The response of atmospheric nitrous oxide to climate variations during the last glacial period

Detailed insight into natural variations of the greenhouse gas nitrous oxide (N2O) in response to changes in the Earth's climate system is provided by new measurements along the ice core of the North Greenland Ice Core Project (NGRIP). The presented record reaches from the early Holocene back into the previous interglacial with a mean time resolution of about 75 years. Between 11 and 120 kyr BP, atmospheric N2O concentrations react substantially to the last glacial-interglacial transition (Termination 1) and millennial time scale climate variations of the last glacial period. For long-lasting Dansgaard/Oeschger (DO) events, the N2O increase precedes Greenland temperature change by several hundred years with an increase rate of about 0.8-1.3 ppbv/century, which accelerates to about 3.8-10.7 ppbv/century at the time of the rapid warming in Greenland. Within each bundle of DO events, the new record further reveals particularly low N2O concentrations at the approximate time of Heinrich events. This suggests that the response of marine and/or terrestrial N2O emissions on a global scale are different for stadials with and without Heinrich events.

A reconstruction of atmospheric carbon dioxide and its stable carbon isotopic composition from the penultimate glacial maximum to the last glacial inception

The reconstruction of the stable carbon isotope evolution in atmospheric CO2 (δ13Catm), as archived in Antarctic ice cores, bears the potential to disentangle the contributions of the different carbon cycle fluxes causing past CO2 variations. Here we present a new record of δ13Catm before, during and after the Marine Isotope Stage 5.5 (155 000 to 105 000 yr BP). The dataset is archived on the data repository PANGEA® (www.pangea.de) under 10.1594/PANGAEA.817041. The record was derived with a well established sublimation method using ice from the EPICA Dome C (EDC) and the Talos Dome ice cores in East Antarctica. We find a 0.4‰ shift to heavier values between the mean δ13Catm level in the Penultimate (~ 140 000 yr BP) and Last Glacial Maximum (~ 22 000 yr BP), which can be explained by either (i) changes in the isotopic composition or (ii) intensity of the carbon input fluxes to the combined ocean/atmosphere carbon reservoir or (iii) by long-term peat buildup. Our isotopic data suggest that the carbon cycle evolution along Termination II and the subsequent interglacial was controlled by essentially the same processes as during the last 24 000 yr, but with different phasing and magnitudes. Furthermore, a 5000 yr lag in the CO2 decline relative to EDC temperatures is confirmed during the glacial inception at the end of MIS5.5 (120 000 yr BP). Based on our isotopic data this lag can be explained by terrestrial carbon release and carbonate compensation.

A reconstruction of radiocarbon production and total solar irradiance from the Holocene ¹⁴C and CO₂ records: implications of data and model uncertainties

Radiocarbon production, solar activity, total solar irradiance (TSI) and solar-induced climate change are reconstructed for the Holocene (10 to 0 kyr BP), and TSI is predicted for the next centuries. The IntCal09/SHCal04 radiocarbon and ice core CO2 records, reconstructions of the geomagnetic dipole, and instrumental data of solar activity are applied in the Bern3D-LPJ, a fully featured Earth system model of intermediate complexity including a 3-D dynamic ocean, ocean sediments, and a dynamic vegetation model, and in formulations linking radiocarbon production, the solar modulation potential, and TSI. Uncertainties are assessed using Monte Carlo simulations and bounding scenarios. Transient climate simulations span the past 21 thousand years, thereby considering the time lags and uncertainties associated with the last glacial termination. Our carbon-cycle-based modern estimate of radiocarbon production of 1.7 atoms cm−2 s−1 is lower than previously reported for the cosmogenic nuclide production model by Masarik and Beer (2009) and is more in-line with Kovaltsov et al. (2012). In contrast to earlier studies, periods of high solar activity were quite common not only in recent millennia, but throughout the Holocene. Notable deviations compared to earlier reconstructions are also found on decadal to centennial timescales. We show that earlier Holocene reconstructions, not accounting for the interhemispheric gradients in radiocarbon, are biased low. Solar activity is during 28% of the time higher than the modern average (650 MeV), but the absolute values remain weakly constrained due to uncertainties in the normalisation of the solar modulation to instrumental data. A recently published solar activity–TSI relationship yields small changes in Holocene TSI of the order of 1 W m−2 with a Maunder Minimum irradiance reduction of 0.85 ± 0.16 W m−2. Related solar-induced variations in global mean surface air temperature are simulated to be within 0.1 K. Autoregressive modelling suggests a declining trend of solar activity in the 21st century towards average Holocene conditions.

An optimized multi-proxy, multi-site Antarctic ice and gas orbital chronology (AICC2012): 120--800 ka

An accurate and coherent chronological framework is essential for the interpretation of climatic and environmental records obtained from deep polar ice cores. Until now, one common ice core age scale had been developed based on an inverse dating method (Datice), combining glaciological modelling with absolute and stratigraphic markers between 4 ice cores covering the last 50 ka (thousands of years before present) (Lemieux-Dudon et al., 2010). In this paper, together with the companion paper of Veres et al. (2013), we present an extension of this work back to 800 ka for the NGRIP, TALDICE, EDML, Vostok and EDC ice cores using an improved version of the Datice tool. The AICC2012 (Antarctic Ice Core Chronology 2012) chronology includes numerous new gas and ice stratigraphic links as well as improved evaluation of background and associated variance scenarios. This paper concentrates on the long timescales between 120–800 ka. In this framework, new measurements of δ18Oatm over Marine Isotope Stage (MIS) 11–12 on EDC and a complete δ18Oatm record of the TALDICE ice cores permit us to derive additional orbital gas age constraints. The coherency of the different orbitally deduced ages (from δ18Oatm, δO2/N2 and air content) has been verified before implementation in AICC2012. The new chronology is now independent of other archives and shows only small differences, most of the time within the original uncertainty range calculated by Datice, when compared with the previous ice core reference age scale EDC3, the Dome F chronology, or using a comparison between speleothems and methane. For instance, the largest deviation between AICC2012 and EDC3 (5.4 ka) is obtained around MIS 12. Despite significant modifications of the chronological constraints around MIS 5, now independent of speleothem records in AICC2012, the date of Termination II is very close to the EDC3 one.

Dose–effect relationship in routine outpatient psychotherapy: Does treatment duration matter?

Objective: There is an ongoing debate concerning how outcome variables change during the course of psychotherapy. We compared the dose–effect model, which posits diminishing effects of additional sessions in later treatment phases, against a model that assumes a linear and steady treatment progress through termination. Method: Session-by-session outcome data of 6,375 outpatients were analyzed, and participants were categorized according to treatment length. Linear and log-linear (i.e., negatively accelerating) latent growth curve models (LGCMs) were estimated and compared for different treatment length categories. Results: When comparing the fit of the various models, the log-linear LGCMs assuming negatively accelerating treatment progress consistently outperformed the linear models irre- spective of treatment duration. The rate of change was found to be inversely related to the length of treatment. Conclusion: As proposed by the dose–effect model, the expected course of improvement in psychotherapy appears to follow a negatively accelerated pattern of change, irrespective of the duration of the treatment. However, our results also suggest that the rate of change is not constant across various treatment lengths. As proposed by the “good enough level” model, longer treatments are associated with less rapid rates of change.

Fruit production in three masting tree species does not rely on stored carbon reserves

Fruiting is typically considered to massively burden the seasonal carbon budget of trees. The cost of reproduction has therefore been suggested as a proximate factor explaining observed mast-fruiting patterns. Here, we used a large-scale, continuous 13C labeling of mature, deciduous trees in a temperate Swiss forest to investigate to what extent fruit formation in three species with masting reproduction behavior (Carpinus betulus, Fagus sylvatica, Quercus petraea) relies on the import of stored carbon reserves. Using a free-air CO2 enrichment system, we exposed trees to 13C-depleted CO2 during 8 consecutive years. By the end of this experiment, carbon reserve pools had significantly lower δ13C values compared to control trees. δ13C analysis of new biomass during the first season after termination of the CO2 enrichment allowed us to distinguish the sources of built-in carbon (old carbon reserves vs. current assimilates). Flowers and expanding leaves carried a significant 13C label from old carbon stores. In contrast, fruits and vegetative infructescence tissues were exclusively produced from current, unlabeled photoassimilates in all three species, including F. sylvatica, which had a strong masting season. Analyses of δ13C in purified starch from xylem of fruit-bearing shoots revealed a complete turn-over of starch during the season, likely due to its usage for bud break. This study is the first to directly demonstrate that fruiting is independent from old carbon reserves in masting trees, with significant implications for mechanistic models that explain mast seeding.

High-resolution late-glacial chronology for the Gerzensee lake record (Switzerland): δ18O correlation between a Gerzensee-stack and NGRIP

Oxygen-isotope variations were analyzed on bulk samples of shallow-water lake marl from Gerzensee, Switzerland, in order to evaluate major and minor climatic oscillations during the late-glacial. To highlight the overall signature of the Gerzensee δ18O record, δ18O records of four parallel sediment cores were first correlated by synchronizing major isotope shifts and pollen abundances. Then the records were stacked with a weighting depending on the differing sampling resolution. To develop a precise chronology, the δ18O-stack was then correlated with the NGRIP δ18O record applying a Monte Carlo simulation, relying on the assumption that the shifts in δ18O were climate-driven and synchronous in both archives. The established chronology on the GICC05 time scale is the basis for (1) comparing the δ18O changes recorded in Gerzensee with observed climatic and environmental fluctuations over the whole North Atlantic region, and (2) comparing sedimentological and biological changes during the rapid warming with smaller climatic variations during the Bølling/Allerød period. The δ18O record of Gerzensee is characterized by two major isotope shifts at the onset and at the termination of the Bølling/Allerød warm period, as well as four intervening negative shifts labeled GI-1e2, d, c2, and b, which show a shift of one third to one fourth of the major δ18O shifts at the beginning and end of the Bølling/Allerød. Despite some inconsistency in terminology, these oscillations can be observed in various climatic proxies over wide regions in the North Atlantic region, especially in reconstructed colder temperatures, and they seem to be caused by hemispheric climatic variations.

Synchronization and desynchronization in epilepsy: controversies and hypotheses

Epilepsy has been historically seen as a functional brain disorder associated with excessive synchronization of large neuronal populations leading to a hypersynchronous state. Recent evidence showed that epileptiform phenomena, particularly seizures, result from complex interactions between neuronal networks characterized by heterogeneity of neuronal firing and dynamical evolution of synchronization. Desynchronization is often observed preceding seizures or during their early stages; in contrast, high levels of synchronization observed towards the end of seizures may facilitate termination. In this review we discuss cellular and network mechanisms responsible for such complex changes in synchronization. Recent work has identified cell-type-specific inhibitory and excitatory interactions, the dichotomy between neuronal firing and the non-local measurement of local field potentials distant to that firing, and the reflection of the neuronal dark matter problem in non-firing neurons active in seizures. These recent advances have challenged long-established views and are leading to a more rigorous and realistic understanding of the pathophysiology of epilepsy.

A novel phosphorylation-independent interaction between SMG6 and UPF1 is essential for human NMD

Eukaryotic mRNAs with premature translation-termination codons (PTCs) are recognized and eliminated by nonsense-mediated mRNA decay (NMD). NMD substrates can be degraded by different routes that all require phosphorylated UPF1 (P-UPF1) as a starting point. The endonuclease SMG6, which cleaves mRNA near the PTC, is one of the three known NMD factors thought to be recruited to nonsense mRNAs via an interaction with P-UPF1, leading to eventual mRNA degradation. By artificial tethering of SMG6 and mutants thereof to a reporter mRNA combined with knockdowns of various NMD factors, we demonstrate that besides its endonucleolytic activity, SMG6 also requires UPF1 and SMG1 to reduce reporter mRNA levels. Using in vivo and in vitro approaches, we further document that SMG6 and the unique stalk region of the UPF1 helicase domain, along with a contribution from the SQ domain, form a novel interaction and we also show that this region of the UPF1 helicase domain is critical for SMG6 function and NMD. Our results show that this interaction is required for NMD and for the capability of tethered SMG6 to degrade its bound RNA, suggesting that it contributes to the intricate regulation of UPF1 and SMG6 enzymatic activities.

Mechanistic aspects of NMD in human cells

Eukaryotic mRNAs with premature translation termination codons (PTCs) are recognized and degraded through a process termed nonsense-mediated mRNA decay (NMD). To get more insight into the recruitment of the central NMD factor UPF1 to target mRNAs, we mapped transcriptome-wide UPF1-binding sites by individual-nucleotide-resolution UV cross-linking and immunoprecipitation (iCLIP) in human cells and found that UPF1 preferentially associated with 3′ UTRs in translationally active cells but underwent significant redistribution toward coding regions (CDS) upon translation inhibition. This indicates that UPF1 binds RNA before translation and gets displaced from the CDS by translating ribosomes. Corroborated by RNA immunoprecipitation and by UPF1 cross-linking to long noncoding RNAs, our evidence for translation-independent UPF1-RNA interaction suggests that the triggering of NMD occurs after UPF1 binding to mRNA, presumably through activation of RNA-bound UPF1 by aberrant translation termination. Unlike in yeast, in mammalian cells NMD has been reported to be restricted to cap-binding complex (CBC)–bound mRNAs during the pioneer round of translation. However, we compared decay kinetics of two NMD reporter genes in mRNA fractions bound to either CBC or the eukaryotic initiation factor 4E (eIF4E) in human cells and show that NMD destabilizes eIF4E-bound transcripts as efficiently as those associated with CBC. These results corroborate an emerging unified model for NMD substrate recognition, according to which NMD can ensue at every aberrant translation termination event.

Mechanistic aspects of mRNA targeting for nonsense-mediated mRNA decay in human cells

The nonsense-mediated mRNA decay (NMD) pathway is best known as a translation-coupled quality control system that recognizes and degrades aberrant mRNAs with ORF-truncating premature termination codons (PTCs), but a more general role of NMD in posttranscriptional regulation of gene expression is indicated by transcriptome-wide mRNA profilings that identified a plethora of physiological mRNAs as NMD substrates. We try to decipher the mechanism of mRNA targeting to the NMD pathway in human cells. Recruitment of the conserved RNA-binding helicase UPF1 to target mRNAs has been reported to occur through interaction with release factors at terminating ribosomes, but evidence for translation-independent interaction of UPF1 with the 3’ untranslated region (UTR) of mRNAs has also been reported. We have transcriptome-wide determined the UPF1 binding sites by individual-nucleotide resolution UV crosslinking and immunoprecipitation (iCLIP) in human cells, untreated or after inhibiting translation. We detected a strongly enriched association of UPF1 with 3’ UTRs in undisturbed, translationally active cells. After translation inhibition, a significant increase in UPF1 binding to coding sequence (CDS) was observed, indicating that UPF1 binds RNA before translation and gets displaced from the CDS by translating ribosomes. This suggests that the decision to trigger NMD occurs after association of UPF1 with mRNA, presumably through activation of RNA-bound UPF1 by aberrant translation termination. In a second recent study, we re-visited the reported restriction of NMD in mammals to the ‘pioneer round of translation’, i.e. to cap-binding complex (CBC)-bound mRNAs. The limitation of mammalian NMD to early rounds of translation would indicate a – from an evolutionary perspective – unexpected mechanistic difference to NMD in yeast and plants, where PTC-containing mRNAs seem to be available to NMD at each round of translation. In contrast to previous reports, our comparison of decay kinetics of two NMD reporter genes in mRNA fractions bound to either CBC or the eukaryotic initiation factor 4E (eIF4E) in human cells revealed that NMD destabilizes eIF4E-bound transcripts as efficiently as those associated with CBC. These results corroborate an emerging unified model for NMD substrate recognition, according to which NMD can ensue at every aberrant translation termination event.

eIF4E-bound mRNPs are substrates for nonsense-mediated mRNA decay in mammalian cells

Eukaryotic mRNAs with premature translation-termination codons (PTCs) are recognized and degraded by a process referred to as nonsense-mediated mRNA decay (NMD). The evolutionary conservation of the core NMD factors UPF1, UPF2 and UPF3 would imply a similar basic mechanism of PTC recognition in all eukaryotes. However, unlike NMD in yeast, which targets PTC-containing mRNAs irrespectively of whether their 5' cap is bound by the cap-binding complex (CBC) or by the eukaryotic initiation factor 4E (eIF4E), mammalian NMD has been claimed to be restricted to CBC-bound mRNAs during the pioneer round of translation. In our recent study we compared decay kinetics of two NMD reporter systems in mRNA fractions bound to either CBC or eIF4E in human cells. Our findings reveal that NMD destabilizes eIF4E bound transcripts as efficiently as those associated with CBC. These results corroborate an emerging unified model for NMD substrate recognition, according to which NMD can ensue at every aberrant translation termination event. Additionally, our results indicate that the closed loop structure of mRNA forms only after the replacement of CBC with eIF4E at the 5' cap.

eIF4E‐bound mRNPs are substrates for nonsense‐mediated mRNA decay in mammalian cells

Eukaryotic mRNAs with premature translation-termination codons (PTCs) are recognized and degraded by a process referred to as nonsense-mediated mRNA decay (NMD). The evolutionary conservation of the core NMD factors UPF1, UPF2 and UPF3 would imply a similar basic mechanism of PTC recognition in all eukaryotes. However, unlike NMD in yeast, which targets PTC-containing mRNAs irrespectively of whether their 5' cap is bound by the cap-binding complex (CBC) or by the eukaryotic initiation factor 4E (eIF4E), mammalian NMD has been claimed to be restricted to CBC-bound mRNAs during the pioneer round of translation. In our recent study we compared decay kinetics of two NMD reporter systems in mRNA fractions bound to either CBC or eIF4E in human cells. Our findings reveal that NMD destabilizes eIF4E bound transcripts as efficiently as those associated with CBC. These results corroborate an emerging unified model for NMD substrate recognition, according to which NMD can ensue at every aberrant translation termination event. Additionally, our results indicate that the closed loop structure of mRNA forms only after the replacement of CBC with eIF4E at the 5' cap.

eIF4E-bound mRNPs are substrates for nonsense-mediated mRNA decay in mammalian cells

Eukaryotic mRNAs with premature translation-termination codons (PTCs) are recognized and degraded by a process referred to as nonsense-mediated mRNA decay (NMD). The evolutionary conservation of the core NMD factors UPF1, UPF2 and UPF3 would imply a similar basic mechanism of PTC recognition in all eukaryotes. However, unlike NMD in yeast, which targets PTC-containing mRNAs irrespectively of whether their 5' cap is bound by the cap-binding complex (CBC) or by the eukaryotic initiation factor 4E (eIF4E), mammalian NMD has been claimed to be restricted to CBC-bound mRNAs during the pioneer round of translation. In our recent study we compared decay kinetics of two NMD reporter systems in mRNA fractions bound to either CBC or eIF4E in human cells. Our findings reveal that NMD destabilizes eIF4E bound transcripts as efficiently as those associated with CBC. These results corroborate an emerging unified model for NMD substrate recognition, according to which NMD can ensue at every aberrant translation termination event. Additionally, our results indicate that the closed loop structure of mRNA forms only after the replacement of CBC with eIF4E at the 5' cap.

eIF4E‐bound mRNPs are substrates for nonsense‐mediated mRNA decay in mammalian cells

Eukaryotic mRNAs with premature translation-termination codons (PTCs) are recognized and degraded by a process referred to as nonsense-mediated mRNA decay (NMD). The evolutionary conservation of the core NMD factors UPF1, UPF2 and UPF3 would imply a similar basic mechanism of PTC recognition in all eukaryotes. However, unlike NMD in yeast, which targets PTC-containing mRNAs irrespectively of whether their 5' cap is bound by the cap-binding complex (CBC) or by the eukaryotic initiation factor 4E (eIF4E), mammalian NMD has been claimed to be restricted to CBC-bound mRNAs during the pioneer round of translation. In our recent study we compared decay kinetics of two NMD reporter systems in mRNA fractions bound to either CBC or eIF4E in human cells. Our findings reveal that NMD destabilizes eIF4E bound transcripts as efficiently as those associated with CBC. These results corroborate an emerging unified model for NMD substrate recognition, according to which NMD can ensue at every aberrant translation termination event. Additionally, our results indicate that the closed loop structure of mRNA forms only after the replacement of CBC with eIF4E at the 5' cap.