Human cytomegalovirus immediate-early 1 protein rewires upstream STAT3 to downstream STAT1 signaling switching an IL6-type to an IFNγ-like response

MN and CP were supported by the Wellcome Trust (www.wellcome.ac.uk) Institutional Strategic Support Fund and CP was supported by the Deutsche Forschungsgemeinschaft (PA 815/2-1; www.dfg.de).The human cytomegalovirus (hCMV) major immediate-early 1 protein (IE1) is best known for activating transcription to facilitate viral replication. Here we present transcriptome data indicating that IE1 is as significant a repressor as it is an activator of host gene expression. Human cells induced to express IE1 exhibit global repression of IL6- and oncostatin M-responsive STAT3 target genes. This repression is followed by STAT1 phosphorylation and activation of STAT1 target genes normally induced by IFNγ. The observed repression and subsequent activation are both mediated through the same region (amino acids 410 to 445) in the C-terminal domain of IE1, and this region serves as a binding site for STAT3. Depletion of STAT3 phenocopies the STAT1-dependent IFNγ-like response to IE1. In contrast, depletion of the IL6 receptor (IL6ST) or the STAT kinase JAK1 prevents this response. Accordingly, treatment with IL6 leads to prolonged STAT1 instead of STAT3 activation in wild-type IE1 expressing cells, but not in cells expressing a mutant protein (IE1dl410-420) deficient for STAT3 binding. A very similar STAT1-directed response to IL6 is also present in cells infected with a wild-type or revertant hCMV, but not an IE1dl410-420 mutant virus, and this response results in restricted viral replication. We conclude that IE1 is sufficient and necessary to rewire upstream IL6-type to downstream IFNγ-like signaling, two pathways linked to opposing actions, resulting in repressed STAT3- and activated STAT1-responsive genes. These findings relate transcriptional repressor and activator functions of IE1 and suggest unexpected outcomes relevant to viral pathogenesis in response to cytokines or growth factors that signal through the IL6ST-JAK1-STAT3 axis in hCMV-infected cells. Our results also reveal that IE1, a protein considered to be a key activator of the hCMV productive cycle, has an unanticipated role in tempering viral replication.Publisher PDFPeer reviewe

A spontaneous ad hoc network to share www access

In this paper, we propose a secure spontaneous ad-hoc network, based on direct peer-to-peer interaction, to grant a quick, easy, and secure access to the users to surf the Web. The paper shows the description of our proposal, the procedure of the nodes involved in the system, the security algorithms implemented, and the designed messages. We have taken into account the security and its performance. Although some people have defined and described the main features of spontaneous ad-hoc networks, nobody has published any design and simulation until today. Spontaneous networking will enable a more natural form of wireless computing when people physically meet in the real world. We also validate the success of our proposal through several simulations and comparisons with a regular architecture, taking into account the optimization of the resources of the devices. Finally, we compare our proposal with other caching techniques published in the related literature. The proposal has been developed with the main objective of improving the communication and integration between different study centers of low-resource communities. That is, it lets communicate spontaneous networks, which are working collaboratively and which have been created on different physical places.Authors want to give thanks to the anonymous reviewers for their valuable suggestions, useful comments, and proofreading of this paper. This work was partially supported by the Ministerio de Educacion y Ciencia, Spain, under Grant no. TIN2008-06441-C02-01, and by the "Ayudas complementarias para proyectos de I+D para grupos de calidad de la Generalitat Valenciana" (ACOMP/2010/005).Lacuesta Gilaberte, R.; Lloret, J.; García Pineda, M.; Peñalver Herrero, ML. (2010). A spontaneous ad hoc network to share www access. EURASIP Journal on Wireless Communications and Networking. 2010:1-16. https://doi.org/10.1155/2010/232083S1162010Preuß S, Cap CH: Overview of spontaneous networking-evolving concepts and technologies. In Rostocker Informatik-Berichte. Volume 24. Fachbereich Informatik der Universit at Rostock; 2000:113-123.Gallo S, Galluccio L, Morabito G, Palazzo S: Rapid and energy efficient neighbor discovery for spontaneous networks. Proceedings of the 7th ACM International Symposium on Modeling, Analysis and Simulation of Wireless and Mobile Systems, October 2004, Venice, ItalyLatvakoski J, Pakkala D, Pääkkönen P: A communication architecture for spontaneous systems. IEEE Wireless Communications 2004, 11(3):36-42. 10.1109/MWC.2004.1308947Zarate Silva VH, De Cruz Salgado EI, Quintana FR: AWISPA: an awareness framework for collaborative spontaneous networks. Proceedings of the 36th ASEE/IEEE Frontiers in Education Conference (FIE '06), October 2006 1-6.Feeney LM, Ahlgren B, Westerlund A: Spontaneous networking: an application-oriented approach to ad hoc networking. IEEE Communications Magazine 2001, 39(6):176-181. 10.1109/35.925687Perkins CE, Bhagwat P: Highly dynamic destination-sequenced distance-vector routing (DSDV) for mobile computers. Proceedings of the Conference on Communications Architectures, Protocols and Applications (SIGCOMM '94), August 1994 234-244.Johnson DB, Maltz DA, Broch J: DSR: The Dynamic Source Routing Protocol for Multihop Wireless Ad Hoc Networks, Ad Hoc Networking. Addison-Wesley Longman Publishing, Boston, Mass, USA; 2001.Perkins C, Belding-Royer E, Das S: Ad hoc on-demand distance vector (AODV) routing. RFC 3561, July 2003Park V, Corson MS: IETF MANET Internet Draft "draft-ietf-MANET-tora-spe03.txt". 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Proceedings of the International Conference on Emerging Security Information, Systems and Technologies (SECURWARE '07), October 2007, Valencia, SpainFoulks EF: Social network therapies and society: an overview. Contemporary Family Therapy 1985, 3(4):316-320.Wang Y, Wu H: DFT-MSN: the delay/fault-tolerant mobile sensor network for pervasive information gathering. Proceedings of the 25th IEEE International Conference on Computer Communications (INFOCOM '06), April 2006Kindberg T, Zhang K: Validating and securing spontaneous associations between wireless devices. In Proceedings of the 6th Information Security Conference (ISC '03), 2003. Springer; 44-53.Al-Jaroodi J: Routing security in open/dynamic mobile ad hoc networks. The International Arab Journal of Information Technology 2007, 4(1):17-25.Stajano F, Anderson RJ: The resurrecting duckling: security issues for ad-hoc wireless networks. Proceedings of the 7th International Workshop on Security Protocols, April 1999 172-194.Zhou L, Haas ZJ: Securing ad hoc networks. IEEE Network 1999, 13(6):24-30. 10.1109/65.806983Hauspie M, Simplot-Ryl I: Cooperation in ad hoc networks: enhancing the virtual currency based models. Proceedings of the 1st International Conference on Integrated Internet Ad Hoc and Sensor Networks (InterSense '06), May 2006, Nice, FranceWang X, Dai F, Qian L, Dong H: A way to solve the threat of selfish and malicious nodes for ad hoc networks. Proceedings of the International Symposium on Information Science and Engieering (ISISE '08), December 2008, Shanghai, China 1: 368-370.Kargl F, Klenk A, Weber M, Schlott S: Sensors for detection of misbehaving nodes in MANETs. Detection of Intrusion and Malware and Vulnerability Assessment (DIMVA '04), July 2004, Dortmund, Germany 83-97.Kargl F, Geiss A, Scholott S, Weber M: Secure dynamic source routing. Proceedings of the 38th Annual Hawaii International Conference on System Sciences (HICSS '05), January 2005, Big Island, Hawaii, USAGokhale S, Dasgupta P: Distributed authentication for peer-to-peer networks. Proceedings of the Symposium on Applications and the Internet Workshops, January 2003 347-353.Capkun S, Buttyán L, Hubaux J-P: Self-organized public-key management for mobile ad hoc networks. IEEE Transactions on Mobile Computing 2003, 2(1):52-64. 10.1109/TMC.2003.1195151Stajano F, Anderson R: The resurrecting duckling security issues for ad-hoc wireless networks. In Proceedings of the 7th International Workshop on Security Protocols, 1999, Berlin, Germany, Lecture Notes in Computer Science. Volume 1796. Springer; 172-194.Balfanz D, Smetters DK, Stewart P, Wong HC: Talking to strangers: authentication in ad-hoc wireless networks. Proceedings of the International Symposium on Network and Distributed Systems Security (NDSS '02), February 2002, San Diego, Calif, USABarbara D, Imielinski T: Sleepers and workaholics: caching strategies in mobile environments. Proceedings of the ACM SIGMOD International Conference on Management of Data, May 1994 1-12.Cao G: A scalable low-latency cache invalidation strategy for mobile environments. IEEE Transactions on Knowledge and Data Engineering 2003, 15(5):1251-1265. 10.1109/TKDE.2003.1232276Hu Q, Lee D: Cache algorithms based on adaptive invalidation reports for mobile environments. Cluster Computing 1998, 1(1):39-50. 10.1023/A:1019012927328Jing J, Elmagarmid A, Helal A, Alonso R: Bit-sequences: an adaptive cache invalidation method in mobile client/server environments. Mobile Networks and Applications 1997, 2(2):115-127. 10.1023/A:1013616213333Kahol A, Khurana S, Gupta S, Srimani P: An efficient cache management scheme for mobile environment. 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IEEE Transactions on Mobile Computing 2005, 4(1):68-83.Wessels D, Claffy K: Internet cache protocol (IC) v.2. http://www.ietf.org/rfc/rfc2186.txtFan L, Cao P, Almeida J, Broder AZ: Summary cache: a scalable wide-area web cache sharing protocol. IEEE/ACM Transactions on Networking 2000, 8(3):281-293. 10.1109/90.851975Dykes SG, Robbins KA: A viability analysis of cooperative proxy caching. Proceedings of the 20th Annual Joint Conference of the IEEE Computer and Communications Societies (INFOCOM '01), April 2001, Anchorage, Alaska, USA 3: 1205-1214.Wessels D, Claffy K: RFC 2186: Internet cache protocol (ICP), version 2. The Internet Engineering Taskforce, September 1997Wessels D, Claffy K: RFC 2187: application of internet cache protocol (ICP), version 2. The Internet Engineering Taskforce, September 1997Ren Q, Dunhan MH: Using semantic caching to manage location dependent data in mobile computing. 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P2RX7 Purinoceptor: A Therapeutic Target for Ameliorating the Symptoms of Duchenne Muscular Dystrophy

open access articleDuchenne muscular dystrophy (DMD) is the most common inherited muscle disease, leading to severe disability and death in young men. Death is caused by the progressive degeneration of striated muscles aggravated by sterile inflammation. The pleiotropic effects of the mutant gene also include cognitive and behavioral impairments and low bone density. Current interventions in DMD are palliative only as no treatment improves the long-term outcome. Therefore, approaches with a translational potential should be investigated, and key abnormalities downstream from the absence of the DMD product, dystrophin, appear to be strong therapeutic targets. We and others have demonstrated that DMD mutations alter ATP signaling and have identified P2RX7 purinoceptor up-regulation as being responsible for the death of muscles in the mdx mouse model of DMD and human DMD lymphoblasts. Moreover, the ATP–P2RX7 axis, being a crucial activator of innate immune responses, can contribute to DMD pathology by stimulating chronic inflammation. We investigated whether ablation of P2RX7 attenuates the DMD model mouse phenotype to assess receptor suitability as a therapeutic target

A global experiment on motivating social distancing during the COVID-19 pandemic

Finding communication strategies that effectively motivate social distancing continues to be a global public health priority during the COVID-19 pandemic. This crosscountry, preregistered experiment (n = 25,718 from 89 countries) tested hypotheses concerning generalizable positive and negative outcomes of social distancing messages that promoted personal agency and reflective choices (i.e., an autonomy-supportive message) or were restrictive and shaming (i.e., a controlling message) compared with no message at all. Results partially supported experimental hypotheses in that the controlling message increased controlled motivation (a poorly internalized form of motivation relying on shame, guilt, and fear of social consequences) relative to no message. On the other hand, the autonomy-supportive message lowered feelings of defiance compared with the controlling message, but the controlling message did not differ from receiving no message at all. Unexpectedly, messages did not influence autonomous motivation (a highly internalized form of motivation relying on one's core values) or behavioral intentions. Results supported hypothesized associations between people's existing autonomous and controlled motivations and self-reported behavioral intentions to engage in social distancing. Controlled motivation was associated with more defiance and less long-term behavioral intention to engage in social distancing, whereas autonomous motivation was associated with less defiance and more short- and long-term intentions to social distance. Overall, this work highlights the potential harm of using shaming and pressuring language in public health communication, with implications for the current and future global health challenges

A global experiment on motivating social distancing during the COVID-19 pandemic

Significance Communicating in ways that motivate engagement in social distancing remains a critical global public health priority during the COVID-19 pandemic. This study tested motivational qualities of messages about social distancing (those that promoted choice and agency vs. those that were forceful and shaming) in 25,718 people in 89 countries. The autonomy-supportive message decreased feelings of defying social distancing recommendations relative to the controlling message, and the controlling message increased controlled motivation, a less effective form of motivation, relative to no message. Message type did not impact intentions to socially distance, but people’s existing motivations were related to intentions. Findings were generalizable across a geographically diverse sample and may inform public health communication strategies in this and future global health emergencies. Abstract Finding communication strategies that effectively motivate social distancing continues to be a global public health priority during the COVID-19 pandemic. This cross-country, preregistered experiment (n = 25,718 from 89 countries) tested hypotheses concerning generalizable positive and negative outcomes of social distancing messages that promoted personal agency and reflective choices (i.e., an autonomy-supportive message) or were restrictive and shaming (i.e., a controlling message) compared with no message at all. Results partially supported experimental hypotheses in that the controlling message increased controlled motivation (a poorly internalized form of motivation relying on shame, guilt, and fear of social consequences) relative to no message. On the other hand, the autonomy-supportive message lowered feelings of defiance compared with the controlling message, but the controlling message did not differ from receiving no message at all. Unexpectedly, messages did not influence autonomous motivation (a highly internalized form of motivation relying on one’s core values) or behavioral intentions. Results supported hypothesized associations between people’s existing autonomous and controlled motivations and self-reported behavioral intentions to engage in social distancing. Controlled motivation was associated with more defiance and less long-term behavioral intention to engage in social distancing, whereas autonomous motivation was associated with less defiance and more short- and long-term intentions to social distance. Overall, this work highlights the potential harm of using shaming and pressuring language in public health communication, with implications for the current and future global health challenges

Diagnostic difficulties with central nervous system actinomycosis

When faced with expanding brain lesions of unknown origin showing a ring-shaped enhancement on post-contrast imaging, we use definite criteria to direct further investigation and distinguish among a number of possible diagnostic hypotheses. However, a correct diagnosis may be difficult in some cases, especially when dealing with less frequent conditions. This is the case of actinomycosis, a highly treatable but insidious infection for which nowadays there may be a low level of attention. Brain localization is associated with a significant morbidity and may represent a true diagnostic pitfall. Here we report the difficulties encountered with a case of central nervous system actinomycosis.</p