Cleavage of caspases-1, -3, -6, -8 and -9 substrates by proteases in skeletal muscles from mice undergoing cancer cachexia

A prominent feature of several type of cancer is cachexia. This syndrome causes a marked loss of lean body mass and muscle wasting, and appears to be mediated by cytokines and tumour products. There are several proteases and proteolytic pathways that could be responsible for the protein breakdown. In the present study, we investigated whether caspases are involved in the proteolytic process of skeletal muscle catabolism observed in a murine model of cancer cachexia (MAC16), in comparison with a related tumour (MAC13), which does not induce cachexia. Using specific peptide substrates, there was an increase of 54% in the proteolytic activity of caspase-1, 84% of caspase-8, 98% of caspase-3 151% to caspase-6 and 177% of caspase-9, in the gastrocnemius muscle of animals bearing the MAC16 tumour (up to 25% weight loss), in relation to muscle from animals bearing the MAC13 tumour (1–5% weight loss). The dual pattern of 89 kDa and 25 kDa fragmentation of poly (ADP-ribose) polymerase (PARP) occurred in the muscle samples from animals bearing the MAC16 tumour and with a high amount of caspase-like activity. Cytochrome c was present in the cytosolic fractions of gastrocnemius muscles from both groups of animals, suggesting that cytochrome c release from mitochondria may be involved in caspase activation. There was no evidence for DNA fragmentation into a nucleosomal ladder typical of apoptosis in the muscles of either group of mice. This data supports a role for caspases in the catabolic events in muscle involved in the cancer cachexia syndrome. © 2001 Cancer Research Campaign http://www.bjcancer.co

Surface magnetism in ZnO/Co3O4 mixtures

We recently reported the observation of room temperature ferromagnetism in mixtures of ZnO and Co3O4 despite the diamagnetic and antiferromagnetic character of these oxides respectively. Here we present a detailed study on the electronic structure of this material in order to account for this unexpected ferromagnetism. Electrostatic interactions between both oxides lead to a dispersion of Co3O4 particles over the surface of ZnO larger ones. As a consequence, the reduction of Co+3 to Co2+ at the particle surface takes place as evidenced by XAS measurements and optical spectrocopy. This reduction allows to xplain the observed ferromagnetic signal within the well established theories of magnetism.Comment: Accepted in Journal of Applied Physic

Global maps of soil temperature

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 Pa

Insights into the room temperature magnetism of ZnO/Co3O4 mixtures

The origin of room temperature (RT) ferromagneticlike behavior in ZnO-based diluted magnetic semiconductors is still an unclear topic. The present work concentrates on the appearance of RT magnetic moments in just mixed ZnO/Co3O4 mixtures without thermal treatment. In this study, it is shown that the magnetism seems to be related to surface reduction of the Co3O4 nanoparticles, in which, an antiferromagnetic Co3O4 nanoparticle (core) is surrounded by a CoO-like shell. This singular superficial magnetism has also been found in other mixtures with semiconductors such as TiO2 and insulators such as Al2O3

Activation of ATP-ubiquitin-dependent proteolysis in skeletal muscle in vivo and murine myoblasts in vitro by a proteolysis-inducing factor (PIF)

Loss of skeletal muscle is a major factor in the poor survival of patients with cancer cachexia. This study examines the mechanism of catabolism of skeletal muscle by a tumour product, proteolysis-inducing factor (PIF). Intravenous administration of PIF to normal mice produced a rapid decrease in body weight (1.55 ± 0.12 g in 24 h) that was accompanied by increased mRNA levels for ubiquitin, the Mr 14 000 ubiquitin carrier-protein, E2, and the C9 proteasome subunit in gastrocnemius muscle. There was also increased protein levels of the 20S proteasome core and 19S regulatory subunit, detectable by immunoblotting, suggesting activation of the ATP-ubiquitin-dependent proteolytic pathway. An increased protein catabolism was also seen in C2C12 myoblasts within 24 h of PIF addition with a bell-shaped dose–response curve and a maximal effect at 2–4 nM. The enhanced protein degradation was attenuated by anti-PIF antibody and by the proteasome inhibitors MG115 and lactacystin. Glycerol gradient analysis of proteasomes from PIF-treated cells showed an elevation in chymotrypsin-like activity, while Western analysis showed a dose-related increase in expression of MSSI, an ATPase that is a regulatory subunit of the proteasome, with a dose–response curve similar to that for protein degradation. These results confirm that PIF acts directly to stimulate the proteasome pathway in muscle cells and may play a pivotal role in protein catabolism in cancer cachexia. © 2001 Cancer Research Campaign http://www.bjcancer.co