Early SIV and HIV infection promotes the LILRB2/MHC-I inhibitory axis in cDCs

Classical dendritic cells (cDCs) play a pivotal role in the early events that tip the immune response toward persistence or viral control. In vitro studies indicate that HIV infection induces the dysregulation of cDCs through binding of the LILRB2 inhibitory receptor to its MHC-I ligands and the strength of this interaction was proposed to drive disease progression. However, the dynamics of the LILRB2/MHC-I inhibitory axis in cDCs during early immune responses against HIV are yet unknown. Here, we show that early HIV-1 infection induces a strong and simultaneous increase of LILRB2 and MHC-I expression on the surface of blood cDCs. We further characterized the early dynamics of LILRB2 and MHC-I expression by showing that SIVmac251 infection of macaques promotes coordinated up-regulation of LILRB2 and MHC-I on cDCs and monocytes/macrophages, from blood and lymph nodes. Orientation towards the LILRB2/MHC-I inhibitory axis starts from the first days of infection and is transiently induced in the entire cDC population in acute phase. Analysis of the factors involved indicates that HIV-1 replication, TLR7/8 triggering, and treatment by IL-10 or type I IFNs increase LILRB2 expression. Finally, enhancement of the LILRB2/MHC-I inhibitory axis is specific to HIV-1 and SIVmac251 infections, as expression of LILRB2 on cDCs decreased in naturally controlled chikungunya virus infection of macaques. Altogether, our data reveal a unique up-regulation of LILRB2 and its MHC-I ligands on cDCs in the early phase of SIV/HIV infection, which may account for immune dysregulation at a critical stage of the anti-viral response.     

Multimodel Approach for Intelligent Control and Applications

IntroductionThemultimodelapproachappearsasapowerfultechniquetodealwithcomplex,nonlinearand/orilldefinedsystemsrepresentedusingasetofsimplelinearorsmoothlynonlinearmodelseachofthemallowingthegenerationofapartialcontroller.Differentapproachesexistintheliterature[1,2]tocopewiththetwokeypointsofthemultimodel/multicontrolstrategy:themodelbasisdeterminationandtheuseofpartialcontrollersinordertoderiveaglobalone.Hence,itappearsobviousthatoneofthemainobjectstofocusoninthemultimodel/multicontrolapproach…     

Drosophila and the genetics of the internal milieu

'Homeostasis', from the Greek words for 'same' and 'steady', refers to ways in which the body acts to maintain a stable internal environment despite perturbations. Recent studies in Drosophila exemplify the conservation of regulatory mechanisms involved in metabolic homeostasis. These new findings underscore the use of Drosophila as a model for the study of various human disorders.     

Late Holocene methane rise caused by orbitally controlled increase in tropical sources

Considerable debate surrounds the source of the apparently 'anomalous' increase of atmospheric methane concentrations since the mid-Holocene (5,000?years ago) compared to previous interglacial periods as recorded in polar ice core records. Proposed mechanisms for the rise in methane concentrations relate either to methane emissions from anthropogenic early rice cultivation or an increase in natural wetland emissions from tropical or boreal sources. Here we show that our climate and wetland simulations of the global methane cycle over the last glacial cycle (the past 130,000?years) recreate the ice core record and capture the late Holocene increase in methane concentrations. Our analyses indicate that the late Holocene increase results from natural changes in the Earth's orbital configuration, with enhanced emissions in the Southern Hemisphere tropics linked to precession-induced modification of seasonal precipitation. Critically, our simulations capture the declining trend in methane concentrations at the end of the last interglacial period (115,000-130,000?years ago) that was used to diagnose the Holocene methane rise as unique. The difference between the two time periods results from differences in the size and rate of regional insolation changes and the lack of glacial inception in the Holocene. Our findings also suggest that no early agricultural sources are required to account for the increase in methane concentrations in the 5,000?years before the industrial era.     

Informational Branching Universe

This paper suggests an epistemic interpretation of Belnap’s branching space-times theory based on Everett’s relative state formulation of the measurement operation in quantum mechanics. The informational branching models of the universe are evolving structures defined from a partial ordering relation on the set of memory states of the impersonal observer. The totally ordered set of their information contents defines a linear “time” scale to which the decoherent alternative histories of the informational universe can be referred—which is quite necessary for assigning them a probability distribution. The “historical” state of a physical system is represented in an appropriate extended Hilbert space and an algebra of multi-branch operators is developed. An age operator computes the informational depth of historical states and its standard deviation can be used to provide a universal information/energy uncertainty relation. An information operator computes the encoding complexity of historical states, the rate of change of its average value accounting for the process of correlation destruction inherent to the branching dynamics. In the informational branching models of the universe, the asymmetry of phenomena in nature appears as a mere consequence of the subject’s activity of measuring, which defines the flow of time-information.     

Alteration of humoral antibody production following in vivo administration of phytohemagglutinin

Zusammenfassung Es wird gezeigt, dass Phythämagglutinin (PHA) die Antikörperbildung gegenBrucella abortus bei der Maus merklich herabsetzt, aber nur dann, wenn PHA vor dem Antigenstimulus verabreicht wird und die immunologische Zweitreaktion (secondary response) unverändert bleibt.

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This work was supported by a General Research Support Grant N.I.H.