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Metastases in the brain are the most severe and devastating complication of cancer. The incidence of brain metastasis is increasing. Therefore, the need of finding specific druggable targets for brain metastasis is demanding. The aim of this study was to compare the brain (immune) response to brain metastases of the most common tumor lineages, viz., lung adenocarcinoma and breast cancer. Targeted gene expression profiles of 11 brain metastasis of lung adenocarcinoma (BM-LUAD) were compared to 11 brain metastasis of breast cancer (BCBM) using NanoString nCounter PanCancer IO 360™ Panel. The most promising results were validated spatially using the novel GeoMx™ Digital Spatial Profiler (DSP) Technology. Additionally, Immune cell profiles and expression of drug targets were validated by multiplex immunohistochemistry. We found a more active immune response in BM-LUAD as compared to BCBM. In the BM-LUAD, 138 genes were upregulated as compared to BCBM (adj. p ≤ 0.05). Conversely, in BCBM 28 genes were upregulated (adj. p ≤ 0.05). Additionally, genes related to CD45 + cells, T cells, and cytotoxic T cells showed to be expressed higher in BM-LUAD compared to BCBM (adj. p = 0.01, adj. p = 0.023, adj. p = 0.023, respectively). The spatial quantification of the immune cells using the GeoMx DSP technique revealed the significantly higher quantification of CD14 and CD163 in tumor regions of BM-LUAD as compared to BCBM. Importantly, the immune checkpoint VISTA and IDO1 were identified as highly expressed in the BM-LUAD. Multiplex immunohistochemistry confirmed the finding and showed that VISTA is expressed mainly in BM-LUAD tumor cells, CD3 + cells, and to fewer levels in some microglial cells in BM-LUAD. This is the first report on differences in the brain immune response between metastatic tumors of different lineages. We found a far more extensive infiltration of immune cells in BM-LUAD as compared to BCBM. In addition, we found higher expression of VISTA and IDO1 in BM-LUAD. Taken together, targeted immune therapy should be considered to treat patients with BM-LUAD.

The magnitude of the 2022 multi-country monkeypox virus (MPXV) outbreak has surpassed any preceding outbreak. It is unclear whether asymptomatic or otherwise undiagnosed infections are fuelling this epidemic. In this study, we aimed to assess whether undiagnosed infections occurred among men attending a Belgian sexual health clinic in May 2022. We retrospectively screened 224 samples collected for gonorrhea and chlamydia testing using an MPXV PCR assay and identified MPXV-DNA-positive samples from four men. At the time of sampling, one man had a painful rash, and three men had reported no symptoms. Upon clinical examination 21-37 days later, these three men were free of clinical signs, and they reported not having experienced any symptoms. Serology confirmed MPXV exposure in all three men, and MPXV was cultured from two cases. These findings show that certain cases of monkeypox remain undiagnosed and suggest that testing and quarantining of individuals reporting symptoms may not suffice to contain the outbreak. Findings of unrecognized or asymptomatic monkeypox virus (MPXV) infections with replication-competent virus in humans suggest that a lack of recognized, clinical symptoms could play a role in virus transmission and the magnitude of the 2022 MPXV outbreak.

Single-molecule FRET experiments with human A2A adenosine receptor in its apo and agonist-bound states in lipid nanodiscs provide insights into its conformational dynamics and activation. The complex pharmacology of G-protein-coupled receptors (GPCRs) is defined by their multi-state conformational dynamics. Single-molecule Forster Resonance Energy Transfer (smFRET) is well suited to quantify dynamics for individual protein molecules; however, its application to GPCRs is challenging. Therefore, smFRET has been limited to studies of inter-receptor interactions in cellular membranes and receptors in detergent environments. Here, we performed smFRET experiments on functionally active human A(2A) adenosine receptor (A(2A)AR) molecules embedded in freely diffusing lipid nanodiscs to study their intramolecular conformational dynamics. We propose a dynamic model of A(2A)AR activation that involves a slow (>2 ms) exchange between the active-like and inactive-like conformations in both apo and antagonist-bound A(2A)AR, explaining the receptor's constitutive activity. For the agonist-bound A(2A)AR, we detected faster (390 +/- 80 mu s) ligand efficacy-dependent dynamics. Our work establishes a general smFRET platform for GPCR investigations that can potentially be used for drug screening and/or mechanism-of-action studies. A.L., A.B., and V.B. are thankful for the Ministry of Science and Higher Education of the Russian Federation (agreement #075-03-2023-106, project FSMG-2020-0003). IM acknowledges the UHasselt Special Research Fund. Measurements of surface expression and Gs-signaling were supported by the Russian Science Foundation (project no. 22-74- 10036; https://rscf.ru/project/22-74-10036/). Computational simulations were supported by the National Natural Science Foundation of China, grant #32250410316 (to PO). We acknowledge the Advanced Optical Microscopy Centre at Hasselt University for support with microscopy experiments. Microscopy was made possible by the Research Foundation Flanders (FWO, projects G0B4915, G0B9922N, and G0H3716N).

Objectives: New drugs and methods to efficiently fight carbapenem-resistant gram-negative pathogens are sorely needed. In this study, we characterized the preclinical pharmacokinetics (PK) and pharmacodynamics of the clinical stage drug candidate apramycin in time kill and mouse lung infection models. Based on in vitro and in vivo data, we developed a mathematical model to predict human efficacy. Methods: Three pneumonia-inducing gram-negative species Acinetobacter baumannii, Pseudomonas aeruginosa, and Klebsiella pneumoniae were studied. Bactericidal kinetics were evaluated with time-kill curves; in vivo PK were studied in healthy and infected mice, with sampling in plasma and epithelial lining fluid after subcutaneous administration; in vivo efficacy was measured in a neutropenic mouse pneumonia model. A pharmacokinetic-pharmacodynamic model, integrating all the data, was developed and simulations were performed. Results: Good lung penetration of apramycin in epithelial lining fluid (ELF) was shown (area under the curve (AUC)(ELF)/ALI(Cplasma) = 88%). Plasma clearance was 48% lower in lung infected mice compared to healthy mice. For two out of five strains studied, a delay in growth (similar to 5 h) was observed in vivo but not in vitro. The mathematical model enabled integration of lung PK to drive mouse PK and pharmacodynamics. Simulations predicted that 30 mg/kg of apramycin once daily would result in bacteriostasis in patients. Discussion: Apramycin is a candidate for treatment of carbapenem-resistant gram-negative pneumonia as demonstrated in an integrated modeling framework for three bacterial species. We show that mathematical modelling is a useful tool for simultaneous inclusion of multiple data sources, notably plasma and lung in vivo PK and simulation of expected scenarios in a clinical setting, notably lung infections.

We measured community-level traits of vascular plants, lichens, and bryophytes in an alpine Dryas octopetala L. heath in Finse, Norway, after nearly two decades of experimental warming by open-top chambers. We hypothesized that under warming (1) vascular plant traits would shift from resource conservative towards more resource acquisitive, and (2) lichen and bryophyte traits would shift to those associated with drier conditions, due to increased evapotranspiration. Both hypotheses were not supported, as vascular plant nitrogen concentration decreased, whereas carbon to nitrogen ratio increased with warming, indicative of a less resource acquisitive strategy, and lichen specific thallus area and water holding capacity were unresponsive. Bryophyte specific shoot length increased, and carbon concentration and water holding capacity tended to decrease under warming, concurrent with increased vegetation height and litter cover indicating stronger competition from vascular plants. Intraspecific variation was most important for vascular plant and lichen traits, whereas species turnover was the main driver of bryophyte trait variation. This indicates that bryophytes may be affected more strongly by future warming than vascular plants and lichens in our study system. We highlight the importance of studying traits of different primary producer groups simultaneously, as they may respond differently to the same environmental changes.

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

Vaccination is an effective method to suppress COVID-19 transmission, but injection-based vaccination is less effective due to its inability to induce mucosal immunity. This study aimed to determine the effects of vaccine formulations on bacteria viability and antigen expression to find the optimal formulation. Three intranasal preparation formulations (F1, F2, and F3) were created with different ingredient compositions, along with a control. Physicochemical tests were conducted on day 0 and day 14 to assess bacterial viability, and antigen expression was evaluated using the western blot method. Formula 2, containing sodium alginate (0.615%), trehalose (4.125%), polyvinyl alcohol (0.1%), and calcium chloride (5%), exhibited the best viability test results, although no significant differences were observed among the groups. The study concluded that variations in composition concentrations could affect bacterial stability, with Formula 2 showing the best results in terms of bacteria viability and antigen expression up to 14 days after formulation.

Reduced glomerular filtration rate (GFR) can progress to kidney failure. Risk factors include genetics and diabetes mellitus (DM), but little is known about their interaction. We conducted genome-wide association meta-analyses for estimated GFR based on serum creatinine (eGFR), separately for individuals with or without DM (nDM = 178,691, nnoDM = 1,296,113). Our genome-wide searches identified (i) seven eGFR loci with significant DM/noDM-difference, (ii) four additional novel loci with suggestive difference and (iii) 28 further novel loci (including CUBN) by allowing for potential difference. GWAS on eGFR among DM individuals identified 2 known and 27 potentially responsible loci for diabetic kidney disease. Gene prioritization highlighted 18 genes that may inform reno-protective drug development. We highlight the existence of DM-only and noDM-only effects, which can inform about the target group, if respective genes are advanced as drug targets. Largely shared effects suggest that most drug interventions to alter eGFR should be effective in DM and noDM. Published version The Deutsche Forschungsgemeinschaft (DFG, German Research Foundation) supported the meta-analysis—Project-ID 387509280—SFB1350 (Subproject C6 to I.M.H.). A.M.H., B.R., and R.T. were supported by VACSR&D MVP grant CX001897. This research is based on data from the Million Veteran Program, Office of Research and Development, Veterans Health Administration, and was supported by VACSR&D MVP grant CX001897 (A.M.H.). This publication does not represent the views of the Department of Veteran Affairs or the United States Government. We conducted this research using the UK Biobank resource under the application number 20272.

Many natural objects exhibit radial or axial symmetry in a single plane. However, a universal tool for simulating and fitting the shapes of such objects is lacking. Herein, we present an R package called 'biogeom' that simulates and fits many shapes found in nature. The package incorporates novel universal parametric equations that generate the profiles of bird eggs, flowers, linear and lanceolate leaves, seeds, starfish, and tree-rings, and three growth-rate equations that generate the profiles of ovate leaves and the ontogenetic growth curves of animals and plants. 'biogeom' includes several empirical datasets comprising the boundary coordinates of bird eggs, fruits, lanceolate and ovate leaves, tree rings, seeds, and sea stars. The package can also be applied to other kinds of natural shapes similar to those in the datasets. In addition, the package includes sigmoid curves derived from the three growth-rate equations, which can be used to model animal and plant growth trajectories and predict the times associated with maximum growth rate. 'biogeom' can quantify the intra- or interspecific similarity of natural outlines, and it provides quantitative information of shape and ontogenetic modification of shape with important ecological and evolutionary implications for the growth and form of the living world.

Biologics represent the fastest growing group of therapeutics, but many advanced recombinant protein moieties remain difficult to produce. Here, we identify metabolic engineering targets limiting expression of recombinant human proteins through a systems biology analysis of the transcriptomes of CHO and HEK293 during recombinant expression. In an expression comparison of 24 difficult to express proteins, one third of the challenging human proteins displayed improved secretion upon host cell swapping from CHO to HEK293. Guided by a comprehensive transcriptomics comparison between cell lines, especially highlighting differences in secretory pathway utilization, a co-expression screening of 21 secretory pathway components validated ATF4, SRP9, JUN, PDIA3 and HSPA8 as productivity boosters in CHO. Moreover, more heavily glycosylated products benefitted more from the elevated activities of the N- and O-glycosyltransferases found in HEK293. Collectively, our results demonstrate the utilization of HEK293 for expression rescue of human proteins and suggest a methodology for identification of secretory pathway components for metabolic engineering of HEK293 and CHO.

Pistachio bushy top syndrome (PBTS) is a serious problem for pistachio growers in the western United States, but the cause of this disorder remains controversial. Recently, it was proposed that the Rhodococcus species R. fascians and R. corynebacterioides caused PBTS outbreaks in 2011 and 2015. To investigate the association of Rhodococcus spp. with PBTS in California's pistachio-growing region, Rhodococcus-like isolates were collected from diverse hosts and environments, including pistachio nurseries and orchards. Whole genome sequence analysis of 231 isolates revealed their evolutionary relationships and identified six Rhodococcus species. Combined with data on geography and host of origin, the data reveal that Rhodococcus generally, and R. fascians specifically, is ubiquitous in nature, frequently occurring in both symptomatic and asymptomatic pistachio trees and on other woody and native species. Core gene and single nucleotide polymorphism-based phylogenies and pangenome analyses differentiate R. fascians into distinct genotypes. Although we found examples of common genotypes shared between nurseries and orchards, the observed patterns are most consistent with an environmental source of strains and do not support a scenario in which individual nurseries are point sources of Rhodococcus. Moreover, none of the collected strains harbored known virulence genes, calling into question the role of these common environmental bacteria in causing PBTS. [Formula: see text] Copyright © 2022 The Author(s). This is an open access article distributed under the CC BY-NC-ND 4.0 International license .

Purpose Intramedullary nailing (IMN) of fractures is associated with increased rates of inflammatory complications. The pathological mechanism underlying this phenomenon is unclear. However, polymorphonuclear granulocytes (PMNs) seem to play an important role. We hypothesized that a femur fracture and standardized IMN in pigs is associated with altered appearance of PMNs in circulation and enhanced activation status of these cells. Methods A porcine model including a femur fracture and IMN was utilized. Animals were randomized for control [anesthesia + mechanical ventilation only (A/MV)] and intervention [A/MV and unilateral femur fracture (FF) + IMN] conditions. PMN numbers and responsiveness, integrin (CD11b), L-selectin (CD62L) and Fcγ-receptor (CD16 and CD32)-expression levels were measured by flowcytometry of blood samples. Animals were observed for 72 h. Results Circulatory PMN numbers did not differ between groups. Early PMN-responsiveness was retained after insult. PMN-CD11b expression increased significantly upon insult and peaked after 24 h, whereas CD11b in control animals remained unaltered (P = 0.016). PMN-CD16 expression levels in the FF + IMN-group rose gradually over time and were significantly higher compared with control animals, after 48 h (P = 0.016) and 72 h (P = 0.032). PMN-CD62L and CD32 expression did not differ significantly between conditions. Conclusion This study reveals that a femur fracture and subsequent IMN in a controlled setting in pigs is associated with enhanced activation status of circulatory PMNs, preserved PMN-responsiveness and unaltered circulatory PMN-presence. Indicating that monotrauma plus IMN is a specific and substantial stimulus for the cellular immune system. Early alterations of circulatory PMN receptor expression dynamics may be predictive for the intensity of the post traumatic response.

The stress hormone cortisol modulates fuel metabolism, cardiovascular homoeostasis, mood, inflammation and cognition. The CORtisol NETwork (CORNET) consortium previously identified a single locus associated with morning plasma cortisol. Identifying additional genetic variants that explain more of the variance in cortisol could provide new insights into cortisol biology and provide statistical power to test the causative role of cortisol in common diseases. The CORNET consortium extended its genome-wide association meta-analysis for morning plasma cortisol from 12,597 to 25,314 subjects and from ~2.2 M to ~7 M SNPs, in 17 population-based cohorts of European ancestries. We confirmed the genetic association with SERPINA6/SERPINA1. This locus contains genes encoding corticosteroid binding globulin (CBG) and α1-antitrypsin. Expression quantitative trait loci (eQTL) analyses undertaken in the STARNET cohort of 600 individuals showed that specific genetic variants within the SERPINA6/SERPINA1 locus influence expression of SERPINA6 rather than SERPINA1 in the liver. Moreover, trans-eQTL analysis demonstrated effects on adipose tissue gene expression, suggesting that variations in CBG levels have an effect on delivery of cortisol to peripheral tissues. Two-sample Mendelian randomisation analyses provided evidence that each genetically-determined standard deviation (SD) increase in morning plasma cortisol was associated with increased odds of chronic ischaemic heart disease (0.32, 95% CI 0.06–0.59) and myocardial infarction (0.21, 95% CI 0.00–0.43) in UK Biobank and similarly in CARDIoGRAMplusC4D. These findings reveal a causative pathway for CBG in determining cortisol action in peripheral tissues and thereby contributing to the aetiology of cardiovascular disease.

Arbuscular mycorrhizal fungi (AMF) have evolved associations with roots of 60% plant species, but the net benefit for plants vary broadly from mutualism to parasitism. Yet, we lack a general understanding of the evolutionary and ecological forces driving such variation. To this end, we conducted a comparative phylogenetic experiment with 24 species of Plantago, encompassing worldwide distribution, to address the effect of evolutionary history and environment on plant growth and chemical defenses in response to AMF colonization. We demonstrate that different species within one plant genus vary greatly in their ability to associate with AMF, and that AMF arbuscule colonization intensity decreases monotonically with increasing phylogenetic branch length, but not with concomitant changes in pedological and climatic conditions across species. Moreover, we demonstrate that species with the highest colonization levels are also those that change their defensive chemistry the least. We propose that the costs imposed by high AMF colonization in terms of reduced changes in secondary chemistry might drive the observed macroevolutionary decline in mycorrhization., iScience, 26 (5), ISSN:2589-0042

BackgroundSex differences in the susceptibility of sarcoidosis are unknown. The study aims to identify sex-dependent genetic variations in two clinical sarcoidosis phenotypes: Löfgren’s syndrome (LS) and non-Löfgren’s syndrome (non-LS).MethodsA meta-analysis of genome-wide association studies was conducted on Europeans and African Americans, totaling 10,103 individuals from three population-based cohorts, Sweden (n = 3,843), Germany (n = 3,342), and the United States (n = 2,918), followed by an SNP lookup in the UK Biobank (UKB, n = 387,945). A genome-wide association study based on Immunochip data consisting of 141,000 single nucleotide polymorphisms (SNPs) was conducted in the sex groups. The association test was based on logistic regression using the additive model in LS and non-LS sex groups independently. Additionally, gene-based analysis, gene expression, expression quantitative trait loci (eQTL) mapping, and pathway analysis were performed to discover functionally relevant mechanisms related to sarcoidosis and biological sex.ResultsWe identified sex-dependent genetic variations in LS and non-LS sex groups. Genetic findings in LS sex groups were explicitly located in the extended Major Histocompatibility Complex (xMHC). In non-LS, genetic differences in the sex groups were primarily located in the MHC class II subregion and ANXA11. Gene-based analysis and eQTL enrichment revealed distinct sex-specific gene expression patterns in various tissues and immune cell types. In LS sex groups, a pathway map related to antigen presentation machinery by IFN-gamma. In non-LS, pathway maps related to immune response lectin-induced complement pathway in males and related to maturation and migration of dendritic cells in skin sensitization in females were identified.ConclusionOur findings provide new evidence for a sex bias underlying sarcoidosis genetic architecture, particularly in clinical phenotypes LS and non-LS. Biological sex likely plays a role in disease mechanisms in sarcoidosis.

The Amaryllidaceae species are well-known as a rich source of bioactive compounds in nature. Although Hymenocallis littoralis has been studied for decades, its polar components were rarely explored. The current phytochemical investigation of Amaryllidaceae alkaloids from H. littoralis led to the identification of three previously undescribed compounds: O-demethyl-norlycoramine (1), (-)-2-epi-pseudolycorine (2) and (+)-2-epi-pseudolycorine (3), together with eight known compounds: 6α-hydroxyhippeastidine (4), 6β-hydroxyhippeastidine (5), lycorine (6), 2-epi-lycorine (7), zephyranthine (8), ungeremine (9), pancratistatin (10) and 9-O-demethyl-7-O-methyllycorenine (11). Among the eight previously reported compounds, five were isolated from H. littoralis for the first time (compounds 4, 5, 7, 8, and 9). Compounds 1, 4, 5, 7, 8, and 11 exhibited weak anti-SARS-CoV-2 activity (EC50 = 40-77 µM) at non-cytotoxic concentrations. Assessment of cytotoxicity on the Vero-E6 cell line revealed lycorine and pancratistatin as cytotoxic substances with CC50 values of 1.2 µM and 0.13 µM, respectively. The preliminary structure-activity relationship for the lycorine-type alkaloids in this study was further investigated, and as a result ring C appears to play a crucial role in their anti-SARS-CoV-2 activity. ispartof: MOLECULES vol:28 issue:7 ispartof: location:Switzerland status: published

BACKGROUND: The presentation of mpox clade IIb during the 2022 outbreak overlaps with a range of other diseases. Understanding the factors associated with mpox is important for clinical decision making. METHODS: We described the characteristics of mpox patients who sought care at Belgian sexual health clinic. Furthermore we compared their characteristics to those of patients with a clinical suspicion of mpox but who tested negative on polymerase chain reaction. RESULTS: Between May 23 and September 20, 2022, 155 patients were diagnosed with mpox, and 51 patients with suspected symptoms tested negative. All mpox patients self-identified as men and 148/155 (95.5%) as gay or bisexual MSM. Systemic symptoms were present in 116/155 (74.8%) patients. All but 10 patients (145/155, 93.5%) presented with skin lesions. Other manifestations were lymphadenopathy (72/155, 46.5%), proctitis (50/155, 32.3%), urethritis (12/155, 7.7%), tonsillitis (2/155, 1.3%). Complications involved bacterial skin infection (13/155, 8.4%) and penile oedema with or without paraphimosis (4/155, 2.6%). In multivariable logistic regression models, the presence of lymphadenopathy (OR 3.79 95% CI 1.44-11.49), skin lesions (OR 4.35 95% CI 1.15-17.57) and proctitis (OR 9.41 95% CI 2.72-47.07) were associated with the diagnosis of mpox. There were no associations with age, HIV status, childhood smallpox vaccination, number of sexual partners and international travel. CONCLUSIONS: The presence of proctitis, lymphadenopathies and skin lesions should increase clinical suspicion of mpox in patients with compatible symptoms. ispartof: NEW MICROBES AND NEW INFECTIONS vol:52 ispartof: location:England status: published

Prolyl carboxypeptidase (PRCP) is involved in metabolic disorders by hydrolyzing anorexigenic peptides. A link between serum PRCP activity and obesity has been reported, but its origin/source is still unclear. Previously proven correlations between human serum PRCP activity and the amount of adipose tissue may suggest that adipose tissue is an important source of circulating PRCP. We investigated PRCP activity in visceral, subcutaneous adipose tissue (VAT and SCAT), skeletal muscle tissue and serum of lean and obese men with or without type 2 diabetes (T2D). Correlations between PRCP activity, metabolic and biochemical parameters and immune cell populations were assessed. PRCP activity was the highest in VAT, compared to SCAT, and was very low in skeletal muscle tissue in the overall group. Serum PRCP activity was significantly higher in T2-diabetic obese men, compared to lean and obese non-diabetic men, and was positively correlated with glycemic control. A positive correlation was observed between serum PRCP activity and VAT immune cell populations, which might indicate that circulating PRCP activity is deriving rather from the immune fraction than from adipocytes. In conclusion, PRCP activity was observed in human adipose tissue for the first time and serum PRCP activity is correlated with T2D in obese men. This research was funded by the Research Foundation Flanders (grant numbers FWO-SB 1S22417N and FWO-SBO S001017N) and by a GOA BOF 2015 grant of the University of Antwerp (No. 30729; www.uantwerp.be). Part of this work was supported by internal resources from Hasselt University. This study was financed by The Netherlands Organization for Scientific Research (NWO) (Veni 916.12.056), The Netherlands Heart Foundation (2013T143) and a Seventh Framework Program (FP7) Grant (CIG 322070). We thank University Biobank Limburg (UBiLim, Jessa Hospital, Belgium) for their technical support in sample handling and storage. Conflicts of Interest: The authors declare no conflict of interest.

Background For muscle-invasive bladder cancer (MIBC), no tissue biomarkers are available for clinical use to predict response to neoadjuvant chemotherapy. Objective To investigate how molecular subtypes impact pathological response and survival in patients receiving preoperative cisplatin-based chemotherapy. Design, setting, and participants Classification of a retrospective cohort of 149 patients was performed by tumor transcriptomic profiling and immunostaining. A cohort treated with radical cystectomy alone and public data sets were used for comparison and external validation. Outcome measurements and statistical analysis Complete pathological response in the cystectomy specimen (ypT0N0) and survival were compared in predefined molecular subtypes. Differential gene expression and chemotherapy response were explored beyond molecular subtypes. Results and limitations Patients with genomically unstable (GU) and urothelial-like (Uro) tumors had higher proportions of complete pathological response (16/31 [52%] and 17/54 [31%]), versus five out of 24 (21%) with the basal/squamous (Ba/Sq) subtype following neoadjuvant chemotherapy and radical cystectomy. Molecular subtype was independently associated with improved survival for patients with GU tumors (hazard ratio [HR] 0.29, 95% confidence interval [CI]: 0.11–0.79) and UroC tumors (HR 0.37, 95% CI: 0.14–0.94) compared with Ba/Sq tumors, adjusting for clinical stage. In addition, expression of the gene coding for osteopontin (SPP1) showed a subtype-dependent effect on chemotherapy response. Conclusions Urothelial cancer of the luminal-like (GU and Uro) subtypes is more responsive to cisplatin-based neoadjuvant chemotherapy. A second-generation of subtype-specific biomarkers, for example, SPP1, may be a way forward to develop a more precision-based treatment approach for neoadjuvant chemotherapy in MIBC. Patient summary This study shows that tumor classification by gene expression profiling and molecular subtyping can identify patients who are more likely to benefit from chemotherapy before radical cystectomy for muscle-invasive bladder cancer. Together with other markers for response, molecular subtypes could have a role in selective administration of such chemotherapy.

Trophoblast-specific expression of human leukocyte antigen G (HLA-G) induces immune tolerance for the developing fetus. Pathological HLA-G expression later in life might contribute to immune escape of various cancers. We studied the still controversial role of HLA-G in colorectal carcinoma (CRC) using the MEM-G/1 antibody and a tissue microarray series of CRC tumors (n=317). HLA-G expression appeared in 20% of the tumors and showed high intratumoral heterogeneity. HLA-G positivity was associated with better differentiation (p=0.002) and non-mucinous histology (p=0.008). However, HLA-G expression alone showed no prognostic value: 5-years disease-specific survival among patients with HLA-G expression was 68.9% (95% CI: 62.7-75.0%) compared to 74.8% (95% CI: 63.2-86.3%) among those without expression. These results support a modulatory role of HLA-G in CRC. This article is protected by copyright. All rights reserved.

Phosphorus (P) limitation is pervasive in tropical forests. Here the authors analyse the dependence of photosynthesis on leaf N and P in tropical forests, and show that incorporating leaf P constraints in a terrestrial biosphere model enhances its predictive power. Tropical forests take up more carbon (C) from the atmosphere per annum by photosynthesis than any other type of vegetation. Phosphorus (P) limitations to C uptake are paramount for tropical and subtropical forests around the globe. Yet the generality of photosynthesis-P relationships underlying these limitations are in question, and hence are not represented well in terrestrial biosphere models. Here we demonstrate the dependence of photosynthesis and underlying processes on both leaf N and P concentrations. The regulation of photosynthetic capacity by P was similar across four continents. Implementing P constraints in the ORCHIDEE-CNP model, gross photosynthesis was reduced by 36% across the tropics and subtropics relative to traditional N constraints and unlimiting leaf P. Our results provide a quantitative relationship for the P dependence for photosynthesis for the front-end of global terrestrial C models that is consistent with canopy leaf measurements.

Cancer therapy frequently fails due to the emergence of resistance. Many tumors include phenotypically immature tumor cells, which have been implicated in therapy resistance. Neuroblastoma cells can adopt a lineage-committed adrenergic (ADRN) or an immature mesenchymal (MES) state. They differ in epigenetic landscape and transcription factors, and MES cells are more resistant to chemotherapy. Here we analyzed the response of MES cells to targeted drugs. Activating anaplastic lymphoma kinase (ALK) mutations are frequently found in neuroblastoma and ALK inhibitors (ALKi) are in clinical trials. ALKi treatment of ADRN neuroblastoma cells with a tumor-driving ALK mutation induced cell death. Conversely, MES cells did not express either mutant or wild-type ALK and were resistant to ALKi, and MES cells formed tumors that progressed under ALKi therapy. In assessing the role of MES cells in relapse development, TRAIL was identified to specifically induce apoptosis in MES cells and to suppress MES tumor growth. Addition of TRAIL to ALKi treatment of neuroblastoma xenografts delayed relapses in a subset of the animals, suggesting a role for MES cells in relapse formation. While ADRN cells resembled normal embryonal neuroblasts, MES cells resembled immature precursor cells, which also lacked ALK expression. Resistance to targeted drugs can therefore be an intrinsic property of immature cancer cells based on their resemblance to developmental precursors. Significance: In neuroblastoma, mesenchymal tumor cells lack expression of the tumor-driving ALK oncogene and are resistant to ALKi, but dual treatment with ALKi and mesenchymal cell–targeting TRAIL delays tumor relapse.

Gray mold caused by Botrytis cinerea is a common postharvest disease in strawberries, reducing shelf life considerably. We investigated the potential of the yeast-like biocontrol fungus Aureobasidium pullulans (AP-SLU6) vectored by bumblebees (Bombus terrestris) in the Flying Doctors® system to inhibit the pathogen and increase the shelf life of harvested strawberries (cultivar Sonata). Using bumblebees as vectors of various biocontrol agents is becoming increasingly popular, but any potentially negative effects on bee performance have been understudied. Our results show that, over the 4-week period of the trial, the performance and activity of the bees were not negatively affected by A. pullulans. The bees successfully picked up the powder formulation; then, they carried and deposited it on the flowers. The vectoring of the biocontrol agent significantly reduced gray mold development on the harvested fruits by 45% and increased shelf life by 100% in comparison with control treatments. This suggests that the biocontrol fungus applied during flowering successfully reduced Botrytis infection and thus, effectively protected the fruits from gray mold. In addition, the bee-vectored application of the biocontrol agent was found to be significantly more effective than spray application because the latter may temporarily increase humidity around the flower, thereby creating a suitable environment for the pathogen to thrive. In summary, our study demonstrates that A. pullulans vectored by bumblebees can decrease gray mold infection and improve the shelf life of strawberries without adversely affecting the bees, thus providing a basis for the sustainable and efficient control of gray mold on strawberry. [Formula: see text] Copyright © 2022 The Author(s). This is an open access article distributed under the CC BY 4.0 International license .

Previous research suggests that everyday expressions are commonly used in students’ descriptions of nutrient uptake. This study investigate a classroom context in year 5 with a focus on signs of scientific meaning-making about nutrient uptake with an animation as a resource in two different schools. In one of the schools there was also a teacher review. The aim of this study is to investigate the pedagogical affordances of scientific terms and everyday expressions in the animation and in classroom teaching. Further, students’ signs of scientific meaning-making at the meso and submicro organizational level in group discussions and written descriptions are analyzed and if taking part of a teacher review influenced the students’ use of scientific terms and everyday expressions.The results show that the students who had a teacher review use everyday expressions at the meso and submicro level to a greater extent than the students who did not have an teacher review. The everyday expressions are often used as a kind of translation from the scientific terms in the students’ drawings.

Fresh-market tomatoes are produced on a raised-bed plasticulture system that relies heavily on soil-applied preplant fumigants for the management of soilborne pathogens, nematodes, and weeds. Since the transition from methyl bromide to alternative fumigants, growers have experienced a resurgence of several soilborne pests and pathogens, including root-knot nematode caused by Meloidogyne spp. and Fusarium wilt caused by Fusarium oxysporum f. sp. lycopersici race 3. This resurgence is attributed to the inability of the alternative fumigants to effectively disperse through the soil in the same manner as methyl bromide. Two supplemental fumigation strategies, the application of chloropicrin (PIC) below bed edges (herein “supplemental PIC”) and broadcast deep-shank applications of 1,3-dichloropropene (1,3-D), were evaluated in conjunction with standard raised-bed applications of Pic-Clor 60, Pic-Clor 80, and Pic 100 covered with a virtually impermeable film or a totally impermeable film. Large-plot replicated studies were conducted in two separate commercial tomato fields with a history of production losses caused by root-knot nematode and Fusarium wilt. Deep-shank 1,3-D applications significantly reduced the recovery of root-knot and total parasitic nematodes across field sites before the preparation of raised beds. Both supplemental PIC and deep-shank 1,3-D reduced root-knot galling and Fusarium wilt incidence, but the latter supplemental treatment statistically had the greatest impact. Fumigant applied within raised beds or plastic film had no significant effect on root-knot galling or Fusarium wilt. Although both supplemental fumigation strategies had a significant effect on pest and disease pressure, neither statistically improved tomato yields based on small subplot harvests. Controlled laboratory experiments confirmed the fungicidal activity of 1,3-D against F. oxysporum f. sp. lycopersici, with 75, 90, 95, and 99% lethal doses corresponding to estimated field application rates of 56.1, 93.5, 121.6, and 184.7 liters/ha, respectively. The results demonstrate how fumigant placement can improve pest and disease control activity with current fumigant alternatives to methyl bromide and further support the broader pesticidal activity of some chemical fumigants.

Objectives Mortality among patients with carbapenem-resistant Acinetobacter baumannii (CRAB) infections varies between studies. We examined whether in vivo fitness of CRAB strains is associated with clinical outcomes in patients with CRAB infections. Methods Isolates were collected from patients enrolled in the AIDA trial with hospital-acquired pneumonia, bloodstream infections and/or urinary tract infections caused by CRAB. The primary outcome was 14-day clinical failure, defined as failure to meet all criteria: alive; haemodynamically stable; improved or stable Sequential Organ Failure Assessment (SOFA) score; improved or stable oxygenation; and microbiological cure of bacteraemia. The secondary outcome was 14-day mortality. We tested in vivo growth using a neutropenic murine thigh infection model. Fitness was defined based on the CFU count 24 hours after injection of an inoculum of 105 CFU. We used mixed-effects logistic regression to test the association between fitness and the two outcomes. Results The sample included 266 patients; 215 (80.8%) experienced clinical failure. CRAB fitness ranged from 5.23 to 10.08 log CFU/g. The odds of clinical failure increased by 62% for every 1-log CFU/g increase in fitness (OR 1.62, 95% CI 1.04–2.52). After adjusting for age, Charlson score, SOFA score and acquisition in the intensive care unit, fitness remained significant (adjusted OR 1.63, 95% CI 1.03–2.59). CRAB fitness had a similar effect on 14-day mortailty, although the association was not statistically significant (OR 1.56, 95% CI 0.95–2.57). It became significant after adjusting for age, Charlson score, SOFA score and recent surgery (adjusted OR 1.88, 95% CI 1.09–3.25). Conclusions In vivo CRAB fitness was associated with clinical failure in patients with CRAB infection.

5 fluorouracil (5FU), an antineoplastic drug, is often utilized in the therapeutic regimen for several types of cancer, including the hepatoblastoma in children. The effects of 5FU on the population of ovarian preantral follicles, which is the largest oocyte reservoir, is still poorly understood. The integrity of the ovarian preantral follicle pool is important for lifelong fertility. The better understanding of such effects may favor intervention strategies to protect fertility in 5FU-treated children and women coping with cancer. To analyze the effects of 5FU on isolated murine secondary follicles in vitro, ovaries were collected from young mice (28-30 days old), and secondary follicles were isolated and cultured for 12 days in basic culture medium, with or without 5FU at concentrations of 0.3 mM, 1 mM, 3 mM, 10 mM, and 30 mM. In the in vitro study, we analyzed the percentage of morphologically normal follicles, antrum formation, follicular diameter, and hormone production. On day 12, oocytes were recovered for in vitro maturation. 5FU treatment did not alter the percentage of morphologically normal follicles. On day 12, only 1, 10, and 30 mM 5FU significantly reduced the percentage of antrum. From day 4 onwards, 5FU treatments significantly reduced follicle diameter. The meiosis resumption rate was significantly lower in all 5FU treatments. 5FU concentrations ≥3 mM reduced estradiol levels. In conclusion, 5FU does not affect follicular morphology. However, 5FU deleteriously affects follicular growth, estradiol production, and oocyte maturation in isolated ovarian follicles.

In this study, we investigated the variation in the microbial community present in bulk tank milk samples and the potential effect of different farm management factors. Bulk tank milk samples were collected repeatedly over one year from 42 farms located in northern Sweden. Total and thermoresistant bacteria counts and 16S rRNA gene-based amplicon sequencing were used to characterize microbial community composition. The microbial community was in general heterogeneous both within and between different farms and the community composition in the bulk tank milk was commonly dominated by Pseudomonas, Acinetobacter, Streptococcus, unclassified Peptostreptococcaceae, and Staphylococcus. Principal component analysis including farm factor variables and microbial taxa data revealed that the microbial community in milk was affected by type of milking system. Milk from farms using an automatic (robot) milking system (AMS) and loose housing showed different microbial community composition compared with milk from tiestall farms. A discriminant analysis model revealed that this difference was dependent on several microbial taxa. Among farms using an automatic milking system, there were further differences in the microbial community composition depending on the brand of the milking robot used. On tiestall farms, routines for teat preparation and cleaning of the milking equipment affected the microbial community composition in milk. Total bacteria count (TBC) in milk differed between the farm types, and TBC were higher on AMS than tiestall farms (log 4.05 vs. log 3.79 TBC/mL for AMS and tiestalls, respectively). Among tiestall farms, milk from farms using a chemical agent in connection to teat preparation and a more frequent use of acid to clean the milking equipment had lower TBC in milk, than milk from farms using water for teat preparation and a less frequent use of acid to clean the milking equipment (log 3.68 vs. 4.02 TBC/mL). There were no significant differences in the number of thermoresistant bacteria between farm types. The evaluated factors explained only a small proportion of total variation in the microbiota data, however, despite this, the study highlights the effect of routines associated with teat preparation and cleaning of the milking equipment on raw milk microbiota, irrespective of type of milking system used.

This study was conducted to estimate the apparent digestibility coefficients (ADC) of the nutrients and energy contained in banana peel, cassava peel, cocoa husk, copra waste, and sugarcane bagasse in GIFT Nile tilapia (initial body weight 22.38 ± 0.33 g). A reference diet was formulated to satisfy the nutrient requirement of the fish. Five test diets were formulated to contain 70% of the reference diet and 30% of each test ingredient. The experiment lasted 42 days. The ADCs of dry matter (DM), crude lipid (CL), ash, crude fiber (CF), total carbohydrate (TC), and gross energy (GE) were 16.19%, 6.56%, 11.40%, 38.98% and 15.68% for banana peel; the ADCs of DM, crude protein (CP), CL, ash, CF, TC, and GE were 69.11%, 31.61%, 61.07%, 68.88%, 73.14%, 71.24%, and 69.00% for cassava peel; the ADCs of DM, ash, CF, TC, and GE were 10.56%, 0.84%, 28.70%, 2.82%, and 8.459.69% for cocoa husk; the ADCs of DM, CP, CL, ash, CF, TC, and GE were 63.08%, 20.14%, 66.60%, 32.53%, 69.70%, 66.21%, and 64.06% for copra waste; and the ADCs of DM, CF, TC, and GE were 15.22%, 36.71%, 34.34%, and 15.55% for sugarcane bagasse in tilapia respectively. This experiment generated basic information for the use of these ingredients in diet formulation for tilapia. However, considering the relatively low ADCs of nutrients observed in the present experiment, further processing could be an interesting avenue in improving the nutritional value and digestibility of these ingredients.

Plants produce many secondary metabolites showing considerable inter- and intraspecific diversity of concentration and composition as a strategy to cope with environmental stresses. The evolution of plant defenses against herbivores and pathogens can be unraveled by understanding the mechanisms underlying chemical diversity. Pyrrolizidine alkaloids are a class of secondary metabolites with high diversity. We performed a qualitative and quantitative analysis of 80 pyrrolizidine alkaloids with liquid chromatography-tandem mass spectrometry of leaves from 17 Jacobaea species including one to three populations per species with 4–10 individuals per population grown under controlled conditions in a climate chamber. We observed large inter- and intraspecific variation in pyrrolizidine alkaloid concentration and composition, which were both species-specific. Furthermore, we sequenced 11 plastid and three nuclear regions to reconstruct the phylogeny of the 17 Jacobaea species. Ancestral state reconstruction at the species level showed mainly random distributions of individual pyrrolizidine alkaloids. We found little evidence for phylogenetic signals, as nine out of 80 pyrrolizidine alkaloids showed a significant phylogenetic signal for Pagel's λ statistics only, whereas no significance was detected for Blomberg's K measure. We speculate that this high pyrrolizidine alkaloid diversity is the result of the upregulation and downregulation of specific pyrrolizidine alkaloids depending on ecological needs rather than gains and losses of particular pyrrolizidine alkaloid biosynthesis genes during evolution.

The reuse of construction components is considered as a higher value process in a Circular Economy (CE) than recycling. However, this is not yet widely adopted as many barriers still prevent the successful integration of the concept. The ISO20887 standard advocates that the implementation of construction standards will benefit circular reuse. Yet, these standards still need to be developed. To better understand the views of the construction sector, a survey was sent to the network of the Green Deal on Circular Construction (GDCC), led by Circular Flanders. The survey (number of recipients = 629, response rate = 16%) investigates the current implementation of Design for Disassembly and the reuse of construction components. Additionally, it investigates the respondents’ view on how a further morphological standardisation of components and connections, as well as standardisation of procedures can facilitate this reuse of construction components. The result is a concrete set of action points and corresponding actors who need to take responsibility. The stakeholders point out that there is no legal framework for component reuse. Yet, this framework can only be created through their largescale cooperation to create the needed construction standards that will truly enable the circular reuse of components.

Soil life supports the functioning and biodiversity of terrestrial ecosystems. Springtails (Collembola) are among the most abundant soil arthropods regulating soil fertility and flow of energy through above- and belowground food webs. However, the global distribution of springtail diversity and density, and how these relate to energy fluxes remains unknown. Here, using a global dataset representing 2470 sites, we estimate the total soil springtail biomass at 27.5 megatons carbon, which is threefold higher than wild terrestrial vertebrates, and record peak densities up to 2 million individuals per square meter in the tundra. Despite a 20-fold biomass difference between the tundra and the tropics, springtail energy use (community metabolism) remains similar across the latitudinal gradient, owing to the changes in temperature with latitude. Neither springtail density nor community metabolism is predicted by local species richness, which is high in the tropics, but comparably high in some temperate forests and even tundra. Changes in springtail activity may emerge from latitudinal gradients in temperature, predation and resource limitation in soil communities. Contrasting relationships of biomass, diversity and activity of springtail communities with temperature suggest that climate warming will alter fundamental soil biodiversity metrics in different directions, potentially restructuring terrestrial food webs and affecting soil functioning. The article is an outcome of the #GlobalCollembola community initiative that is voluntarily supported by researchers around the world. Data collection and analysis was supported by the Russian Science Foundation (19-74-00154 to A.P.) and by Deutsche Forschungsgemeinschaft (493345801 to A.P. and 192626868—SFB 990 to S.S.). We acknowledge support by the Open Access Publication Funds of the Göttingen University. The following funding bodies provided support for individual contributors: ARC SRIEAS Grant SR200100005 Securing Antarctica’s Environmental Future to S.L.C., Slovak Scientific Grant Agency VEGA 1/0438/22 to Ľ.K., RFBR 19-516-60002 to N.A.K., Carl Tryggers Stiftelse för Vetenskaplig Forskning and Qatar Petroleum to J.M.A., BIO 27 (2013-2014)-MAGyP and PICTO 2084 (2012)-ANPCyT to V.B., DAAD-19-10 and MSM200962001 to T.C., grant TE, PN-III-P1-1.1-TE-2019-0358 to C.F., NWO grant 821.01.015 to O.F., National Natural Sciences Foundation of China No 41471037 and 41871042 to M.G., BIO 27 (2013-2014), MAGyP; PICT 2084 (2012), FONCyT to D.F.G., NRF South African National Antarctic Programme grant 110734 to M.G., Natural Resources Canada (NRCan), EcoEnergy Innovation Initiative under the Office of Energy Research and Development, and the Natural Sciences and Engineering Research Council of Canada (NSERC) to I.T.H., L.A.V. and L.R., Independent Research Fund Denmark grant no. DFF-4002-00384 to M.H., Estonian Science Foundation G9145 to M.I., SA-France bilateral grant to C.J., SA (NRF)/Russia (RFBR) Joint Science and Technology Research Collaboration project no. 19-516-60002 (FRBR) and no. 118904 (NRF) to M.P. and C.J., European Research Council (ERC), European Union’s Horizon 2020 research and innovation programme (grant agreement no. 677232; to N.E.); iDiv, German Research Foundation (DFG–FZT 118, 202548816) to M.J. and N.E., French National Agency of Research (ANR) (JASSUR research project; ANR-12-VBDU-0011), «Ministère de l’Agriculture et de la Pêche» and «Ministère de l’Education Nationale de la Recherche et de la Technologie» (ACTA programme), «Ministère de l’Aménagement du Territoire et de l’Environnement» (Pnetox programme), EU-funded project, ECOGEN QLK5-CT-2002-01666 (www.ecogen.dk), “Agence de l’Environnement et de la Maîtrise de l'Énergie” (BIOINDICATEUR 2, BIOTECHNOSOL), ANDRA and GISFI (www.gisfi.fr) to S.J., GRR SER-BIODIV (Région Normandie, France) to MCha, ESF9258, B02 to A.K., Fundamental Research Funds for the Central Universities (grant no. 2018CDXYCH0014) to D.L., DFG 316045089 to J.L., Massey University Research Fund grant to M.A.M., DFG SCHE 376/38-2 to M.M.P., grant from the Austria Academy of Science: Heritage_2020-043_Modeling-Museum to P.Q., Slovak Scientific Grant Agency: VEGA Nos. 1/0441/03 and 1/3267/06 to N.R., Higher Education Commission of Pakistan to M.I.R., RSF 21-74-00126 to R.A.S., Austrian Federal Government and European Union (Rural Development 2014-2020) to J.S., АААА-А17-122040600025-2 to A.A.T., Brazilian Council for Scientific and Technological Development—CNPq (grant no. 152717/2016-1) to B.R.W., 309030/2018-8 to D.Z. and 305426/2018-4 to B.C.B., National Natural Science Foundation of China (31970434, 31772491) to N.N.G., Research and Innovation Support Foundation of Santa Catarina (FAPESC) (6.309/2011-6/FAPESC) and the CNPq (563251/2010-7/CNPq) to L.C.I.O.F., O.K.-F., the Latvian Council of Science Grants no. 90.108, 93.140, 96.0110, 01.0344 to E.J., CNPq for the Research Productivity Grant (305939/2018-1) to D.B., FPI-MICINN grant in the project INTERCAPA (CGL2014-56739-R) to P.H, the Natural Sciences and Engineering Research Council of Canada (NSERC) to Z.L., Ministry of Innovation and Technology of Hungary TKP2021-NKTA-43 to D.W. Authors are grateful to Penelope Greenslade for providing the literature on Australian Collembola communities. Authors are grateful to Frans Janssens for providing the global checklist of Collembola.

Oxyhydroxides, soil texture and soil organic carbon (SOC) fractions are key parameters determining organic carbon cycling in soils. Standard laboratory methods to determine these soil properties are, however, time --consuming and expensive. Visible near infrared (Vis-NIR) and mid infrared (MIR) spectroscopy have been recognized as a promising alternative, but previous studies have not explicitly considered the above-mentioned soil properties as compositional data. The fractional components in compositional data are interrelated but their sum should be unity - these features should be represented in the spectral modeling process to minimize the prediction bias. In this study, two unique datasets were used to test these premises. The first one consisted of 655 samples collected from agricultural terraces and lynchets across Europe, which were scanned to acquire MIR spectra, while in the second one 4516 samples from private gardens across Flanders, Belgium were used to acquire Vis-NIR spectra. Memory-based learning models were optimized using both raw data (conventional method) and transformed data of soil properties by additive log-ratio (alr), centered log-ratio (clr), and isometric log-ratio (ilr) transformation methods. Results showed that the log-ratio transformation methods produced predictions as accurate as the conventional method, whilst also added two significant benefits: (1) they ensured the predicted fractions added up to 100% and (2) they reduced the number of samples with extreme prediction errors. We found that for 11 out of 18 investigated soil properties, the three log-ratio transformation methods provided similar model performance, whilst ilr outperformed clr for the prediction of silt and sand content of garden soils, for coarse particulate SOC (>250 mu m) and microaggregate-associated SOC (250-53 mu m) of terrace soils. For the remaining three properties (Al oxyhydroxides) alr outperformed ilr. Fair to excellent predictive models (RPD from 1.4 to 4.3; R2 from 0.50 to 0.95) were achieved for soil oxyhydroxides (Fe, Al, Mn) and soil texture from MIR spectra. Our approach also enabled accurate predictions of silt and sand content of garden soils using Vis-NIR spectra (RPD = 1.9; R2 = 0.72), although accuracy for clay was lower (RPD = 1.3; R2 = 0.49). This study demonstrates that combining soil infrared spectroscopy with a compositional data analysis is a promising technique that enables cost-effective and reliable quantification of soil properties relevant to SOC stability, thus offering a practical opportunity to assess the role of SOC in global C cycling.

Oligodendrocyte-lineage cells of patients and animal models undergo prominent changes in various neurodegenerative disorders. This raises the question of how myelinating cells interact with neurodegenerative processes. Here, we investigated the role of oligodendrocyte precursor cells (NG2 glia) in prion infections. We found that NG2 glia were activated in prion-infected cerebellar organotypic cultured slices (COCS) and in brains of prion-inoculated mice. In both model systems, depletion of NG2 glia exacerbated prion-induced neurodegeneration and accelerated prion pathology, suggesting a protective effect for NG2 glia. Loss of NG2 glia unleashed a microglial reaction promoting the biosynthesis of prostaglandin E2 (PGE2), which augmented prion toxicity in HovS cells and COCS through binding to the EP1 and EP4 receptors. Pharmacological or genetic inhibition of PGE2 biosynthesis attenuated prion-induced neurodegeneration in COCS and mice, antagonized the enhanced neurodegeneration in NG2 glia-depleted COCS and brains after prion infection, and dampened the acceleration of prion disease in NG2 glia-depleted mice. These data unveil a non-cell-autonomous interaction involving NG2 glia and microglia in prion disease and suggest that PGE2 signaling may represent an actionable target against prion diseases.