Interferons and their potential in the treatment of ocular inflammation

Since their discovery in the 1950s interferons have been the scope of investigation in many diseases as therapeutic as well as pathogenetic factors. We know they have immune stimulatory and immune regulatory effects. This apparently counter-intuitive mechanism can be summarized as immunomodulatory action and seems to be very effective in a number of ocular inflammatory diseases. We review the current knowledge of interferons in immunity and autoimmunity and show their use in clinical ophthalmologic practice

Evidence for elevated alkalinity in the glacial Southern Ocean

An increase in whole ocean alkalinity during glacial periods could account, in part, for the drawdown of atmospheric CO2 into the ocean. Such an increase was inevitable due to the near elimination of shelf area for the burial of coral reef alkalinity. We present evidence, based on downcore measurements of benthic foraminiferal B/Ca and Mg/Ca from a core in the Weddell Sea, that the deep ocean carbonate ion concentration, [CO32-], was elevated by similar to 25 mu mol/kg during each glacial period of the last 800 kyr. The heterogeneity of the preservation histories in the different ocean basins reflects control of the carbonate chemistry of the deep glacial ocean in the Atlantic and Pacific by the changing ventilation and chemistry of Weddell Sea waters. These waters are more corrosive than interglacial northern sourced waters but not as undersaturated as interglacial southern sourced waters. Our inferred increase in whole ocean alkalinity can be reconciled with reconstructions of glacial saturation horizon depth and the carbonate budget if carbonate burial rates also increased above the saturation horizon as a result of enhanced pelagic calcification. The Weddell records display low [CO32-] during deglaciations and peak interglacial warmth, coincident with maxima in percent CaCO3 in the Atlantic and Pacific oceans. Should the burial rate of alkalinity in the more alkaline glacial deep waters outstrip the rate of alkalinity supply, then pelagic carbonate production by the coccolithophores at the end of the glacial maximum could drive a decrease in ocean [CO32-] and act to trigger the deglacial rise in pCO(2)

Insensitivity of alkenone carbon isotopes to atmospheric CO₂ at low to moderate CO₂ levels

Atmospheric pCO2 is a critical component of the global carbon system and is considered to be the major control of Earth’s past, present and future climate. Accurate and precise reconstructions of its concentration through geological time are, therefore, crucial to our understanding of the Earth system. Ice core records document pCO2 for the past 800 kyrs, but at no point during this interval were CO2 levels higher than today. Interpretation of older pCO2 has been hampered by discrepancies during some time intervals between two of the main ocean-based proxy methods used to reconstruct pCO2: the carbon isotope fractionation that occurs during photosynthesis as recorded by haptophyte biomarkers (alkenones) and the boron isotope composition (δ11B) of foraminifer shells. Here we present alkenone and δ11B-based pCO2 reconstructions generated from the same samples from the Plio-Pleistocene at ODP Site 999 across a glacial-interglacial cycle. We find a muted response to pCO2 in the alkenone record compared to contemporaneous ice core and δ11B records, suggesting caution in the interpretation of alkenone-based records at low pCO2 levels. This is possibly caused by the physiology of CO2 uptake in the haptophytes. Our new understanding resolves some of the inconsistencies between the proxies and highlights that caution may be required when interpreting alkenone-based reconstructions of pCO2

Carbon isotope offsets between benthic foraminifer species of the genus Cibicides (Cibicidoides) in the glacial sub-Antarctic Atlantic

©2016. American Geophysical Union. All Rights Reserved. Epibenthic foraminifer δ 13 C measurements are valuable for reconstructing past bottom water dissolved inorganic carbon δ 13 C (δ 13 C DIC ), which are used to infer global ocean circulation patterns. Epibenthic δ 13 C, however, may also reflect the influence of 13 C-depleted phytodetritus, microhabitat changes, and/or variations in carbonate ion concentrations. Here we compare the δ 13 C of two benthic foraminifer species, Cibicides kullenbergi and Cibicides wuellerstorfi, and their morphotypes, in three sub-Antarctic Atlantic sediment cores over several glacial-interglacial transitions. These species are commonly assumed to be epibenthic, living above or directly below the sediment-water interface. While this might be consistent with the small δ 13 C offset that we observe between these species during late Pleistocene interglacial periods (Δδ 13 C = −0.19 ± 0.31‰, N = 63), it is more difficult to reconcile with the significant δ 13 C offset that is found between these species during glacial periods (Δδ 13 C = −0.76 ± 0.44‰, N = 44). We test possible scenarios by analyzing Uvigerina spp. δ 13 C and benthic foraminifer abundances: (1) C. kullenbergi δ 13 C is biased to light values either due to microhabitat shifts or phytodetritus effects and (2) C. wuellerstorfi δ 13 C is biased to heavy values, relative to long-term average conditions, for instance by recording the sporadic occurrence of less depleted deepwater δ 13 C DIC . Neither of these scenarios can be ruled out unequivocally. However, our findings emphasize that supposedly epibenthic foraminifer δ 13 C in the sub-Antarctic Atlantic may reflect several factors rather than being solely a function of bottom water δ 13 C DIC . This could have a direct bearing on the interpretation of extremely light South Atlantic δ 13 C values at the Last Glacial Maximum

Eastern Mediterranean surface water temperatures and d18O composition during deposition of sapropels in the late Quaternary

Water column stratification increased at climatic transitions from cold to warm periods during the lateQuaternary and led to anoxic conditions and sapropel formation in the deep eastern Mediterranean basins. Highresolutiondata sets on sea-surface temperatures (SST) (estimated from U37k0 indices) and d18O of planktonicforaminifer calcite (d18Ofc) across late Pleistocene sapropel intervals show that d18Ofc decreased (between 1 and4.6%) and SST increased (between 0.7 and 6.7 C). Maximal d18Oseawater depletion of eastern Mediterraneansurface waters at the transition is between 0.5 and 3.0%, and in all but one case exceeded the depletion seen in awestern Mediterranean core. The depletion in d18Oseawater is most pronounced at sapropel bases, in agreementwith an initial sudden input of monsoon-derived freshwater. Most sapropels coincide with warming trends ofSST. The density decrease by initial freshwater input and continued warming of the sea surface pooled freshwater in the surface layer and prohibited deep convection down to ageing deep water emplaced during cold andarid glacial conditions. An exception to this pattern is glacial sapropel S6; its largest d18Oseawater depletion(3%) is almost matched by the depletion in the western Mediterranean Sea, and it is accompanied by surfacewater cooling following an initially rapid warming phase. A second period of significant isotopic depletion is inisotope stage 6 at the 150 kyr insolation maximum. While not expressed as a sapropel due to cold SST, it is inaccord with a strengthened monsoon in the southern catchment

Composição isotópica de Nd na componente terrígena de sedimentos como marcador de eventos de Heinrich:estudo de um caso na margem continental NW Ibérica

The OMEX core KC 024-19 was studied aiming at to assess the influence of climate changes on the origin and transport of the sediments of the Galician continental slope, in the last 40 ka. The results show that sea level variation played a major role in the supply of the terrigenous sediments coming from the nearby continental areas, whose basement has a Variscan age. Additionally, coarse-grained clastic materials, corresponding to ice-rafted debris (IRD), were deposited through melting of icebergs during the Heinrich events (HE), in the last glaciation. The last four HE were identified in the core. The measured Nd isotope ratios reveal that there was a strong contribution of continental crustal sources significantly older than the Variscan basement for HE 1, 2 and 4. The most likely provenance of the coarse clasts deposited during these three events lie in NE America or Greenland, and the carrier icebergs should be fragments of the Laurentide Ice Sheet. In contrast, the HE 3 layer displays εNd values in the range of the compositions of the most common sediments in the core and, therefore, its IRD should have European source(s), which supports previous results obtained in other places of the European Atlantic margin.O core OMEX KC 024-19 foi estudado tendo em vista avaliar o papel das mudanças climáticas nos processos de transporte e nas fontes de sedimentos depositados no talude continental da Galiza, durante os últimos 40 ka. Os resultados obtidos, usando diferentes metodologias, apontam para uma grande influência das mudanças do nível do mar no fornecimento de sedimentos terrígenos a partir das áreas continentais próximas, cujo soco é de idade varisca. Para além disso, nos eventos de Heinrich (HE), ocorridos durante a última glaciação, foram recebidos nesta área materiais detríticos grosseiros transportados por icebergues em fusão (IRD). Foram identificados, neste core, os quatro últimos HE. As razões isotópicas de Nd revelam que durante os HE 1, 2 e 4 houve contribuição importante de fontes de crusta continental significativamente mais antiga do que a ibérica. A origem provável dos IRD desses três eventos estará no NE da América ou na Gronelândia, podendo os icebergues que os transportaram ter origem na LIS (Laurentide Ice Sheet). Já o HE 3, não se distingue, em termos de εNd, dos sedimentos mais comuns no core, pelo que os IRD correspondentes deverão ter origem europeia, o que corrobora resultados obtidos noutros locais da margem atlântica europeia

Did North Atlantic overturning halt 17,000 years ago?

Author Posting. © American Geophysical Union, 2008. This article is posted here by permission of American Geophysical Union for personal use, not for redistribution. The definitive version was published in Paleoceanography 23 (2008): PA1101, doi:10.1029/2007PA001500.Models indicate that a complete shutdown of deep and intermediate water production is a possible consequence of extreme climate conditions in the northern North Atlantic, and the high ratio of 231Pa to 230Th on Bermuda Rise is evidence that this might have happened ∼17 ka during Heinrich event 1 (H1). However, new radiocarbon data from bivalves that lived at ∼4.6 km on the Bermuda Rise during H1 lead to a different conclusion. The bivalve data do indeed indicate ventilation of the deep western North Atlantic was suppressed during H1 but not as much as it was during the last glacial maximum. We propose that high diatom flux to the Bermuda Rise during H1 is at least in part responsible for increased 231Pa/230Th at that time. Although we cannot say for sure why opal production was so high in a gyre center location at that time, increased leakage of silica rich waters from the Southern Ocean to the North Atlantic is one possibility.This work was funded by a grant from the Comer Foundation to WHOI’s Ocean and Climate Change Institute

Genetic control of mammalian T-cell proliferation with synthetic RNA regulatory systems

RNA molecules perform diverse regulatory functions in natural biological systems, and numerous synthetic RNA-based control devices that integrate sensing and gene-regulatory functions have been demonstrated, predominantly in bacteria and yeast. Despite potential advantages of RNA-based genetic control strategies in clinical applications, there has been limited success in extending engineered RNA devices to mammalian gene-expression control and no example of their application to functional response regulation in mammalian systems. Here we describe a synthetic RNA-based regulatory system and its application in advancing cellular therapies by linking rationally designed, drug-responsive, ribozyme-based regulatory devices to growth cytokine targets to control mouse and primary human T-cell proliferation. We further demonstrate the ability of our synthetic controllers to effectively modulate T-cell growth rate in response to drug input in vivo. Our RNA-based regulatory system exhibits unique properties critical for translation to therapeutic applications, including adaptability to diverse ligand inputs and regulatory targets, tunable regulatory stringency, and rapid response to input availability. By providing tight gene-expression control with customizable ligand inputs, RNA-based regulatory systems can greatly improve cellular therapies and advance broad applications in health and medicine

Genetic Variants in P-Selectin and C-Reactive Protein Influence Susceptibility to Cognitive Decline After Cardiac Surgery

ObjectivesWe hypothesized that candidate gene polymorphisms in biologic pathways regulating inflammation, cell matrix adhesion/interaction, coagulation-thrombosis, lipid metabolism, and vascular reactivity are associated with postoperative cognitive deficit (POCD).BackgroundCognitive decline is a common complication of coronary artery bypass graft (CABG) surgery and is associated with a reduced quality of life.MethodsIn a prospective cohort study of 513 patients (86% European American) undergoing CABG surgery with cardiopulmonary bypass, a panel of 37 single-nucleotide polymorphisms (SNPs) was genotyped by mass spectrometry. Association between these SNPs and cognitive deficit at 6 weeks after surgery was tested using multiple logistic regression accounting for age, level of education, baseline cognition, and population structure. Permutation analysis was used to account for multiple testing.ResultsWe found that minor alleles of the CRP1059G/C SNP (odds ratio [OR] 0.37, 95% confidence interval [CI] 0.16 to 0.78; p = 0.013) and the SELP1087G/A SNP (OR 0.51, 95% CI 0.30 to 0.85; p = 0.011) were associated with a reduction in cognitive deficit in European Americans (n = 443). The absolute risk reduction in the observed incidence of POCD was 20.6% for carriers of the CRP1059C allele and 15.2% for carriers of the SELP1087A allele. Perioperative serum C-reactive protein (CRP) and degree of platelet activation were also significantly lower in patients with a copy of the minor alleles, providing biologic support for the observed allelic association.ConclusionsThe results suggest a contribution of P-selectin and CRP genes in modulating susceptibility to cognitive decline after cardiac surgery, with potential implications for identifying populations at risk who might benefit from targeted perioperative antiinflammatory strategies