CD4+ T-cell responses to Epstein-Barr virus (EBV) latent-cycle antigens and the recognition of EBV-transformed lymphoblastoid cell lines

There is considerable interest in the potential of Epstein-Barr virus (EBV) latent antigen-specific CD4$^+$ T cells to act as direct effectors controlling EBV-induced B lymphoproliferations. Such activity would require direct CD4$^+$ T-cell recognition of latently infected cells through epitopes derived from endogenously expressed viral proteins and presented on the target cell surface in association with HLA class II molecules. It is therefore important to know how often these conditions are met. Here we provide CD4$^+$ epitope maps for four EBV nuclear antigens, EBNA1, -2, -3A, and -3C, and establish CD4$^+$ T-cell clones against 12 representative epitopes. For each epitope we identify the relevant HLA class II restricting allele and determine the efficiency with which epitope-specific effectors recognize the autologous EBV-transformed B-lymphoblastoid cell line (LCL). The level of recognition measured by gamma interferon release was consistent among clones to the same epitope but varied between epitopes, with values ranging from 0 to 35% of the maximum seen against the epitope peptide-loaded LCL. These epitope-specific differences, also apparent in short-term cytotoxicity and longer-term outgrowth assays on LCL targets, did not relate to the identity of the source antigen and could not be explained by the different functional avidities of the CD4$^+$ clones; rather, they appeared to reflect different levels of epitope display at the LCL surface. Thus, while CD4$^+$ T-cell responses are detectable against many epitopes in EBV latent proteins, only a minority of these responses are likely to have therapeutic potential as effectors directly recognizing latently infected target cells

Climate Stabilization at 2°C and Net Zero Carbon Emissions

The goal to stabilize global average surface temperature at lower than 2°C above pre-industrial level has been extensively discussed in climate negotiations. A number of publications state that achieving this goal will require net anthropogenic carbon emissions (defined as anthropogenic emissions minus anthropogenic sinks such as carbon capture and sequestration and reforestation) to be reduced to zero between years 2050 and 2100. At the same time, it is also shown in the literature that decreases of non-CO2 emissions can significantly affect the allowable carbon budget. In this study, we explore possible emission pathways under which surface warming will not exceed 2°C, by means of emission-driven climate simulations with an Earth System Model of Intermediate Complexity linked to an Economic Projection and Policy Analysis Model. We carried out a number of simulations from 1861 to 2500 for different values of parameters defining the strength of the climate system response to radiative forcing and the strength of the natural carbon sources and sinks under different anthropogenic emission projections. Although net anthropogenic emissions need to be reduced to zero eventually to achieve climate stabilization, the results of our simulations suggest that, by including significant reductions in non-CO2 emissions, net carbon emissions do not have to be zero by 2050 or even 2100 to meet the 2°C target because of offsets due to the natural carbon sinks in the oceans and terrestrial ecosystems. We show that net anthropogenic carbon emissions falling from today’s 9.5 GtC/year to 2.5–7 GtC/year by 2050 and then to 1–2.8 GtC/year by 2100 are consistent with a 2°C target for a range of climate sensitivities (2.0–4.5°C) similar to the IPCC likely range. Changes in the surface temperature beyond 2100 depend on the emission profiles after 2100. For post-2100 carbon emissions decreasing at a rate of about 1.5% per year along with continued decreases in non-CO2 emissions, our projections indicate that natural ecosystems will be able to absorb enough carbon to prevent surface temperature from rising further. A major reason for our results is that the land and ocean uptake rates are a function of the total atmospheric CO2 concentration and, due to the very long lifetime of CO2, this does not decrease anywhere near as fast as the imposed CO2 emissions. The required mixes of energy technologies and the overall costs to achieve the 2°C target are highly dependent on the assumptions about the future costs of low-carbon and zero-carbon emitting technologies. In all our projections, the global energy system requires substantial transformations in a relatively short time.The MIT Joint Program is funded by a consortium of government, industrial and foundation sponsors (for the complete list, see: http://globalchange.mit.edu/sponsors). Martin Haigh represents the Scenarios Team at Shell International Ltd

Targeting, import, and dimerization of a mammalian mitochondrial ATP binding cassette (ABC) transporter, ABCB10 (ABC-me)

Author Posting. © American Society for Biochemistry and Molecular Biology, 2004. This article is posted here by permission of American Society for Biochemistry and Molecular Biology for personal use, not for redistribution. The definitive version was published in Journal of Biological Chemistry 279 (2004): 42954-42963, doi:10.1074/jbc.M405040200.ATP binding cassette (ABC) transporters are a diverse superfamily of energy-dependent membrane translocases. Although responsible for the majority of transmembrane transport in bacteria, they are relatively uncommon in eukaryotic mitochondria. Organellar trafficking and import, in addition to quaternary structure assembly, of mitochondrial ABC transporters is poorly understood and may offer explanations for the paucity of their diversity. Here we examine these processes in ABCB10 (ABC-me), a mitochondrial inner membrane erythroid transporter involved in heme biosynthesis. We report that ABCB10 possesses an unusually long 105-amino acid mitochondrial targeting presequence (mTP). The central subdomain of the mTP (amino acids (aa) 36–70) is sufficient for mitochondrial import of enhanced green fluorescent protein. The N-terminal subdomain (aa 1–35) of the mTP, although not necessary for the trafficking of ABCB10 to mitochondria, participates in the proper import of the molecule into the inner membrane. We performed a series of amino acid mutations aimed at changing specific properties of the mTP. The mTP requires neither arginine residues nor predictable {alpha}-helices for efficient mitochondrial targeting. Disruption of its hydrophobic character by the mutation L46Q/I47Q, however, greatly diminishes its efficacy. This mutation can be rescued by cryptic downstream (aa 106–715) mitochondrial targeting signals, highlighting the redundancy of this protein's targeting qualities. Mass spectrometry analysis of chemically cross-linked, immunoprecipitated ABCB10 indicates that ABCB10 embedded in the mitochondrial inner membrane homodimerizes and homo-oligomerizes. A deletion mutant of ABCB10 that lacks its mTP efficiently targets to the endoplasmic reticulum. Quaternary structure assembly of ABCB10 in the ER appears to be similar to that in the mitochondria.This work was supported by National Institutes of Health Grants R01HL071629, P41RR001395, and P01HL032262

Drought Early Warning and the Timing of Range Managers’ Drought Response

\u27e connection between drought early warning information and the timing of rangeland managers’ response actions is not well understood. \u27is study investigates U.S. Northern Plains range and livestock managers’ decision-making in response to the 2016 flash drought, by means of a postdrought survey of agricultural landowners and using the Protective Action Decision Model theoretical framework. \u27e study found that managers acted in response to environmental cues, but that their responses were significantly delayed compared to when drought conditions emerged. External warnings did not influence the timing of their decisions, though on-farm monitoring and assessment of conditions did. \u27ough this case focused only on a one-year flash drought characterized by rapid drought intensification, waiting to destock pastures was associated with greater losses to range productivity and health and diversity. \u27is study finds evidence of unrealized potential for drought early warning information to support proactive response and improved outcomes for rangeland management

Fertilizer inspection, analysis and use, 1945

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Visible light communication with efficient far-red/near-infrared polymer light-emitting diodes

Visible light communication (VLC) is a wireless technology that relies on optical intensity modulation and is potentially a game changer for internet-of-things (IoT) connectivity. However, VLC is hindered by the low penetration depth of visible light in non-transparent media. One solution is to extend operation into the “nearly (in)visible” near-infrared (NIR, 700–1000 nm) region, thus also enabling VLC in photonic bio-applications, considering the biological tissue NIR semitransparency, while conveniently retaining vestigial red emission to help check the link operativity by simple eye inspection. Here, we report new far-red/NIR organic light-emitting diodes (OLEDs) with a 650–800 nm emission range and external quantum efficiencies among the highest reported in this spectral range (>2.7%, with maximum radiance and luminance of 3.5 mW/cm2 and 260 cd/m2, respectively). With these OLEDs, we then demonstrate a “real-time” VLC setup achieving a data rate of 2.2 Mb/s, which satisfies the requirements for IoT and biosensing applications. These are the highest rates ever reported for an online unequalised VLC link based on solution-processed OLEDs

Atomically resolved chemical ordering at the nm-thick TiO precipitate/matrix interface in V-4Ti-4Cr alloy

We have used advanced analytical electron microscopy to characterise the local structure and chemistry at the interface between nm-thick TiO precipitates and the V-based matrix in a V-4Ti-4Cr alloy. Our results reveal the presence of an intergrowth between the fcc TiO and bcc vanadium structures, with a repeat lattice distance that equals 2.5 times the vanadium lattice parameter along the c-axis. Our atomic resolution analysis of the interface will impact the mechanistic understanding of its interaction with interstitials and radiation-induced lattice defects, and consequently trigger the development of improved alloy structures with interfaces engineered for enhanced radiation tolerance

Large-scale forcing of the European Slope Current and associated inflows to the North Sea

Drifters drogued at 50?m in the European Slope Current at the Hebridean shelf break follow a wide range of pathways, indicating highly variable Atlantic inflow to the North Sea. Slope Current pathways, timescales and transports over 1988–2007 are further quantified in an eddy-resolving ocean model hindcast. Particle trajectories calculated with model currents indicate that Slope Current water is largely ''recruited'' from the eastern subpolar North Atlantic. Observations of absolute dynamic topography and climatological density support theoretical expectations that Slope Current transport is to first order associated with meridional density gradients in the eastern subpolar gyre, which support a geostrophic inflow towards the slope. In the model hindcast, Slope Current transport variability is dominated by abrupt 25–50?% reductions of these density gradients over 1996–1998. Concurrent changes in wind forcing, expressed in terms of density gradients, act in the same sense to reduce Slope Current transport. This indicates that coordinated regional changes of buoyancy and wind forcing acted together to reduce Slope Current transport during the 1990s. Particle trajectories further show that 10–40?% of Slope Current water is destined for the northern North Sea within 6 months of passing to the west of Scotland, with a clear decline in this Atlantic inflow over 1988–2007. The influence of variable Slope Current transport on the northern North Sea is also expressed in salinity, which declines through the hindcast period, and there is evidence for a similar freshening trend in observational records. A proxy for Atlantic inflow may be found in sea level records. Variability of Slope Current transport is implicit in mean sea level differences between Lerwick (Shetland) and Torshavn (Faeroes), in both tide gauge records and a longer model hindcast spanning 1958–2013. Potential impacts of this variability on North Sea biogeochemistry and ecosystems, via associated changes in seasonal stratification and nutrient fluxes, are discussed