Cracking the antigenic code of mycobacteria: CFP-10/ESAT-6 tuberculosis skin test and misleading results.

There are different tuberculosis diagnostic tools available that detect an antigen-specific immune response. The present study aims to evaluate the potential of cross-reactive responses of a CFP-10 and ESAT-6 antigen-based TB test using bioinformatics tools. The study found that the presence of the sequences coding for the CFP-10 and ESAT-6 antigens in mycobacterial genomes is not associated with their pathogenicity, and not even consistent within a single species among its strains, which can lead to either false positive or false negative test results. The data that was analyzed included genome assemblies of all available mycobacterial strains obtained from the NCBI Genome database, while the standalone BLAST and tblastn programs were utilized to detect the presence of the CFP-10 and ESAT-6 sequences. The findings revealed that a number of non-pathogenic mycobacteria contained the aforementioned sequences, while some pathogenic mycobacteria did not, indicating that a standard tuberculin skin test should be more preferable for detecting various pathogenic mycobacteria compared to antigen-specific tests. In the Mycobacterium tuberculosis complex (MTBC), the proportion of positive strains varied within individual species, indicating a complex relationship. Among non-tuberculous mycobacteria (NTMB), more than half of the analyzed species did not contain these sequences which is consistent with their non-pathogenicity. Further research is necessary to fully comprehend the relationship between MTBC pathogenicity and the CFP-10 and ESAT-6 sequences. This could lead to a conclusion that a standard tuberculin skin test, although non-specific due to the undefined antigen content, may be able to detect various pathogenic mycobacteria in a more reliable manner than antigen-specific tests.

Moderate greenhouse climate and rapid carbonate formation after Marinoan snowball Earth.

When the Marinoan snowball Earth deglaciated in response to high atmospheric carbon dioxide (CO2) concentrations, the planet warmed rapidly. It is commonly hypothesized that the ensuing supergreenhouse climate then declined slowly over hundreds of thousands of years through continental weathering. However, how the ocean affected atmospheric CO2 in the snowball Earth aftermath has never been quantified. Here we show that the ocean's carbon cycle drives the supergreenhouse climate evolution via a set of different mechanisms, triggering scenarios ranging from a rapid decline to an intensification of the supergreenhouse climate. We further identify the rapid formation of carbonate sediments from pre-existing ocean alkalinity as a possible explanation for the enigmatic origin of Marinoan cap dolostones. This work demonstrates that a moderate and relatively short-lived supergreenhouse climate following the Marinoan snowball Earth is a plausible scenario that is in accordance with geological data, challenging the previous hypothesis.

Historical increases in land-derived nutrient inputs may alleviate effects of a changing physical climate on the oceanic carbon cycle.

The implications of climate change and other human perturbations on the oceanic carbon cycle are still associated with large uncertainties. Global-scale modelling studies are essential to investigate anthropogenic perturbations of oceanic carbon fluxes but, until now, they have not considered the impacts of temporal changes in riverine and atmospheric inputs of P and N on the marine net biological productivity (NPP) and air-sea CO2 exchange (FCO2 ). To address this, we perform a series of simulations using an enhanced version of the global ocean biogeochemistry model HAMOCC to isolate effects arising from (1) increasing atmospheric CO2  levels, (2) a changing physical climate and (3) alterations in inputs of terrigenous P and N on marine carbon cycling over the 1905-2010 period. Our simulations reveal that our first-order approximation of increased terrigenous nutrient inputs causes an enhancement of 2.15 Pg C year-1 of the global marine NPP, a relative increase of +5% over the simulation period. This increase completely compensates the simulated NPP decrease as a result of increased upper ocean stratification of -3% in relative terms. The coastal ocean undergoes a global relative increase of 14% in NPP arising largely from increased riverine inputs, with regional increases exceeding 100%, for instance on the shelves of the Bay of Bengal. The imprint of enhanced terrigenous nutrient inputs is also simulated further offshore, inducing a 1.75 Pg C year-1 (+4%) enhancement of the NPP in the open ocean. This finding implies that the perturbation of carbon fluxes through coastal eutrophication may extend further offshore than that was previously assumed. While increased nutrient inputs are the largest driver of change for the CO2 uptake at the regional scale and enhance the global coastal ocean CO2 uptake by 0.02 Pg C year-1 , they only marginally affect the FCO2 of the open ocean over our study's timeline.

The Climate Response to Emissions Reductions Due to COVID-19: Initial Results From CovidMIP.

Many nations responded to the corona virus disease-2019 (COVID-19) pandemic by restricting travel and other activities during 2020, resulting in temporarily reduced emissions of CO2, other greenhouse gases and ozone and aerosol precursors. We present the initial results from a coordinated Intercomparison, CovidMIP, of Earth system model simulations which assess the impact on climate of these emissions reductions. 12 models performed multiple initial-condition ensembles to produce over 300 simulations spanning both initial condition and model structural uncertainty. We find model consensus on reduced aerosol amounts (particularly over southern and eastern Asia) and associated increases in surface shortwave radiation levels. However, any impact on near-surface temperature or rainfall during 2020-2024 is extremely small and is not detectable in this initial analysis. Regional analyses on a finer scale, and closer attention to extremes (especially linked to changes in atmospheric composition and air quality) are required to test the impact of COVID-19-related emission reductions on near-term climate.

Time of Emergence and Large Ensemble Intercomparison for Ocean Biogeochemical Trends.

Anthropogenically forced changes in ocean biogeochemistry are underway and critical for the ocean carbon sink and marine habitat. Detecting such changes in ocean biogeochemistry will require quantification of the magnitude of the change (anthropogenic signal) and the natural variability inherent to the climate system (noise). Here we use Large Ensemble (LE) experiments from four Earth system models (ESMs) with multiple emissions scenarios to estimate Time of Emergence (ToE) and partition projection uncertainty for anthropogenic signals in five biogeochemically important upper-ocean variables. We find ToEs are robust across ESMs for sea surface temperature and the invasion of anthropogenic carbon; emergence time scales are 20-30 yr. For the biological carbon pump, and sea surface chlorophyll and salinity, emergence time scales are longer (50+ yr), less robust across the ESMs, and more sensitive to the forcing scenario considered. We find internal variability uncertainty, and model differences in the internal variability uncertainty, can be consequential sources of uncertainty for projecting regional changes in ocean biogeochemistry over the coming decades. In combining structural, scenario, and internal variability uncertainty, this study represents the most comprehensive characterization of biogeochemical emergence time scales and uncertainty to date. Our findings delineate critical spatial and duration requirements for marine observing systems to robustly detect anthropogenic change.

Tracking Improvement in Simulated Marine Biogeochemistry Between CMIP5 and CMIP6.

Purpose of Review: The changes or updates in ocean biogeochemistry component have been mapped between CMIP5 and CMIP6 model versions, and an assessment made of how far these have led to improvements in the simulated mean state of marine biogeochemical models within the current generation of Earth system models (ESMs). Recent Findings: The representation of marine biogeochemistry has progressed within the current generation of Earth system models. However, it remains difficult to identify which model updates are responsible for a given improvement. In addition, the full potential of marine biogeochemistry in terms of Earth system interactions and climate feedback remains poorly examined in the current generation of Earth system models. Summary: Increasing availability of ocean biogeochemical data, as well as an improved understanding of the underlying processes, allows advances in the marine biogeochemical components of the current generation of ESMs. The present study scrutinizes the extent to which marine biogeochemistry components of ESMs have progressed between the 5th and the 6th phases of the Coupled Model Intercomparison Project (CMIP).

Detection of unprecedented allene oxide synthase member of CYP74B subfamily: CYP74B33 of carrot (Daucus carota).

Enzymes of CYP74 family widespread in higher plants control the metabolism of fatty acid hydroperoxides to numerous bioactive oxylipins. Hydroperoxide lyases (HPLs, synonym: hemiacetal synthases) of CYP74B subfamily belong to the most common CYP74 enzymes. HPLs isomerize the hydroperoxides to the short-lived hemiacetals, which are spontaneously decomposed to aldehydes and aldoacids. All CYP74Bs studied yet except the CYP74B16 (flax divinyl ether synthase, LuDES) possessed the 13-HPL activity. Present work reports the cloning of the expressed CYP74B33 gene of carrot (Daucus carota L.) and studies of catalytic properties of the recombinant CYP74B33 protein. In contrast to all CYP74B proteins studied yet, CYP74B33 behaved differently in few respects. Firstly, the preferred substrates of CYP74B33 are 9-hydroperoxides. Secondly and most importantly, CYP74B33 exhibits the 9-allene oxide synthase (AOS) activity. For example, the 9(S)-hydroperoxide of linoleic acid (9-HPOD) underwent the conversion to α-ketol via the short-lived allene oxide. Uncommonly, the 9-HPOD conversion affords a minority of cis-10-oxo-11-phytoenoic acid, which is also produced by CYP74C but not the CYP74A AOSs. The similar product patterns were observed upon the incubations of CYP74B33 with 9(S)-hydroperoxide of α-linolenic acid. The enzyme possessed a mixed HPL, AOS, and the epoxyalcohol synthase activity toward the 13-hydroperoxides, but the total activity was much lower than toward 9-hydroperoxides. Thus, the obtained results show that CYP74B33 is an unprecedented 9-AOS within the CYP74B subfamily.

Decadal trends in the ocean carbon sink.

Measurements show large decadal variability in the rate of [Formula: see text] accumulation in the atmosphere that is not driven by [Formula: see text] emissions. The decade of the 1990s experienced enhanced carbon accumulation in the atmosphere relative to emissions, while in the 2000s, the atmospheric growth rate slowed, even though emissions grew rapidly. These variations are driven by natural sources and sinks of [Formula: see text] due to the ocean and the terrestrial biosphere. In this study, we compare three independent methods for estimating oceanic [Formula: see text] uptake and find that the ocean carbon sink could be responsible for up to 40% of the observed decadal variability in atmospheric [Formula: see text] accumulation. Data-based estimates of the ocean carbon sink from [Formula: see text] mapping methods and decadal ocean inverse models generally agree on the magnitude and sign of decadal variability in the ocean [Formula: see text] sink at both global and regional scales. Simulations with ocean biogeochemical models confirm that climate variability drove the observed decadal trends in ocean [Formula: see text] uptake, but also demonstrate that the sensitivity of ocean [Formula: see text] uptake to climate variability may be too weak in models. Furthermore, all estimates point toward coherent decadal variability in the oceanic and terrestrial [Formula: see text] sinks, and this variability is not well-matched by current global vegetation models. Reconciling these differences will help to constrain the sensitivity of oceanic and terrestrial [Formula: see text] uptake to climate variability and lead to improved climate projections and decadal climate predictions.

Developments in the MPI-M Earth System Model version 1.2 (MPI-ESM1.2) and Its Response to Increasing CO2.

A new release of the Max Planck Institute for Meteorology Earth System Model version 1.2 (MPI-ESM1.2) is presented. The development focused on correcting errors in and improving the physical processes representation, as well as improving the computational performance, versatility, and overall user friendliness. In addition to new radiation and aerosol parameterizations of the atmosphere, several relatively large, but partly compensating, coding errors in the model's cloud, convection, and turbulence parameterizations were corrected. The representation of land processes was refined by introducing a multilayer soil hydrology scheme, extending the land biogeochemistry to include the nitrogen cycle, replacing the soil and litter decomposition model and improving the representation of wildfires. The ocean biogeochemistry now represents cyanobacteria prognostically in order to capture the response of nitrogen fixation to changing climate conditions and further includes improved detritus settling and numerous other refinements. As something new, in addition to limiting drift and minimizing certain biases, the instrumental record warming was explicitly taken into account during the tuning process. To this end, a very high climate sensitivity of around 7 K caused by low-level clouds in the tropics as found in an intermediate model version was addressed, as it was not deemed possible to match observed warming otherwise. As a result, the model has a climate sensitivity to a doubling of CO2 over preindustrial conditions of 2.77 K, maintaining the previously identified highly nonlinear global mean response to increasing CO2 forcing, which nonetheless can be represented by a simple two-layer model.

The immunomodulatory activity of the extracts and complexes of biologically active compounds of Galium verum L. herb.

The present article discusses the results of an immunomodulatory activity of Galii veri herba, Galium verum herb (Galium verum L., Rubiaceae) fluid water extract and the effect of the polysaccharide and phenolic complexes of the letter on the immunomodulatory activity. The same extract was fractionated into a polysaccharide complex (PSC) and a polyphenolic complex (PPC). In the obtained substances, the contents of hydroxycinnamic derivates, flavonoids and polyphenols were determined spectrophotometrically; polysaccharides were quantified gravimetrically; the immunomodulatory activity of the substances was determined in the reaction of lymphocyte blast transformation. It has been established that the fluid extract of Galium verum herb contains 6.3% polysaccharides, 4.2% hydroxycinnamic derivates expressed as chlorogenic acid, 0.4% flavonoids expressed as rutin, 3.7% polyphenols expressed as gallic acid. PPC contains 4.48% hydroxycinnamic derivates expressed as chlorogenic acid, 0.43% flavonoids expressed as rutin, and 3.95% polyphenols expressed as gallic acid. The lowest immunomodulatory activity was found for PPC. A significantly higher activity was determined for PSC. The highest immunomodulatory activity was established for the fluid extract at a dilution of 1/20, its activity being by 59.4% higher compared with the lymphocyte spontaneous transformation and by 18.5% higher than that of the reference substance PHA. The obtained results enable an assumption of a synergistic effect of PPC and PSC of Galium verum herb fluid extract on the potency of its immunomodulatory activity. Key words: Galium verum L. • immunomodulatory activity • lymphocyte blast transformation • fluid water extract • polysaccharide complex • polyphenols complex.

Allene Oxide Synthase Pathway in Cereal Roots: Detection of Novel Oxylipin Graminoxins.

Young roots of wheat, barley, and sorghum, as well as methyl jasmonate pretreated rice seedlings, undergo an unprecedented allene oxide synthase pathway targeted to previously unknown oxylipins 1-3. These Favorskii-type products, (4Z)-2-pentyl-4-tridecene-1,13-dioic acid (1), (2'Z)-2-(2'-octenyl)-decane-1,10-dioic acid (2), and (2'Z,5'Z)-2-(2',5'-octadienyl)-decane-1,10-dioic acid (3), have a carboxy function at the side chain, as revealed by their MS and NMR spectral data. Compounds 1-3 were the major oxylipins detected, along with the related α-ketols. Products 1-3 were biosynthesized from (9Z,11E,13S)-13-hydroperoxy-9,11-octadecadienoic acid, (9S,10E,12Z)-9-hydroperoxy-10,12-octadecadienoic acid (9-HPOD), and (9S,10E,12Z,15Z)-9-hydroperoxy-10,12,15-octadecatrienoic acid, respectively, via the corresponding allene oxides and cyclopropanones. The data indicate that conversion of the allene oxide into the cyclopropanone is controlled by soluble cyclase. The short-lived cyclopropanones are hydrolyzed to products 1-3. The collective name "graminoxins" has been ascribed to oxylipins 1-3.

Double function hydroperoxide lyases/epoxyalcohol synthases (CYP74C) of higher plants: identification and conversion into allene oxide synthases by site-directed mutagenesis.

The CYP74C subfamily of fatty acid hydroperoxide transforming enzymes includes hydroperoxide lyases (HPLs) and allene oxide synthases (AOSs). This work reports a new facet of the putative CYP74C HPLs. Initially, we found that the recombinant CYP74C13_MT (Medicago truncatula) behaved predominantly as the epoxyalcohol synthase (EAS) towards the 9(S)-hydroperoxide of linoleic acid. At the same time, the CYP74C13_MT mostly possessed the HPL activity towards the 13(S)-hydroperoxides of linoleic and α-linolenic acids. To verify whether this dualistic behaviour of CYP74C13_MT is occasional or typical, we also examined five similar putative HPLs (CYP74C). These were CYP74C4_ST (Solanum tuberosum), CYP74C2 (Cucumis melo), CYP74C1_CS and CYP74C31 (both of Cucumis sativus), and CYP74C13_GM (Glycine max). All tested enzymes behaved predominantly as EAS toward 9-hydroperoxide of linoleic acid. Oxiranyl carbinols such as (9S,10S,11S,12Z)-9,10-epoxy-11-hydroxy-12-octadecenoic acids were the major EAS products. Besides, the CYP74C31 possessed an additional minor 9-AOS activity. The mutant forms of CYP74C13_MT, CYP74C1_CS, and CYP74C31 with substitutions at the catalytically essential domains, namely the "hydroperoxide-binding domain" (I-helix), or the SRS-1 domain near the N-terminus, showed strong AOS activity. These HPLs to AOSs conversions were observed for the first time. Until now a large part of CYP74C enzymes has been considered as 9/13-HPLs. Notwithstanding, these results show that all studied putative CYP74C HPLs are in fact the versatile HPL/EASs that can be effortlessly mutated into specific AOSs.

Rapid emergence of climate change in environmental drivers of marine ecosystems.

Climate change is expected to modify ecological responses in the ocean, with the potential for important effects on the ecosystem services provided to humankind. Here we address the question of how rapidly multiple drivers of marine ecosystem change develop in the future ocean. By analysing an ensemble of models we find that, within the next 15 years, the climate change-driven trends in multiple ecosystem drivers emerge from the background of natural variability in 55% of the ocean and propagate rapidly to encompass 86% of the ocean by 2050 under a 'business-as-usual' scenario. However, we also demonstrate that the exposure of marine ecosystems to climate change-induced stress can be drastically reduced via climate mitigation measures; with mitigation, the proportion of ocean susceptible to multiple drivers within the next 15 years is reduced to 34%. Mitigation slows the pace at which multiple drivers emerge, allowing an additional 20 years for adaptation in marine ecological and socio-economic systems alike.

Physiological and Biochemical Mechanisms of Lifespan Regulation in Rats Kept Under Various Light Conditions.

BACKGROUND: The present study was aimed to identify how age-related changes in some physiological and biochemical systems are related to changes in the life span of rats with long-term pineal gland hypo- and hyperfunction induced by constant light and constant darkness, respectively. METHODS: At the age of 25 days the rats were randomly divided into 3 groups: standard light/dark regimen (LD), constant light (LL) and constant darkness (DD). Age-related Antioxidant System (AOS) changes in liver tissues, alteration of immunoreactivity in blood smears were investigated, pubescence and lifespan of the animals were determined. RESULTS: Modification of the level of melatonin synthesis induced by constant light results in interrelated rearrangements in the functioning of the investigated physiological systems. Elevated activity of the antioxidant system extends the lifespan, while at the same time slowing down pubescence and altering the morpho-functional properties of leukocytes in blood. CONCLUSION: The absence of light/dark alternation (constant light and constant darkness) affects only those physiological indices that follow the organism's circadian rhythms (Activity of Antioxidant Enzymes (AOE), levels of individual immune system cell types), whereas changes in the parameters not governed by circadian fluctuations (vitamin concentrations, pubescence, and aging) depend on the level of melatonin produced by the pineal gland.

Decadal predictions of the North Atlantic CO2 uptake.

As a major CO2 sink, the North Atlantic, especially its subpolar gyre region, is essential for the global carbon cycle. Decadal fluctuations of CO2 uptake in the North Atlantic subpolar gyre region are associated with the evolution of the North Atlantic Oscillation, the Atlantic meridional overturning circulation, ocean mixing and sea surface temperature anomalies. While variations in the physical state of the ocean can be predicted several years in advance by initialization of Earth system models, predictability of CO2 uptake has remained unexplored. Here we investigate the predictability of CO2 uptake variations by initialization of the MPI-ESM decadal prediction system. We find large multi-year variability in oceanic CO2 uptake and demonstrate that its potential predictive skill in the western subpolar gyre region is up to 4-7 years. The predictive skill is mainly maintained in winter and is attributed to the improved physical state of the ocean.

Net primary productivity estimates and environmental variables in the Arctic Ocean: An assessment of coupled physical-biogeochemical models.

The relative skill of 21 regional and global biogeochemical models was assessed in terms of how well the models reproduced observed net primary productivity (NPP) and environmental variables such as nitrate concentration (NO3), mixed layer depth (MLD), euphotic layer depth (Zeu), and sea ice concentration, by comparing results against a newly updated, quality-controlled in situ NPP database for the Arctic Ocean (1959-2011). The models broadly captured the spatial features of integrated NPP (iNPP) on a pan-Arctic scale. Most models underestimated iNPP by varying degrees in spite of overestimating surface NO3, MLD, and Zeu throughout the regions. Among the models, iNPP exhibited little difference over sea ice condition (ice-free versus ice-influenced) and bottom depth (shelf versus deep ocean). The models performed relatively well for the most recent decade and toward the end of Arctic summer. In the Barents and Greenland Seas, regional model skill of surface NO3 was best associated with how well MLD was reproduced. Regionally, iNPP was relatively well simulated in the Beaufort Sea and the central Arctic Basin, where in situ NPP is low and nutrients are mostly depleted. Models performed less well at simulating iNPP in the Greenland and Chukchi Seas, despite the higher model skill in MLD and sea ice concentration, respectively. iNPP model skill was constrained by different factors in different Arctic Ocean regions. Our study suggests that better parameterization of biological and ecological microbial rates (phytoplankton growth and zooplankton grazing) are needed for improved Arctic Ocean biogeochemical modeling.

Scenarios of temporal and spatial evolution of hexabromocyclododecane in the North Sea.

Spatial and temporal distribution of the flame retardant hexabromocyclododecane (HBCD) in the North Sea was examined for the period from 1995 to 2005 using a pollutant transport model FANTOM. Model calculations allow conclusions on relevant sinks and fluxes in and out of the North Sea and on the time needed to establish a steady state. Calculations were performed for two additional scenarios with different rates of primary degradation ranging from fast degrading to absolute persistency. Concentrations calculated in the scenarios with degradation are in line with the monitoring data available for HBCD. Concentrations calculated in the "persistent" scenario disagree with measured data. According to our model calculations, steady state is established within months for the water and the top layer sediment with no evidence for a temporal trend, except for the "persistent" scenario, in which concentrations increase continuously in the southeastern part of the North Sea, where hydrographic and circulation characteristics produce areas of converging currents. Our model study enables a better understanding of the fate of HBCD in the North Sea, its potential for transport and overall elimination. We discuss these findings in the light of different concerns for PBT substances.