A negative carbon isotope excursion recorded in terrestrial and marine archives reflects massive carbon emissions into the exogenic carbon reservoir during the Paleocene-Eocene Thermal Maximum. Yet, ...discrepancies in carbon isotope excursion estimates from different sample types lead to substantial uncertainties in the source, scale, and timing of carbon emissions. Here we show that membrane lipids of marine planktonic archaea reliably record both the carbon isotope excursion and surface ocean warming during the Paleocene-Eocene Thermal Maximum. Novel records of the isotopic composition of crenarchaeol constrain the global carbon isotope excursion magnitude to -4.0 ± 0.4‰, consistent with emission of >3000 Pg C from methane hydrate dissociation or >4400 Pg C for scenarios involving emissions from geothermal heating or oxidation of sedimentary organic matter. A pre-onset excursion in the isotopic composition of crenarchaeol and ocean temperature highlights the susceptibility of the late Paleocene carbon cycle to perturbations and suggests that climate instability preceded the Paleocene-Eocene Thermal Maximum.
Archaeal membrane lipids known as glycerol dibiphytanyl glycerol tetraethers (GDGTs) are the basis of the TEX86 paleotemperature proxy. Because GDGTs preserved in marine sediments are thought to ...originate mainly from planktonic, ammonia-oxidizing Thaumarchaeota, the basis of the correlation between TEX86 and sea surface temperature (SST) remains unresolved: How does TEX86 predict surface temperatures, when maximum thaumarchaeal activity occurs below the surface mixed layer and TEX86 does not covary with in situ growth temperatures? Here we used isothermal studies of the model thaumarchaeon Nitrosopumilus maritimus SCM1 to investigate how GDGT composition changes in response to ammonia oxidation rate. We used continuous culture methods to avoid potential confounding variables that can be associated with experiments in batch cultures. The results show that the ring index scales inversely (R² = 0.82) with ammonia oxidation rate (ϕ), indicating that GDGT cyclization depends on available reducing power. Correspondingly, the TEX86 ratio decreases by an equivalent of 5.4 °C of calculated temperature over a 5.5 fmol·cell−1·d−1 increase in ϕ. This finding reconciles other recent experiments that have identified growth stage and oxygen availability as variables affecting TEX86. Depth profiles from the marine water column show minimum TEX86 values at the depth of maximum nitrification rates, consistent with our chemostat results. Our findings suggest that the TEX86 signal exported from the water column is influenced by the dynamics of ammonia oxidation. Thus, the global TEX86–SST calibration potentially represents a composite of regional correlations based on nutrient dynamics and global correlations based on archaeal community composition and temperature.
DNA-based vaccines have been safe but weakly immunogenic in humans to date.
We sought to determine the safety, tolerability, and immunogenicity of ADVAX, a multigenic HIV-1 DNA vaccine candidate, ...injected intramuscularly by in vivo electroporation (EP) in a Phase-1, double-blind, randomized placebo-controlled trial in healthy volunteers. Eight volunteers each received 0.2 mg, 1 mg, or 4 mg ADVAX or saline placebo via EP, or 4 mg ADVAX via standard intramuscular injection at weeks 0 and 8. A third vaccination was administered to eleven volunteers at week 36. EP was safe, well-tolerated and considered acceptable for a prophylactic vaccine. EP delivery of ADVAX increased the magnitude of HIV-1-specific cell mediated immunity by up to 70-fold over IM injection, as measured by gamma interferon ELISpot. The number of antigens to which the response was detected improved with EP and increasing dosage. Intracellular cytokine staining analysis of ELISpot responders revealed both CD4+ and CD8+ T cell responses, with co-secretion of multiple cytokines.
This is the first demonstration in healthy volunteers that EP is safe, tolerable, and effective in improving the magnitude, breadth and durability of cellular immune responses to a DNA vaccine candidate.
ClinicalTrials.gov NCT00545987.
Parents raising youth in high-risk communities at times rely on active, involved monitoring strategies in order to increase both knowledge about youth activities and the likelihood that adolescents ...will abstain from problem behavior. Key monitoring literature suggests that some of these active monitoring strategies predict increases in adolescent problem behavior rather than protect against it. However, this literature has studied racially homogenous, low-risk samples, raising questions about generalizability. With a diverse sample of youth (N = 753; 58% male; 46% Black) and families living in high-risk neighborhoods, bidirectional longitudinal relations were examined among three aspects of monitoring (parental discussions of daily activities, parental curfew rules, and adolescent communication with parents), parental knowledge, and youth delinquency. Parental discussion of daily activities was the strongest predictor of parental knowledge, which negatively predicted delinquency. However, these aspects of monitoring did not predict later delinquency. Findings were consistent across gender and race/urbanicity. Results highlight the importance of active and involved parental monitoring strategies in contexts where they are most needed.
•Maximum GDGT concentration occurred at the base of the NO2− maximum.•Between 0 and 1000 m, > 98% of GDGT inventory present below the NO2− maximum.•GDGT export from ca. 80–250 m consistent with TEX86 ...and 2/3 ratio in sediments.•TEX86 remarkably insensitive to change in modeled export depth.•Local productivity an important control on exported GDGT ratio values.
The TEX86 paleotemperature proxy is based on the distribution of archaeal glycerol dibiphytanyl glycerol tetraether (GDGT) lipids preserved in marine sediments, yet both the influence of different physiological factors on the structural distribution of GDGTs and the mechanism(s) by which GDGTs is(are) exported to marine sediments remain(s) unresolved. We investigated the abundance and structural distribution of GDGTs in the South-west and Equatorial Atlantic Ocean in four water column profiles spanning 48 degrees of latitude. The depth distribution was consistent with production by ammonia-oxidizing Thaumarchaeota; maximum GDGT concentration occurred at the base of the NO2− maximum, core GDGTs dominated the structural distribution in surface waters above the NO2− maximum, and intact polar GDGTs – potentially indicating live cells – were more abundant below the NO2− maximum. Between 0 and1000 m, > 98% of the integrated GDGT inventory was present in waters at and below the NO2− maximum. Depth profiles of TEX86 temperature values displayed local minima at the NO2− maximum, while the ratio of GDGT-2:GDGT-3 increased with depth. A model based on the results predicts an average depth of origin for GDGTs exported to sediments between ca. 80–250 m. In the model, exported TEX86 values are remarkably insensitive to change in the average depth of origin of GDGTs. However, TEX86 values exported from the water column appear to reflect euphotic zone productivity, possibly due to the correlative intensity of organic matter remineralization providing substrates for ammonia oxidation. Predicting the influence of these regional controls on sedimentary TEX86 records requires a better understanding of the interaction between GDGT production, particle dynamics, and the depth of origin for exported organic matter.
Physical activity (PA) is a well-documented and accepted adjunct therapy for the maintenance and improvement of long-term health in cystic fibrosis (CF). Although the benefits of PA for CF ...populations are well-established, adherence to PA programmes within this population remains low. This study aimed to investigate the factors that influence engagement in physical activity, and to explore exercise preferences, among adults with cystic fibrosis (CF).
Semi-structured telephone interviews were conducted. Participants were twenty-one adults (mean age 35 years, SD ± 8) with an established diagnosis of CF, living in Ireland. Interview scripts were digitally recorded and transcribed verbatim. Thematic analysis was used to analyse the data.
Four main themes emerged: barriers, motives, value of exercise-related outcomes, and exercise preferences. The main barriers included: low energy levels, time, the weather, and exercise-related confidence. Enjoyment and perceived competence underpinned autonomous motivation. Participants who self-identified as being regularly active valued personally identified exercise-related outcomes such as, accomplishment and affect regulation. Participants indicated a preference for home-based physical activity programs compared to gym- or facility-based programs.
Interventions aimed at promoting physical activity among adults with CF should involve programs that foster autonomous motivation, enjoyable activities, personally identified outcomes, competence and that can be conducted from the home environment.
To increase physical activity participation among adults with CF, interventions that can be conducted from the home environment, that pay attention to the patients' personally-valued exercise outcomes may be required.
Gray wolves (Canis lupus) were reintroduced to Idaho, USA, in 1995–1996. The removal of Endangered Species Act protections in 2011 transferred wolf management to the state where wolves were ...subsequently classified as a harvested (i.e., hunted, trapped) big game species. We implemented a camera‐based survey across Idaho from 2016–2021 as part of a population monitoring program. We used the resulting camera images in multi‐year, dynamic and single‐season occupancy models to examine potential changes in the asymptotic proportion of area occupied by wolves and assess the effect of cumulative wolf harvest from 2016–2021 on occupancy in the last year of the study, 2021. We also wanted to understand how habitat, prey, humans, harvest, livestock, and prey‐related wolf removals affected wolf occupancy through their effects on colonization and extinction of occupancy cells through time. Statewide wolf occupancy did not change appreciably over the course of our study, with the proportion of survey cells occupied at an estimated high of 0.44 ± 0.03 (SE) in 2018 and a low of 0.39 ± 0.03 in 2020. Wolf colonization (i.e., probability that a cell switched from unoccupied to occupied between years) was positively associated with forest cover, images of humans, and the percent of neighboring cells that were occupied. Cell extinction (i.e., probability of switching from occupied to unoccupied between years) was negatively associated with neighboring cell occupancy. There were non‐linear relationships between wolf harvest, colonization, and extinction. The single‐season occupancy model demonstrated a positive relationship between harvest and occupancy at low to moderate levels of harvest (10–30%), but there was also evidence that high levels of harvest (>30%) reduce occupancy. Our results indicate that although harvest might influence wolf occupancy at local scales, wolf occupancy remained relatively constant across the state and wolves remained well distributed across Idaho during the study.
We implemented a camera‐based survey for wolves across Idaho from 2016–2021 as part of a population monitoring program. Our results indicate that although harvest might influence wolf occupancy at local scales, wolf occupancy remained relatively constant and wolves remained well distributed across Idaho during the study.
Thaumarchaeota, the major sources of marine glycerol dibiphytanyl glycerol tetraether lipids (GDGTs), are believed to fix the majority of their carbon directly from dissolved inorganic carbon (DIC). ...The delta super(13)C values of GDGTs ( delta super(13)C sub(GDGT)) may be powerful tools for reconstructing variations in the ocean carbon cycle, including paleoproductivity and water mass circulation, if they can be related to values of delta super(13)C sub(DIC). To date, isotope measurements primarily are made on the C sub(40) biphytane skeletons of GDGTs, rather than on complete tetraether structures. This approach erases information revealed by the isotopic heterogeneity of GDGTs within a sample and may impart an isotopic fractionation associated with the ether cleavage. To circumvent these issues, we present delta super(13)C values for GDGTs from twelve recent sediments representing ten continental margin locations. Samples are purified by orthogonal dimensions of HPLC, followed by measurement of delta super(13)C values by Spooling Wire Microcombustion (SWiM)-isotope ratio mass spectrometry (IRMS) with 1 sigma precision and accuracy of plus or minus 0.25ppt. Using this approach, we confirm that GDGTs, generally around -19ppt, are isotopically "heavy" compared to other marine lipids. However, measured delta super(13)C sub(GDGT) values are inconsistent with predicted values based on the super(13)C content of DIC in the overlying water column and the previously-published biosynthetic isotope fractionation for a pure culture of an autotrophic marine thaumarchaeon. In some sediments, the isotopic composition of individual GDGTs differs, indicating multiple source inputs. The data appear to confirm that crenarchaeol primarily is a biomarker for Thaumarchaeota, but its delta super(13)C values still cannot be explained solely by autotrophic carbon fixation. Overall the complexity of the results suggests that both organic carbon assimilation (ca. 25% of total carbon) and multiple source(s) of exogenous GDGTs (contributing generally <30% of input to sediments) are necessary to explain the observed delta super(13)C sub(GDGT) values. The results suggest caution when interpreting the total inputs of GDGTs to sedimentary records. Biogenic or open-slope sediments, rather than clastic basinal or shallow shelf sediments, are preferred locations for generating minimally-biased GDGT proxy records.
Ancestral cyanobacteria are assumed to be prominent primary producers after the Great Oxidation Event ≈2.4 to 2.0 billion years (Ga) ago, but carbon isotope fractionation by extant marine ...cyanobacteria (α-cyanobacteria) is inconsistent with isotopic records of carbon fixation by primary producers in the mid-Proterozoic eon (1.8 to 1.0 Ga ago). To resolve this disagreement, we quantified carbon isotope fractionation by a wild-type planktic β-cyanobacterium (
sp. PCC 7002), an engineered Proterozoic analog lacking a CO
-concentrating mechanism, and cyanobacterial mats. At mid-Proterozoic pH and
CO
values, carbon isotope fractionation by the wild-type β-cyanobacterium is fully consistent with the Proterozoic carbon isotope record, suggesting that cyanobacteria with CO
-concentrating mechanisms were apparently the major primary producers in the pelagic Proterozoic ocean, despite atmospheric CO
levels up to 100 times modern. The selectively permeable microcompartments central to cyanobacterial CO
-concentrating mechanisms ("carboxysomes") likely emerged to shield rubisco from O
during the Great Oxidation Event.
We conducted a Phase I dose-escalation trial of ADMVA, a Clade-B'/C-based HIV-1 candidate vaccine expressing env, gag, pol, nef, and tat in a modified vaccinia Ankara viral vector. Sequences were ...derived from a prevalent circulating HIV-1 recombinant form in Yunnan, China, an area of high HIV incidence. The objective was to evaluate the safety and immunogenicity of ADMVA in human volunteers.
ADMVA or placebo was administered intramuscularly at months 0, 1 and 6 to 50 healthy adult volunteers not at high risk for HIV-1. In each dosage group 1x10(7) (low), 5x10(7) (mid), or 2.5x10(8) pfu (high) volunteers were randomized in a 3:1 ratio to receive ADMVA or placebo in a double-blinded design. Subjects were followed for local and systemic reactogenicity, adverse events including cardiac adverse events, and clinical laboratory parameters. Study follow up was 18 months. Humoral immunogenicity was evaluated by anti-gp120 binding ELISA, immunoflourescent staining, and HIV-1 neutralization. Cellular immunogenicity was assessed by a validated IFNgamma ELISpot assay and intracellular cytokine staining. Anti-vaccinia binding titers were measured by ELISA. ADMVA was generally well-tolerated, with no vaccine-related serious adverse events or cardiac adverse events. Local or systemic reactogenicity events were reported by 77% and 78% of volunteers, respectively. The majority of events were of mild intensity. The IFNgamma ELISpot response rate to any HIV antigen was 0/12 (0%) in the placebo group, 3/12 (25%) in the low dosage group, 6/12 (50%) in the mid dosage group, and 8/13 (62%) in the high dosage group. Responses were often multigenic and occasionally persisted up to one year post vaccination. Antibodies to gp120 were detected in 0/12 (0%), 8/13 (62%), 6/12 (50%) and 10/13 (77%) in the placebo, low, mid, and high dosage groups, respectively. Antibodies persisted up to 12 months after vaccination, with a trend toward agreement with the ability to neutralize HIV-1 SF162 in vitro. Two volunteers mounted antibodies that were able to neutralize clade-matched viruses.
ADMVA was well-tolerated and elicited durable humoral and cellular immune responses.
Clinicaltrials.gov NCT00252148.
PDF
