Description: We report new major, trace and volatile element contents (H2O, CO2, F, S, Cl), and new Sr, Nd, Pb and He isotopes on submarine glasses from the Galapagos Archipelago from several dredging expeditions. Four groups are distinguishable on the basis of composition and geographical distribution: the Fernandina group (3He/4He 〉 22 RA), which is similar to the less degassed primitive mantle; the Sierra Negra group (enriched Pb and Sr isotopes, 3He/4He = 8–20 RA), produced by mixing the Floreana (HIMU-type) and Fernandina end-members; the Pinta group (high Δ7/4, Δ8/4 and Th/La ratios, 3He/4He = 6–9 RA), an enriched mantle (EM)-type mantle indicative of recycled material in the source; and the depleted mantle (DM) group, characterized by an isotopic composition similar to mid-ocean ridge basalts (MORB). Only a single submarine glass with the isotopic composition of the Floreana end-member has been identified in the sample suite. Degassing has significantly lowered the glass CO2 content with little effect on the H2O concentration. Volatile data for oceanic basalts reveal that CO2–H2O gas–melt equilibration at eruption depth is common in ocean island basalts (OIB) and rare in MORB, suggesting different ratios of melt transport to bubble formation and gas–melt equilibration. The Galapagos glasses range from sulfide saturated to undersaturated, and a subset of samples indicate that S degasses at pressures ≤ 400 bars. Assimilation of hydrothermally altered material affected the volatile contents of a number of samples in the groups. Once shallow-level processes have been accounted for, we evaluate the volatile contents in the different Galapagos mantle sources. Ratios between volatile and refractory elements with similar incompatibilities are used to estimate the volatile budget of the Galapagos mantle plume. Most of the glasses from the Fernandina, Sierra Negra and Pinta groups have high volatile/refractory element ratios, whereas a few pristine DM group lavas have ratios similar to those measured in MORB. The volatile/refractory element ratios are consistent with previous reports for the high 3He/4He, HIMU and MORB components. The values measured for the Pinta group, however, are higher than those found in other OIB associated with the presence of recycled material (EM-type). Our data suggest that mixing between the different mantle components is pervasive throughout the archipelago, which acts to normalize the volatile data between the groups. The Fernandina component can be modeled by a 6–20% mixture of the high 3He/4He primitive mantle component with the MORB source, assuming a two-layered mantle and using existing estimates of helium concentrations. The resulting estimated volatile content and H/C mass ratio for the high 3He/4He primitive mantle are consistent with previous estimates, but calculated C/3He ratios are lower than the canonical ratio. This indicates the following: (1) the estimates require ∼20–50 times higher C or lower 3He contents, which is difficult to reconcile with the measured volatile/refractory ratios in oceanic basalts; (2) the C/3He ratio is not constant throughout the mantle; (3) an impact erosion model, rather than a two-layered mantle model, is more consistent with the relatively constant C/3He ratios observed in oceanic basalts, although it is unclear how representative oceanic basalts are of the lower mantle. The high volatile content of the high 3He/4He component will affect mantle dynamics and melt migration during plume–ridge interaction as this component would be predicted to be less viscous than the ambient mantle. The lower viscosity material would have an enhanced vertical upwelling, which could explain the buoyancy flux of the Galapagos plume without the need for a temperature anomaly. A lower viscosity, high 3He/4He component could also provide an explanation for the lack of high 3He/4He in Galapagos Spreading Center lavas erupting in the vicinity of the Galapagos plume.

Description: IL-15 bound to the IL-15Rα–chain (IL-15Rα) is presented in trans to cells bearing the IL-2Rβ–chain and common -chain. As IL-15 transpresentation occurs in the context of cell-to-cell contacts, it has the potential for regulation by and of other receptor–ligand interactions. In this study, human NK cells were tested for the sensitivity of IL-15 transpresentation to inhibitory receptors. Human cells expressing HLA class I ligands for inhibitory receptors KIR2DL1, KIR2DL2/3, or CD94-NKG2A were transfected with IL-15Rα. Proliferation of primary NK cells in response to transpresented IL-15 was reduced by engagement of either KIR2DL1 or KIR2DL2/3 by cognate HLA-C ligands. Inhibitory KIR–HLA-C interactions did not reduce the proliferation induced by soluble IL-15. Therefore, transpresentation of IL-15 is subject to downregulation by MHC class I–specific inhibitory receptors. Similarly, proliferation of the NKG2A + cell line NKL induced by IL-15 transpresentation was inhibited by HLA-E. Coengagement of inhibitory receptors, either KIR2DL1 or CD94-NKG2A, did not inhibit phosphorylation of Stat5 but inhibited selectively phosphorylation of Akt and S6 ribosomal protein. IL-15Rα was not excluded from, but was evenly distributed across, inhibitory synapses. These findings demonstrate a novel mechanism to attenuate IL-15–dependent NK cell proliferation and suggest that inhibitory NK cell receptors contribute to NK cell homeostasis.

Description: Objective Animal and in vitro studies suggest that viral acute respiratory infection (VARI) can predispose to pneumococcal infection. These findings suggest that the prevention of VARI can yield additional benefits for the control of pneumococcal disease (PD). In population-based studies, however, the evidence is not in accordance, possibly due to a variety of methodological challenges and problems in these studies. We aimed to summarise and critically review the methods and results from these studies in order to inform future studies. Methods We conducted a systematic review of population-based studies that analysed the association between preceding seasonal VARI and subsequent PD. We searched MEDLINE, Embase and Global Health databases using tailored search strategies. Results A total of 28 studies were included. After critically reviewing the methodologies and findings, 11 studies did not control for seasonal factors shared by VARI and PD. This, in turn, could lead to an overestimation of the association between the two illnesses. One case–control study was limited by its small sample size (n case=13). The remaining 16 studies that controlled for seasonal factors suggested that influenza and/or respiratory syncytial virus (RSV) infections were likely to be associated with the subsequent occurrence of PD (influenza: 12/14 studies; RSV: 4/5 studies). However, these 16 studies were unable to conduct individual patient data-based analyses. Nevertheless, these studies suggested the association between VARI and subsequent PD was related to additional factors such as virus type and subtype, age group, comorbidity status, presentation of PD and pneumococcal serotype. Conclusions Population-based studies do not give consistent support for an association between preceding seasonal VARI and subsequent PD incidence. The main methodological challenges of existing studies include the failure to use individual patient data, control for seasonal factors of VARI and PD, or include other factors related to the association (eg, virus, age, comorbidity and pneumococcal serotype).

Description: Binding of NK cell inhibitory receptors to MHC class I (MHC-I) confers increased responsiveness to NK cells by a process known as NK cell licensing/education. Reduced MHC-I expression or a lack of inhibitory receptors for MHC-I results in diminished NK cell responsiveness. In this study, we evaluated the effect of human and mouse NK cell licensing on early stages of natural cytotoxicity. Unlicensed NK cells did not form as many stable conjugates with target cells. The reduction of NK cell conjugation to target cells was not attributed to altered β 2 integrin LFA-1 properties but was instead due to reduced inside-out signaling to LFA-1 by activating receptors. For those unlicensed NK cells that did form conjugates, LFA-1–dependent granule polarization was similar to that in licensed NK cells. Thus, licensing controls signals as proximal as inside-out signaling by activating receptors but not integrin outside-in signaling for granule polarization.

Description: Olivine-hosted melt inclusions from both Fernandina and Santiago islands in the Galapagos Archipelago have compositions indicating that plagioclase played an important role in the magmatic evolution of these volcanic islands. The major and trace element chemistry of the Santiago melt inclusions indicates simple plagioclase assimilation. In contrast, Fernandina inclusions have compositions for which the plagioclase appears to be present only as a ‘ghost’ trace element signature (i.e. ‘ghost plagioclase’ signature). Two competing hypotheses have been proposed to explain this unique signature: (1) incorporation of an ancient recycled plagioclase-rich cumulate into the mantle; (2) shallow-level interaction between melts and plagioclase-rich cumulates in the present-day lower oceanic crust. Here we present new Pb isotope measurements for olivine-hosted melt inclusions from Fernandina and Santiago islands to distinguish between the two models. The new Pb isotope data are within the range previously reported for whole-rock basalts from those islands. Melting and mixing models involving ancient (~0·5–1 Ga) recycled plagioclase-rich cumulates cannot reproduce the observed trace element and Pb isotopic characteristics of the Fernandina melt inclusions with a ghost plagioclase signature. Shallow-level diffusive interactions between basalt and present-day plagioclase-rich cumulates provide the simplest explanation for the observed trace element compositions and Pb isotope ratios of melt inclusions from Fernandina and Santiago islands.