COST Lecture 2019 AE GM Barcelona: International Network to Encourage the Use of Monitoring and Forecasting Dust Products (InDust)

Amongst the most significant extreme meteorological phenomena are the Sand and Dust Storms (SDS). Owing to significant amounts of airborne mineral dust particles generated during these events, SDS have impacts on climate, the environment, human health, and many socio-economic sectors (e.g. aviation, solar energy management). Many studies and reports have underlined that the society has to understand, manage and mitigate the risks and effects of SDS on life, health, property, the environment and the economy in a more unified way. The EU-funded European Cooperation in Science and Technology (COST) Action 'InDust: International network to encourage the use of monitoring and forecasting Dust products' has an overall objective to establish a network involving research institutions, service providers and potential end users on airborne dust information. We are a multidisciplinary group of international experts on aerosol measurements, aerosol modelling, stakeholders and social scientists working together, exchanging ideas to better coordinate and harmonize the process of transferring dust observation and prediction data to users, as well as to assist the diverse socio-economic sectors affected by the presence of high concentrations of airborne mineral dust. This article highlights the importance of being actively engaged in research networking activities, supported by EU and COST actions since common efforts help not only each scientist by shaping their expertise and strengthening their position, but also all communities

From crystalline to amorphous calcium pyrophosphates:a solid state Nuclear Magnetic Resonance perspective

Hydrated calcium pyrophosphates (CPP, Ca2P2O7·nH2O) are a fundamental family of materials among osteoarticular pathologic calcifications. In this contribution, a comprehensive multinuclear NMR (Nuclear Magnetic Resonance) study of four crystalline and two amorphous phases of this family is presented. 1H, 31P and 43Ca MAS (Magic Angle Spinning) NMR spectra were recorded, leading to informative fingerprints characterizing each compound. In particular, different 1H and 43Ca solid state NMR signatures were observed for the amorphous phases, depending on the synthetic procedure used. The NMR parameters of the crystalline phases were determined using the GIPAW (Gauge Including Projected Augmented Wave) DFT approach, based on first-principles calculations. In some cases, relaxed structures were found to improve the agreement between experimental and calculated values, demonstrating the importance of proton positions and pyrophosphate local geometry in this particular NMR crystallography approach. Such calculations serve as a basis for the future ab initio modeling of the amorphous CPP phases. Statement of significance The general concept of NMR crystallography is applied to the detailed study of calcium pyrophosphates (CPP), whether hydrated or not, and whether crystalline or amorphous. CPP are a fundamental family of materials among osteoarticular pathologic calcifications. Their prevalence increases with age, impacting on 17.5% of the population after the age of 80. They are frequently involved or associated with acute articular arthritis such as pseudogout. Current treatments are mainly directed at relieving the symptoms of joint inflammation but not at inhibiting CPP formation nor at dissolving these crystals. The combination of advanced NMR techniques, modeling and DFT based calculation of NMR parameters allows new original insights in the detailed structural description of this important class of biomaterials

CIB1 is an endogenous inhibitor of agonist-induced integrin αIIbβ3 activation

In response to agonist stimulation, the αIIbβ3 integrin on platelets is converted to an active conformation that binds fibrinogen and mediates platelet aggregation. This process contributes to both normal hemostasis and thrombosis. Activation of αIIbβ3 is believed to occur in part via engagement of the β3 cytoplasmic tail with talin; however, the role of the αIIb tail and its potential binding partners in regulating αIIbβ3 activation is less clear. We report that calcium and integrin binding protein 1 (CIB1), which interacts directly with the αIIb tail, is an endogenous inhibitor of αIIbβ3 activation; overexpression of CIB1 in megakaryocytes blocks agonist-induced αIIbβ3 activation, whereas reduction of endogenous CIB1 via RNA interference enhances activation. CIB1 appears to inhibit integrin activation by competing with talin for binding to αIIbβ3, thus providing a model for tightly controlled regulation of αIIbβ3 activation

Advances in the application and utility of subseasonal-to-seasonal predictions

The joint WWRP–WCRP Subseasonal to Seasonal Prediction Project (e.g., Robertson et al. 2014) created a global repository of experimental or operational near-real-time S2S forecasts and reforecasts (hindcasts) from 11 international meteorological institutions, cohosted by ECMWF and CMA (Vitart et al. 2017). These data are publicly accessible by researchers and users (https://apps.ecmwf.int/datasets/data/s2s and http://s2s.cma.cn/index). With the exception of the fourth case study, which uses GloSea5 forecasts (MacLachlan et al. 2015), all case studies use selected S2S forecasts and reforecasts that are available from this repository, providing a consistent basis for S2S forecast skill assessment and evaluation of their utility.The subseasonal-to-seasonal (S2S) predictive time scale, encompassing lead times ranging from 2 weeks to a season, is at the frontier of forecasting science. Forecasts on this time scale provide opportunities for enhanced application-focused capabilities to complement existing weather and climate services and products. There is, however, a “knowledge–value” gap, where a lack of evidence and awareness of the potential socioeconomic benefits of S2S forecasts limits their wider uptake. To address this gap, here we present the first global community effort at summarizing relevant applications of S2S forecasts to guide further decision-making and support the continued development of S2S forecasts and related services. Focusing on 12 sectoral case studies spanning public health, agriculture, water resource management, renewable energy and utilities, and emergency management and response, we draw on recent advancements to explore their application and utility. These case studies mark a significant step forward in moving from potential to actual S2S forecasting applications. We show that by placing user needs at the forefront of S2S forecast development—demonstrating both skill and utility across sectors—this dialogue can be used to help promote and accelerate the awareness, value, and cogeneration of S2S forecasts. We also highlight that while S2S forecasts are increasingly gaining interest among users, incorporating probabilistic S2S forecasts into existing decision-making operations is not trivial. Nevertheless, S2S forecasting represents a significant opportunity to generate useful, usable, and actionable forecast applications for and with users that will increasingly unlock the potential of this forecasting time scale.DD gratefully acknowledges support from the Swiss National Science Foundation through project PP00P2_170523. For case study 1, ACP and WTKH were funded by the U.K. Climate Resilience Programme, supported by the UKRI Strategic Priorities Fund. RWL was funded by NERC Grant NE/P00678/1 and by the BER DOE Office of Science Federal Award DE-SC0020324. TS was funded by NERC Independent Research Fellowship (NE/P018637/1). CMG and DB were funded by the Helmholtz Young Investigator Group “SPREADOUT” Grant VH-NG-1243. Case study 2 was supported by the U.K. Global Challenges Research Fund NE/P021077/1 (GCRF African SWIFT) and the Tertiary Education Trust Fund (TETFUND) of Nigeria TETFund/DR&D/CE/NRF/STI/73/VOL.1. EO thanks Adrian Tomkins of ICTP, Italy, for his contribution. Case study 3 was undertaken as part of the Columbia World Project, ACToday, Columbia University (https://iri.columbia.edu/actoday/). Case study 4 was supported by the ForPAc (Towards Forecast-based Preparedness Action) project within the NERC/FCDO SHEAR Programme NE/P000428/1, NE/P000673/1, and NE/P000568/1. Case study 5 was undertaken as part of the International Research Applications Project, funded by the U.S. National Oceanic and Atmospheric Administration. EO thanks IRAP project colleagues at The University of Arizona, Indian Meteorological Department, Regional Integrated Multi-Hazard Early Warning System for Africa and Asia, and two of Bihar’s State Agricultural Universities for their contributions. For case study 6, CASC thanks Conselho Nacional de Desenvolvimento Científico e Tecnológico Process 305206/2019-2 and Fundação de Amparo à Pesquisa do Estado de São Paulo Process 2015/50687-8 (CLIMAX Project) for their support. For case study 7, DW’s contributions were carried out under contract with the National Aeronautics and Space Administration. Case study 8 was funded by the EU Horizon 2020 Research and Innovation Programme Grant 7767874 (S2S4E). We also acknowledge the Subseasonal-to-Seasonal Project’s Real-Time Pilot Initiative for providing access to real-time forecasts. For case study 9, TIC-LCPE Hydro-04 was funded by the University of Strathclyde’s Low Carbon Power and Energy program. JB was supported by EPSRC Innovation Fellowship EP/R023484/1. We thank Andrew Low and Richard Hearnden from SSE Renewables for their input. Case study 10 was supported by the Earth Systems and Climate Change Hub under the Australian Government’s National Environmental Science Program, and the Decadal Climate Forecasting Project (CSIRO). Case study 11 was funded by the Technologies for Sustainable Built Environments Centre, Reading University, in conjunction with the EPSRC Grant EP/G037787/1 and BT PLC. Case study 12 was funded through the framework service contract for operating the EFAS Computational Center Contract 198702 and the Copernicus Fire Danger Computations Contract 389730 295 in support of the Copernicus Emergency Management Service and Early Warning Systems between the Joint Research Centre and ECMWF.Peer Reviewed"Article signat per 60 autors/es: Christopher J. White, Daniela I. V. Domeisen, Nachiketa Acharya, Elijah A. Adefisan, Michael L. Anderson, Stella Aura, Ahmed A. Balogun, Douglas Bertram, Sonia Bluhm, David J. Brayshaw, Jethro Browell, Dominik Büeler, Andrew Charlton-Perez, Xandre Chourio, Isadora Christel, Caio A. S. Coelho, Michael J. DeFlorio, Luca Delle Monache, Francesca Di Giuseppe, Ana María García-Solórzano, Peter B. Gibson, Lisa Goddard, Carmen González Romero, Richard J. Graham, Robert M. Graham, Christian M. Grams, Alan Halford, W. T. Katty Huang, Kjeld Jensen, Mary Kilavi, Kamoru A. Lawal, Robert W. Lee, David MacLeod, Andrea Manrique-Suñén, Eduardo S. P. R. Martins, Carolyn J. Maxwell, William J. Merryfield, Ángel G. Muñoz, Eniola Olaniyan, George Otieno, John A. Oyedepo, Lluís Palma, Ilias G. Pechlivanidis, Diego Pons, F. Martin Ralph, Dirceu S. Reis Jr., Tomas A. Remenyi, James S. Risbey, Donald J. C. Robertson, Andrew W. Robertson, Stefan Smith, Albert Soret, Ting Sun, Martin C. Todd, Carly R. Tozer, Francisco C. Vasconcelos Jr., Ilaria Vigo, Duane E. Waliser, Fredrik Wetterhall, and Robert G. Wilson"Postprint (author's final draft

Effect of early-stage human breast carcinoma on monocyte programming

Circulating monocytes are a major source of tumor-associated macrophages (TAMs). TAMs in human breast cancer (BC) support primary tumor growth and metastasis. Neoadjuvant chemotherapy (NAC) is a commonly used treatment for BC patients. The absence of the response to NAC has major negative consequences for the patient: increase of tumor mass, delayed surgery, and unnecessary toxicity. We aimed to identify the effect of BC on the subpopulation content and transcriptome of circulating monocytes. We examined how monocyte phenotypes correlate with the response to NAC. The percentage of CD14-, CD16-, CD163-, and HLA-DR-expressing monocytes was quantified by flow cytometry for patients with T1-4N0-3M0 before NAC. The clinical efficacy of NAC was assessed by RECIST criteria of RECIST 1.1 and by the pathological complete response (pCR). The percentage of CD14+ and СD16+ monocytes did not differ between healthy women and BC patients and did not differ between NAC responders and non-responders. The percentage of CD163-expressing CD14lowCD16+ and CD14+CD16+ monocytes was increased in BC patients compared to healthy women (99.08% vs. 60.00%, p = 0.039, and 98.08% vs. 86.96%, p = 0.046, respectively). Quantitative immunohistology and confocal microscopy demonstrated that increased levels of CD163+ monocytes are recruited in the tumor after NAC. The percentage of CD14lowCD16+ in the total monocyte population positively correlated with the response to NAC assessed by pCR: 8.3% patients with pCR versus 2.5% without pCR (p = 0.018). Search for the specific monocyte surface markers correlating with NAC response evaluated by RECIST 1.1 revealed that patients with no response to NAC had a significantly lower amount of CD14lowCD16+HLA-DR+ cells compared to the patients with clinical response to NAC (55.12% vs. 84.62%, p = 0.005). NGS identified significant changes in the whole transcriptome of monocytes of BC patients. Regulators of inflammation and monocyte migration were upregulated, and genes responsible for the chromatin remodeling were suppressed in monocyte BC patients. In summary, our study demonstrated that presence of BC before distant metastasis is detectable, significantly effects on both monocyte phenotype and transcriptome. The most striking surface markers were CD163 for the presence of BC, and HLA-DR (CD14lowCD16+HLA-DR+) for the response to NAC

Geomorphological processes and landforms of glacier forelands in the upper Aktru River basin (Gornyi Altai), Russia : evidence for rapid recent retreat and paraglacial adjustment

The glaciers in the Aktru River basin of Gornyi Altai, Russia currently represent some of the fastest receding glaciers in the world. Formation of the morainic complexes closest to the contemporary glaciers in the Aktru River basin took place during the 17th - 18th centuries with recession commencing at the end of the 18th century. Coupled with this glacial retreat, earth surface processes and vegetation succession are responding to shape the glacier forelands. This article presents the first geomorphological maps for the upper reaches of the Aktru River basin and focuses on the geomorphological landforms that occur in the rapidly changing glacier forelands. Geomorphological mapping is difficult in steep mountainous regions and, thus, mapping was completed using satellite imagery, field mapping and observations coupled with highresolution aerial photography obtained from Unmanned Aerial Vehicles (UAVs). Critical steps of the procedure used to process UAV imagery and difficulties encountered in this mountainous terrain are noted. The acquired spatial data enable the mapping and classification of small-scale transient geomorphological features such as talus, glacial and glaciofluvial landforms. Their dynamics provide insights into supraglacial and subglacial processes of the glaciers of the Aktru River basin and subsequent paraglacial adjustment. The presented highresolution spatial data, which can also be obtained at high temporal resolutions in the future, can act as a reference frame for geomorphologists and ecologists studying the temporal evolution of glacier forelands of the Aktru River basin during paraglacial adjustment and subsequent colonisation and stabilisation by biota.Incentive Funding for Rated Researchers Programme from the National Research Foundation South Africa, the BRICS Network University International Thematic Groups Seed-Funding and the Tomsk State University Competitive Improvement Programme.https://www.springer.com/journal/116292021-04-11hj2020Geography, Geoinformatics and Meteorolog

Autosomal recessive retinitis pigmentosa E150K opsin mice exhibit photoreceptor disorganization

The pathophysiology of the E150K mutation in the rod opsin gene associated with autosomal recessive retinitis pigmentosa (arRP) has yet to be determined. We generated knock-in mice carrying a single nucleotide change in exon 2 of the rod opsin gene resulting in the E150K mutation. This novel mouse model displayed severe retinal degeneration affecting rhodopsin’s stabilization of rod outer segments (ROS). Homozygous E150K (KK) mice exhibited early-onset retinal degeneration, with disorganized ROS structures, autofluorescent deposits in the subretinal space, and aberrant photoreceptor phagocytosis. Heterozygous (EK) mice displayed a delayed-onset milder retinal degeneration. Further, mutant receptors were mislocalized to the inner segments and perinuclear region. Though KK mouse rods displayed markedly decreased phototransduction, biochemical studies of the mutant rhodopsin revealed only minimally affected chromophore binding and G protein activation. Ablation of the chromophore by crossing KK mice with mice lacking the critical visual cycle protein LRAT slowed retinal degeneration, whereas blocking phototransduction by crossing KK mice with GNAT1-deficient mice slightly accelerated this process. This study highlights the importance of proper higher-order organization of rhodopsin in the native tissue and provides information about the signaling properties of this mutant rhodopsin. Additionally, these results suggest that patients heterozygous for the E150K mutation should be periodically reevaluated for delayed-onset retinal degeneration