Migration of Th1 Lymphocytes Is Regulated by CD152 (CTLA-4)-Mediated Signaling via PI3 Kinase-Dependent Akt Activation

Efficient adaptive immune responses require the localization of T lymphocytes in secondary lymphoid organs and inflamed tissues. To achieve correct localization of T lymphocytes, the migration of these cells is initiated and directed by adhesion molecules and chemokines. It has recently been shown that the inhibitory surface molecule CD152 (CTLA-4) initiates Th cell migration, but the molecular mechanism underlying this effect remains to be elucidated. Using CD4 T lymphocytes derived from OVA-specific TCR transgenic CD152-deficient and CD152-competent mice, we demonstrate that chemokine-triggered signal transduction is differentially regulated by CD152 via phosphoinositide 3-kinase (PI3K)-dependent activation of protein kinase B (PKB/Akt). In the presence of CD152 signaling, the chemoattractant CCL4 selectively induces the full activation of Akt via phosphorylation at threonine 308 and serine 473 in pro-inflammatory Th lymphocytes expressing the cognate chemokine receptor CCR5. Akt signals lead to cytoskeleton rearrangements, which are indispensable for migration. Therefore, this novel Akt-modulating function of CD152 signals affecting T cell migration demonstrates that boosting CD152 or its down-stream signal transduction could aid therapies aimed at sensitizing T lymphocytes for optimal migration, thus contributing to a precise and effective immune response

Current transport versus continental inputs in the eastern Indian Ocean: Radiogenic isotope signatures of clay size sediments

Analyses of radiogenic neodymium (Nd), strontium (Sr), and lead (Pb) isotope compositions of clay-sized detrital sediments allow detailed tracing of source areas of sediment supply and present and past transport of particles by water masses in the eastern Indian Ocean. Isotope signatures in surface sediments range from −21.5 (ɛNd), 0.8299 (87Sr/86Sr), and 19.89 (206Pb/204Pb) off northwest Australia to +0.7 (ɛNd), 0.7069 (87Sr/86Sr), and 17.44 (206Pb/204Pb) southwest of Java. The radiogenic isotope signatures primarily reflect petrographic characteristics of the surrounding continental bedrocks but are also influenced by weathering-induced grain size effects of Pb and Sr isotope systems with superimposed features that are caused by current transport of clay-sized particles, as evidenced off Australia where a peculiar isotopic signature characterizes sediments underlying the southward flowing Leeuwin Current and the northward flowing West Australian Current (WAC). Gravity core FR10/95-GC17 off west Australia recorded a major isotopic change from Last Glacial Maximum values of −10 (ɛNd), 0.745 (87Sr/86Sr), and 18.8 (206Pb/204Pb) to Holocene values of −22 (ɛNd), 0.8 (87Sr/86Sr), and 19.3 (206Pb/204Pb), which documents major climatically driven changes of the WAC and in local riverine particle supply from Australia during the past 20 kyr. In contrast, gravity core FR10/95-GC5 located below the present-day pathway of the Indonesian throughflow (ITF) shows a much smaller isotopic variability, indicating a relatively stable ITF hydrography over most of the past 92 kyr. Only the surface sediments differ significantly in their isotopic composition, indicating substantial changes in erosional sources attributed to a change of the current regime during the past 5 kyr

Neutrophil Paralysis in Plasmodium vivax Malaria

Plasmodium vivax is responsible for approximately 60–80% of the malaria cases in the world, and contributes to significant social and economic instability in the developing countries of Latin America and Asia. The pathogenesis of P. vivax malaria is a consequence of host derived inflammatory mediators. Hence, a better understanding of the mechanisms involved in induction of systemic inflammation during P. vivax malaria is critical for the clinical management and prevention of severe disease. The innate immune receptors recognize Plasmodium sp. and initiate a broad spectrum of host defense mechanisms that mediate resistance to infection. However, the innate immune response is the classic “two-edged sword”, and clinical malaria is associated with high levels of circulating pro-inflammatory cytokines. Our findings show that both monocytes and neutrophils are highly activated during malaria. Monocytes produced high levels of IL-1β, IL-6 and TNF-α during acute malaria. On the other hand, neutrophils were a poor source of cytokines, but displayed an enhanced phagocytic activity and superoxide production. Unexpectedly, we noticed an impaired chemotaxis of neutrophils towards an IL-8 (CXCL8) gradient. We proposed that neutrophil paralysis is in part responsible for the enhanced susceptibility to bacterial infection observed in malaria patients

On ecological conceptualizations of perceptual systems and action systems

This article examines Gibson's concept of perceptual system and Reed's concept of action system. After discussing several assumptions underlying these concepts, the ontological status of these systems is considered. It is argued that perceptual systems and action systems should be conceptualized neither as parts of an animal's body nor as softly (temporarily) assembled devices; rather, they are best understood as animals' abilities to achieve functional relationships, that is, as dispositional properties. This conceptualization entails that these systems are relatively permanent properties of the animal that are causally supported by, though not identical to, anatomical substrates. Further, it entails that it is the animal that perceives and acts, not its perceptual and action systems

Palaeoarchaean felsic magmatism: A melt inclusion study of 3.45Ga old rhyolites from the Barberton Greenstone Belt, South Africa

© 2015 Elsevier B.V. The 3.45 Ga old felsic volcanic rocks from the Barberton Greenstone Belt of southern Africa include a submarine succession of felsic lavas and volcaniclastic rocks and shallow subvolcanic intrusions. Sea floor alteration strongly affected rock compositions shortly after emplacement, making comparisons with coeval intrusions challenging. We analysed well-preserved quartz-hosted melt inclusions from the felsic rocks, which offers a unique opportunity to gain insight into pre-alteration melt compositions. Melt inclusion compositions are then compared with whole-rock analyses to evaluate the significance of the volcanic complex in the context of Archaean felsic magmatism in the Barberton Greenstone Belt. Whole-rock immobile trace element concentrations, including high-field strength and rare earth elements, indicate strong similarities with coeval tonalite-trondhjemite-granodiorite intrusions. These same geochemical characteristics distinguish these rocks from other Archaean felsic rocks in the Barberton Greenstone Belt (e.g. the 3.54Ga Theespruit Formation), which have characteristically higher Th, Nb and REE. Low CaO (=1wt.%) and relatively high Nb and Th (mostly =9 and =13ppm, respectively) in comparison with least altered whole-rock samples, and the presence of negative Eu anomalies are consistent with the melt inclusions being relatively evolved, rather than representing primitive compositions. Melt inclusion analyses suggest the presence of two melts with varying K2O/Na2O. Melt inclusions from extrusive samples, which contain remnants of K-feldspar phenocrysts, have K2O/Na2O>1 by weight, whereas subvolcanic intrusions, which contain Na-rich plagioclase, have K2O/Na2O<1. Moderately high Cl contents (Cl=0.7wt.%) of melt inclusions may record interaction of the melting protolith with sea water prior to melting. We speculate that the varying K2O/Na2O in the felsic volcanic rocks was due to melting of a greenstone succession heterogeneously affected by sea floor alteration