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As a set of seven Learning Activity Packages (LAPs) for individualized instruction in chemistry, the units cover problems in stoichiometry, energy levels, chemical bonding, matter and its forms, electrochemical processes, chemical kinetics and equilibrium, metals, and non-metals. Each unit contains a rationale for the material; a list of behavioral objectives for the unit; a list of resources including texts, periodical articles, laboratory experiments, audiovisual aids, and science activities; a problem set for student self-evaluation; and suggestions for advanced study. A related chemistry LAP is SE 016 425. (CC)

As a set of seven Learning Activity Packages (LAPs) for individualized instruction in chemistry, the units cover the unit system, matter, energy, atomic structures, chemical formulas, physical states of matter, solutions and suspensions, ionization, acids, bases, and salts. Each unit contains a rationale for the material; a list of behavioral objectives for the unit; a list of resources including texts, laboratory experiments, audiovisual aids, science activities, and specified questions; a problem set for student self-evaluation; suggestions for advanced study; and references. A related chemistry LAP set is SE 016 426. Pages in LAP 25 will reproduce poorly. (CC)

Gene therapy (GT) has rapidly attracted renewed interest as a treatment for otherwise incurable diseases, with several GT products already on the market and many more entering clinical testing for selected indications. Clonal tracking techniques based on vector integration enable monitoring of the fate of engineered cells in the blood of patients receiving GT and allow assessment of the safety and efficacy of these procedures. However, owing to the limited number of cells that can be tested and the impracticality of studying cells residing in peripheral organs without performing invasive biopsies, this approach provides only a partial snapshot of the clonal repertoire and dynamics of genetically modified cells and reduces the predictive power as a safety readout. In this study, we developed liquid biopsy integration site sequencing, or LiBIS-seq, a polymerase chain reaction technique optimized to quantitatively retrieve vector integration sites from cell-free DNA released into the bloodstream by dying cells residing in several tissues. This approach enabled longitudinal monitoring of in vivo liver-directed GT and clonal tracking in patients receiving hematopoietic stem cell GT, improving our understanding of the clonal composition and turnover of genetically modified cells in solid tissues and, in contrast to conventional analyses based only on circulating blood cells, enabling earlier detection of vector-marked clones that are aberrantly expanding in peripheral tissues.

The use of chimeric antigen receptor (CAR)-engineered regulatory T cells (Tregs) has emerged as a promising strategy to promote immune tolerance. However, in conventional T cells (Tconvs), CAR expression is often associated with tonic signaling, which can induce CAR-T cell dysfunction. The extent and effects of CAR tonic signaling vary greatly according to the expression intensity and intrinsic properties of the CAR. Here, we show that the 4-1BB CSD-associated tonic signal yields a more dramatic effect in CAR-Tregs than in CAR-Tconvs with respect to activation and proliferation. Compared to CD28 CAR-Tregs, 4-1BB CAR-Tregs exhibit decreased lineage stability and reduced in vivo suppressive capacities. Transient exposure of 4-1BB CAR-Tregs to a Treg stabilizing cocktail, including an mTOR inhibitor and vitamin C, during ex vivo expansion sharply improves their in vivo function and expansion after adoptive transfer. This study demonstrates that the negative effects of 4-1BB tonic signaling in Tregs can be mitigated by transient mTOR inhibition., Chimeric antigen receptor engineering in T cells has been shown to be of great potential therapeutic benefit in a range of immune pathologies, although the functionality of such cell therapies can be limited due to tonic signalling and the induction of dysfunction. Here the authors show transient inhibition of mTOR can rescue their 41-BB-CAR-Tregs from tonic signalling-induced dysfunction.

JJL received funding from the Research Foundation Flanders (grant nr. 12P1819N). The project received funding from the Research Foundation Flanders (grants nrs, G018919N, W001919N). JVDH and TWC received funding from DOB Ecology. JA received funding from the University of Helsinki, Faculty of Science (MICROCLIM, grant nr. 7510145) and Academy of Finland Flagship (grant no. 337552). PDF, CM and PV received funding from the European Research Council (ERC) under the European Union's Horizon 2020 research and innovation programme (ERC Starting Grant FORMICA 757833). JK received funding from the Arctic Interactions at the University of Oulu and Academy of Finland (318930, Profi 4), Maaja vesitekniikan tuki ry., Tiina and Antti Herlin Foundation, Nordenskiold Samfundet and Societas pro Fauna et Flora Fennica. MK received funding from the Czech Science Foundation (grant nr. 20-28119S) and the Czech Academy of Sciences (grant nr. RVO 67985939). TWC received funding from National Geographic Society grant no. 9480-14 and WW-240R-17. MA received funding from CISSC (program ICRP (grant nr:2397) and INSF (grant nr: 96005914). The Royal Botanic Garden Edinburgh is supported by the Scottish Government's Rural and Environment Science and Analytical Services Division. JMA received funding from the Funding Org. Qatar Petroleum (grant nr. QUEX-CAS-QP-RD-18/19). JMA received funding from the European Union's Horizon 2020 research and innovation program (grant no. 678841) and from the Swiss National Science Foundation (grant no. 31003A_176044). JA was supported by research grants LTAUSA19137 (program INTER-EXCELLENCE, subprogram INTER-ACTION) provided by Czech Ministry of Education, Youth and Sports and 20-05840Y of the Czech Science Foundation. AA was supported by the Ministry of Science and Higher Education of the Russian Federation (grant FSRZ-2020-0014). SN, UAT, JJA, and JvO received funding from the Independent Research Fund Denmark (7027-00133B). LvdB, KT, MYB and RC acknowledge funding from the German Research Foundation within the Priority Program SPP-1803 'EarthShape: Earth Surface Shaping by Biota' (grant TI 338/14-1&2 and BA 3843/6-1). PB was supported by grant project VEGA of the Ministry of Education of the Slovak Republic and the Slovak Academy of Sciences No. 2/0132/18. Forest Research received funding from the Forestry Commission (climate change research programme). JCB acknowledges the support of Universidad Javeriana. JLBA received funding from the Direccion General de Cambio Climatico del Gobierno de Aragon; JLBA acknowledges fieldwork assistance by Ana Acin, the Ordesa y Monte Perdido National Park, and the Servicio de Medio Ambiente de Soria de la Junta de Castilla y Leon. RGB and MPB received funding from BECC - Biodiversity and Ecosystem services in a Changing Climate. MPB received funding from The European Union's Horizon 2020 research and innovation program under the Marie Skodowska-Curie Grant Agreement No. 657627 and The Swedish Research Council FORMAS - future research leaders No. 2016-01187. JB received funding from the Czech Academy of Sciences (grant nr. RVO 67985939). NB received funding from the SNF (grant numbers 40FA40_154245, 20FI21_148992, 20FI20_173691, 407340_172433) and from the EU (contract no. 774124). ICOS EU research infrastructure. EU FP7 NitroEurope. EU FP7 ECLAIRE. The authors from Biological Dynamics of Forest Fragments Project, PDBFF, Instituto Nacional de Pesquisas da Amazonia, Brazil were supported by the MCTI/CNPq/FNDCT - AcAo Transversal no68/2013 - Programa de Grande Escala da Biosfera-Atmosfera na Amazonia - LBA; Project 'Como as florestas da Amazonia Central respondem as variacoes climaticas? Efeitos sobre dinamica florestal e sinergia com a fragmentacAo florestal'. This is the study 829 of the BDFFP Technical Series. to The EUCFLUX Cooperative Research Program and Forest Science and Research Institute-IPEF. NC acknowledges funding by Stelvio National Park. JC was funded by the Spanish government grant CGL2016-78093-R. ANID-FONDECYT 1181745 AND INSTITUTO ANTARTICO CHILENO (INACH FR-0418). SC received funding from the German Research Foundation (grant no. DFG- FZT 118, 202548816). The National Science Foundation, Poland (grant no. UMO-2017/27/B/ST10/02228), within the framework of the 'Carbon dioxide uptake potential of sphagnum peatlands in the context of atmospheric optical parameters and climate changes' (KUSCO2) project. SLC received funding from the South African National Research Foundation and the Australian Research Council. FM, M, KU and MU received funding from Slovak Research and Development Agency (no. APVV-19-0319). Instituto Antartico Chileno (INACH_RT-48_16), Iniciativa Cientifica Milenio Nucleo Milenio de Salmonidos Invasores INVASAL, Institute of Ecology and Biodiversity (IEB), CONICYT PIA APOYO CCTE AFB170008. PC is supported by NERC core funding to the BAS 'Biodiversity, Evolution and Adaptation Team. EJC received funding from the Norwegian Research Council (grant number 230970). GND was supported by NERC E3 doctoral training partnership grant (NE/L002558/1) at the University of Edinburgh and the Carnegie Trust for the Universities of Scotland. Monitoring stations on Livingston Island, Antarctica, were funded by different research projects of the Gobern of Spain (PERMAPLANET CTM2009-10165-E; ANTARPERMA CTM2011-15565-E; PERMASNOW CTM2014-52021-R), and the PERMATHERMAL arrangement between the University of Alcala and the Spanish Polar Committee. GN received funding from the Autonomous Province of Bolzano (ITA). The infrastructure, part of the UK Environmental Change Network, was funded historically in part by ScotNature and NERC National Capability LTS-S: UK-SCAPE; NE/R016429/1). JD was supported by the Czech Science Foundation (GA17-19376S) and MSMT (LTAUSA18007). ED received funding from the Kempe Foundation (JCK-1112 and JCK-1822). The infrastructure was supported by the Ministry of Education, Youth and Sports of the Czech Republic within the National Sustainability Programme I (NPU I), grant number LO1415 and by the project for national infrastructure support CzeCOS/ICOS Reg. No. LM2015061. NE received funding from the German Research Foundation (DFG- FZT 118, 202548816). BE received funding from the GLORIA-EU project no EVK2-CT2000-00056, the Autonomous Province of Bolzano (ITA), from the Tiroler Wissenschaftsfonds and from the University of Innsbruck. RME was supported by funding to the SAFE Project from the Sime Darby Foundation. OF received funding from the German Research Foundation (DFG- FZT 118, 202548816). EFP was supported by the Jardin Botanico Atlantico (SV-20-GIJON-JBA). MF was funded by the German Federal Ministry of Education and Research (BMBF) in the context of The Future Okavango (Grant No. 01LL0912) and SASSCAL (01LG1201M; 01LG1201N) projects. EFL received funding from ANID PIA / BASAL FB210006. RAG received funding from Fondecyt 11170516, CONICYT PIA AFB170008 and ANID PIA / BASAL FB210006. MBG received funding from National Parks (DYNBIO, #1656/2015) and The Spanish Research Agency (VULBIMON, #CGL2017-90040-R). MG received funding from the Swiss National Science Foundation (ICOS-CH Phase 2 20FI20_173691). FG received funding from the German Research Foundation (DFG- FZT 118, 202548816). KG and TS received funding from the UK Biotechnology and Biological Research Council (grant = 206/D16053). SG was supported by the Research Foundation Flanders (FWO) (project G0H1517N). KJ and PH received funding from the EU Horizon2020 INFRAIA project eLTER-PLUS (871128), the project LTER-CWN (FFG, F&E Infrastrukturforderung, project number 858024) and the Austrian Climate Research Program (ACRP7 - CentForCSink - KR14AC7K11960). SH and ARB received funding through iDiv funded by the German Research Foundation (DFG- FZT 118, 202548816). LH received funding from the Czech Science Foundation (grant nr. 20-28119S) and the Czech Academy of Sciences (grant nr. RVO 67985939). MH received funding from the Baden-Wurttemberg Ministry of Science, Research and Arts via the project DRIeR (Drought impacts, processes and resilience: making the in-visible visible). LH received funding from International Polar Year, Weston Foundation, and ArcticNet. DH received funding from Natural Sciences and Engineering Council (Canada) (RGPIN-06691). TTH received funding from Independent Research Fund Denmark (grant no. 8021-00423B) and Villum Foundation (grant no. 17523). Ministry of Education, Youth and Sports of the Czech Republic (projects LM2015078, VAN2020/01 and CZ.02.1.01/0.0/0.0/16_013/0001708). KH, CG and CJD received funding from Bolin Centre for Climate Research, Stockholm University and from the Swedish research council Formas [grant n:o 2014-00530 to KH]. JJ received funding from the Funding Org. Swedish Forest Society Foundation (grant nr. 2018-485-Steg 2 2017) and Swedish Research Council FORMAS (grant nr. 2018-00792). AJ received funding from the German Federal Ministry of Education and Research BMBF (Grant Nr. FKZ 031B0516C SUSALPS) and the Oberfrankenstiftung (Grant Nr. OFS FP00237). ISJ received funding from the Energy Research Fund (NYR-11 - 2019, NYR-18 - 2020). TJ was supported by a UK NERC Independent Research Fellowship (grant number: NE/S01537X/1). RJ received funding from National Science Centre of Poland (grant number: 2016/21/B/ST10/02271) and Polish National Centre for Research and Development (grant number: Pol-Nor/203258/31/2013). VK received funding from the Czech Academy of Sciences (grant nr. RVO 67985939). AAK received funding from MoEFCC, Govt of India (AICOPTAX project F. No. 22018/12/2015/RE/Tax). NK received funding from FORMAS (grants nr. 2018-01781, 2018-02700, 2019-00836), VR, support from the research infrastructure ICOS-SE. BK received funding from the National Research, Development and Innovation Fund of Hungary (grant nr. K128441). Ministry of Education, Youth and Sports of the Czech Republic (projects LM2015078 and CZ.02.1.01/0.0/0.0/16_013/0001708). Project B1-RNM-163-UGR-18-Programa Operativo FEDER 2018, partially funded data collection. Norwegian Research Council (NORKLIMA grants #184912 and #244525) awarded to Vigdis Vandvik. MM received funding from the Czech Science Foundation (grant nr. 20-28119S) and the Czech Academy of Sciences (grant nr. RVO 67985939). Project CONICYT-PAI 79170119 and ANID-MPG 190029 awarded to Roy Mackenzie. This work was partly funded by project MIUR PON Cluster OT4CLIMA. RM received funding from the SNF project number 407340_172433. FM received funding from the Stelvio National Park. PM received funding from AIAS-COFUND fellowship programme supported by the Marie Skodowska- Curie actions under the European Union's Seventh Framework Pro-gramme for Research, Technological development and Demonstration (grant agreement no 609033) and the Aarhus University Research Foundation, Denmark. RM received funding from the Ministry of Education, Youth and Sports of the Czech Republic (project LTT17033). SM and VM received funding from EU FP6 NitroEurope (grant nr. 17841), EU FP7 ECLAIRE (grant nr. 282910), the Ministry of Education and Science of Ukraine (projects nr. 505, 550, 574, 602), GEF-UNEP funded "Toward INMS" project (grant nr. NEC05348) and ENI CBC BSB PONTOS (grant nr. BSB 889). The authors from Biological Dynamics of Forest Fragments Project, PDBFF, Instituto Nacional de Pesquisas da Amazonia, Brazil were supported by the MCTI/CNPq/FNDCT - AcAo Transversal no68/2013 - Programa de Grande Escala da Biosfera-Atmosfera na Amazonia - LBA; Project 'Como as florestas da Amazonia Central respondem as variacoes climaticas? Efeitos sobre dinamica florestal e sinergia com a fragmentacAo florestal'. FJRM was financially supported by the Netherlands Organization for Scientific Research (VICI grant 016.VICI.170.072) and Research Foundation Flanders (FWO-SBO grant S000619N). STM received funding from New Frontiers in Research Fund-Exploration (grant nr. NFRF-2018-02043) and NSERC Discovery. MMR received funding from the Australian Research Council Discovery Early Career Research Award (grant nr. DE180100570). JAM received funding from the National Science Foundation (DEB 1557094), International Center for Advanced Renewable Energy and Sustainability (I-CARES) at Washington University in St. Louis, ForestGEO, and Tyson Research Center. IM-S was funded by the UK Natural Environment Research Council through the ShrubTundra Project (NE/M016323/1). MBN received funding from FORMAS, VR, Kempe Foundations support from the research infrastructures ICOS and SITES. MDN received funding from CONICET (grant nr. PIP 112-201501-00609). Spanish Ministry of Science grant PID2019-110521GB-I00 and Catalan government grant 2017-1005. French National Research Agency (ANR) in the frame of the Cluster of Excellence COTE (project HydroBeech, ANR-10-LABX-45). VLIR-OUS, under the Institutional University Coorperation programme (IUC) with Mountains of the Moon University. Project LAS III 77/2017/B entitled: \"Estimation of net carbon dioxide fluxes exchanged between the forest ecosystem on post-agricultural land and between the tornado-damaged forest area and the atmosphere using spectroscopic and numerical methods\", source of funding: General Directorate of State Forests, Warsaw, Poland. Max Planck Society (Germany), RFBR, Krasnoyarsk Territory and Krasnoyarsk Regional Fund of Science, project number 20-45-242908. Estonian Research Council (PRG609), and the European Regional Development Fund (Centre of Excellence EcolChange). Canada-Denmark Arctic Research Station Early Career Scientist Exchange Program, from Polar knowledge Canada (POLAR) and the Danish Agency for Science and Higher Education. AP received funding from Fondecyt 1180205, CONICYT PIA AFB170008 and ANID PIA / BASAL FB210006. MP received funding from the Funding Org. Knut and Alice Wallenberg Foundation (grant nr. 2015.0047), and acknowledges funding from the Swedish Research Council (VR) with contributing research institutes to both the SITES and ICOS Sweden infrastructures. JP and RO were funded by the Spanish Ministry of Science grant PID2019-110521GB-I00, the fundacion Ramon Areces grant ELEMENTAL-CLIMATE, and the Catalan government grant 2017-1005. MPB received funding from the Svalbard Environmental Protection Fund (grant project number 15/128) and the Research Council of Norway (Arctic Field Grant, project number 269957). RP received funding from the Ministry of Education, Youth and Sports of the Czech Republic (grant INTER-TRANSFER nr. LTT20017). LTSER Zone Atelier Alpes; Federation FREE-Alpes. RP received funding from a Humboldt Fellowship for Experienced Researchers. Prokushkin AS and Zyryanov VI contribution has been supported by the RFBR grant #18-05-60203-Arktika. RPu received founding from the Polish National Science Centre (grant project number 2017/27/B/NZ8/00316). ODYSSEE project (ANR-13-ISV7-0004, PN-II-ID-JRP-RO-FR-2012). KR was supported through an Australian Government Research Training Program Scholarship. Fieldwork was supported by the Global Challenges program at the University of Wollongong, the ARC the Australian Antarctic Division and INACH. DR was funded by the project SUBANTECO IPEV 136 (French Polar Institute Paul-Emile Victor), Zone Atelier CNRS Antarctique et Terres Australes, SAD Region Bretagne (Project INFLICT), BiodivERsa 2019-2020 BioDivClim call 'ASICS' (ANR-20-EBI5-0004). SAR received funding from the Australian Research Council. NSF grant #1556772 to the University of Notre Dame. Pavia University (Italy). OR received funding from EU-LEAP-Agri (RAMSES II), EU-DESIRA (CASSECS), EU-H2020 (SustainSahel), AGROPOLIS and TOTAL Foundations (DSCATT), CGIAR (GLDC). AR was supported by the Russian Science Foundation (Grant 18-74-10048). Parc national des Ecrins. JS received funding from Vetenskapsradet grant nr (No: 2014-04270), ALTER-net multi-site grant, River LIFE project (LIFE08 NAT/S/000266), Flexpeil. Helmholtz Association long-term research program TERENO (Terrestrial Environmental Observatories). PS received funding from the Polish Ministry of Science and Higher Education (grant nr. N N305 304840). AS acknowledges funding by ETH Zurich project FEVER ETH-27 19-1. LSC received funding from NSERC Canada Graduate Scholarship (Doctoral) Program; LSC was also supported by ArcticNet-NCE (insert grant #). Conselho Nacional de Desenvolvimento Cientifico e Tecnologico (141513/2017-9); FundacAo Carlos Chagas Filho de Amparo a Pesquisa do Estado do Rio de Janeiro (E26/200.84/2019). ZS received funding from the SRDA (grants nos. APVV-16-0325 and APVV-20-0365) and from the ERDF (grant no. ITMS 313011S735, CE LignoSilva). JS, MB and CA received funding from core budget of ETH Zurich. State excellence Program M-V \"WETSCAPES\". AfricanBioServices project funded by the EU Horizon 2020 grant number 641918. The authors from KIT/IMK-IFU acknowledge the funding received within the German Terrestrial Environmental Observatories (TERENO) research program of the Helmholtz Association and from the Bavarian Ministry of the Environment and Public Health (UGV06080204000). Deutsche Forschungsgemeinschaft (DFG, German Research Foundation), project number 192626868, in the framework of the collaborative German-Indonesian research project CRC 990 (SFB): 'EFForTS, Ecological and Socioeconomic Functions of Tropical Lowland Rainforest Transformation Systems (Sumatra, Indonesia)'. MS received funding from the Ministry of Education, Youth and Sports of the Czech Republic (grant nr. INTER-TRANSFER LTT19018). TT received funding from the Swedish National Space Board (SNSB Dnr 95/16) and the CASSECS project supported by the European Union. HJDT received funding from the UK Natural Environment Research Council (NERC doctoral training partnership grant NE/L002558/1). German Science Foundation (DFG) GraKo 2010 \"Response\". PDT received funding from the MEMOIRE project (PN-III-P1-1.1-PD2016-0925). Arctic Challenge for Sustainability II (ArCS II; JPMXD1420318865). JU received funding from Czech Science Foundation (grant nr. 21-11487S). TU received funding from the Romanian Ministry of Education and Research (CCCDI - UEFISCDI -project PN-III-P2-2.1-PED-2019-4924 and PN2019-2022/19270201-Ctr. 25N BIODIVERS 3-BIOSERV). AV acknowledge funding from RSF, project 21-14-00209. GFV received funding from the Dutch Research Council NWO (Veni grant, no. 863.14.013). Australian Research Council Discovery Early Career Research Award DE140101611. FGAV received funding from the Portuguese Science Foundation (FCT) under CEECIND/02509/2018, CESAM (UIDP/50017/2020+UIDB/50017/2020), FCT/MCTES through national funds, and the co-funding by the FEDER, within the PT2020 Partnership Agreement and Compete 2020. Ordesa y Monte Perdido National Park. MVI received funding from the Spanish Ministry of Science and Innovation through a doctoral grant (FPU17/05869). JW received funding from the Czech Science Foundation (grant nr. 20-28119S) and the Czech Academy of Sciences (grant nr. RVO 67985939). CR and SW received funding from the Swiss Federal Office for the Environment (FOEN) and the de Giacomi foundation. YY received funding from the National Natural Science Foundation of China (Grant no. 41861134039 and 41941015). ZY received funding from the National Natural Science Foundation of China (grant nr. 41877458). FZ received funding from the Swiss National Science Foundation (grant nr. 172198 and 193645). PZ received funding from the Funding Org. Knut and Alice Wallenberg Foundation (grant no. 2015.0047). JL received funding from (i) the Agence Nationale de la Recherche (ANR), under the framework of the young investigators (JCJC) funding instrument (ANR JCJC Grant project NoANR-19-CE32-0005-01: IMPRINT) (ii) the Centre National de la Recherche Scientifique (CNRS) (Defi INFINITI 2018: MORFO); and the Structure Federative de Recherche (SFR) Condorcet (FR CNRS 3417: CREUSE). Fieldwork in the Arctic got facilitated by funding from the EU INTERACT program. SN, UAT, JJA and JvO would like to thank the field team of the Vegetation Dynamics group for their efforts and hard work. We acknowledge Dominique Tristan for letting access to the field. For the logistic support the crew of INACH and Gabriel de Castilla Station team on Deception Island. We thank the Inuvialuit and Kluane First Nations for the opportunity to work on their land. MAdP acknowledges fieldwork assistance and logistics support to Unidad de Tecnologia Marina CSIC, and the crew of Juan Carlos I and Gabriel de Castilla Spanish Antarctic Stations, as well as to the different colleagues from UAH that helped on the instrument maintenance. ERF acknowledges fieldwork assistance by Martin Heggli. MBG acknowledges fieldwork and technical assistance by P Abadia, C Benede, P Bravo, J Gomez, M Grasa, R Jimenez, H Miranda, B Ponz, J Revilla and P Tejero and the Ordesa and Monte Perdido National Park staff. LH acknowledges field assistance by John Jacobs, Andrew Trant, Robert Way, Darroch Whitaker; we acknowledge the Inuit of Nunatsiavut, and the Co-management Board of Torngat Mountains National Park for their support of this project and acknowledge that the field research was conducted on their traditional lands. We thank our many bear guides, especially Boonie, Eli, Herman, John and Maria Merkuratsuk. AAK acknowledges field support of Akhtar Malik, Rameez Ahmad. Part of microclimatic records from Saxony was funded by the Saxon Switzerland National Park Administration. Tyson Research Center. JP acknowledges field support of Emmanuel Malet (Edytem) and Rangers of Reserves Naturelles de Haute-Savoie (ASTERS). Practical help: Roel H. Janssen, N. Huig, E. Bakker, Schools in the tepaseforsoket, Forskar fredag, Erik Herberg. The support by the Bavarian Forest National Park administration is highly appreciated. LvdB acknowledges CONAF and onsite support from the park rangers from PN Pan de Azucar, PN La Campana, PN Nahuelbuta and from communidad agricola Quebrada de Talca. JL and FS acknowledge Manuel Nicolas and all forest officers from the Office National des Forets (ONF) who are in charge of the RENECOFOR network and who provided help and local support for the installation and maintenance of temperature loggers in the field., Research in global change ecology relies heavily on global climatic grids derived from estimates of air temperature in open areas at around 2 m above the ground. These climatic grids do not reflect conditions below vegetation canopies and near the ground surface, where critical ecosystem functions occur and most terrestrial species reside. Here, we provide global maps of soil temperature and bioclimatic variables at a 1-km2 resolution for 0–5 and 5–15 cm soil depth. These maps were created by calculating the difference (i.e. offset) between in situ soil temperature measurements, based on time series from over 1200 1-km2 p ixels ( summarized f rom 8 519 u nique t emperature sensors) across all the world's major terrestrial biomes, and coarse-grained air temperature estimates from ERA5-Land (an atmospheric reanalysis by the European Centre for Medium-Range Weather Forecasts). We show that mean annual soil temperature differs markedly from the corresponding gridded air temperature, by up to 10°C (mean = 3.0 ± 2.1°C), with substantial variation across biomes and seasons. Over the year, soils in cold and/or dry biomes are substantially warmer (+3.6 ± 2.3°C) than gridded air temperature, whereas soils in warm and humid environments are on average slightly cooler (−0.7 ± 2.3°C). The observed substantial and biome-specific offsets emphasize that the projected impacts of climate and climate change on near-surface biodiversity and ecosystem functioning are inaccurately assessed when air rather than soil temperature is used, especially in cold environments. The global soil-related bioclimatic variables provided here are an important step forward for any application in ecology and related disciplines. Nevertheless, we highlight the need to fill remaining geographic gaps by collecting more in situ measurements of microclimate conditions to further enhance the spatiotemporal resolution of global soil temperature products for ecological applications., FWO G018919N W001919N 12P1819N, DOB Ecology, University of Helsinki, Faculty of Science (MICROCLIM) 7510145, European Research Council (ERC) FORMICA 757833, Arctic Interactions at the University of Oulu, Academy of Finland 318930 337552, Maaja vesitekniikan tuki ry., Tiina and Antti Herlin Foundation, Nordenskiold Samfundet, Societas pro Fauna et Flora Fennica, Grant Agency of the Czech Republic 20-28119S 20-05840Y GA17-19376S 21-11487S, Czech Academy of Sciences RVO 67985939, National Geographic Society 9480-14 WW-240R-17, CISSC (program ICRP) 2397, Iran National Science Foundation (INSF) 96005914, Scottish Government's Rural and Environment Science and Analytical Services Division, Qatar Petroleum QUEX-CAS-QP-RD-18/19, European Union's Horizon 2020 research and innovation program 678841, Swiss National Science Foundation (SNSF), European Commission 172198 193645 31003A_176044, Ministry of Education, Youth & Sports - Czech Republic LTAUSA19137, Ministry of Science and Higher Education of the Russian Federation FSRZ-2020-0014, Independent Research Fund Denmark 8021-00423B 7027-00133B, German Research Foundation (DFG) DFG- FZT 118 202548816 TI 338/14-1 TI 338/14-2 BA 3843/6-1, grant project VEGA of the Ministry of Education of the Slovak Republic Slovak Academy of Sciences 2/0132/18, Forestry Commission, Universidad Javeriana, Direccion General de Cambio Climatico del Gobierno de Aragon, European Union's Horizon 2020 research and innovation program under the Marie Skodowska-Curie Grant 657627 SNF 407340_172433 40FA40_154245 20FI21_148992 20FI20_173691, European Commission 17841 774124, MCTI/CNPq/FNDCT 68/2013, Project 'Como as florestas da Amazonia Central respondem as variacoes climaticas? Efeitos sobre dinamica florestal e sinergia com a fragmentacAo florestal', Spanish Government, European Commission CGL2016-78093-R, ANID-FONDECYT 1181745, National Science Foundation, Poland UMO-2017/27/B/ST10/02228, National Research Foundation - South Africa, Australian Research Council, Slovak Research and Development Agency APVV-19-0319, Instituto Antartico Chileno INACH_RT-48_16 INACH FR-0418, Comision Nacional de Investigacion Cientifica y Tecnologica (CONICYT) PIA APOYO CCTE AFB170008 PIA AFB170008, UK Research & Innovation (UKRI), Natural Environment Research Council (NERC), Research Council of Norway, European Commission 230970, NERC E3 doctoral training partnership grant at the University of Edinburgh NE/L002558/1, Carnegie Trust for the Universities of Scotland, Gobern of Spain PERMAPLANET CTM2009-10165-E ANTARPERMA CTM2011-15565-E PERMASNOW CTM2014-52021-R, University of Alcala, Spanish Polar Committee, Autonomous Province of Bolzano (ITA), ScotNature, NERC National Capability LTS-S: UK-SCAPE NE/R016429/1, Ministry of Education, Youth & Sports - Czech Republic LTAUSA18007, Kempe Foundation JCK-1112 JCK-1822, Ministry of Education, Youth and Sports of the Czech Republic within the National Sustainability Programme I (NPU I) LO1415, project for national infrastructure support CzeCOS/ICOS LM2015061 GLORIA-EU EVK2-CT2000-00056, Tiroler Wissenschaftsfonds, University of Innsbruck, Sime Darby Foundation, Jardin Botanico Atlantico SV-20-GIJON-JBA, Federal Ministry of Education & Research (BMBF) 01LL0912 01LG1201M 01LG1201N, Comision Nacional de Investigacion Cientifica y Tecnologica (CONICYT) CONICYT FONDECYT 11170516 1180205, ANID PIA / BASAL FB210006, National Parks (DYNBIO) 1656/2015, Spanish Research Agency (VULBIMON) CGL2017-90040-R, Swiss National Science Foundation (SNSF) 20FI20_173691, Biotechnology and Biological Sciences Research Council (BBSRC) 206/D16053 FWO G0H1517N, EU Horizon2020 INFRAIA project eLTER-PLUS 871128, project LTER-CWN (FFG, F&E Infrastrukturforderung) 858024, Austrian Climate Research Program ACRP7 - CentForCSink - KR14AC7K11960, iDiv by the German Research Foundation DFG- FZT 118 202548816, Baden-Wurttemberg Ministry of Science, Research and Arts, Weston Foundation, ArcticNet, Natural Sciences and Engineering Research Council of Canada (NSERC) RGPIN-06691, Villum Foundation 17523, Ministry of Education, Youth & Sports - Czech Republic LM2015078 VAN2020/01 CZ.02.1.01/0.0/0.0/16_013/0001708 LTT17033 LTT20017 INTER-TRANSFER LTT19018, Bolin Centre for Climate Research, Stockholm University, Swedish Research Council Swedish Research Council Formas 2014-00530 2018-00792 2016-01187, Swedish Forest Society Foundation 2018-485-Steg 2 2017, Federal Ministry of Education & Research (BMBF) FKZ 031B0516C SUSALPS, Oberfrankenstiftung OFS FP00237, Energy Research Fund NYR-11 - 2019 NYR-18 - 2020, UK NERC Independent Research Fellowship NE/S01537X/1, National Science Centre, Poland 2016/21/B/ST10/02271, Polish National Centre for Research and Development Pol-Nor/203258/31/2013, MoEFCC, Govt of India (AICOPTAX project) 22018/12/2015/RE/Tax, Swedish Research Council Formas 2018-01781 2018-02700 2019-00836, research infrastructure ICOS-SE, National Research, Development and Innovation Fund of Hungary K128441, Programa Operativo FEDER 2018 B1-RNM-163-UGR-18, Norwegian Research Council (NORKLIMA grants) 184912 244525, CONICYT-PAI 79170119, ANID-MPG 190029, project MIUR PON Cluster OT4CLIMA, Stelvio National Park, AIAS-COFUND fellowship programme - Marie Skodowska- Curie actions under the European Union's Seventh Framework Pro-gramme for Research, Technological development and Demonstration 609033, Aarhus University Research Foundation, Denmark, EU FP6 NitroEurope 17841, EU FP7 ECLAIRE 282910, Ministry of Education and Science of Ukraine 505 550 574 602, GEF-UNEP NEC05348, ENI CBC BSB PONTOS BSB 889, Netherlands Organization for Scientific Research (NWO) 016.VICI.170.072, New Frontiers in Research Fund-Exploration NFRF-2018-02043, Natural Sciences and Engineering Research Council of Canada (NSERC), Australian Research Council DE180100570, National Science Foundation (NSF) DEB 1557094, International Center for Advanced Renewable Energy and Sustainability (I-CARES) at Washington University in St. Louis, Smithsonian Institution Smithsonian Tropical Research Institute, Tyson Research Center, UK Natural Environment Research Council through the ShrubTundra Project NE/M016323/1, Swedish Research Council Formas Swedish Research Council, Kempe Foundations - research infrastructure ICOS Kempe Foundations - research infrastructure SITES, Consejo Nacional de Investigaciones Cientificas y Tecnicas (CONICET) PIP 112-201501-00609, Spanish Government PID2019-110521GB-I00, Catalan government 2017-1005, French National Research Agency (ANR) ANR-10-LABX-45, General Directorate of State Forests, Warsaw, Poland, Max Planck Society, Russian Foundation for Basic Research (RFBR), Krasnoyarsk Territory Krasnoyarsk Regional Fund of Science 20-45-242908, Estonian Research Council PRG609, Knut & Alice Wallenberg Foundation 2015.0047, Swedish Research Council, fundacion Ramon Areces grant ELEMENTAL-CLIMATE, Svalbard Environmental Protection Fund 15/128, Research Council of Norway 269957, Humboldt Fellowship for Experienced Researchers, Russian Foundation for Basic Research (RFBR) 18-05-60203-Arktika, Polish National Science Centre 2017/27/B/NZ8/00316, ODYSSEE project (PN-II-ID-JRP-RO-FR-2012) ANR-13-ISV7-0004, Australian Government, Department of Industry, Innovation and Science, Global Challenges program at the University of Wollongong, ARC the Australian Antarctic Division, INACH, project SUBANTECO IPEV 136 (French Polar Institute Paul-Emile Victor), Zone Atelier CNRS Antarctique et Terres Australes, SAD Region Bretagne (Project INFLICT), BiodivERsa 2019-2020 BioDivClim call 'ASICS' ANR-20-EBI5-0004, National Science Foundation (NSF) 1556772, EU-LEAP-Agri (RAMSES II) EU-DESIRA (CASSECS) EU-H2020 (SustainSahel), AGROPOLIS, Total SA, CGIAR, Russian Science Foundation (RSF) 18-74-10048, Swedish Research Council 2014-04270, ALTER-net multi-site grant, River LIFE project LIFE08 NAT/S/000266, Flexpeil, Ministry of Science and Higher Education, Poland N N305 304840, ETH Zurich FEVER ETH-27 19-1, NSERC Canada Graduate Scholarship (Doctoral) Program, ArcticNet-NCE, Conselho Nacional de Desenvolvimento Cientifico e Tecnologico (CNPQ) 141513/2017-9, Fundacao Carlos Chagas Filho de Amparo a Pesquisa do Estado do Rio De Janeiro (FAPERJ) E26/200.84/2019, SRDA APVV-16-0325 APVV-20-0365, ERDF (CE LignoSilva) ITMS 313011S735, ETH Zurich, EU Horizon 2020 641918, German Terrestrial Environmental Observatories (TERENO) research program of the Helmholtz Association, Bavarian Ministry of the Environment and Public Health UGV06080204000 German Research Foundation (DFG) 192626868, Swedish National Space Board (SNSB) 95/16, CASSECS project by the European Union, Natural Environment Research Council (NERC) NE/L002558/1, MEMOIRE project PN-III-P1-1.1-PD2016-0925, Arctic Challenge for Sustainability II (ArCS II) JPMXD1420318865, Consiliul National al Cercetarii Stiintifice (CNCS), Unitatea Executiva pentru Finantarea Invatamantului Superior, a Cercetarii, Dezvoltarii si Inovarii (UEFISCDI) PN-III-P2-2.1-PED-2019-4924 PN2019-2022/19270201, 25N BIODIVERS 3-BIOSERV, Russian Science Foundation (RSF) 21-14-00209., Netherlands Organization for Scientific Research (NWO) 863.14.013, Australian Research Council DE140101611, Portuguese Foundation for Science and Technology CEECIND/02509/2018 CESAM UIDP/50017/2020+UIDB/50017/2020, Portuguese Foundation for Science and Technology European Commission, FEDER, within the PT2020 Partnership Agreement, Compete 2020, Spanish Government FPU17/05869, Swiss Federal Office for the Environment (FOEN), Giacomi foundation, National Natural Science Foundation of China (NSFC) 41861134039 41941015 41877458, French National Research Agency (ANR) ANR-19-CE32-0005-01 Centre National de la Recherche Scientifique (CNRS), Structure Federative de Recherche (SFR) Condorcet (FR CNRS 3417: CREUSE), EU INTERACT program, Inuit of Nunatsiavut, Co-management Board of Torngat Mountains National Park, Saxon Switzerland National Park Administration, Bavarian Forest National Park administration, BECC - Biodiversity and Ecosystem services in a Changing Climate, Research Foundation Flanders (FWO-SBO) S000619N

International audience; Two types of bicyclic N-cyclopropyl glycine ester derivatives have been prepared and put under scrutiny as possible precursors of azomethine ylides. The results demonstrate that they can indeed participate in 1,3-dipolar cycloaddition reactions with dipolarophiles, as illustrated in the cases of phenyl vinyl sulfone, N-phenylmaleimide, diethyl fumarate and diethyl maleate. The relative configurations of the major diastereoisomers produced are consistent with the predicted generation of azomethine ylide species, reacting in concerted cycloaddition processes. This unprecedented way of generating such 1,3-dipoles provides access to functionalised pyrrolizidine and pyrrolidine derivatives, that would be difficult to make directly by more classic methods. It was also found that using phenyl vinyl sulfone or N-phenylmaleimide as the dipolarophile reactant, a domino nucleophilic conjugate addition/1,3-dipolar cycloaddition process may operate competitively.

T-cell acute lymphoblastic leukemia (T-ALL) represents the malignant expansion of immature T cells blocked in their differentiation. T-ALL is still associated with a poor prognosis, mainly related to occurrence of relapse or refractory disease. A critical medical need therefore exists for new therapies to improve the disease prognosis. Adenylate kinase 2 (AK2) is a mitochondrial kinase involved in adenine nucleotide homeostasis recently reported as essential in normal T-cell development, as defective AK2 signaling pathway results in a severe combined immunodeficiency with a complete absence of T-cell differentiation. In this study, we show that AK2 is constitutively expressed in T-ALL to varying levels, irrespective of the stage of maturation arrest or the underlying oncogenetic features. T-ALL cell lines and patient T-ALL–derived xenografts present addiction to AK2, whereas B-cell precursor ALL cells do not. Indeed, AK2 knockdown leads to early and massive apoptosis of T-ALL cells that could not be rescued by the cytosolic isoform AK1. Mechanistically, AK2 depletion results in mitochondrial dysfunction marked by early mitochondrial depolarization and reactive oxygen species production, together with the depletion of antiapoptotic molecules (BCL-2 and BCL-XL). Finally, T-ALL exposure to a BCL-2 inhibitor (ABT-199 [venetoclax]) significantly enhances the cytotoxic effects of AK2 depletion. We also show that AK2 depletion disrupts the oxidative phosphorylation pathway. Combined with pharmaceutical inhibition of glycolysis, AK2 silencing prevents T-ALL metabolic adaptation, resulting in dramatic apoptosis. Altogether, we pinpoint AK2 as a genuine and promising therapeutic target in T-ALL.

International audience; In tetrahydrofuran, the electrochemical reduction of Cp2TiIVCl2 (2 mM) generated three titanium(III) complexes which were in equilibrium: [Cp2TiCl2]•−, [Cp2TiCl]• and (Cp2TiCl)2. Although the anion radical [Cp2TiCl2]•− was the main species produced under these conditions, cyclic voltammetry investigations clearly showed that the proportion of the three electrogenerated TiIII complexes can be modified as a function of the amounts of chloride ion present in the solution. Accordingly, the presence of Mg2+ ions, which led to the consumption of chloride ions through the formation of MgCl2, favoured the formation of [Cp2TiCl]• and, consequently, of the corresponding dimer (Cp2TiCl)2. The electrochemical behaviours of Cp2TiIVCl2 and of the electrogenerated low-valent Ti complexes were also investigated in the presence of amide and alkyne derivatives. Under these conditions, titanium complexes could not only interact with the amide carbonyl group, but also with the alkyne triple bond, provided the latter was not sterically hindered. Interestingly, the carbonyl group and the triple bond had antagonist effects on redox properties of titanium(III) complexes.

The function of the uncoupling protein 2 (UCP2) is different for each cancer cell. However, the mechanism of expression is still unclear. DNA methylation affects protein expression and is one factor that transforms normal cells into cancer cells. In this study, the hepatocellular carcinoma Hep3B and HepG2 cells and colorectal cancer HT-29 cells were treated with 5-azacytidine (5-aza), a DNA demethylation agent, to observe the modification of UCP2 expression and the methylation degree in the UCP2 promoter region. Promoter basal activity and degree of UCP2 expression were measured in Hep3B, HepG2, and HT-29 cells. In addition, methylation-specific PCR (MSP) was performed to investigate the degree of methylation in the UCP2 promoter region. The methylation region in the UCP2 promoter was confirmed based on bisulfite sequencing. In Hep3B cells in which UCP2 mRNA was not transcribed, the promoter basal activity was significantly higher than in HT-29 or HepG2 cells in which UCP2 mRNA was transcribed. Treatment with 5-aza increased UCP2 expression in Hep3B and HT-29 cells; however, the expression in HepG2 cells was unchanged. The UCP2 promoter in Hep3B cells has numerous methylated regions compared with HT-29 and HepG2 cells. The results of the present study revealed that inhibition of UCP2 expression in Hep3B cells was due to methylation of the promoter region. Investigating the mechanism that induces UCP2 expression in cancer cells is important to understand the function of UCP2, which could aid in cancer treatment.

Nitrogen (N) management in cropping systems needs adjustments because constraints to crop production are mostly related to high inputs and low recovery of N fertilizers. We used the DayCent model to predict regional N inputs, outputs, and balances of Swiss soils under (1) a range of N fertilizer input levels (0–300% of recommended crop-specific rates) and (2) organic fertilization, reduced tillage or cover cropping at the recommended input of N. The crops included wheat, maize, and root/tuber crops and legumes. Decreasing N inputs reduced the environmental impact by 13.5–51.3 kg N ha $$^{-1}$$ , but it also reduced the yield by 6.8–44.8 kg N ha $$^{-1}$$ . Increasing N inputs led to an increase in yield by 5.6–29.5 kg N ha $$^{-1}$$ , but with additional losses of 14.9–181.8 kg N ha $$^{-1}$$ into the environment. Harvested crop N and $$\hbox {NO}_3^{-}$$ leaching accounted for 30–59% and 27–62% of fertilizer-derived changes in total N output, respectively. Converting conventional to organic cropping led to a mean increase in soil N balance by 0.3–62.6 kg N ha $$^{-1}$$ . The soil N balance increased the most by using partially decomposed organic fertilizer in combination with cover cropping and reduced tillage. However, this positive N balance was mainly due to a reduction in N removal with harvest and $$\hbox {NO}_3^{-}$$ leaching. The use of highly decomposable organic matter and cover cropping did not lead to any N yield penalty while decreasing $$\hbox {NO}_3^{-}$$ leaching. These results highlight that organic practices combined with reduced tillage and cover cropping can optimize the use and recovery of N resources.

The acoel flatworm Symsagittifera roscoffensis lives in obligatory symbiosis with the microalgal chlorophyte Tetraselmis convolutae. Although this interaction has been studied for more than a century, little is known on the potential reciprocal benefits of both partners, a subject that is still controversial. In order to provide new insights into this question, we have compared the photophysiology of the free-living microalgae to the symbiotic form in the flatworm, both acclimated at different light irradiances. Photosynthesis – Irradiance curves showed that the free-living T. convolutae had greater photosynthetic performance (i.e., oxygen production rates, ability to harvest light) than their symbiotic form, regardless of the light acclimation. However, they were affected by photoinhibition under high irradiances, which did not happen for the symbiotic form. The resistance of symbiotic microalgae to photoinhibition were corroborated by pigment analyses, which evidenced the induction of photoprotective mechanisms such as xanthophyll cycle as well as lutein and β-carotene accumulation. These processes were induced even under low light acclimation and exacerbated upon high light acclimation, suggesting a global stress situation for the symbiotic microalgae. We hypothesize that the internal conditions in the sub-epidermal zone of the flatworm (e.g., osmotic and pH), as well as the phototaxis toward high light imposed by the worm in its environment, would be major reasons for this chronic stress situation. Overall, our study suggests that the relationship between S. roscoffensis and T. convolutae may be a farming strategy in favor of the flatworm rather than a symbiosis with mutual benefits.

Gram-negative bacteria possess an asymmetric outer membrane (OM) composed primarily of lipopolysaccharides (LPSs) on the outer leaflet and phospholipids (PLs) on the inner leaflet. The loss of this asymmetry due to mutations in the LPS biosynthesis or transport pathways causes the externalization of PLs to the outer leaflet of the OM and leads to OM permeability defects. Here, we used metabolic labeling to detect a compromised OM in intact bacteria. Phosphatidylcholine synthase expression in Escherichia coli allowed for the incorporation of exogenous propargylcholine into phosphatidyl(propargyl)choline and exogenous 1-azidoethyl-choline (AECho) into phosphatidyl(azidoethyl)choline (AEPC), as confirmed by LC/MS analyses. A fluorescent copper-free click reagent poorly labeled AEPC in intact wild-type cells but readily labeled AEPC from lysed cells. Fluorescence microscopy and flow cytometry analyses confirmed the absence of significant AEPC labeling from intact wild-type E. coli strains and revealed significant AEPC labeling in an E. coli LPS transport mutant (lptD4213) and an LPS biosynthesis mutant (E. coli lpxC101). Our results suggest that metabolic PL labeling with AECho is a promising tool for detecting a compromised bacterial OM, revealing aberrant PL externalization, and identifying or characterizing novel cell-active inhibitors of LPS biosynthesis or transport.­

Soil stores over 2500 Pg carbon (C), with the majority of C stored in deep soil layers (> 30 cm). Soil C can be lost to the atmosphere when organic compounds are mineralized to carbon dioxide (CO2, via oxidative decay or respiration) and moved upward through the soil profile (via diffusion). Soil moisture status can influence the balance between respiration and diffusion, thereby altering the soil CO2 concentration and flux. However, it is unclear how wetting and drying influence soil CO2 dynamics in surface vs. deep soil layers. Thus, we irrigated three soil profiles in Mediterranean arable land and continuously monitored soil CO2 concentration at 15, 30, 50, 70 and 90 cm during wetting and drying phases under ambient temperature conditions. We estimated gas diffusivity, CO2 flux, and temperature responses of soil CO2 concentration during the experiment. Decreases in gas diffusivity during the wetting period coincided with increases in soil CO2 concentrations. However, the negative gas diffusivity-soil CO2 concentration relationship did not hold true all the time, implying that CO2 production was the driving factor for the apparent soil CO2 concentration. We observed hysteretic responses of soil CO2 concentration to temperature as soil moisture varied, with deeper soil CO2 concentration being more sensitive to temperature than surface soil CO2 concentration, especially during the drying phase. The movement of CO2 was upward at all depths during the ambient phase, but the direction and the magnitude of CO2 fluxes varied across the depth gradient during the wetting and drying phases. This study highlights that the relative contribution of gas diffusivity vs. CO2 production to soil CO2 concentration changes with wetting and drying, and that the responses of soil CO2 concentration to temperature are dependent on the antecedent environmental conditions. Also, the downward movement of CO2 during the wetting and drying phases suggests that quantifying surface soil CO2 efflux may underestimate dynamic C processes in deeper soils.

The tumor suppressor gene, p53, is inactivated in the human hepatocellular carcinoma cells line, Hep3B. Berberine has been reported to inhibit the proliferation of cancer cells. This study examined whether apoptosis was induced in berberine-treated Hep3B cells and observed the association between apoptosis and the expression of p53 and DNA methyltransferase (DNMT). The cell viability was measured using an MTT assay. Apoptosis of Hep3B was measured using annexin V flow cytometry. Berberine-treated cells were examined for their DNMT enzymatic activity, mRNA expression, and protein synthesis. The p53 levels were examined by Western blot analysis. The berberine treatment resulted in increased Hep3B cell death and apoptosis in a time- and dose-dependent manner. The DNMT3b activity, mRNA expression, and protein levels all decreased after the berberine treatment. In contrast, the p53 protein levels increased with a concomitant decrease in DNMT3b. No change in the expression of ERK was observed, but the P-ERK levels decreased in a dose dependent manner. These results indicate that a treatment of Hep3B cells with berberine can reduce the expression of DNMT3b, leading to an increase in the tumor suppressant gene p53 and an increase in cell apoptosis. This shows that berberine can effectively suppress the proliferation of liver cancer cells.

Biogeochemical analysis of a chronosequence of secondary forest succession in lowland Central Africa suggests that calcium becomes an increasingly scarce and potentially limiting resource with stand age and ecosystem calcium storage shifts from soil to woody biomass. Secondary forests constitute an increasingly important component of tropical forests worldwide. Although cycling of essential nutrients affects recovery trajectories of secondary forests, the effect of nutrient limitation on forest regrowth is poorly constrained. Here we use three lines of evidence from secondary forest succession sequences in central Africa to identify potential nutrient limitation in regrowing forests. First, we show that atmospheric phosphorus supply exceeds demand along forest succession, whereas forests rely on soil stocks to meet their base cation demands. Second, soil nutrient metrics indicate that available phosphorus increases along the succession, whereas available cations decrease. Finally, fine root, foliar and litter stoichiometry show that tissue calcium concentrations decline relative to those of nitrogen and phosphorus during succession. Taken together, these observations suggest that calcium becomes an increasingly scarce resource in central African forests during secondary succession. Furthermore, ecosystem calcium storage shifts from soil to woody biomass over succession, making it a vulnerable nutrient in the wake of land-use change scenarios that involve woody biomass export. Our results thus call for a broadened focus on elements other than nitrogen and phosphorus regarding tropical forest biogeochemical cycles and identify calcium as a scarce and potentially limiting nutrient in an increasingly disturbed and dynamic tropical forest landscape.

Agricultural intensification and forest conservation are often seen as incompatible. Agricultural interventions can help boost food security for poor rural communities but in certain cases can exacerbate deforestation, known as the rebound effect. We tested whether coupling agricultural interventions with participatory forest zoning could improve food security and promote forest conservation in the Democratic Republic of the Congo. Simple agricultural interventions led to a >60% increase in cassava yields and a spill-over effect of improved cassava variety uptake in non-intervention zones. Household surveys conducted at the end of the 8 year project implementation period revealed that households that received agricultural interventions had more favorable attitudes toward forest zoning and conservation. The surveys also showed that farmers in the intervention domain practiced less land-intensive field and fallow management strategies compared to those practiced in the non-intervention domain. However, an 18 year time series analysis of Landsat satellite data revealed that agricultural expansion persisted in areas both with and without intervention assistance, and there is risk of a rebound effect. Approximately 70% of the tree cover loss that occurred outside of the agricultural areas was located within a 3 km buffer zone surrounding the outermost edges of the agricultural areas, which suggested that the majority of tree cover loss was caused by agricultural expansion. Within that 3 km buffer, average annual tree cover loss during the post-intervention period was higher in the intervention domain compared to the non-intervention domain (0.17% yr(-1) compared to 0.11% yr(-1) respectively, p < 0.001), suggesting risk of a rebound effect. The disconnection between household perceptions of zoning adherence and actual behavior indicates the importance of strengthening governance structures for community-based monitoring and enforcement., Environmental Research Letters, 17 (6), ISSN:1748-9326, ISSN:1748-9318

Globally, tropical forests are assumed to be an important source of atmospheric nitrous oxide (N2O) and sink for methane (CH4). Yet, although the Congo Basin comprises the second largest tropical forest and is considered the most pristine large basin left on Earth, in situ N2O and CH4 flux measurements are scarce. Here, we provide multi-year data derived from on-ground soil flux (n = 1558) and riverine dissolved gas concentration (n = 332) measurements spanning montane, swamp, and lowland forests. Each forest type core monitoring site was sampled at least for one hydrological year between 2016 - 2020 at a frequency of 7-14 days. We estimate a terrestrial CH4 uptake (in kg CH4-C ha−1 yr−1) for montane (−4.28) and lowland forests (−3.52) and a massive CH4 release from swamp forests (non-inundated 2.68; inundated 341). All investigated forest types were a N2O source (except for inundated swamp forest) with 0.93, 1.56, 3.5, and −0.19 kg N2O-N ha−1 yr−1 for montane, lowland, non-inundated swamp, and inundated swamp forests, respectively., Nature Communications, 13, ISSN:2041-1723

Gram-negative bacteria producing carbapenemases are resistant to a variety of β-lactam antibiotics and pose a significant health risk. Given the dearth of new antibiotics, combinations of new broad-spectrum β-lactamase inhibitors (BLIs) with approved β-lactams have provided treatment options for resistant bacterial infections. Taniborbactam (formerly VNRX-5133) is an investigational BLI that is effective against both serine- and metallo-β-lactamases, including the serine carbapenemase KPC. In the current study, we assessed the effectiveness of taniborbactam to restore antibacterial activity of cefepime against KPC-3-producing Escherichia coli by inhibiting the KPC-3-dependent hydrolysis of cefepime. Time-lapse microscopy revealed that cells treated with greater than 1× MIC of cefepime (128 μg/ml) and cefepime-taniborbactam (4 μg/ml cefepime and 4 μg/ml taniborbactam) exhibited significant elongation, whereas cells treated with taniborbactam alone did not owing to a lack of standalone antibacterial activity of the BLI. The elongated cells also had frequent cellular voids thought to be formed by attempted cell divisions and pinching of the cytoplasmic membrane. Additionally, the effect of taniborbactam continued even after its removal from the growth medium. Pretreatment with 4 μg/ml taniborbactam helped to restore the antibacterial action of cefepime by neutralizing the effect of the KPC-3 β-lactamase. IMPORTANCE β-lactam (BL) antibiotics are the most prescribed antimicrobial class. The efficacy of β-lactams is threatened by the production of β-lactamase enzymes, the predominant resistance mechanism impacting these agents in Gram-negative bacterial pathogens. This study visualizes the effects of a combination treatment of taniborbactam, a broad spectrum β-lactamase inhibitor (BLI), and the BL antibiotic cefepime on a carbapenemase-producing E. coli strain. While this treatment has been described in the context of other cephalosporin-resistant bacteria, this is the first description of a microscopic evaluation of a KPC-3-producing strain of E. coli challenged by this BL-BLI combination. Live-cell microscopy analysis of cells treated with taniborbactam and cefepime demonstrated the antimicrobial effects on cellular morphology and highlighted the long-lasting inhibition of β-lactamases by taniborbactam even after it was removed from the medium. This research speaks to the importance of taniborbactam in fighting BL-mediated antibiotic resistance.

This study aimed to extend the shelf-life of coffee-containing milk beverage by adding Theobroma cacao (cacao nibs) extract. To prepare the beverage sample containing cacao nibs extract, 0.8% cacao nibs hydrothermal extract was aseptically injected. Qualitative changes in the beverage samples, including antioxidant effect, peroxide value (POV), caffeine content, and sensory parameters were monitored regularly during storage at 10°C, 20°C, and 30°C for 4 wk. The inclusion of cacao nibs extract produced higher antioxidant activity compared to the control. As the storage temperature increased, the POV of all samples increased. Samples with cacao nibs extract generally displayed lower POV than the control. The caffeine content of all samples tended to decrease during storage, with the decrease accentuated by higher storage temperatures. In the shelf-life prediction using the Arrhenius model, the kinetic regressions of the cacao nibs extract-added sample and control were YPOV=1.2212X–2.1141 (r2=0.9713) and YPOV=1.8075X–2.0189 (r2=0.9883), respectively. Finally, the predicted shelf-life of cacao nibs-added group and control to reach the quality limit (20 meq/kg POV) were approximately 18.11 and 12.18 wk, respectively. The results collectively indicate that the addition of cacao nibs extract extends the shelf-life of the coffee-containing milk beverage and heightened the antioxidant effect.

Effective land-based solutions to climate change mitigation require actions that maximize soil carbon storage without generating surplus nitrogen. Land management for carbon sequestration is most often informed by bulk soil carbon inventories, without considering the form in which carbon is stored, its capacity, persistency and nitrogen demand. Here, we present coupling of European-wide databases with soil organic matter physical fractionation to determine continental-scale forest and grassland topsoil carbon and nitrogen stocks and their distribution between mineral-associated and particulate organic matter pools. Grasslands and arbuscular mycorrhizal forests store more soil carbon in mineral-associated organic carbon, which is more persistent but has a higher nitrogen demand and saturates. Ectomycorrhizal forests store more carbon in particulate organic matter, which is more vulnerable to disturbance but has a lower nitrogen demand and can potentially accumulate indefinitely. The share of carbon between mineral-associated and particulate organic matter and the ratio between carbon and nitrogen affect soil carbon stocks and mediate the effects of other variables on soil carbon stocks. Understanding the physical distribution of organic matter in pools of mineral-associated versus particulate organic matter can inform land management for nitrogen-efficient carbon sequestration, which should be driven by the inherent soil carbon capacity and nitrogen availability in ecosystems. Land management strategies for enhancing soil carbon sequestration need to be tailored to different soil types, depending on how much organic matter is stored in pools of mineral-associated and particulate organic matter, suggests an analysis of soil organic matter across Europe.

This study aimed to extend the retention of flavor in coffee-containing milk beverage by microencapsulation. The core material was caramel flavor, and the primary and secondary coating materials were medium-chain triglyceride and maltodextrin, respectively. Polyglycerol polyricinoleate was used as the primary emulsifier, and the secondary emulsifier was polyoxyethylene sorbitan monolaurate. Response surface methodology was employed to determine optimum microencapsulation conditions, and headspace solid-phase microextraction was used to detect the caramel flavor during storage. The microencapsulation yield of the caramel flavor increased as the ratio of primary to secondary coating material increased. The optimum ratio of core to primary coating material for the water-in-oil (W/O) phase was 1:9, and that of the W/O phase to the secondary coating material was also 1:9. Microencapsulation yield was observed to be approximately 93.43%. In case of in vitro release behavior, the release rate of the capsules in the simulated gastric environment was feeble; however, the release rate in the simulated intestinal environment rapidly increased within 30 min, and nearly 70% of the core material was released within 120 min. The caramel flavor-supplemented beverage sample exhibited an exponential degradation in its flavor components. However, microcapsules containing flavor samples showed sustained flavor release compared to caramel flavor-filled samples under higher storage temperatures. In conclusion, the addition of coffee flavor microcapsules to coffee-containing milk beverages effectively extended the retention of the coffee flavor during the storage period.

By processing large quantities of crop residues, earthworms enhance the mineralization of organic matter but have also been shown to stabilize soil organic carbon (SOC) into soil fractions like microaggregates (53-250 mu m) within macroaggregates (> 250 mu m) especially in no-till soils. Our objective was to find direct evidence on the impact of an anecic, soil surface-feeding earthworm, Lumbricus terrestris L., on the redistribution of SOC and soil nitrogen (N) into macroaggregate-occluded soil fractions of boreal soils. We sampled soil (0-5 cm depth) from the middens of L. terrestris (mounds of collected residue and surface casts at the openings of its permanent burrows) and the adjacent non-midden (bulk) soil at three no-till sites in southern Finland: two clayey sites (sites 1-2) and one coarse textured site (site 3). Compared to bulk soil, the soil in L. terrestris middens featured general increase in aggregate size and content of SOC and N within the large macroaggregates (> 2000 mu m) at the clayey sites. The microaggregates within the large macroaggregates had accumulated more SOC and N in the midden soil especially at site 1 where 99% of the difference in total SOC between midden and bulk soil was associated with this type of SOC stabilization. At site 2, the increase in SOC found in the large macroaggregates was counteracted by a decrease in SOC in microaggregates within the small macroaggregates (250-2000 mu m). No differences in SOC stored in soil fractions were found between midden and non-midden soil at the coarse soil site 3 with higher top soil decomposition rate compared to sites 1 and 2. Across the study sites, the total amount of SOC was 6% higher in midden soil compared to the bulk soil. These results suggest L. terrestris mediates the storage of SOC and N into better protected soil fractions in clay soils under boreal conditions.

International audience; Dextran-covered poly(D,L-lactide) (PLA) nano-and microparticles were prepared by emulsion/solvent evaporation (or diffusion) process with the aim of encapsulating alkyl gallates (AGs). In the first step, a solution of PLA and AG in ethyl acetate was emulsified into an aqueous phase containing a hydrophobically modified dextran which acted as stabilizer. The second step consisted in solvent evaporation or diffusion. Emulsification conditions were varied which allowed preparing nano-and microparticle suspensions covering a wide range of surface-average particle diameters between 0.1 µm (in the case of sonication) and 500 µm (in the case of stirring with magnetic barrel) with narrow and reproducible size distributions. Continuous microfluidic emulsification in a flow focusing system led to well-defined microparticles, within the 10-50 µm range. Particles loaded with octyl gallate (OG) and nonyl gallate (NG) were obtained with the three processes and we showed that the encapsulation efficiency of OG and NG varied significantly according to emulsification process. The effect of particle size on the mechanism of in vitro release of encapsulated AGs was investigated. According to the pH of external medium, the kinetics of release was controlled either by Fickian diffusion within solid core or by swelling and hydrolytic degradation of PLA matrix.

BACKGROUND: Pathogen inactivation and cold or cryopreservation of platelets (PLTs) both significantly affect PLT function. It is not known how PLTs function when both are combined. STUDY DESIGN AND METHODS: Standard PLT concentrates (PCs) were compared to pathogen-inactivated PCs treated with amotosalen photochemical treatment (AS-PCT) when stored at room (RT, 22 degrees C), cold (4 degrees C, n = 6), or cryopreservation (-80 degrees C, n = 8) temperatures. The impact of alternative storage methods on both arms was studied in flow cytometry, light transmittance aggregometry, and hemostasis in collagen-coated microfluidic flow chambers. RESULTS Platelet aggregation of cold-stored AS-PCT PLTs was 44% +/- 11% compared to 57% +/- 14% for cold-stored standard PLTs and 58% +/- 21% for RT-stored AS-PCT PLTs. Integrin activation of cold-stored AS-PCT PLTs was 53% +/- 9% compared to 77% +/- 6% for cold-stored standard PLTs and 69% +/- 13% for RT-stored AS-PCT PLTs. Coagulation of cold-stored AS-PCT PLTs started faster under flow (836 +/- 140 sec) compared to cold-stored standard PLTs (960 +/- 192 sec) and RT-stored AS-PCT PLTs (1134 +/- 220 sec). Fibrin formation rate under flow was also highest for cold-stored AS-PCT PLTs. This was in line with thrombin generation in static conditions because cold-stored AS-PCT PLTs generated 297 +/- 47 nmol/L thrombin compared to 159 +/- 33 nmol/L for cold-stored standard PLTs and 83 +/- 25 nmol/L for RT-stored AS-PCT PLTs. So despite decreased PLT activation and aggregation, cold storage of AS-PCT PLTs promoted coagulation. PLT aggregation of cryopreserved AS-PCT PLTs (23% +/- 10%) was not significantly different from cryopreserved standard PLTs (25% +/- 8%). CONCLUSION: This study shows that cold storage of AS-PCT PLTs further affects PLT activation and aggregation but promotes (pro)coagulation. Increased procoagulation was not observed after cryopreservation.

Background and objectives: Several sources of haematopoietic stem cells have been used for static culture of megakaryocytes to produce platelets in vitro. This study compares and characterizes platelets produced in shear flow using precursor cells from either umbilical (UCB) or adult peripheral blood (PB). Materials and methods: The efficiency of platelet production of the cultured cells was studied after perfusion in custom-built von Willebrand factor-coated microfluidic flow chambers. Platelet receptor expression and morphology were investigated by flow cytometry and microscopy, respectively. Results: Proliferation of stem cells isolated out of UCB was significantly higher (P < 0 center dot 0001) compared to PB. Differentiation of these cells towards megakaryocytes was significantly lower from PB compared to UCB where the fraction of CD42b/CD41 double positive events was 44 +/- 9% versus 76 +/- 11%, respectively (P < 0 center dot 0001). However, in vitro platelet production under hydrodynamic conditions was more efficient with 7 center dot 4 platelet-like particles per input cell from PB compared to 4 center dot 2 from UCB (P = 0 center dot 02). The percentage of events positive for CD42b, CD41 and CD61 was comparable between both stem cell sources. The mean number of receptors per platelet from UCB and PB was similar to that on blood bank platelets with on average 28 000 CD42b, 57 000 CD61 and 5500 CD49b receptors. Microscopy revealed platelets appearing similar to blood bank platelets in morphology, size and actin cytoskeleton, alongside smaller fragments and source megakaryocytes. Conclusion: This characterization study suggests that platelets produced in vitro under flow either from UCB or from PB share receptor expression and morphology with donor platelets stored in the blood bank.

Germline RUNX1 mutations underlie a syndrome, RUNX1-familial platelet disorder (RUNX1-FPD), characterized by bleeding symptoms that result from quantitative and/or qualitative defect in platelets and a significantly increased risk for developing hematologic malignancies. Myeloid neoplasms are the most commonly diagnosed hematologic malignancies, followed by lymphoid malignancies of T-cell origin. Here, we describe the first 2 cases of B-cell acute lymphoblastic leukemia (B-ALL) in patients with confirmed germline RUNX1 mutations. While 1 of the patients had a known diagnosis of RUNX1-FPD with a RUNX1 p.P240Hfs mutation, the other was the index patient of a kindred with a novel RUNX1 variant, RUNX1 c.587C>T (p.T196I), noted on a targeted genetic testing of the B-ALL diagnostic sample. We discuss the clinical course, treatment approaches, and the outcome for the 2 patients. Additionally, we describe transient resolution of the mild thrombocytopenia and bleeding symptoms during therapy, as well as the finding of clonal hematopoiesis with a TET2 mutant clone in 1 of the patients. It is critical to consider testing for germline RUNX1 mutations in patients presenting with B-ALL who have a personal or family history of thrombocytopenia, bleeding symptoms, or RUNX1 variants identified on genetic testing at diagnosis.

International audience; Herein, we report a multistep synthesis of novel (meth)acrylate monomers based on gallic acid (GA), a biosourced phenolic acid. The objective of this work was to obtain bio-based polymers exhibiting antioxidant properties provided by monomers derived from gallic acid. The phenolic groups of GA, which are responsible for antioxidant properties, need to be protected for two reasons. On the one hand, functionalization to transform GA into polymerizable monomers must not take place at the phenolic groups because they must remain free to maintain the maximum antioxidant activity in the final polymers. On the other hand, their protection is necessary to prevent radical scavenging during the radical polymerization. After synthesis of such monomers, protected GA-based polymers were thus produced through a photo-mediated RAFT polymerization at room temperature by evaluating two trithiocarbonate-type chain transfer agents (CTAs). The kinetics and molecular weight distributions were studied depending on the monomers and the CTAs. Protected polymers were then deprotected to afford polymeric chains carrying one free gallic acid moiety on each monomer unit. The antioxidant activity of these free GA-based polymers was demonstrated either through the DPPH free radical scavenging property or through the inhibition of methyl linoleate oxidation.

International audience

Iron is an indispensable metabolic cofactor in both pro- and eukaryotes, which engenders a natural competition for the metal between bacterial pathogens and their human or animal hosts. Bacteria secrete siderophores that extract Fe(3+) from tissues, fluids, cells, and proteins; the ligand gated porins of the Gram-negative bacterial outer membrane actively acquire the resulting ferric siderophores, as well as other iron-containing molecules like heme. Conversely, eukaryotic hosts combat bacterial iron scavenging by sequestering Fe(3+) in binding proteins and ferritin. The variety of iron uptake systems in Gram-negative bacterial pathogens illustrates a range of chemical and biochemical mechanisms that facilitate microbial pathogenesis. This document attempts to summarize and understand these processes, to guide discovery of immunological or chemical interventions that may thwart infectious disease.

In the present study, innovative doxorubicin-loaded nanoparticles (NPs) made of a photosensitive poly(o-nitrobenzyl acrylate) (PNBA) hydrophobic matrix and an hydrophilic dextran (Dex) shell were f...

The Last Deglaciation (21-10 ka) is the most recent transition from a glacial to interglacial state. It is characterized by a pronounced sea level change of 95 m resulting in flooding of land areas and changes of coastlines. This period is also marked by several millennial events like the Heinrich Event 1 with diverse effects on sea level, oceanic circulation, climate and carbon cycle. In case of flooding of land surfaces during periods of sea level rise, carbon and nutrients stored in terrestrial organic matter in vegetation and soils are transferred to the ocean, potentially impacting the global ocean biogeochemical cycle and the uptake/release of CO2 once being remineralized. Changes in the ocean biogeochemical cycles are also indirectly related to the poorly constrained stoichiometry and remineralization time-scales of terrestrial organic matter, which both differ from the well-known parameters for marine organic matter.We present here the first coupled transient simulation over the Last Deglaciation using the global ocean biogeochemical model HAMOCC (HAMburg Ocean Carbon Cycle) as part of the paleo-version of the MPI-ESM (Max Planck Institute Earth System Model) to study the impact of terrestrial organic matter input on the ocean biogeochemical cycle and oceanic CO2 fluxes during large sea level variations. This model version combines (1) a fully interactive adaptation of the ocean bathymetry with corresponding changes of the land-sea distribution, (2) a transient river routing and (3) the land-sea terrestrial organic matter transfer after flooding. Our simulation provides new insights on the land carbon inputs to the ocean carbon inventory (water column and sediment) due to flooding, with 170 GtC between 21-10 ka, of which 21.1 GtC and 36.8 GtC are within two 1000 years large freshwater discharge events (between 15-14 ka and 12-11 ka). These inputs of carbon rich material to the ocean during flooding events have however only a local effect on ocean CO2 outgassing, the global ocean remaining a sink of CO2. To infer the response of CO2 fluxes in this context, sensitivity experiments can be performed during the type of Heinrich event (15-14 ka) to evaluate and better constrain the terrestrial organic matter remineralization parameters.

Anthropogenic activities, particularly fertilisation, have resulted in significant increases in reactive nitrogen (rN) in soils globally, leading to eutrophication, acidification, poor air quality, and emissions of the important greenhouse gas N2O. Understanding the partitioning of rN losses into different environmental compartments is critical to mitigate negative impacts, however, loss pathways are poorly quantified, and potential changes driven by climate warming and societal shifts are highly uncertain. We present a coupled soil-atmosphere isotope model (IsoTONE; ISOtopic Tracing Of Nitrogen in the Environment) to partition rN losses into leaching, harvest, NH3 volatilization, and production of NO, N2 and N2O based on a global dataset of soil δ15N, as well as numerous other geoclimatic and experimental datasets. The model was optimized in a Bayesian framework using a time series of N2O mixing ratios and isotopic compositions since the preindustrial era, as well as a global dataset of N2O emission factors (EF). The posterior model results showed that the total anthropogenic flux in 2020 (7.8 Tg N2O-N a-1) was dominated by indirect emissions resulting from N deposition, while the growth rate and trend in anthropogenic N2O was driven by both direct N fertilisation and deposition inputs. In contrast, inputs from fixation N drive natural N2O emissions, and were responsible for subdecadal interannual variability in total emissions.Total N gas (N2O + NO + N2) production and N2O losses were strongly dependent on geoclimate and thus spatially variable, therefore the spatial pattern of N inputs strongly impacted resulting EFs and total N2O emissions. The area-weighted global EF for N2O was 1% of anthropogenic N inputs in 2020, similar to the current IPCC default of 1.4%, however the N input-weighted global EF was 4.3%. Shifts in fertilisation inputs from the temperate Northern hemisphere towards warmer regions with higher EFs such as India and China have led to accelerating N2O emissions (1.02±0.7 Tg N2O-N a-1). In addition, N2O emissions have increased over the past decades due to climate warming (0.76±0.4 Tg N2O-N a-1). Predicted increases in fertilisation in India and Africa in the coming decades could further accelerate N2O-driven climate warming, unless mitigation measures are implemented to increase fertiliser N use efficiency and reduce N2O emission factors.

Information on soils' composition and physical, chemical and biological properties is paramount to elucidate agroecosystem functioning in space and over time. For this purposes we developed a national Swiss soil spectral library (SSL; n = 4374) in the mid-infrared (mid-IR), calibrating 17 properties from legacy measurements on soils from the Swiss biodiversity monitoring program (n = 3778; 1094 sites) and the Swiss long-term monitoring network (n = 596; 71 sites). General models were trained with the interpretable rule-based learner CUBIST, testing combinations of {5, 10, 20, 50, 100} committees of rules and {2, 5, 7, 9} neighbors to localize predictions with repeated by location grouped ten-fold cross-validation. To evaluate the information in spectra to facilitate long-term soil monitoring at a plot-level, we conducted 71 model transfers for the NABO sites to induce locally relevant information from the SSL, using the data-driven sample selection method rs-local. Eleven soil properties were estimated with discrimination capacity suitable for screening (R2 > 0.6), out of which total carbon (C), organic C (OC), total N, organic matter content, pH, and clay showed accuracy eligible for accurate diagnostics (R2 > 0.8). Cubist and the spectra estimated total C accurately with RMSE = 0.84 % while the measured range was 0.1–⁠58.3 %, and OC with RMSE = 1.20 % (measured range 0.0–⁠27.3 %). Compared to general estimates of properties from Cubist, local modeling on average reduced the root mean square error of total C per site fourfold. We found that the selected SSL subsets were highly dissimilar in terms of both their spectral input space and the measured values. This suggests that data-driven selection with RS-LOCAL leverages chemical diversity in composition rather than similarity. Our results suggest that mid-IR soil estimates were sufficiently accurate to support many soil applications that require a large volume of input data, such as precision agriculture, soil C accounting and monitoring, and digital soil mapping. This SSL can be updated continuously, for example with samples from deeper profiles and organic soils, so that the measurement of key soil properties becomes even more accurate and efficient in the near future.

The stable carbon isotopic composition (δ13 C) is an important variable to study the ocean carbon cycle across different timescales. We include a new representation of the stable carbon isotope 13 C into the HAMburg Ocean Carbon Cycle model (HAMOCC), the ocean biogeochemical component of the Max Planck Institute Earth System Model (MPI-ESM). 13 C is explicitly resolved for all oceanic carbon pools considered. We account for fractionation during air–sea gas exchange and for biological fractionation ϵp associated with photosynthetic carbon fixation during phytoplankton growth. We examine two ϵp parameterisations of different complexity: ϵ p Popp varies with surface dissolved CO 2 concentration ( Popp et al. , 1989 ) , while ϵ p Laws additionally depends on local phytoplankton growth rates ( Laws et al. , 1995 ) . When compared to observations of δ13 C of dissolved inorganic carbon (DIC), both parameterisations yield similar performance. However, with regard to δ13 C in particulate organic carbon (POC) ϵ p Popp shows a considerably improved performance compared to ϵ p Laws . This is because ϵ p Laws produces too strong a preference for 12 C, resulting in δ13 C POC that is too low in our model. The model also well reproduces the global oceanic anthropogenic CO 2 sink and the oceanic 13 C Suess effect, i.e. the intrusion and distribution of the isotopically light anthropogenic CO 2 in the ocean. The satisfactory model performance of the present-day oceanic δ13 C distribution using ϵ p Popp and of the anthropogenic CO 2 uptake allows us to further investigate the potential sources of uncertainty of the Eide et al. ( 2017 a ) approach for estimating the oceanic 13 C Suess effect. Eide et al. ( 2017 a ) derived the first global oceanic 13 C Suess effect estimate based on observations. They have noted a potential underestimation, but their approach does not provide any insight about the cause. By applying the Eide et al. ( 2017 a ) approach to the model data we are able to investigate in detail potential sources of underestimation of the 13 C Suess effect. Based on our model we find underestimations of the 13 C Suess effect at 200 m by 0.24 ‰ in the Indian Ocean, 0.21 ‰ in the North Pacific, 0.26 ‰ in the South Pacific, 0.1 ‰ in the North Atlantic and 0.14 ‰ in the South Atlantic. We attribute the major sources of underestimation to two assumptions in the Eide et al. ( 2017 a ) approach: the spatially uniform preformed component of δ13 C DIC in year 1940 and the neglect of processes that are not directly linked to the oceanic uptake and transport of chlorofluorocarbon-12 (CFC-12) such as the decrease in δ13 C POC over the industrial period. The new 13 C module in the ocean biogeochemical component of MPI-ESM shows satisfying performance. It is a useful tool to study the ocean carbon sink under the anthropogenic influences, and it will be applied to investigating variations of ocean carbon cycle in the past.

Simple Summary Odor emission from swine production facilities can irritate the people living in surrounding areas, although the farmers consider odor emission as a part of farming practice. Despite the governmental and institutional efforts, odor-related complaints from the neighborhood communities around the swine farms are rapidly increasing and have been identified as a key concern to sustaining progress of the swine industry globally. Bio-liquor circulation systems (BCSs) in swine farms have become popular among the farmers as an odor reduction technology in Korea. However, due to the lack of appropriate operating strategies, the odor reduction capacity of BCSs is often depleted. In this lab-scale study, a real-time control strategy based on oxidation–reduction potential (ORP) and pH (mV) time profiles was developed and applied for BCS operation. This study shows the potential effectiveness of using ORP and pH (mV) time profiles as operational parameters for the BCS to improve swine manure properties in slurry pits and thus reduce odor emission. Abstract In this study, an attempt was made to develop a real-time control strategy using oxidation–reduction potential (ORP) and pH (mV) time profiles for the efficient operation of bio-liquor circulation system (BCS) in swine farms and its effectiveness in reducing odor emission through improving manure properties in the slurry pit was evaluated. The lab-scale BCS used in this study comprised a bioreactor and a slurry pit. The bioreactor was operated in a sequence of inflow of swine manure → anoxic phase → aerobic phase → circulation to the slurry pit. The improvement in swine manure properties was elucidated by comparing the results of the BCS slurry pit (circulation type, CT) and conventional slurry pit (non-circulation type, NCT). The results revealed that the ORP time profile successfully detected the nitrate knee point (NKP) in the anoxic phase. However, it was less stable in detecting the nitrogen break point (NBP) in the aerobic phase. The pH (mV) time profile showed a more efficient detection of NBP. Compared to the NCT slurry pit, concentrations of ammonium nitrogen (NH4-N) and soluble total organic carbon (STOC) and other analyzed swine manure properties were much lower in the CT slurry pit. In the aspect of odor reduction, around 98.3% of NH3 was removed in the CT slurry pit. The real-time controlled BCS can overcome the drawbacks of fixed time-based BCS operation and therefore can be considered as a useful tool to reduce odor emission from intensive swine farming operations. However, further studies and refinement in control algorithms might be required prior to its large-scale application.

The recycling of organic waste in biogas plants is proposed as a measure to close nutrient cycles and possibly reduce nitrogen losses such as nitrous oxide emissions and nitrate leaching. Ammonia volatilization after fertilizer spreading is yet another nitrogen loss pathway which is often understudied and not yet fully understood but the knowledge is needed in order to optimize fertilizer management. We therefore aimed to quantify the volatilization of ammonia after the trail-hose application of digestates compared to cattle slurry. We hypothesize that digestates have larger and longer lasting nitrogen losses via ammonia volatilization due to higher NH4+ contents and pH values compared to fresh manure. In this project, digested and un-digested organic fertilizers were applied twice per year in a 2.5-years field experiment with three consecutive arable crops (maize, winter wheat and winter barley) under organic farming. We used Automated Low Cost Impinger Systems to measure ammonia emissions after fertilizer application. The emissions were then modeled using the backwards Langrangian stochastic dispersal model with respect to wind conditions. A preliminary presentation of the data indicates that ammonia emissions from the cattle slurry, slurry-based digestate, and industrial digestate are alternately higher or lower. In 2018, emissions from cattle slurry tended to be lower than those from slurry-based digestate and industrial digestate, while in 2019 and 2020 all three liquid organic fertilizers had similar emissions. In the measurement period after the second fertilizer application in 2018, which took place at the end of May, conspicuously high emissions were measured. This can be explained by the high temperatures during this period. Adaptive strategies in fertilizer management should thus consider reduced inputs of organic fertilizers during warm periods.

Information on soil properties is crucial for soil preservation, the improvement of food security, and the provision of ecosystem services. In particular, for the African continent, spatially explicit information on soils and their ability to sustain these services is still scarce. To address data gaps, infrared spectroscopy has achieved great success as a cost-effective solution to quantify soil properties in recent decades. Here, we present a mid-infrared soil spectral library (SSL) for central Africa (CSSL) that can predict key soil properties, allowing for future soil estimates with a minimal need for expensive and time-consuming wet chemistry. Currently, our CSSL contains over 1800 soil samples from 10 distinct geoclimatic regions throughout the Congo Basin and along the Albertine Rift. For the analysis, we selected six regions from the CSSL, for which we built predictive models for total carbon (TC) and total nitrogen (TN) using an existing continental SSL (African Soil Information Service, AfSIS SSL; n=1902) that does not include central African soils. Using memory-based learning (MBL), we explored three different strategies at decreasing degrees of geographic extrapolation, using models built with (1) the AfSIS SSL only, (2) AfSIS SSL combined with the five remaining central African regions, and (3) a combination of AfSIS SSL, the remaining five regions, and selected samples from the target region (spiking). For this last strategy we introduce a method for spiking MBL models. We found that when using the AfSIS SSL only to predict the six central African regions, the root mean square error of the predictions (RMSEpred) was between 3.85–8.74 and 0.40–1.66 g kg−1 for TC and TN, respectively. The ratio of performance to the interquartile distance (RPIQpred) ranged between 0.96–3.95 for TC and 0.59–2.86 for TN. While the effect of the second strategy compared to the first strategy was mixed, the third strategy, spiking with samples from the target regions, could clearly reduce the RMSEpred to 3.19–7.32 g kg−1 for TC and 0.24–0.89 g kg−1 for TN. RPIQpred values were increased to ranges of 1.43–5.48 and 1.62–4.45 for TC and TN, respectively. In general, predicted TC and TN for soils of each of the six regions were accurate; the effect of spiking and avoiding geographical extrapolation was noticeably large. We conclude that our CSSL adds valuable soil diversity that can improve predictions for the Congo Basin region compared to using the continental AfSIS SSL alone; thus, analyses of other soils in central Africa will be able to profit from a more diverse spectral feature space. Given these promising results, the library comprises an important tool to facilitate economical soil analyses and predict soil properties in an understudied yet critical region of Africa. Our SSL is openly available for application and for enlargement with more spectral and reference data to further improve soil diagnostic accuracy and cost-effectiveness.

Nitrogen (N) pollution has mostly been controlled using command-and-control instruments. However, nitrogen surplus permits (NSPs), which are tradeable, can be more cost-efficient in addressing the problem. To model this instrument, we calculated the individual marginal abatement cost curve for a sample of about 3,400 Swiss farms using farm-optimization models implemented in the agent-based agricultural sector model SWISSland. We also used SWISSland to analyze the effects of two NSP distribution systems (grandfathering and land-based allocation) on different farm types. The results showed that different farm types range in their abatement costs to reduce N surplus from an average of −0.04 CHF kg−1 N on arable farms to 51.06 CHF kg−1 N on special crop farms. We also found that N surpluses hardly explain the level of abatement costs. The biggest differences in effects of the distribution scheme were found in intensive livestock farm types such as pig or poultry farms.

Primary tropical forests generally exhibit large gaseous nitrogen (N) losses, occurring as nitric oxide (NO), nitrous oxide (N2O) or elemental nitrogen (N2). The release of N2O is of particular concern due to its high global warming potential and destruction of stratospheric ozone. Tropical forest soils are predicted to be among the largest natural sources of N2O; however, despite being the world’s second-largest rainforest, measurements of gaseous N-losses from forest soils of the Congo Basin are scarce. In addition, long-term studies investigating N2O fluxes from different forest ecosystem types (lowland and montane forests) are scarce. In this study we show that fluxes measured in the Congo Basin were lower than fluxes measured in the Neotropics, and in the tropical forests of Australia and South East Asia. In addition, we show that despite different climatic conditions, average annual N2O fluxes in the Congo Basin’s lowland forests (0.97 ± 0.53 kg N ha−1 year−1) were comparable to those in its montane forest (0.88 ± 0.97 kg N ha−1 year−1). Measurements of soil pore air N2O isotope data at multiple depths suggests that a microbial reduction of N2O to N2 within the soil may account for the observed low surface N2O fluxes and low soil pore N2O concentrations. The potential for microbial reduction is corroborated by a significant abundance and expression of the gene nosZ in soil samples from both study sites. Although isotopic and functional gene analyses indicate an enzymatic potential for complete denitrification, combined gaseous N-losses (N2O, N2) are unlikely to account for the missing N-sink in these forests. Other N-losses such as NO, N2 via Feammox or hydrological particulate organic nitrogen export could play an important role in soils of the Congo Basin and should be the focus of future research., The ISME Journal, 15, ISSN:1751-7362, ISSN:1751-7370

Worldwide tree species have been observed to be suffering from extended periods of water limitation, for example due to warmer climate that increases soil evaporation and plant transpiration. These conditions likely do not only affect the growth and vitality of trees but may also feed back on the cycling of carbon and nitrogen at the interface between roots and soils. In September 2019, we established a mesocosm experiment to mechanistically study on a seasonal basis how the interactions between plants and soil biotic and abiotic resources are altered during events of drought. The mesocosms feature young Scots pine (Pinus sylvestris L.) trees and soil collected from a drought-affected natural forest in the Rhone valley, Switzerland; and are treated with three different levels of water availability (control, sufficient water; intermediate drought, 40% reduction; severe drought, 75% reduction). One year after the start of the experiment an isotopic labelling campaign with 13CO2 was conducted to trace the natural pathway of photosynthetic assimilates into above- and belowground carbon pools and fluxes. During the first growing season of the experiment, severe drought more than doubled the growth of fine roots when compared to the control treatment. In turn, the mean diameter of the fine roots significantly decreased by 22%, and fewer ectomycorrhizal root tips were observed. These findings suggest that trees exposed to drought invest more in within-plant carbon maintenance and in the growth of root systems, rather than in the allocation of carbon to sustain the biology in the rhizosphere for nutrient acquisition. Moreover, post-label soil pore 13CO2 concentrations and total soil CO2 concentrations were lower under severe drought compared to intermediate and control treatments, indicating a generally reduced carbon metabolism. By tracking the fate of 13C assimilates into fine roots, soils and microbial communities over time we now investigate whether there is a threshold at which Scots pine trees stop investing in providing carbon to the rhizosphere and rather succumb to drought., EGUsphere

Trees within farmers' fields can enhance systems' longer-term productivity e.g., via nutrient amelioration, which is indispensable to attain sustainable agroecosystems. While arbuscular mycorrhizal fungi (AMF) are known to improve plant access to soil nutrients, the potential of AMF to facilitate nutrient transfer from trees to crops is unclear. We used the 15N (nitrogen) natural abundance technique together with root and AMF exclusion plots to assess if Faidherbia albida (faidherbia) trees deliver N to maize via associated AMF in smallholder fields. We show, here, that within one cropping season, maize obtained approximately 35 kg biologically fixed N ha-1 from faidherbia and AMF significantly contribute to this transfer of N. One third of tree-derived N in maize leaves was attributed to transfer via AMF and two thirds were explained by tree leaf litter input. Thus, the faidherbia-AMF association can enhance agroecosystem functioning and as such, attain greater sustainability of low-input cropping systems.

In this study, the technical, economic and environmental attributes of a full-scale nutrient recovery process connected to the centralized swine wastewater treatment facility (CSWTF) were evaluated. The performance of the process was assessed by introducing influent to the recovery reactor from different components of the CSWTF such as sedimentation tank (swine wastewater) and biological treatment reactor (biologically oxidized material and supernatant of the biologically oxidized material). The results of technical performance assessment revealed that the O–P recovery (87.1–90.7%) and NH4–N removal (66.9–72.1%) efficiencies from the influent of biological treatment reactor were significantly higher than the influent from sedimentation tank (81.7 and 19.8%, respectively, p

Due to regular influx of organic matter and nutrients, waste stabilization ponds (WSPs) can release considerable quantities of greenhouse gases (GHGs). To investigate the spatiotemporal variations of GHG emissions from WSPs with a focus on the effects of sludge accumulation and distribution, we conducted a bathymetry survey and two sampling campaigns in Ucubamba WSP (Cuenca, Ecuador). The results indicated that spatial variation of GHG emissions was strongly dependent on sludge distribution. Thick sludge layers in aerated ponds and facultative ponds caused substantial CO2 and CH4 emissions which accounted for 21.3% and 78.7% of the total emissions from the plant. Conversely, the prevalence of anoxic conditions stimulated the N2O consumption via complete denitrification leading to a net uptake from the atmosphere, i.e. up to 1.4±0.2 mg-N m-2 d-1. Double emission rates of CO2 were found in the facultative and maturation ponds during the day compared to night-time emissions, indicating the important role of algal respiration, while no diel variation of the CH4 and N2O emissions was found. Despite the uptake of N2O, the total GHG emissions of the WSP was higher than constructed wetlands and conventional centralized wastewater treatment facilities. Hence, it is recommended that sludge management with proper desludging regulation should be included as an important mitigation measure to reduce the carbon footprint of pond treatment facilities.

The agricultural sector is considered one of the major sources of greenhouse gas (GHG) emissions globally. The livestock industry as a significant contributor, is accounting for about 18% of GHG emissions measured in carbon dioxide (CO2) equivalent from agricultural practices. Depending on farming practices and climatic conditions, GHGs such as methane (CH4) and nitrous oxide (N2O) emissions from livestock agriculture can vary significantly. Country-specific emission factors are, therefore, needed for a precise estimation of GHG emissions and to avoid uncertainties. This study was aimed at estimating the CH4 and N2O emission fluxes from Hanwoo (the most famous and popular Korean native cattle) manure management systems. CH4 and N2O emission fluxes from litter in the Hanwoo cattle barn and composting lot were monitored and calculated for 52 weeks using the dynamic chamber method. The calculated monthly average fluxes of CH4 and N2O from litter in the cattle barn ranged from 0.0 to 30.0 &plusmn, 13.7 and 0.896 &plusmn, 0.557 to 2.925 &plusmn, 2.853 &mu, g/m2 s, respectively during the whole measurement period. While during the composting period, the monthly average of CH4 and N2O emission fluxes were varied from 1.449 &plusmn, 0.783 to 86.930 &plusmn, 19.092 and 0.511 &plusmn, 0.410 to 2.629 &plusmn, 1.105 &mu, g/m2 s, respectively. The calculated emission fluxes of CH4 and N2O from manure management systems in this study were almost 5.4 and 2.1 times, respectively higher than the values reported for the Asian, South and North American countries in the 2006 Intergovernmental Panel on Climate Change (IPCC) Guidelines for National Greenhouse Gas Inventories. Overall, this study initiates the process along with signifies the importance of developing country-specific GHG inventories for the effective reduction of GHG emissions from the livestock sector in Korea.

International audience; Necrotizing pneumonia induced by Panton-Valentine leukocidin–secreting Staphylococcus aureus is a rare but life-threatening infection that has been described in patients after they had influenza. We report a fatal case of this superinfection in a young adult who had coronavirus disease.

The isotopic composition of nitrous oxide (N2 O) provides useful information for evaluating N2 O sources and budgets. Due to the co-occurrence of multiple N2 O transformation pathways, it is, however, challenging to use isotopic information to quantify the contribution of distinct processes across variable spatiotemporal scales. Here, we present an overview of recent progress in N2 O isotopic studies and provide suggestions for future research, mainly focusing on: analytical techniques; production and consumption processes; and interpretation and modelling approaches. Comparing isotope-ratio mass spectrometry (IRMS) with laser absorption spectroscopy (LAS), we conclude that IRMS is a precise technique for laboratory analysis of N2 O isotopes, while LAS is more suitable for in situ/inline studies and offers advantages for site-specific analyses. When reviewing the link between the N2 O isotopic composition and underlying mechanisms/processes, we find that, at the molecular scale, the specific enzymes and mechanisms involved determine isotopic fractionation effects. In contrast, at plot-to-global scales, mixing of N2 O derived from different processes and their isotopic variability must be considered. We also find that dual isotope plots are effective for semi-quantitative attribution of co-occurring N2 O production and reduction processes. More recently, process-based N2 O isotopic models have been developed for natural abundance and 15 N-tracing studies, and have been shown to be effective, particularly for data with adequate temporal resolution. Despite the significant progress made over the last decade, there is still great need and potential for future work, including development of analytical techniques, reference materials and inter-laboratory comparisons, further exploration of N2 O formation and destruction mechanisms, more observations across scales, and design and validation of interpretation and modelling approaches. Synthesizing all these efforts, we are confident that the N2 O isotope community will continue to advance our understanding of N2 O transformation processes in all spheres of the Earth, and in turn to gain improved constraints on regional and global budgets.

This study addressed the hypothesis that soluble epoxide hydrolase (sEH), which metabolizes endothelium-derived epoxyeicosatrienoic acids, plays a role in vascular calcification. The sEH inhibitor trans-4-(4-(3-adamantan-1-yl-ureido)-cyclohexyloxy)-benzoic acid (t-AUCB) potentiated the increase in calcium deposition of rat aortic rings cultured in high-phosphate conditions. This was associated with increased tissue-nonspecific alkaline phosphatase activity and mRNA expression level of the osteochondrogenic marker Runx2. The procalcifying effect of t-AUCB was prevented by mechanical aortic deendothelialization or inhibition of the production and action of epoxyeicosatrienoic acids using the cytochrome P450 inhibitor fluconazole and the antagonist 14,15-epoxyeicosa-5(Z)-enoic acid (14,15-EEZE), respectively. Similarly, exogenous epoxyeicosatrienoic acids potentiated the calcification of rat aortic rings through a protein kinase A (PKA)-dependent mechanism and of human aortic vascular smooth muscle cells when sEH was inhibited by t-AUCB. Finally, a global gene expression profiling analysis revealed that the mRNA expression level of sEH was decreased in human carotid calcified plaques compared to adjacent lesion-free sites and was inversely correlated with Runx2 expression. These results show that sEH hydrolase plays a protective role against vascular calcification by reducing the bioavailability of epoxyeicosatrienoic acids.