• Ipomoeassin-F disrupts multiple aspects of secretory protein biogenesis

      Roboti, Peristera; email: peristera.roboti@manchester.ac.uk; O’Keefe, Sarah; Duah, Kwabena B.; Shi, Wei Q.; High, Stephen; email: stephen.high@manchester.ac.uk (Nature Publishing Group UK, 2021-06-02)
      Abstract: The Sec61 complex translocates nascent polypeptides into and across the membrane of the endoplasmic reticulum (ER), providing access to the secretory pathway. In this study, we show that Ipomoeassin-F (Ipom-F), a selective inhibitor of protein entry into the ER lumen, blocks the in vitro translocation of certain secretory proteins and ER lumenal folding factors whilst barely affecting others such as albumin. The effects of Ipom-F on protein secretion from HepG2 cells are twofold: reduced ER translocation combined, in some cases, with defective ER lumenal folding. This latter issue is most likely a consequence of Ipom-F preventing the cell from replenishing its ER lumenal chaperones. Ipom-F treatment results in two cellular stress responses: firstly, an upregulation of stress-inducible cytosolic chaperones, Hsp70 and Hsp90; secondly, an atypical unfolded protein response (UPR) linked to the Ipom-F-mediated perturbation of ER function. Hence, although levels of spliced XBP1 and CHOP mRNA and ATF4 protein increase with Ipom-F, the accompanying increase in the levels of ER lumenal BiP and GRP94 seen with tunicamycin are not observed. In short, although Ipom-F reduces the biosynthetic load of newly synthesised secretory proteins entering the ER lumen, its effects on the UPR preclude the cell restoring ER homeostasis.
    • iRFP (near-infrared fluorescent protein) imaging of subcutaneous and deep tissue tumours in mice highlights differences between imaging platforms.

      Hall, C; orcid: 0000-0002-0491-4438; von Grabowiecki, Y; orcid: 0000-0003-2189-6953; Pearce, S P; orcid: 0000-0002-1680-5538; Dive, C; Bagley, S; orcid: 0000-0002-9007-7292; Muller, P A J; orcid: 0000-0002-0926-1499; email: patricia.muller@cruk.manchester.ac.uk (2021-05-03)
      In vivo imaging using fluorescence is used in cancer biology for the detection, measurement and monitoring of tumours. This can be achieved with the expression of fluorescent proteins such as iRFP, which emits light at a wavelength less attenuated in biological tissues compared to light emitted by other fluorescent proteins such as GFP or RFP. Imaging platforms capable of detecting fluorescent tumours in small animals have been developed but studies comparing the performance of these platforms are scarce. Through access to three platforms from Xenogen, Bruker and Li-Cor, we compared their ability to detect iRFP-expressing subcutaneous tumours as well as tumours localised deeper within the body of female NSG mice. Each platform was paired with proprietary software for image analyse, but the output depends on subjective decisions from the user. To more objectively compare platforms, we developed an 'in house' software-based approach which results in lower measured variability between mice. Our comparisons showed that all three platforms allowed for reliable detection and monitoring of subcutaneous iRFP tumour growth. The biggest differences between platforms became apparent when imaging deeper tumours with the Li-Cor platform detecting most tumours and showing the highest dynamic range.
    • iRFP (near-infrared fluorescent protein) imaging of subcutaneous and deep tissue tumours in mice highlights differences between imaging platforms.

      Hall, C; orcid: 0000-0002-0491-4438; von Grabowiecki, Y; orcid: 0000-0003-2189-6953; Pearce, S P; orcid: 0000-0002-1680-5538; Dive, C; Bagley, S; orcid: 0000-0002-9007-7292; Muller, P A J; orcid: 0000-0002-0926-1499; email: patricia.muller@cruk.manchester.ac.uk (2021-05-03)
      <h4>Background</h4>In vivo imaging using fluorescence is used in cancer biology for the detection, measurement and monitoring of tumours. This can be achieved with the expression of fluorescent proteins such as iRFP, which emits light at a wavelength less attenuated in biological tissues compared to light emitted by other fluorescent proteins such as GFP or RFP. Imaging platforms capable of detecting fluorescent tumours in small animals have been developed but studies comparing the performance of these platforms are scarce.<h4>Results</h4>Through access to three platforms from Xenogen, Bruker and Li-Cor, we compared their ability to detect iRFP-expressing subcutaneous tumours as well as tumours localised deeper within the body of female NSG mice. Each platform was paired with proprietary software for image analyse, but the output depends on subjective decisions from the user. To more objectively compare platforms, we developed an 'in house' software-based approach which results in lower measured variability between mice.<h4>Conclusions</h4>Our comparisons showed that all three platforms allowed for reliable detection and monitoring of subcutaneous iRFP tumour growth. The biggest differences between platforms became apparent when imaging deeper tumours with the Li-Cor platform detecting most tumours and showing the highest dynamic range.
    • Iron induces two distinct Ca

      Guan, Wenzheng; Xia, Maosheng; Ji, Ming; Chen, Beina; Li, Shuai; Zhang, Manman; Liang, Shanshan; Chen, Binjie; Gong, Wenliang; Dong, Chengyi; et al. (2021-05-05)
      Iron is the fundamental element for numerous physiological functions. Plasmalemmal divalent metal ion transporter 1 (DMT1) is responsible for cellular uptake of ferrous (Fe ), whereas transferrin receptors (TFR) carry transferrin (TF)-bound ferric (Fe ). In this study we performed detailed analysis of the action of Fe ions on cytoplasmic free calcium ion concentration ([Ca ] ) in astrocytes. Administration of Fe or Fe in μM concentrations evoked [Ca ] in astrocytes in vitro and in vivo. Iron ions trigger increase in [Ca ] through two distinct molecular cascades. Uptake of Fe by DMT1 inhibits astroglial Na -K -ATPase, which leads to elevation in cytoplasmic Na concentration, thus reversing Na /Ca exchanger and thereby generating Ca influx. Uptake of Fe by TF-TFR stimulates phospholipase C to produce inositol 1,4,5-trisphosphate (InsP ), thus triggering InsP receptor-mediated Ca release from endoplasmic reticulum. In summary, these findings reveal the mechanisms of iron-induced astrocytic signalling operational in conditions of iron overload.
    • Iron induces two distinct Ca<sup>2+</sup> signalling cascades in astrocytes.

      Guan, Wenzheng; Xia, Maosheng; Ji, Ming; Chen, Beina; Li, Shuai; Zhang, Manman; Liang, Shanshan; Chen, Binjie; Gong, Wenliang; Dong, Chengyi; et al. (2021-05-05)
      Iron is the fundamental element for numerous physiological functions. Plasmalemmal divalent metal ion transporter 1 (DMT1) is responsible for cellular uptake of ferrous (Fe<sup>2+</sup>), whereas transferrin receptors (TFR) carry transferrin (TF)-bound ferric (Fe<sup>3+</sup>). In this study we performed detailed analysis of the action of Fe ions on cytoplasmic free calcium ion concentration ([Ca<sup>2+</sup>]<sub>i</sub>) in astrocytes. Administration of Fe<sup>2+</sup> or Fe<sup>3+</sup> in μM concentrations evoked [Ca<sup>2+</sup>]<sub>i</sub> in astrocytes in vitro and in vivo. Iron ions trigger increase in [Ca<sup>2+</sup>]<sub>i</sub> through two distinct molecular cascades. Uptake of Fe<sup>2+</sup> by DMT1 inhibits astroglial Na<sup>+</sup>-K<sup>+</sup>-ATPase, which leads to elevation in cytoplasmic Na<sup>+</sup> concentration, thus reversing Na<sup>+</sup>/Ca<sup>2+</sup> exchanger and thereby generating Ca<sup>2+</sup> influx. Uptake of Fe<sup>3+</sup> by TF-TFR stimulates phospholipase C to produce inositol 1,4,5-trisphosphate (InsP<sub>3</sub>), thus triggering InsP<sub>3</sub> receptor-mediated Ca<sup>2+</sup> release from endoplasmic reticulum. In summary, these findings reveal the mechanisms of iron-induced astrocytic signalling operational in conditions of iron overload.
    • Iron Is Filtered by the Kidney and Is Reabsorbed by the Proximal Tubule

      Wareing, Mark; Smith, Craig P.; email: craig.smith@manchester.ac.uk (Frontiers Media S.A., 2021-09-30)
      The aim of this study was to determine the iron (Fe) concentration profile within the lumen of the S2 renal proximal convoluted tubule (PCT) and to resolve whether this nephron segment transported Fe. To do this, we performed in vivo renal micropuncture on Wistar rats, collected PCT tubular fluid from superficial nephrons, and measured Fe concentration. The Fe concentration profile along the S2 PCT suggested significant Fe reabsorption. Proximal tubules were also microperfused in vivo with physiological solutions containing Fe and Zn, Cu, Mn, or Cd. PCTs perfused with 12μmol.l−1 55FeCl3 reabsorbed 105.2±12.7 fmol.mm−1.min−1 Fe, 435±52pmol.mm-1.min−1 Na, and 2.7±0.2nl.mm−1.min−1 water (mean ± SEM; n=19). Addition of ascorbate (1mmol.l−1) to the perfusate did not significantly alter Fe, Na, or water reabsorption. Supplementing the control perfusate with 60μmol.l−1 FeSO4 significantly decreased 55Fe uptake. Recalculating for the altered molar activity following addition of unlabeled Fe revealed a three-fold increase in Fe flux. Addition to the perfusate 12μmol.l−1 CuSO4, MnSO4, CdSO4, or ZnSO4 did not affect Fe, Na, or water flux. In conclusion, (1) in vivo, S2 PCTs of rat reabsorb Fe and (2) Fe is reabsorbed along the PCT via a pathway that is insensitive to Cu, Mn, Cd, or Zn. Together, these data demonstrate for the first time the hitherto speculated process of renal Fe filtration and subsequent tubular Fe reabsorption in a living mammal.
    • Is Breast Cancer Risk Associated with Menopausal Hormone Therapy Modified by Current or Early Adulthood BMI or Age of First Pregnancy?

      Leventea, Eleni; orcid: 0000-0002-7213-1048; email: eleni.leventea@addenbrookes.nhs.uk; Harkness, Elaine F.; orcid: 0000-0001-6625-7739; email: Elaine.F.Harkness@manchester.ac.uk; Brentnall, Adam R.; email: a.brentnall@qmul.ac.uk; Howell, Anthony; email: Anthony.Howell@manchester.ac.uk; Evans, D. Gareth; orcid: 0000-0002-8482-5784; email: Gareth.Evans@mft.nhs.uk; Harvie, Michelle; orcid: 0000-0001-9761-3089; email: michelle.harvie@manchester.ac.uk (MDPI, 2021-05-31)
      Menopausal hormone therapy (MHT) has an attenuated effect on breast cancer (BC) risk amongst heavier women, but there are few data on a potential interaction with early adulthood body mass index (at age 20 years) and age of first pregnancy. We studied 56,489 women recruited to the PROCAS (Predicting Risk of Cancer at Screening) study in Manchester UK, 2009-15. Cox regression models estimated the effect of reported MHT use at entry on breast cancer (BC) risk, and potential interactions with a. self-reported current body mass index (BMI), b. BMI aged 20 and c. First pregnancy >30 years or nulliparity compared with first pregnancy 30 years. Analysis was adjusted for age, height, family history, age of menarche and menopause, menopausal status, oophorectomy, ethnicity, self-reported exercise and alcohol. With median follow up of 8 years, 1663 breast cancers occurred. BC risk was elevated amongst current users of combined MHT compared to never users (Hazard ratioHR 1.64, 95% CI 1.32–2.03), risk was higher than for oestrogen only users (HR 1.03, 95% CI 0.79–1.34). Risk of current MHT was attenuated by current BMI (interaction HR 0.80, 95% CI 0.65–0.99) per 5 unit increase in BMI. There was little evidence of an interaction between MHT use, breast cancer risk and early and current BMI or with age of first pregnancy.
    • ‘Is climate science taking over the science?’: A corpus-based study of competing stances on bias, dogma and expertise in the blogosphere

      Pérez-González, Luis; orcid: 0000-0003-1756-9458; email: Luis.Perez-Gonzalez@manchester.ac.uk (Palgrave Macmillan UK, 2020-09-15)
      Abstract: Climate change science has become an increasingly polarized site of controversy, where discussions on epistemological rigour are difficult to separate from debates on the impact that economic and political interests have on the production of evidence and the construction of knowledge. Little research has been conducted so far on the antagonistic discursive processes through which climate knowledge is being contested and traditional forms of expertise are being (de-)legitimized—whether by members of the scientific community or non-scientist actors. This corpus-based study contributes to previous scholarship on the climate science controversy in a number of respects. Unlike earlier studies based on the analysis of mainstream media articles, this paper interrogates a corpus of climate change blog posts published by scientists, journalists, researchers and lobbyists laying claim to core, contributory and interactional forms of expertise—as conceptualized within the third wave of science studies. Further, the corpus informing this study has been designed to reflect the complex and multivoiced nature of the climate knowledge production process. Drawn from five different blogs, the views represented are not confined to the two poles between which the entrenched dialectic of ‘alarmists’ versus ‘deniers’ is typically played out in the climate science debate. Following a systemic functional conceptualization of dialogic engagement as a means of positioning authorial voices vis-à-vis competing perspectives construed and referenced in a text, this paper reports on bloggers’ use of three lexical items (bias, dogma and peer review) to expose their reliance on (non-)epistemic values. Concordances and a range of visualization tools are used to gain systematic insights into the network of lexical choices that obtain around these items, and to gauge whether/how bloggers construct coherent authorial subjectivities in a bid to claim expert status and/or question the recognition of other players in the debate.
    • Is global dietary change an effective strategy to curb climate change?

      Bradfield, James; orcid: 0000-0002-1010-2372; Trigueiro, Helena; Ray, Sumantra; orcid: 0000-0003-3295-168X (2020-07-02)
    • Is health research undertaken where the burden of disease is greatest? Observational study of geographical inequalities in recruitment to research in England 2013–2018

      Bower, Peter; email: peter.bower@manchester.ac.uk; Grigoroglou, Christos; Anselmi, Laura; Kontopantelis, Evangelos; Sutton, Matthew; Ashworth, Mark; Evans, Philip; Lock, Stephen; Smye, Stephen; Abel, Kathryn (BioMed Central, 2020-05-18)
      Abstract: Background: Research is fundamental to high-quality care, but concerns have been raised about whether health research is conducted in the populations most affected by high disease prevalence. Geographical distribution of research activity is important for many reasons. Recruitment is a major barrier to research delivery, and undertaking recruitment in areas of high prevalence could be more efficient. Regional variability exists in risk factors and outcomes, so research done in healthier populations may not generalise. Much applied health research evaluates interventions, and their impact may vary by context (including geography). Finally, fairness dictates that publically funded research should be accessible to all, so that benefits of participating can be fairly distributed. We explored whether recruitment of patients to health research is aligned with disease prevalence in England. Methods: We measured disease prevalence using the Quality and Outcomes Framework in England (total long-term conditions, mental health and diabetes). We measured research activity using data from the NIHR Clinical Research Network. We presented descriptive data on geographical variation in recruitment rates. We explored associations between the recruitment rate and disease prevalence rate. We calculated the share of patient recruitment that would need to be redistributed to align recruitment with prevalence. We assessed whether associations between recruitment rate and disease prevalence varied between conditions, and over time. Results: There was significant geographical variation in recruitment rates. When areas were ranked by disease prevalence, recruitment was not aligned with prevalence, with disproportionately low recruitment in areas with higher prevalence of total long-term and mental health conditions. At the level of 15 local networks, analyses suggested that around 12% of current recruitment activity would need to be redistributed to align with disease prevalence. Overall, alignment showed little change over time, but there was variation in the trends over time in individual conditions. Conclusions: Geographical variations in recruitment do not reflect the suitability of the population for research. Indicators should be developed to assess the fit between research and need, and to allow assessment of interventions among funders, researchers and patients to encourage closer alignment between research activity and burden.
    • Is it time for biocatalysis in fragment-based drug discovery?

      Ramsden, Jeremy I; Cosgrove, Sebastian C; orcid: 0000-0001-9541-7201; email: sebastian.cosgrove@manchester.ac.uk; Turner, Nicholas J; orcid: 0000-0002-8708-0781 (2020-10-07)
      The use of biocatalysts for fragment-based drug discovery has yet to be fully investigated, despite the promise enzymes hold for the synthesis of poly-functional, non-protected small molecules. Here we analyze products of the biocatalysis literature to demonstrate the potential for not only fragment generation, but also the enzyme-mediated elaboration of these fragments. Our analysis demonstrates that biocatalytic products can readily populate 3D chemical space, offering diverse catalytic approaches to help generate new, bioactive molecules.
    • Is it time for biocatalysis in fragment-based drug discovery?

      Ramsden, Jeremy I; Cosgrove, Sebastian C; orcid: 0000-0001-9541-7201; email: sebastian.cosgrove@manchester.ac.uk; Turner, Nicholas J; orcid: 0000-0002-8708-0781 (2020-10-07)
      The use of biocatalysts for fragment-based drug discovery has yet to be fully investigated, despite the promise enzymes hold for the synthesis of poly-functional, non-protected small molecules. Here we analyze products of the biocatalysis literature to demonstrate the potential for not only fragment generation, but also the enzyme-mediated elaboration of these fragments. Our analysis demonstrates that biocatalytic products can readily populate 3D chemical space, offering diverse catalytic approaches to help generate new, bioactive molecules. [Abstract copyright: This journal is © The Royal Society of Chemistry.]
    • Is the Morphological Subtype of Extra-Pulmonary Neuroendocrine Carcinoma Clinically Relevant?

      Frizziero, Melissa; email: melissa.frizziero@cruk.manchester.ac.uk; Durand, Alice; orcid: 0000-0002-0193-9058; email: alice.durand@chu-lyon.fr; Taboada, Rodrigo G.; orcid: 0000-0001-5674-2669; email: gomes.taboada@gmail.com; Zaninotto, Elisa; email: elisa.zaninotto@gmail.com; Luchini, Claudio; orcid: 0000-0003-4901-4908; email: claudio.luchini@univr.it; Chakrabarty, Bipasha; email: bipasha.chakrabarty@nhs.net; Hervieu, Valérie; email: valerie.hervieu@chu-lyon.fr; Claro, Laura C. L.; email: laura.claro@accamargo.org.br; Zhou, Cong; orcid: 0000-0002-6938-4685; email: cong.zhou@cruk.manchester.ac.uk; Cingarlini, Sara; email: cingarlini@icloud.com; et al. (MDPI, 2021-08-18)
      Extra-pulmonary neuroendocrine carcinomas (EP-NECs) are lethal cancers with limited treatment options. Identification of contributing factors to the observed heterogeneity of clinical outcomes within the EP-NEC family is warranted, to enable identification of effective treatments. A multicentre retrospective study investigated potential differences in “real-world” treatment/survival outcomes between small-cell (SC) versus (vs.) non-SC EP-NECs. One-hundred and seventy patients were included: 77 (45.3%) had SC EP-NECs and 93 (54.7%) had non-SC EP-NECs. Compared to the SC subgroup, the non-SC subgroup had the following features: (1) a lower mean Ki-67 index (69.3% vs. 78.7%; p = 0.002); (2) a lower proportion of cases with a Ki-67 index of ≥55% (73.9% vs. 88.7%; p = 0.025); (3) reduced sensitivity to first-line platinum/etoposide (objective response rate: 31.6% vs. 55.1%, p = 0.015; and disease control rate; 59.7% vs. 79.6%, p = 0.027); (4) worse progression-free survival (PFS) (adjusted-HR = 1.615, p = 0.016) and overall survival (OS) (adjusted-HR = 1.640, p = 0.015) in the advanced setting. Within the advanced EP-NEC cohort, subgroups according to morphological subtype and Ki-67 index (55% vs. ≥55%) had significantly different PFS (adjusted-p = 0.021) and OS (adjusted-p = 0.051), with the non-SC subgroup with a Ki-67 index of 55% and non-SC subgroup with a Ki-67 index of ≥55% showing the best and worst outcomes, respectively. To conclude, the morphological subtype of EP-NEC provides complementary information to the Ki-67 index and may aid identification of patients who could benefit from alternative first-line treatment strategies to platinum/etoposide.
    • Ischemic Heart Disease in Nigeria: Exploring the Challenges, Current Status, and Impact of Lifestyle Interventions on Its Primary Healthcare System

      Nnate, Daniel A.; orcid: 0000-0002-8432-9377; email: DNNATE200@caledonian.ac.uk; Eleazu, Chinedum O.; email: chinedum.eleazu@funai.edu.ng; Abaraogu, Ukachukwu O.; orcid: 0000-0002-1967-1459; email: ukachukwu.abaraogu@unn.edu.ng (MDPI, 2021-12-25)
      The burden of ischemic heart disease in Nigeria calls for an evidence-based, innovative, and interdisciplinary approach towards decreasing health inequalities resulting from individual lifestyle and poor socioeconomic status in order to uphold the holistic health of individuals to achieve global sustainability and health equity. The poor diagnosis and management of ischemic heart disease in Nigeria contributes to the inadequate knowledge of its prognosis among individuals, which often results in a decreased ability to seek help and self-care. Hence, current policies aimed at altering lifestyle behaviour to minimize exposure to cardiovascular risk factors may be less suitable for Nigeria’s diverse culture. Mitigating the burden of ischemic heart disease through the equitable access to health services and respect for the autonomy and beliefs of individuals in view of achieving Universal Health Coverage (UHC) requires comprehensive measures to accommodate, as much as possible, every individual, notwithstanding their values and socioeconomic status.
    • Isopentenol Utilization Pathway for the Production of Linalool in Escherichia coli Using an Improved Bacterial Linalool/Nerolidol Synthase

      Ferraz, Clara A.; Leferink, Nicole G. H.; Kosov, Iaroslav; Scrutton, Nigel S.; orcid: 0000-0002-4182-3500; email: nigel.scrutton@manchester.ac.uk (2021-05-25)
      Abstract: Linalool is a monoterpenoid used as a fragrance ingredient, and is a promising source for alternative fuels. Synthetic biology offers attractive alternative production methods compared to extraction from natural sources and chemical synthesis. Linalool/nerolidol synthase (bLinS) from Streptomyces clavuligerus is a bifunctional enzyme, producing linalool as well as the sesquiterpenoid nerolidol when expressed in engineered Escherichia coli harbouring a precursor terpenoid pathway such as the mevalonate (MVA) pathway. Here we identified two residues important for substrate selection by bLinS, L72 and V214, where the introduction of bulkier residues results in variants with reduced nerolidol formation. Terpenoid production using canonical precursor pathways is usually limited by numerous and highly regulated enzymatic steps. Here we compared the canonical MVA pathway to the non‐canonical isopentenol utilization (IU) pathway to produce linalool using the optimised bLinS variant. The IU pathway uses isoprenol and prenol to produce linalool in only five steps. Adjusting substrate, plasmid system, inducer concentration, and cell strain directs the flux towards monoterpenoids. Our integrated approach, combining enzyme engineering with flux control using the artificial IU pathway, resulted in high purity production of the commercially attractive monoterpenoid linalool, and will guide future efforts towards efficient optimisation of terpenoid production in engineered microbes.
    • Isotopic signatures of methane emissions from tropical fires, agriculture and wetlands: the MOYA and ZWAMPS flights

      MOYA/ZWAMPS Team; Nisbet, Euan G.; orcid: 0000-0001-8379-857X; email: e.nisbet@rhul.ac.uk; Allen, Grant; orcid: 0000-0002-7070-3620; email: grant.allen@manchester.ac.uk; Fisher, Rebecca E.; France, James L.; orcid: 0000-0002-8785-1240; Lee, James D.; Lowry, David; Andrade, Marcos F.; Bannan, Thomas J.; Barker, Patrick; orcid: 0000-0001-8754-4278; et al. (The Royal Society, 2021-12-06)
      We report methane isotopologue data from aircraft and ground measurements in Africa and South America. Aircraft campaigns sampled strong methane fluxes over tropical papyrus wetlands in the Nile, Congo and Zambezi basins, herbaceous wetlands in Bolivian southern Amazonia, and over fires in African woodland, cropland and savannah grassland. Measured methane δ13CCH4 isotopic signatures were in the range −55 to −49‰ for emissions from equatorial Nile wetlands and agricultural areas, but widely −60 ± 1‰ from Upper Congo and Zambezi wetlands. Very similar δ13CCH4 signatures were measured over the Amazonian wetlands of NE Bolivia (around −59‰) and the overall δ13CCH4 signature from outer tropical wetlands in the southern Upper Congo and Upper Amazon drainage plotted together was −59 ± 2‰. These results were more negative than expected. For African cattle, δ13CCH4 values were around −60 to −50‰. Isotopic ratios in methane emitted by tropical fires depended on the C3 : C4 ratio of the biomass fuel. In smoke from tropical C3 dry forest fires in Senegal, δ13CCH4 values were around −28‰. By contrast, African C4 tropical grass fire δ13CCH4 values were −16 to −12‰. Methane from urban landfills in Zambia and Zimbabwe, which have frequent waste fires, had δ13CCH4 around −37 to −36‰. These new isotopic values help improve isotopic constraints on global methane budget models because atmospheric δ13CCH4 values predicted by global atmospheric models are highly sensitive to the δ13CCH4 isotopic signatures applied to tropical wetland emissions. Field and aircraft campaigns also observed widespread regional smoke pollution over Africa, in both the wet and dry seasons, and large urban pollution plumes. The work highlights the need to understand tropical greenhouse gas emissions in order to meet the goals of the UNFCCC Paris Agreement, and to help reduce air pollution over wide regions of Africa. This article is part of a discussion meeting issue 'Rising methane: is warming feeding warming? (part 2)'.
    • “It is not the same”: relationships and dementia

      Benbow, Susan Mary; Tsaroucha, Anna; Sharman, Victoria (Informa UK Limited, 2019-08-28)
    • “It’s about portraying that we are organised …” A case study looking at understanding identity changes within one Free school’s Physical Education and School Sport (PESS) programme

      Williams, Gareth; orcid: 0000-0001-5332-2116; Burrows, Adam; orcid: 0000-0002-2922-9808; Williams, Dean; orcid: 0000-0002-8892-347X (Informa UK Limited, 2021-05-20)