Measuring plume-related exhumation of the British Isles in Early Cenozoic times

Mantle plumes have been proposed to exert a first-order control on the morphology of Earth's surface. However, there is little consensus on the lifespan of the convectively supported topography. Here, we focus on the Cenozoic uplift and exhumation history of the British Isles. While uplift in the absence of major regional tectonic activity has long been documented, the causative mechanism is highly controversial, and direct exhumation estimates are hindered by the near-complete absence of onshore post-Cretaceous sediments (outside Northern Ireland) and the truncated stratigraphic record of many offshore basins. Two main hypotheses have been developed by previous studies: epeirogenic exhumation driven by the proto-Iceland plume, or multiple phases of Cenozoic compression driven by far-field stresses. Here, we present a new thermochronological dataset comprising 43 apatite fission track (AFT) and 102 (U–Th–Sm)/He (AHe) dates from the onshore British Isles. Inverse modelling of vertical sample profiles allows us to define well-constrained regional cooling histories. Crucially, during the Paleocene, the thermal history models show that a rapid exhumation pulse (1–2.5 km) occurred, focused on the Irish Sea. Exhumation is greatest in the north of the Irish Sea region, and decreases in intensity to the south and west. The spatial pattern of Paleocene exhumation is in agreement with the extent of magmatic underplating inferred from geophysical studies, and the timing of uplift and exhumation is synchronous with emplacement of the plume-related British and Irish Paleogene Igneous Province (BIPIP). Prior to the Paleocene exhumation pulse, the Mesozoic onshore exhumation pulse is mainly linked to the uplift and erosion of the hinterland during the complex and long-lived rifting history of the neighbouring offshore basins. The extent of Neogene exhumation is difficult to constrain due to the poor sensitivity of the AHe and AFT systems at low temperatures. We conclude that the Cenozoic topographic evolution of the British Isles is the result of plume-driven uplift and exhumation, with inversion under compressive stress playing a secondary role

Precambrian olistoliths masquerading as sills from Death Valley, California

Olistolith production and magmatism are processes commonly associated with extensional tectonic settings, such as rift basins. We present a cautionary exemplar from one such Precambrian basin, in which we reinterpret metabasite bodies, previously documented as sills, to be olistoliths. We nevertheless demonstrate that, on the basis of field observation alone, the previous but erroneous sill interpretation is parsimonious. Indeed, it is only by using isotopic age and compositional analysis that the true identities of these metabasite olistoliths are revealed. We present new data from metabasites and metasedimentary strata of the Kingston Peak Formation (Cryogenian) and Crystal Spring Formation (Mesoproterozoic) of Death Valley, USA. These include field observations, U?Pb apatite ages, U?Pb zircon ages (detrital and igneous) and whole-rock geochemistry. These data also provide a new maximum age for the base of the Pahrump Group and suggest that the Crystal Spring Diabase was more tholeiitic than previously thought. Similar sill/olistolith misinterpretations may have occurred elsewhere, potentially producing erroneous age and tectonic-setting interpretations of surrounding strata. This is particularly relevant in Precambrian rocks, where fossil age constraints are rare. This is illustrated herein using a potential example from the Neoproterozoic literature of the Lufilian belt, Africa. We caution others against Precambrian olistoliths masquerading as sills.publishersversionPeer reviewe

Functional and immunogenic characterization of diverse HCV glycoprotein E2 variants

© 2018 European Association for the Study of the Liver Background & Aims: Induction of cross-reactive antibodies targeting conserved epitopes of the envelope proteins E1E2 is a key requirement for an hepatitis C virus vaccine. Conserved epitopes like the viral CD81-binding site are targeted by rare broadly neutralizing antibodies. However, these viral segments are occluded by variable regions and glycans. We aimed to identify antigens exposing conserved epitopes and to characterize their immunogenicity. Methods: We created hepatitis C virus variants with mutated glycosylation sites and/or hypervariable region 1 (HVR1). Exposure of the CD81 binding site and conserved epitopes was quantified by soluble CD81 and antibody interaction and neutralization assays. E2 or E1-E2 heterodimers with mutations causing epitope exposure were used to immunize mice. Vaccine-induced antibodies were examined and compared with patient-derived antibodies. Results: Mutant viruses bound soluble CD81 and antibodies targeting the CD81 binding site with enhanced efficacy. Mice immunized with E2 or E1E2 heterodimers incorporating these modifications mounted strong, cross-binding, and non-interfering antibodies. E2-induced antibodies neutralized the autologous virus but they were not cross-neutralizing. Conclusions: Viruses lacking the HVR1 and selected glycosylation sites expose the CD81 binding site and cross-neutralization antibody epitopes. Recombinant E2 proteins carrying these modifications induce strong cross-binding but not cross-neutralizing antibodies. Lay summary: Conserved viral epitopes can be made considerably more accessible for binding of potently neutralizing antibodies by deletion of hypervariable region 1 and selected glycosylation sites. Recombinant E2 proteins carrying these mutations are unable to elicit cross-neutralizing antibodies suggesting that exposure of conserved epitopes is not sufficient to focus antibody responses on production of cross-neutralizing antibodies

(LA,Q)-ICPMS trace-element analyses of Durango and McClure Mountain apatite and implications for making natural LA-ICPMS mineral standards

International audienc

Several Human Liver Cell Expressed Apolipoproteins Complement HCV Virus Production with Varying Efficacy Conferring Differential Specific Infectivity to Released Viruses.

Apolipoprotein E (ApoE), an exchangeable apolipoprotein, is necessary for production of infectious Hepatitis C virus (HCV) particles. However, ApoE is not the only liver-expressed apolipoprotein and the role of other apolipoproteins for production of infectious HCV progeny is incompletely defined. Therefore, we quantified mRNA expression of human apolipoproteins in primary human hepatocytes. Subsequently, cDNAs encoding apolipoproteins were expressed in 293T/miR-122 cells to explore if they complement HCV virus production in cells that are non-permissive due to limiting endogenous levels of human apolipoproteins. Primary human hepatocytes expressed high mRNA levels of ApoA1, A2, C1, C3, E, and H. ApoA4, A5, B, D, F, J, L1, L2, L3, L4, L6, M, and O were expressed at intermediate levels, and C2, C4, and L5 were not detected. All members of the ApoA and ApoC family of lipoproteins complemented HCV virus production in HCV transfected 293T/miR-122 cells, albeit with significantly lower efficacy compared with ApoE. In contrast, ApoD expression did not support production of infectious HCV. Specific infectivity of released particles complemented with ApoA family members was significantly lower compared with ApoE. Moreover, the ratio of extracellular to intracellular infectious virus was significantly higher for ApoE compared to ApoA2 and ApoC3. Since apolipoproteins complementing HCV virus production share amphipathic alpha helices as common structural features we altered the two alpha helices of ApoC1. Helix breaking mutations in both ApoC1 helices impaired virus assembly highlighting a critical role of alpha helices in apolipoproteins supporting HCV assembly. In summary, various liver expressed apolipoproteins with amphipathic alpha helices complement HCV virus production in human non liver cells. Differences in the efficiency of virus assembly, the specific infectivity of released particles, and the ratio between extracellular and intracellular infectivity point to distinct characteristics of these apolipoproteins that influence HCV assembly and cell entry. This will guide future research to precisely pinpoint how apolipoproteins function during virus assembly and cell entry

Hepatitis C reference viruses highlight potent antibody responses and diverse viral functional interactions with neutralising antibodies.

Community-acquired pneumonia by primary or superinfections with Streptococcus pneumoniae can lead to acute respiratory distress requiring mechanical ventilation. The pore-forming toxin pneumolysin alters the alveolar-capillary barrier and causes extravasation of protein-rich fluid into the interstitial pulmonary tissue, which impairs gas exchange. Platelets usually prevent endothelial leakage in inflamed pulmonary tissue by sealing inflammation-induced endothelial gaps. We not only confirm that S pneumoniae induces CD62P expression in platelets, but we also show that, in the presence of pneumolysin, CD62P expression is not associated with platelet activation. Pneumolysin induces pores in the platelet membrane, which allow anti-CD62P antibodies to stain the intracellular CD62P without platelet activation. Pneumolysin treatment also results in calcium efflux, increase in light transmission by platelet lysis (not aggregation), loss of platelet thrombus formation in the flow chamber, and loss of pore-sealing capacity of platelets in the Boyden chamber. Specific anti-pneumolysin monoclonal and polyclonal antibodies inhibit these effects of pneumolysin on platelets as do polyvalent human immunoglobulins. In a post hoc analysis of the prospective randomized phase 2 CIGMA trial, we show that administration of a polyvalent immunoglobulin preparation was associated with a nominally higher platelet count and nominally improved survival in patients with severe S pneumoniae-related community-acquired pneumonia. Although, due to the low number of patients, no definitive conclusion can be made, our findings provide a rationale for investigation of pharmacologic immunoglobulin preparations to target pneumolysin by polyvalent immunoglobulin preparations in severe community-acquired pneumococcal pneumonia, to counteract the risk of these patients becoming ventilation dependent. This trial was registered at www.clinicaltrials.gov as #NCT01420744