: Illustrating Philosophy Through Art (2023), Thomas E. Wartenberg explores the variety of ways in which visual art has illustrated philosophy. Employing a new framework for thinking about the nature of illustration, Wartenberg surveys a wide variety of cases which, he argues, show not only that philosophical concepts can be illustrated but that such illustrations have the capacity to do philosophy in a substantial way. In this interview, Professor Wartenberg and I discuss the book and its central themes, including the nature and aesthetics of illustration, how art can cultivate philosophical understanding, and how it can contribute unique philosophical insight.Peer reviewe
Unearthing the histories of agrarian landscapes : a research framework for terraces as sustainable environments
Get PDFFunding: This project received funding from ARPAMED (PID2020-119365GA-I00) and ECOLOC (EUR2021-122009), Spanish Ministry of Science—UKRI AHRC Terraces as sustainable environments—TerraSAgE (AH/T000104/1) and European Union's Horizon 2020 research and innovation programme under the Marie Skłodowska-Curie grant agreement No. 890561, Historic Landscape and Soil Sustainability (HiLSS).This article presents an interdisciplinary programme for research on historic landscapes that has emerged since 2020 in the framework of the project Terraces as Sustainable Agricultural Environments (‘TerraSAgE’). While the methodology has been tested in specific Mediterranean case studies, it is also applicable in other locations and regions. Our integrated approach provides new insights into the development of terraced agrarian landscapes and the changing dynamics in land management. It can provide knowledge of the extent to which past change has influenced present-day landscapes and has implications for the development of sustainable landscape practices. The research framework proposed here has been tested through case studies in different landscape types across southern Europe, including small-scale mixed farming landscapes of the Aegean islands (Naxos, Greece); terraces for vines and olives (Pelješac, Croatia); a landscape of dairy production (northern Apennines, Italy), which was until quite recently agroforestry; modern cereal cultivation (around Els Prats de Rei, Catalonia, Spain); upland irrigated landscapes on the slopes of the Sierra Nevada (Andalucia, Spain) and mixed farming in a wooded Atlantic environment (Galicia, Spain).Peer reviewe
Mindful moments : using meditation for student and staff wellbeing in the classroom
Get PDFThis article discusses the increasing concerns for student mental health within higher education and the specific need for anthropology to consider the effects of our teaching content on student wellbeing. I reflect on using mindfulness in the classroom as a coping strategy for the challenges faced during the Covid-19 pandemic, and how meditation helped to create a supportive, relaxed learning environment. Acknowledging the limits of this practice, I consider meditation to be one resource within a wider pedagogical toolkit that embraces student-centred learning. My argument does not intend to further burden teaching staff with the responsibilities for student welfare, but instead demonstrates how using pedagogies that prioritise wellbeing can increase student engagement, promote inclusivity and lead to positive transformations for students and staff.Peer reviewe
Modality, truth and mere picture thinking
Get PDFMany draw the distinction between truth in, and truth at, a possible world. The latter notion purportedly allows for propositions to be true relative to worlds even if they do not exist relative to those same worlds. Despite its wide application, the distinction is controversial. Some think that the notion of truth at a world is unintelligible. Here, I outline and discuss the most influential argument for the unintelligibility of truth at a world, The Picture Thinking Argument. I outline and defend a neglected strategy to respond to this, arguing that if we take seriously the idea that possible worlds represent total ways the world could be, the distinction can be drawn intelligibly.Peer reviewe
The tidal deformation and atmosphere of WASP-12b from its phase curve
Get PDFFunding: LCa and CHe acknowledge support from the European Union H2020-MSCA-ITN-2019 under Grant Agreement no. 860470 (CHAMELEON). ACCa and TWi acknowledge support from STFC consolidated grant numbers ST/R000824/1 and ST/V000861/1, and UKSA grant number ST/R003203/1. PM acknowledges support from STFC research grant number ST/M001040/1. NAW acknowledges UKSA grant ST/R004838/1.Context. Ultra-hot Jupiters present a unique opportunity to understand the physics and chemistry of planets, their atmospheres, and interiors at extreme conditions. WASP-12 b stands out as an archetype of this class of exoplanets, with a close-in orbit around its star that results in intense stellar irradiation and tidal effects. Aims. The goals are to measure the planet’s tidal deformation, atmospheric properties, and also to refine its orbital decay rate. Methods. We performed comprehensive analyses of the transits, occultations, and phase curves of WASP-12b by combining new CHEOPS observations with previous TESS and Spitzer data. The planet was modeled as a triaxial ellipsoid parameterized by the second-order fluid Love number of the planet, h2, which quantifies its radial deformation and provides insight into the interior structure. Results. We measured the tidal deformation of WASP-12b and estimated a Love number of h2 = 1.55−0.49+0.45 (at 3.2σ) from its phase curve. We measured occultation depths of 333 ± 24 ppm and 493 ± 29 ppm in the CHEOPS and TESS bands, respectively, while the nightside fluxes are consistent with zero, and also marginal eastward phase offsets. Our modeling of the dayside emission spectrum indicates that CHEOPS and TESS probe similar pressure levels in the atmosphere at a temperature of ~2900 K. We also estimated low geometric albedos of Ag = 0.086 ± 0.017 and Ag = 0.01 ± 0.023 in the CHEOPS and TESS passbands, respectively, suggesting the absence of reflective clouds in the high-temperature dayside of the planet. The CHEOPS occultations do not show strong evidence for variability in the dayside atmosphere of the planet at the median occultation depth precision of 120 ppm attained. Finally, combining the new CHEOPS timings with previous measurements refines the precision of the orbital decay rate by 12% to a value of −30.23 ± 0.82 ms yr−1, resulting in a modified stellar tidal quality factor of Q′★ = 1.70 ± 0.14 × 105. Conclusions. WASP-12 b becomes the second exoplanet, after WASP-103b, for which the Love number has been measured from the effect of tidal deformation in the light curve. However, constraining the core mass fraction of the planet requires measuring h2 with a higher precision. This can be achieved with high signal-to-noise observations with JWST since the phase curve amplitude, and consequently the induced tidal deformation effect, is higher in the infrared.Peer reviewe
Impurity band formation as a route to thermoelectric power factor enhancement in n-type XNiSn half-Heuslers
Get PDFFunding: The EPSRC is acknowledged for support under award EP/N01717X/1, EP/N01703X/1, EP/X02346X/1, EP/L017008/1, EP/R023751/1 and EP/T019298/1 and for a PhD studentship for S.A.B.Bandstructure engineering is a key route for thermoelectric performance enhancement. Here, 20–50% Seebeck (S) enhancement is reported for XNiCuySn half-Heusler samples based on X = Ti. This novel electronic effect is attributed to the emergence of impurity bands of finite extent, due to the Cu dopants. Depending on the dispersion, extent, and offset with respect to the parent material, these bands are shown to enhance S to different degrees. Experimentally, this effect is controllable by the Ti content of the samples, with the addition of Zr/Hf gradually removing the enhancement. At the same time, the mobility remains largely intact, enabling power factors ≥3 mW m−1 K−2 near room temperature, increasing to ≥5 mW m−1 K−2 at high temperature. Combined with reduced thermal conductivity due to the Cu interstitials, this enables high average zT = 0.67–0.72 between 320 and 793 K for XNiCuySn compositions with ≥70% Ti. This work reveals the existence of a new route for electronic performance enhancement in n-type XNiSn materials that are normally limited by their single carrier pocket. In principle, impurity bands can be applied to other materials and provide a new direction for further development.Peer reviewe
Bonobo gestures, meanings, and context
Get PDFFunding: The author is currently funded by the European Union’s 8th Framework Programme, Horizon 2020, under grant agreement no 802719.Although you might not know what a “gesture” is (yet), most people reading this book probably have some experience with gestures. Waving, bowing, clapping, nodding, pantomiming, and pointing, are just some of the many gestures that you may have encountered. As humans, we use many conventionalized gestures that we learn throughout our lives and regularly produce gestures alongside language (Goldin-Meadow 2005). One way of examining the evolution of human gesture, and potentially human language, is to study gestural communication in other species. Researchers in great ape gestural communication tend to define a gesture as an intentional, mechanically ineffective movement of the limbs, head, or body that is used to communicate (Townsend et al. 2016). All great apes use gestures to communicate (Call and Tomasello 2007), and there is growing evidence of gestural communication across the primate taxa (Macaca mulatta, M. nemestrina, M. arctoides, Maestripieri 2005; Macaca radiata, Gupta and Sinha 2016; Macaca Sylvanus, Hesler and Fischer 2007; Papio anubis, Bourjade et al. 2014)
Kinetic and thermodynamic characterization of human 4-oxo-L-proline reductase catalysis
Get PDFFunding: This work was supported by a Cunningham Trust Ph.D. Award (Grant PhD-CT-21-04) to R.G.d.S., which supports a Ph.D. studentship to E.P.The enzyme 4-oxo-l-proline reductase (BDH2) has recently been identified in humans. BDH2, previously thought to be a cytosolic (R)-3-hydroxybutyrate dehydrogenase, actually catalyzes the NADH-dependent reduction of 4-oxo-L-proline to cis-4-hydroxy-L-proline, a compound with known anticancer activity. Here we provide an initial mechanistic characterization of the BDH2-catalyzed reaction. Haldane relationships show the reaction equilibrium strongly favors the formation of cis-4-hydroxy-L-proline. Stereospecific deuteration of NADH C4 coupled with mass spectrometry analysis of the reaction established that the pro-S hydrogen is transferred. NADH is co-purified with the enzyme, and a binding kinetics competition assays with NAD+ defined dissociation rate constants for NADH of 0.13 s–1 at 5 °C and 7.2 s–1 at 25 °C. Isothermal titration calorimetry at 25 °C defined equilibrium dissociation constants of 0.48 and 29 μM for the BDH2:NADH and BDH2:NAD+ complexes, respectively. Differential scanning fluorimetry showed BDH2 is highly thermostabilized by NADH and NAD+. The kcat/KM pH–rate profile indicates that a group with a pKa of 7.3 and possibly another with a pKa of 8.7 must be deprotonated and protonated, respectively, for maximum binding of 4-oxo-L-proline and/or catalysis, while the kcat profile is largely insensitive to pH in the pH range used. The single-turnover rate constant is only 2-fold higher than kcat. This agrees with a pre-steady-state burst of substrate consumption, suggesting that a step after chemistry, possibly product release, contributes to limit kcat. A modest solvent viscosity effect on kcat indicates that this step is only partially diffusional. Taken together, these data suggest chemistry does not limit the reaction rate but may contribute to it.Peer reviewe
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