Transient Earth system responses to cumulative carbon dioxide emissions: linearities, uncertainties, and probabilities in an observation-constrained model ensemble

Information on the relationship between cumulative fossil CO2 emissions and multiple climate targets is essential to design emission mitigation and climate adaptation strategies. In this study, the transient response of a climate or environmental variable per trillion tonnes of CO2 emissions, termed TRE, is quantified for a set of impact-relevant climate variables and from a large set of multi-forcing scenarios extended to year 2300 towards stabilization. An  ∼ 1000-member ensemble of the Bern3D-LPJ carbon–climate model is applied and model outcomes are constrained by 26 physical and biogeochemical observational data sets in a Bayesian, Monte Carlo-type framework. Uncertainties in TRE estimates include both scenario uncertainty and model response uncertainty. Cumulative fossil emissions of 1000 Gt C result in a global mean surface air temperature change of 1.9 °C (68 % confidence interval (c.i.): 1.3 to 2.7 °C), a decrease in surface ocean pH of 0.19 (0.18 to 0.22), and a steric sea level rise of 20 cm (13 to 27 cm until 2300). Linearity between cumulative emissions and transient response is high for pH and reasonably high for surface air and sea surface temperatures, but less pronounced for changes in Atlantic meridional overturning, Southern Ocean and tropical surface water saturation with respect to biogenic structures of calcium carbonate, and carbon stocks in soils. The constrained model ensemble is also applied to determine the response to a pulse-like emission and in idealized CO2-only simulations. The transient climate response is constrained, primarily by long-term ocean heat observations, to 1.7 °C (68 % c.i.: 1.3 to 2.2 °C) and the equilibrium climate sensitivity to 2.9 °C (2.0 to 4.2 °C). This is consistent with results by CMIP5 models but inconsistent with recent studies that relied on short-term air temperature data affected by natural climate variability.

Peripheral responses to attended and unattended angry prosody: a dichotic listening paradigm.

We investigated the effects of angry prosody, varying focus of attention, and laterality of presentation of angry prosody on peripheral nervous system activity. Participants paid attention to either their left or their right ear while performing a sex discrimination task on dichotically presented pseudo-words. These pseudo-words were characterized by either angry or neutral prosody and presented stereophonically (anger/neutral, neutral/anger, or neutral/neutral, for the left/right ear, respectively). Reaction times and physiological responses (heart period, skin conductance, finger and forehead temperature) in this study were differentially sensitive to the effects of anger versus neutral prosody, varying focus of attention, and laterality of presentation of angry prosody.

Fish Immune Responses to Myxozoa

Myxozoans evoke important economic losses in aquaculture production, but there is almost a total lack of disease control methods as no vaccines or commercial treatments are currently available. Knowledge of the immune responses that lead to myxozoan elimination and subsequent disease resistance is vital for shaping the future development of disease control measures. Different fish immune factors triggered by myxozoan parasites are reviewed in this chapter. Detailed information on the phenotypic and underlying molecular aspects of innate and adaptive responses, at both cellular and humoral levels, is provided for some well-studied fishmyxozoan systems. The importance of the local immune response, mainly at mucosal sites, is also highlighted. Myxozoan tactics to disable or avoid immune responses, such as modulation of immune gene transcription and immune evasion, are also reviewed. The existence of innate and acquired resistance to some myxozoan species suggest promising possibilities for controlling myxozooses through immune-based strategies, such as genetic selection for host resistance, vaccination, immune therapies and administration of immunostimulants.

Roots under attack: contrasting plant responses to below- and aboveground insect herbivory

The distinctive ecology of root herbivores, the complexity and diversity of root–microbe interactions, and the physical nature of the soil matrix mean that plant responses to root herbivory extrapolate poorly from our understanding of responses to aboveground herbivores. For example, root attack induces different changes in phytohormones to those in damaged leaves, including a lower but more potent burst of jasmonates in several plant species. Root secondary metabolite responses also differ markedly, although patterns between roots and shoots are harder to discern. Root defences must therefore be investigated in their own ecophysiological and evolutionary context, specifically one which incorporates root microbial symbionts and antagonists, if we are to better understand the battle between plants and their hidden herbivores.

Biotic responses to rapid climatic changes

Qualitative and quantitative changes in fossil flora and fauna have been used in many studies to infer climatic change. Here we ask a different question: how do flora and fauna respond to climatic changes such as rapid warming or cooling? As an independent proxy for paleotemperature we take the ratio of oxygen isotopes in biogenically precipitated lake marl and in ostracod shells. This introductory paper describes the project design and the five sites on an altitudinal transect from 600 m to about 2300 m asl in the western Swiss Alps. As cases of climatic cooling and warming we use the beginning and end of the Younger Dryas as major changes, and the Gerzensee and Preboreal oscillations as minor changes. At the two sites of Gerzensee and Leysin these changes are recorded in stable-isotope ratios, and there the time scales can be derived by correlations to the GRIP ice core (Schwander et al., 2000 and von Grafenstein et al., 2000). Biotic responses to climate changes are treated in individual papers using pollen (Wick, 2000), plant macrofossils (Tobolski and Ammann, 2000), and remains of chironomids (Brooks, 2000), beetles and other insects (Lemdahl, 2000), and chydorid Cladocera (Hofmann, 2000). They are followed by a synthesis focusing on quantification of biotic responses (Ammann et al., 2000). In addition, a reconstruction of summer temperatures for the Allerød and the Younger Dryas at Gerzensee is provided by Lotter et al. (2000).

Quantification of biotic responses to rapid climatic changes around the Younger Dryas — a synthesis

To assess the presence or absence of lags in biotic responses to rapid climatic changes, we: (1) assume that the δ18O in biogenically precipitated carbonates record global or hemispheric climatic change at the beginning and at the end of the Younger Dryas without any lag at our two study sites of Gerzensee and Leysin, Switzerland; (2) derive a time scale by correlating the δ18O record from these two sites with the δ18O record of the GRIP ice core; (3) measure δ18O records in ostracods and molluscs to check the record in the bulk samples and to detect possible hydrological changes; (4) analyse at Gerzensee and Leysin as well as at two additional sites (that lack carbonates and hence a δ18O record) pollen, plant macrofossils, chironomids, beetles and other insects, and Cladocera; (5) estimate our sampling resolution using the GRIP time scale for the isotope stratigraphies and the biostratigraphies; and (6) summarise the major patterns of compositional change in the biostratigraphies by principal component analysis or correspondence analysis. We conclude that, at the major climatic shifts at the beginning and end of the Younger Dryas, hardly any biotic lags occur (within the sampling resolution of 8–30 years) and that upland vegetation responded as fast as aquatic invertebrates. We suggest that the minor climatic changes associated with the Gerzensee and Preboreal oscillations were weakly recorded in the biostratigraphies at the lowland site, but were more distinct at higher altitudes. Individualistic responses of plant and animal species to climatic change may reflect processes in individuals (e.g. productivity and phenology), in populations (e.g. population dynamics), in spatial distributions (e.g. migrations), and in ecosystems (e.g. trophic state). We suggest that biotic responses may be telescoped together into relatively short periods (50 to 150 years), perhaps disrupting functional interactions among species and thus destabilising ecosystems.

Macrofossils as records of plant responses to rapid Late Glacial climatic changes at three sites in the Swiss Alps

Plant macrofossils from the end of the Younger Dryas were analysed at three sites, Gerzensee (603 m asl), Leysin (1230 m asl), and Zeneggen (1510 m asl). For the first two sites an oxygen-isotope record is also available that was used to develop a time scale (Schwander et al., this volume); dates refer therefore to calibrated years according to the GRIP time scale. Around Gerzensee a pine forest with some tree birches grew during the Younger Dryas. With the onset of the isotopic shift initiating the rapid warming (about 11,535 cal. years before 1950), the pine forest became more productive and denser. At Leysin no trees except some juniper scrub grew during the Younger Dryas. Tree birches, pine, and poplar immigrated from lower altitudes and arrived after the end of the isotopic shift (about 11,487 B.P.), i.e., at the beginning of the Preboreal (at about 11,420 B.P.). Zeneggen is situated somewhat higher than Leysin, but single tree birches and pines survived the Younger Dryas at the site. At the beginning of the Preboreal their productivity and population densities increased. Simultaneously shifts from Nitella to Chara and from silt to gyttja are recorded, all indicating rapidly warming conditions and higher nutrient levels of the lake water (and probably of the soils in the catchment). At Gerzensee the beginning of the Younger Dryas was also analysed: the beginning of the isotopic shift correlates within one sample (about 15 years) to rapid decreases of macrofossils of pines and tree birches.

Physiological Responses to Environmental Variation in Intertidal Red Algae: Does Thallus Morphology Matter?

Morphological variation within and among many species of algae show correlated life history traits. The trade-offs of Life history traits among different morphs are presumed to be determined by morphology. Form-function hypotheses also predict that algae of different morphological groups exhibit different tolerances to physiological stress, whereas algae within a morphological group respond similarly to stress. We tested this hypothesis by comparing photosynthetic and respiratory responses to variation in season, light, temperature, desiccation and freezing among the morphologically similar fronds of Chondrus crispus and Mastocarpus stellatus and the alternate stage crust of M. stellatus. Physiological differences between fronds of the 2 species and crusts and fronds were consistent with their patterns of distribution and abundance in the intertidal zone. However, there was no clear relationship between algal morphology and physiological response to environmental variation. These results suggest that among macroalgae the correlation between Life history traits and morphology is not always causal. Rather, the link between life history traits and morphology is constrained by the extent to which physiological characteristics codetermine these features.

IN VITRO INDUCTION OF XENOIMMUNE RESPONSES TO LIPOSOMES CONTAINING HUMAN COLON TUMOR ANTIGENS

Liposomes prepared with human LS174T colon tumor cell membranes induce specific primary and secondary xenogeneic immune responses in BALB/c splenocytes in vitro. The multilamellar vesicular liposomes were prepared by adding sonicated membrane fragments in 8 mM CaCl(,2) to a dried lipid film. Cytoxic splenocytes generated in vivo exhibited specificity for the LS174T cell; liposomes elicited higher levels of cytotoxicity than did membranes (P < 0.01). Secondary blastogenic responses elicited in in vivo-primed spleen cells by liposomes also produced a significantly greater (P < 0.005) response than membranes. Subsequently, in vitro induction of primary blastogenic and cytotoxic responses by liposomes were accomplished and revealed similar kinetics to that of whole LS174T cell immunogens. Specificity of the in vitro-primed spleen cells was clearly demonstrated (P < 0.01) on a variety of human tumor cells using both the primed lymphocyte and cell-mediated cytotoxicity assays. The results of competitive inhibition tests with autologous lymphoblasts demonstrated that 30% of the cytotoxic activity was directed against lymphocyte antigens.^ The adjuvant effect of liposomes was shown to be mediated primarily by tumor antigens exposed on the outer surface of liposomes. Trypsinization of the liposomes which eliminated 96% of the surface protein reduced the ability of liposomes to induce cytotoxic splenocytes. The generation of cytolytic activity with liposomes of increasing protein concentration showed that while 10 (mu)g protein was threshold, 100 (mu)g protein induced maximal responses. In addition, membrane fluidity studies revealed that rigid liposomes were significantly (P < 0.05) more efficacious than fluid liposomes in inducing cytotoxicity.^ The induction of the primary response required the presence of nonadherent splenocytes bearing the Thy-1, Lyt-1, and Lyt-2 surface markers. The role of a Lyt-123 subpopulation was suggested by the inability of both the Lyt-1 and Lyt-2 depleted populations to completely restore the cytolytic levels to normal. In addition, the interaction of I-A('+) spleen adherent cells with liposomes for at least 8 hours was required to generate maximal cytotoxic activity. The phenotype of the cytotoxic effector was Thy-1('+), Lyt-2('+), and I-A('d-).^ Incorporation of tumor antigens into liposomes has thus enabled primary immunization in vitro to human colon cancer antigens and may afford an adaptable means to evaluate and to select specific immune responses, as well as to identify colon tumor-specific determinants.^

Mammalian Snm1 participates in cellular responses to genotoxic and mitotic stress

Eukaryotic cells have evolved a complex network of metabolic processes and regulatory systems to help ensure that hereditary information is protected or restored when exposed to genotoxic agents. Two members of the Snm1 protein family have been characterized; scSNM1/PSO2, a yeast gene responsible for repair of DNA interstrand crosslinks, and hARTEMIS, a human gene that is mutated in radiosensitive severe combined immunodeficiency (RS-SCID). Here we report on another member of this protein family, hSNM1, and its response to DNA damage and mitotic stress. We have found that this protein colocalizes and physically associates with 53BP1, a crucial member of the mammalian response to DNA damage. In addition, hSnm1 interacts with several proteins involved in mitosis, and mSNM1 deficiency causes a mitotic checkpoint defect in mouse embryonic fibroblasts. ^

The cellular and molecular responses to a novel nucleotide analogue, GS-9219

GS-9219 is a cell-permeable double-prodrug of the acyclic nucleotide analogue 9-(2-phosphonylmethoxyethyl)guanine (PMEG). The conversion of GS-9219 to its active metabolite, PMEG diphosphate (PMEGpp), involves several intracellular enzymatic reactions which reduces the concentration of nephrotoxic PMEG in plasma. PMEGpp competes with the natural substrate, dGTP, for incorporation by DNA polymerases. The lack of a 3'-hydroxyl moiety makes PMEGpp a de facto DNA chain-terminator. The incorporation of PMEGpp into DNA during DNA replication causes DNA chain-termination and stalled replication forks. Thus, the primary mechanism of action of GS-9219 in replicating cells is via DNA synthesis inhibition. GS-9219 has substantial antiproliferative activity against activated lymphocytes and tumor cell lines of hematological malignancies. Tumor cell proliferation was significantly reduced as measured by PET/CT scans in dogs with advanced-stage, spontaneously occurring non-Hodgkin's lymphoma (NHL).^ The hypothesis of this dissertation is that the incorporation of PMEGpp into DNA during repair re-synthesis would result in the inhibition of DNA repair and accumulation of DNA damage in chronic lymphocytic leukemia (CLL) cells and activate signaling pathways to cell death.^ To test this hypothesis, CLL cells were treated with DNA-damaging agents to stimulate nucleotide excision repair (NER) pathways, enabling the incorporation of PMEGpp into DNA. When NER was activated by UV, PMEGpp was incorporated into DNA in CLL cells. Following PMEGpp incorporation, DNA repair was inhibited and led to the accumulation of DNA strand breaks. The combination of GS-9219 and DNA-damaging agents resulted in more cell death than the sum of the single agents alone. The presence of DNA strand breaks activated the phosphatidylinositol 3-kinase-like protein kinase (PIKK) family members ataxia-telangiectasia mutated (ATM) and DNA-dependent protein kinase (DNA-PK). The activated ATM initiated signaling to the downstream target, p53, which was subsequently phosphorylated and accumulated to exert its apoptotic functions. P53-targeted pro-apoptotic genes, Puma and Bax, were upregulated and activated when DNA repair was inhibited, likely contributing to cell death. ^

Involvement of HMGB1 in the repair of DNA adducts and the responses to DNA damage in mammalian cells

High mobility group protein B1 (HMGB1) is a multifunctional protein with roles in chromatin structure, transcription, V(D)J recombination, and inflammation. HMGB1 also binds to and bends damaged DNA, but the biological consequence of this interaction is not clearly understood. We have shown previously that HMGB1 binds cooperatively with nucleotide excision repair (NER) damage recognition proteins XPA and RPA to triplex-directed psoralen DNA interstrand crosslinks (ICLs). Based on this we hypothesized that HMGB1 is enhancing the repair of DNA lesions, and through this role, is affecting DNA damage-induced mutagenesis and cell survival. Because HMGB1 is also a chromatin protein, we further hypothesized that it is acting to facilitate chromatin remodeling at the site of the DNA damage, to allow access of the repair machinery to the DNA lesion. We demonstrated here that HMGB1 could bind to triplex-directed psoralen ICLs in a complex with NER proteins XPC-RAD23B, XPA and RPA, which occurred in the presence or absence of DNA. Supporting these findings, we demonstrated that HMGB1 enhanced repair of triplex-directed psoralen ICLs (by nucleotide incorporation), as well as removal of UVC irradiation-induced DNA lesions from the genome (by radioimmunoassay). We also explored HMGB1's role in chromatin remodeling upon DNA damage. Immunoblotting demonstrated that, in contrast to HMGB1 proficient cells, cells lacking HMGB1 showed no increase in histone acetylation after UVC irradiation. Additionally, purified HMGB1 protein enhanced chromatin formation in an in vitro chromatin assembly system. However, HMGB1 also has a role in DNA repair in the absence of chromatin, as shown by measuring UVC-induced nucleotide incorporation on a naked substrate. Upon exploration of HMGB1's effect on several cellular outcomes of DNA damage, we found that mammalian cells lacking HMGB1 were hypersensitive to DNA damage induced by psoralen plus UVA irradiation or UVC radiation, showing less survival and increased mutagenesis. These results reveal a new role for HMGB1 in the error-free repair of DNA lesions in a chromosomal context. As strategies targeting HMGB1 are currently in development for treatment of sepsis and rheumatoid arthritis, our findings draw attention to potential adverse side effects of anti-HMGB1 therapy in patients with inflammatory diseases. ^