Coupled Mg/Ca and clumped isotope analyses of foraminifera provide consistent water temperatures

The reliable determination of past seawater temperature is fundamental to paleoclimate studies. We test the robustness of two paleotemperature proxies by combining Mg/Ca and clumped isotopes (Δ47) on the same specimens of core top planktonic foraminifera. The strength of this approach is that Mg/Ca and Δ47 are measured on the same specimens of foraminifera, thereby providing two independent estimates of temperature. This replication constitutes a rigorous test of individual methods with the advantage that the same approach can be applied to fossil specimens. Aliquots for Mg/Ca and clumped analyses are treated in the same manner following a modified cleaning procedure of foraminifera for trace element and isotopic analyses. We analysed eight species of planktonic foraminifera from coretop samples over a wide range of temperatures from 2 to 29°C. We provide a new clumped isotope temperature calibrations using subaqueous cave carbonates, which is consistent with recent studies. Tandem Mg/Ca–Δ47 results follow an exponential curve as predicted by temperature calibration equations. Observed deviations from the predicted Mg/Ca-Δ47 relationship are attributed to the effects of Fe-Mn oxide coatings, contamination, or dissolution of foraminiferal tests. This coupled approach provides a high degree of confidence in temperature estimates when Mg/Ca and Δ47 yield concordant results, and can be used to infer the past δ18O of seawater (δ18Osw) for paleoclimate studies

Zebularine reactivates silenced E-cadherin but unlike 5-Azacytidine does not induce switching from latent to lytic Epstein-Barr virus infection in Burkitt's lymphoma Akata cells

Epigenetic silencing of regulatory genes by aberrant methylation contributes to tumorigenesis. DNA methyltransferase inhibitors (DNMTI) represent promising new drugs for anti-cancer therapies. The DNMTI 5-Azacytidine is effective against myelodysplastic syndrome, but induces switching of latent to lytic Epstein-Barr virus (EBV) in vitro and results in EBV DNA demethylation with the potential of induction of lytic EBV in vivo. This is of considerable concern given that recurrent lytic EBV has been linked with an increased incidence of EBV-associated lymphomas. Based on the distinct properties of action we hypothesized that the newer DNMTI Zebularine might differ from 5-Azacytidine in its potential to induce switching from latent to lytic EBV. Here we show that both 5-Azacytidine and Zebularine are able to induce expression of E-cadherin, a cellular gene frequently silenced by hypermethylation in cancers, and thus demonstrate that both DNMTI are active in our experimental setting consisting of EBV-harboring Burkitt's lymphoma Akata cells. Quantification of mRNA expression of EBV genes revealed that 5-Azacytidine induces switching from latent to lytic EBV and, in addition, that the immediate-early lytic infection progresses to early and late lytic infection. Furthermore, 5-Azacytidine induced upregulation of the latent EBV genes LMP2A, LMP2B, and EBNA2 in a similar fashion as observed following switching of latent to lytic EBV upon cross-linking of the B-cell receptor. In striking contrast, Zebularine did not exhibit any effect neither on lytic nor on latent EBV gene expression. Thus, Zebularine might be safer than 5-Azacytidine for the treatment of cancers in EBV carriers and could also be applied against EBV-harboring tumors, since it does not induce switching from latent to lytic EBV which may result in secondary EBV-associated malignancies

Quantitative profiling of housekeeping and Epstein-Barr virus gene transcription in Burkitt lymphoma cell lines using an oligonucleotide microarray

BACKGROUND: The Epstein-Barr virus (EBV) is associated with lymphoid malignancies, including Burkitt's lymphoma (BL), and can transform human B cells in vitro. EBV-harboring cell lines are widely used to investigate lymphocyte transformation and oncogenesis. Qualitative EBV gene expression has been extensively described, but knowledge of quantitative transcription is lacking. We hypothesized that transcription levels of EBNA1, the gene essential for EBV persistence within an infected cell, are similar in BL cell lines. RESULTS: To compare quantitative gene transcription in the BL cell lines Namalwa, Raji, Akata, Jijoye, and P3HR1, we developed an oligonucleotide microarray chip, including 17 housekeeping genes, six latent EBV genes (EBNA1, EBNA2, EBNA3A, EBNA3C, LMP1, LMP2), and four lytic EBV genes (BZLF1, BXLF2, BKRF2, BZLF2), and used the cell line B95.8 as a reference for EBV gene transcription. Quantitative polymerase chain reaction assays were used to validate microarray results. We found that transcription levels of housekeeping genes differed considerably among BL cell lines. Using a selection of housekeeping genes with similar quantitative transcription in the tested cell lines to normalize EBV gene transcription data, we showed that transcription levels of EBNA1 were quite similar in very different BL cell lines, in contrast to transcription levels of other EBV genes. As demonstrated with Akata cells, the chip allowed us to accurately measure EBV gene transcription changes triggered by treatment interventions. CONCLUSION: Our results suggest uniform EBNA1 transcription levels in BL and that microarray profiling can reveal novel insights on quantitative EBV gene transcription and its impact on lymphocyte biology

X-ray Emission from Young Stellar Objects in the \epsilon Chamaeleontis Group: the Herbig Ae Star HD 104237 and Associated Low-Mass Stars

We present Chandra-HETGS observations of the Herbig Ae star HD 104237 and the associated young stars comprising lower mass stars, in the 0.15-1.75\msol mass range, in their pre-main sequence phase. The brightest X-ray source in the association is the central system harboring the Herbig Ae primary, and a K3 companion. Its X-ray variability indicates modulation possibly on time scales of the rotation period of the Herbig Ae star, and this would imply that the primary significantly contributes to the overall emission. The spectrum of the Herbig Ae+K3 system shows a soft component significantly more pronounced than in other K-type young stars. This soft emission is reminiscent of the unusually soft spectra observed for the single Herbig Ae stars HD 163296 and AB Aur, and therefore we tentatively attribute it to the Herbig Ae of the binary system. The HETGS spectrum shows strong emission lines corresponding to a wide range of plasma temperatures. The He-like triplet of MgXI and NeIX suggest the presence of plasma at densities of about $10^{12}$ cm$^{-3}$, possibly indicating accretion related X-ray production mechanism. The analysis of the zero-order spectra of the other sources indicates X-ray emission characteristics typical of pre-main sequence stars of similar spectral type, with the exception of the T Tauri HD104237-D, whose extremely soft emission is very similar to the emission of the classical T Tauri star TW Hya, and suggests X-ray production by shocked accreting plasma.Comment: accepted for publication on the Astrophysical Journa

Reducing Uncertainties in Carbonate Clumped Isotope Analysis Through Consistent Carbonate-Based Standardization

About a decade after its introduction, the field of carbonate clumped isotope thermometry is rapidly expanding because of the large number of possible applications and its potential to solve long‐standing questions in Earth Sciences. Major factors limiting the application of this method are the very high analytical precision required for meaningful interpretations, the relatively complex sample preparation procedures, and the mass spectrometric corrections needed. In this paper we first briefly review the evolution of the analytical and standardization procedures and discuss the major remaining sources of uncertainty. We propose that the use of carbonate standards to project the results to the carbon dioxide equilibrium scale can improve interlaboratory data comparability and help to solve long‐standing discrepancies between laboratories and temperature calibrations. The use of carbonates reduces uncertainties related to gas preparation and cleaning procedures and ensures equal treatment of samples and standards. We present a set of carbonate standards of diverse composition, discuss how they can be used to correct for mass spectrometric biases, and demonstrate that their use significantly improves the comparability among four laboratories. We propose that the use of these standards or of a similar set of carbonate standards will improve the comparability of data across laboratories.publishedVersio

Assessment of habitat‐specific competition for oral rabies vaccine baits between raccoons and opossums

Throughout the eastern United States, the National Rabies Management Program (NRMP) distributes oral rabies vaccine (ORV) baits to manage rabies virus circulation in raccoon (Procyon lotor) populations. The consumption of vaccine baits by non‐target species including Virginia opossums (Didelphis virginiana) may reduce the effectiveness of ORV programs, but competition for baits remains poorly quantified in many areas of the southeastern United States. We distributed placebo ORV baits injected with a biomarker across 4 land cover types (bottomland hardwood, upland pine, riparian, isolated wetland) on the Savannah River Site in South Carolina, USA, 2017–2019. We then trapped and collected whiskers from 247 raccoons and 78 opossums to assess biomarker presence using fluorescent microscopy. Our data revealed greater bait uptake probability by raccoons (estimated x̅= 0.30, 95% CI = 0.19–0.44) compared to opossums (estimated x̅ = 0.11, 95% CI = 0.05–0.23) across all cover types surveyed. Probability of bait consumption was not affected by cover type or the abundance of raccoons or opossums. Among raccoons, males were more likely to consume baits than females (estimated x̅ = 0.28, 95% CI = 0.17–0.44 for males and 0.14, 95% CI = 0.05–0.31 for females) and probability of consumption increased by 0.08 with each additional day trapped during the 10‐day trapping session. Uptake rates for raccoons were relatively low compared to other studies and not influenced by competition with opossums. These low consumption rates indicate that additional research addressing the roles of baiting season, bait density, and resource selection will be important to maximize ORV bait uptake by target species in these southeastern landscapes

Influence of landscape attributes on Virginia opossum density

TheVirginia opossum (Didelphis virginiana), North America\u27s only marsupial, has a range extending from southern Ontario, Canada, to the Yucatan Peninsula, Mexico, and from the Atlantic seaboard to the Pacific. Despite the Virginia opossum\u27s taxonomic uniqueness in relation to other mammals in North America and rapidly expanding distribution, its ecology remains relatively understudied. Our poor understanding of the ecology of this important mesopredator is especially pronounced in the rural southeastern United States. Our goal was to estimate effects of habitat on opossum density within an extensive multiyear spatial capture‐recapture study. Additionally, we compared the results of this spatial capture‐recapture analysis with a simple relative abundance index. Opossum densities in the relatively underdeveloped regions of the southeastern United States were lower compared to the more human‐dominated landscapes of the Northeast and Midwest. In the southeastern United States, Virginia opossums occurred at a higher density in bottomland swamp and riparian hardwood forest compared to upland pine (Pinus spp.) plantations and isolated wetlands. These results reinforce the notion that the Virginia opossum is commonly associated with land cover types adjacent to permanent water (bottomland swamps, riparian hardwood). The relatively low density of opossums at isolated wetland sites suggests that the large spatial scale of selection demonstrated by opossums gives the species access to preferable cover types within the same landscape

Long-term trends in hepatitis C prevalence, treatment uptake and liver-related events in the Swiss HIV Cohort Study

BACKGROUND AND AIMS: Treatment for chronic hepatitis C virus (HCV) infections changed dramatically in the last decade. We assessed changes in the prevalence of replicating HCV infection, treatment uptake and liver-related morbidity and mortality in persons with HIV (PWH) and hepatitis C in the Swiss HIV cohort study. METHODS: We included all cohort participants between 2002 and 2021. We assessed yearly prevalence of replicating HCV infection, overall and liver-related mortality, as well as the yearly incidence of liver-related events in persons with at least one documented positive HCV-RNA. RESULTS: Of 14 652 participants under follow-up, 2294 had at least one positive HCV-RNA measurement. Of those, 1316 (57%) ever received an HCV treatment. Treatment uptake increased from 8.1% in 2002 to a maximum of 32.6% in 2016. Overall, prevalence of replicating HCV infection declined from 16.5% in 2004 to 1.3% in 2021. HCV prevalence declined from 63.2% to 7.1% in persons who inject drugs, and from 4.1% to 0.6% in men who have sex with men. Among the 2294 persons with replicating HCV infection, overall mortality declined from a maximum of 3.3 per 100 patient-years (PY) to 1.1 per 100 PY, and incidence of liver-related events decreased from 1.4/100 PY to 0.2/100 PY. CONCLUSIONS: The introduction of DAA therapy was associated with a more than 10-fold reduction in prevalence of replicating HCV infection in PWH, approaching the estimates in the general population. Overall mortality and liver-related events declined substantially in persons living with HIV and hepatitis C

Long-term trends in hepatitis C prevalence, treatment uptake and liver-related events in the Swiss HIV Cohort Study.

BACKGROUND AND AIMS Treatment for chronic hepatitis C virus (HCV) infections changed dramatically in the last decade. We assessed changes in the prevalence of replicating HCV infection, treatment uptake and liver-related morbidity and mortality in persons with HIV (PWH) and hepatitis C in the Swiss HIV cohort study. METHODS We included all cohort participants between 2002 and 2021. We assessed yearly prevalence of replicating HCV infection, overall and liver-related mortality, as well as the yearly incidence of liver-related events in persons with at least one documented positive HCV-RNA. RESULTS Of 14 652 participants under follow-up, 2294 had at least one positive HCV-RNA measurement. Of those, 1316 (57%) ever received an HCV treatment. Treatment uptake increased from 8.1% in 2002 to a maximum of 32.6% in 2016. Overall, prevalence of replicating HCV infection declined from 16.5% in 2004 to 1.3% in 2021. HCV prevalence declined from 63.2% to 7.1% in persons who inject drugs, and from 4.1% to 0.6% in men who have sex with men. Among the 2294 persons with replicating HCV infection, overall mortality declined from a maximum of 3.3 per 100 patient-years (PY) to 1.1 per 100 PY, and incidence of liver-related events decreased from 1.4/100 PY to 0.2/100 PY. CONCLUSIONS The introduction of DAA therapy was associated with a more than 10-fold reduction in prevalence of replicating HCV infection in PWH, approaching the estimates in the general population. Overall mortality and liver-related events declined substantially in persons living with HIV and hepatitis C

Evaluation of Clinical and Immunological Markers for predicting Virological Failure in a HIV/AIDS treatment cohort in Busia, Kenya

In resource-limited settings where viral load (VL) monitoring is scarce or unavailable, clinicians must use immunological and clinical criteria to define HIV virological treatment failure. This study examined the performance of World Health Organization (WHO) clinical and immunological failure criteria in predicting virological failure in HIV patients receiving antiretroviral therapy (ART)