Exploring the impact of climate change on the global distribution of non-spinose planktonic foraminifera using a trait-based ecosystem model.

Planktonic foraminifera are one of the primary calcifiers in the modern ocean, contributing 23%-56% of total global pelagic carbonate production. However, a mechanistic understanding of how physiology and environmental conditions control their abundance and distribution is lacking, hindering the projection of the impact of future climate change. This understanding is important, not only for ecosystem dynamics, but also for marine carbon cycling because of foraminifera's key role in carbonate production. Here we present and apply a global trait-based ecosystem model of non-spinose planktonic foraminifera ('ForamEcoGEnIE') to assess their ecology and global distribution under future climate change. ForamEcoGEnIE considers the traits of calcium carbonate production, shell size, and foraging. It captures the main characteristic of biogeographical patterns of non-spinose species - with maximum biomass concentrations found in mid- to high-latitude waters and upwelling areas. The model also reproduces the magnitude of global carbonate production relatively well, although the foraminifera standing stock is systematically overestimated. In response to future scenarios of rising atmospheric CO2 (RCP6 and RCP8.5), on a regional scale, the modelled foraminifera biomass and export flux increases in the subpolar regions of the North Atlantic and the Southern Ocean while it decreases everywhere else. In the absence of adaptation, the biomass decline in the low-latitude South Pacific suggests extirpation. The model projects a global average loss in non-spinose foraminifera biomass between 8% (RCP6) and 11% (RCP8.5) by 2050 and between 14% and 18% by 2100 as a response to ocean warming and associated changes in primary production and ecological dynamics. Global calcium carbonate flux associated with non-spinose foraminifera declines by 13%-18% by 2100. That decline can slow down the ocean carbonate pump and create short-term positive feedback on rising atmospheric pCO2 .

Rapid ocean acidification and protracted Earth system recovery followed the end-Cretaceous Chicxulub impact.

Mass extinction at the Cretaceous-Paleogene (K-Pg) boundary coincides with the Chicxulub bolide impact and also falls within the broader time frame of Deccan trap emplacement. Critically, though, empirical evidence as to how either of these factors could have driven observed extinction patterns and carbon cycle perturbations is still lacking. Here, using boron isotopes in foraminifera, we document a geologically rapid surface-ocean pH drop following the Chicxulub impact, supporting impact-induced ocean acidification as a mechanism for ecological collapse in the marine realm. Subsequently, surface water pH rebounded sharply with the extinction of marine calcifiers and the associated imbalance in the global carbon cycle. Our reconstructed water-column pH gradients, combined with Earth system modeling, indicate that a partial ∼50% reduction in global marine primary productivity is sufficient to explain observed marine carbon isotope patterns at the K-Pg, due to the underlying action of the solubility pump. While primary productivity recovered within a few tens of thousands of years, inefficiency in carbon export to the deep sea lasted much longer. This phased recovery scenario reconciles competing hypotheses previously put forward to explain the K-Pg carbon isotope records, and explains both spatially variable patterns of change in marine productivity across the event and a lack of extinction at the deep sea floor. In sum, we provide insights into the drivers of the last mass extinction, the recovery of marine carbon cycling in a postextinction world, and the way in which marine life imprints its isotopic signal onto the geological record.

[The Prestige of Housewives in Germany-A Quantitative-Empirical Analysis of Differential Perceptions]. / Das Ansehen von Hausfrauen in Deutschland ­ Eine quantitativ-empirische Analyse differenzieller Wahrnehmungen.

The employment rate of women has increased markedly over the past decades, both internationally and in Germany, whereas the classic male breadwinner model is eroding. Against this background, using current survey data, the aim of this study is to examine the social prestige of the shrinking group of housewives whose main activity is domestic and family work. The analyses address, on the one hand, the question of how high their reputation is generally rated by the population in Germany and, on the other hand, whether the perceptions differ systematically by raters' sociodemographic characteristics. The empirical findings show that the reputation of housewives in Germany is generally rated higher than that of the unemployed and of those in helper jobs but lower than for those in professional jobs at the skilled level. Moreover, the assessments of housewives' prestige vary significantly according to the social group (birth cohort, level of education, labor force participation, gender) to which the respondents belong. Further analyses of interaction effects also reveal a differentiated interaction of the gender variable with the other structural group characteristics. The paper concludes with a detailed discussion of the results and an outlook on future research.

Ecosystem function after the K/Pg extinction: decoupling of marine carbon pump and diversity.

The ocean biological pump is the mechanism by which carbon and nutrients are transported to depth. As such, the biological pump is critical in the partitioning of carbon dioxide between the ocean and atmosphere, and the rate at which that carbon can be sequestered through burial in marine sediments. How the structure and function of planktic ecosystems in the ocean govern the strength and efficiency of the biological pump and its resilience to disruption are poorly understood. The aftermath of the impact at the Cretaceous/Palaeogene (K/Pg) boundary provides an ideal opportunity to address these questions as both the biological pump and marine plankton size and diversity were fundamentally disrupted. The excellent fossil record of planktic foraminifera as indicators of pelagic-biotic recovery combined with carbon isotope records tracing biological pump behaviour, show that the recovery of ecological traits (diversity, size and photosymbiosis) occurred much later (approx. 4.3 Ma) than biological pump recovery (approx. 1.8 Ma). We interpret this decoupling of diversity and the biological pump as an indication that ecosystem function had sufficiently recovered to drive an effective biological pump, at least regionally in the South Atlantic.

Resolution of vascular inflammation in patients with new-onset giant cell arteritis: data from the RIGA study.

OBJECTIVES: Efficacy evaluation of GCA treatment is primarily based on non-specific symptoms and laboratory markers. We aimed to assess the change in vascular inflammation in patients with large vessel (LV)-GCA under different treatments using [18F]FDG PET/CT. METHODS: Observational study on patients with new-onset, active LV-GCA starting treatment with either prednisolone monotherapy (PRED) or combination with MTX or tocilizumab (TOC). All patients underwent baseline and follow-up PET/CT. The aorta and its major branches were assessed using PET vascular activity score (PETVAS) by independent readers. Cumulative glucocorticoid doses and cessation of glucocorticoid treatment were documented in all patients. RESULTS: We included 88 LV-GCA patients, 27 were treated with PRED, 42 with MTX and 19 with TOC. PETVAS decreased from 18.9-8.0 units at follow-up in the overall population (P <0.001). PETVAS changes were numerically higher in patients receiving MTX (-12.3 units) or TOC (-11.7 units) compared with PRED (-8.7). Mean cumulative prednisolone dosages were 5637, 4418 and 2984 mg in patients treated with PRED, MTX and TOC (P =0.002). Risk ratios for glucocorticoid discontinuation at the time of follow-up PET/CT were 6.77 (95% CI: 1.01, 45.29; P =0.049) and 16.25 (95% CI: 2.60, 101.73; P =0.003) for MTX and TOC users compared with PRED users. CONCLUSION: Treatment of LV-GCA inhibits vascular inflammation in the aorta and its major branches. While similar control of vascular inflammation was achieved with PRED, MTX and TOC treatments, TOC showed a strong glucocorticoid sparing effect, supporting the concept of initial combination therapy.

Effects of body-oriented yoga: a RCT study for patients with major depressive disorder.

The major depressive disorder is one of the most common mental illnesses worldwide. Current treatment standards recommend a combined therapy with medication and psychotherapy. As an additive component and to further improvements in treatment, physical activity such as yoga may be integrated into conventional treatment. This study investigates the impact of a 3-month body-oriented yoga in patients with major depressive disorder (MDD). In total, n = 83 patients were included. An intervention group received a vigorous Ashtanga-Yoga three times a week. The waiting-list control group obtained a treatment as usual (TAU). As a primary outcome depression scores (Beck Depression Inventory-II (BDI-II), Montgomery Asberg Depression Rating Scale (MADRS)) were tested at three time points. Secondary outcome was the positive and negative affect [Positive and Negative Affect Scale (PANAS)] and remission rates. To analyze the data, multilevel models and effect sizes were conducted. The results showed an improvement in BDI-II scores for both groups over time [γ = - 3.46, t(165) = - 7.99, p < 0.001] but not between groups [γ = 0.98, t(164) = 1.12, p = 0.263]. An interaction effect (time x group) occurred for MADRS [γ = 2.10, t(164) = 2.10, p < 0.038]. Positive affects improved over time for both groups [γ = 1.65, t(165) = 4.03, p < 0.001]. Negative affects decreased for all over time [γ = - 1.00, t(165) = - 2.51, p = 0.013]. There were no significant group differences in PANAS. Post hoc tests revealed a greater symptom reduction within the first 6 weeks for all measurements. The effect sizes for depression scores showed a positive trend. Remission rates indicated a significant improvement in the yoga group (BDI-II: 46.81%, MADRS: 17.02%) compared to the control group (BDI: 33.33%, MADRS: 8.33%). The findings suggest that there is a trendsetting additive effect of Ashtanga-Yoga after 3 months on psychopathology and mood with a greater improvement at the beginning of the intervention. Further research in this field can help to achieve more differentiated results.

Single-cycle induction chemotherapy before chemoradiotherapy or surgery in functionally inoperable head and neck squamous cell carcinoma: 10-year results.

INTRODUCTION: The response to induction chemotherapy (IC) predicts local control after conservative treatment of laryngeal, meso- and hypopharyngeal head and neck squamous cell carcinoma (HNSCC) and can thus help to avoid surgery. Single-cycle induction chemotherapy may help to maintain a low local recurrence rate while keeping the overall toxicity manageable. However, long-term data on single-cycle IC response by tumor location is lacking. METHODS: N = 102 patients with functionally inoperable primary HNSCC of the larynx (n = 43), hypopharynx (n = 42) or mesopharynx/tongue (n = 17) received one cycle of docetaxel (75 mg/m2, d1) plus cisplatin (30 mg/m2, d1-3) or carboplatin (AUC 1.5, d1-3) and a response evaluation 3 weeks later. Responders (≥ 30% tumor size reduction and ≥ 20% SUVmax decrease in 18F-FDG PET/CT) were recommended chemoradiotherapy (CRT), and non-responders surgery. RESULTS: The overall response rate was 72.5%. All 74 responders and 10 non-responders received primary CRT, and 18 patients received primary surgery after single-cycle IC. Overall 10-year local recurrence-free survival (LRFS) was 73.7%. Three-year LRFS was 88.2% (mesopharynx/tongue), 88.2% (larynx), and 73.3% (hypopharynx); p = 0.17. 3-year distant metastasis-free survival (DMFS) was 94.1% (mesopharynx/tongue), 88.0% (larynx) and 76.4% (hypopharynx); p > 0.05. This influenced the 3-year cancer-specific survival (CSS) for larynx (91.2%) vs. hypopharynx tumors (60.8%); p = 0.003, but CSS was not different to tumors in the mesopharynx/tongue (81.4%); p > 0.05. CONCLUSIONS: A single-cycle induction chemotherapy for HNSCC enables surgery plus adjuvant therapy as well as chemoradiotherapy. The long-term local and distant disease control was good but varied between tumors in the larynx and mesopharynx/tongue vs. hypopharynx.

Educational expansion and educational wage premiums of young male employees: A long-term analysis for West Germany 1976-2010.

For decades, Western societies have experienced educational expansion accompanied by an upgrading of skills. The literature provides competing hypotheses on the consequences for educational wage returns - among them are the positional value theory, routine-biased technological change, and the social closure theory. We test these theoretical perspectives empirically on young, male full-time workers in West Germany between 1976 and 2010 in two ideal-type occupational segments using 2.34 million administrative earnings records (Sample of Integrated Labor Market Biographies, SIAB). Our findings show no credential inflation across all levels of education. Instead, the picture in both segments - negative effects of educational expansion on the returns to medium- but not high-level skills - confirms the predictions of routine-biased technological change. Wage premiums for medium-skilled workers differ between segments: the premiums worsen over time in the general segment whereas social-closure mechanisms seem to weaken this negative trend for vocational graduates in the specific segment.

[Ultrasound of Thyroid Nodules - Ultrasound Characteristics and Risk of Carcinoma]. / Sonografie von Schilddrüsenknoten.

Thyroid ultrasound is used as a first-line diagnostic procedure to evaluate thyroid nodules. Several ultrasound characteristics have been associated with an increased risk of malignancy. Based on these criteria, classification systems are being developed to categorize thyroid nodules and stratify their malignant risk to decide about further evaluation. Up to now only morphological features are taken into account. The results of Doppler ultrasonography have not yet been included in these thyroid imaging and reporting systems (TI-RADS) although predominantly internal flow is associated with malignancy of thyroid follicular neoplasia. Currently, the new systems will be evaluated and may be optimized for clinical practice. Furthermore there are first attempts to standardize the reporting of ultrasound features of thyroid nodules to enhance patient care by optimizing the diagnostic capabilities of an ultrasound examination.

99m Tc-MIP-1404-SPECT/CT for the detection of PSMA-positive lesions in 225 patients with biochemical recurrence of prostate cancer.

BACKGROUND: 99m Tc-MIP-1404 (Progenics Pharmaceuticals, Inc., New York, NY) is a novel, SPECT-compatible 99m Tc-labeled PSMA inhibitor for the detection of prostate cancer. We present results of its clinical use in a cohort of 225 men with histologically confirmed prostate cancer referred for workup of biochemical relapse. METHODS: From April 2013 to April 2017, 99m Tc-MIP1404-scintigraphy was performed in 225 patients for workup of PSA biochemical relapse of prostate cancer. Whole-body planar and SPECT/CT images of the lower abdomen and thorax were obtained 3-4 h p.i. of 710 ± 64 MBq 99m Tc-MIP-1404. Images were visually analyzed for presence and location of abnormal uptake. In addition, quantitative analysis of the SPECT/CT data was carried out on a subset of 125 patients. Follow-up reports of subsequent therapeutic interventions were available for 59% (139) of all patients. RESULTS: Tracer-positive lesions were detected in 77% (174/225) of all patients. Detections occurred at the area of local recurrence in the prostate in 25% of patients (or a total of 56), with metastases in lymph nodes in 47% (105), bone in 27% (60), lung in 5% (12), and other locations in 2% (4) of patients. Detection rates were 90% at PSA levels ≥2 ng/mL and 54% below that threshold. Lesional SUVmax values were, on average, 32.2 ± 29.6 (0.8-142.2), and tumor-to-normal ratios 146.6 ± 160.5 (1.9-1482.4). The PSA level correlated significantly with total uptake of MIP-1404 in tumors (P < 0.001). Furthermore, total tumor uptake was significantly higher in patients with Gleason scores ≥8 compared to those with Gleason scores ≤7 (P < 0.05). In patients with androgen deprivation therapy, the detection rate was significantly higher compared to patients without androgen deprivation therapy (86% vs 71%, P < 0.001). Based on 99m Tc-MIP-1404-imaging and other information, an interdisciplinary tumor board review recommended changes to treatment plans in 74% (104/139) of those patients for whom the necessary documentation was available. CONCLUSION: SPECT/CT with 99m Tc-labeled MIP-1404 has a high probability in detecting PSMA-positive lesions in patients with elevated PSA. Statistical analysis disclosed significant relationship between quantitative 99m Tc-MIP-1404 uptake, PSA level, and Gleason score.

The value of 18F-FDG-PET/CT in identifying the cause of fever of unknown origin (FUO) and inflammation of unknown origin (IUO): data from a prospective study.

BACKGROUND: Fever of unknown origin (FUO) and inflammation of unknown origin (IUO) are diagnostically challenging conditions. Diagnosis of underlying disease may be improved by 18F-fluorodesoxyglucose positron emission tomography (18F-FDG-PET). METHODS: Prospective study to test diagnostic utility of 18F-FDG-PET/CT in a large cohort of patients with FUO or IUO and to define parameters that increase the likelihood of diagnostic 18F-FDG-PET/CT. Patients with FUO or IUO received 18F-FDG-PET/CT scanning in addition to standard diagnostic work-up. 18F-FDG-PET/CT results were classified as helpful or non-helpful in establishing final diagnosis. Binary logistic regression was used to identify clinical parameters associated with a diagnostic 18F-FDG-PET/CT. RESULTS: 240 patients were enrolled, 72 with FUO, 142 with IUO and 26 had FUO or IUO previously (exFUO/IUO). Diagnosis was established in 190 patients (79.2%). The leading diagnoses were adult-onset Still's disease (15.3%) in the FUO group, large vessel vasculitis (21.1%) and polymyalgia rheumatica (18.3%) in the IUO group and IgG4-related disease (15.4%) in the exFUO/IUO group. In 136 patients (56.7% of all patients and 71.6% of patients with a diagnosis), 18F-FDG-PET/CT was positive and helpful in finding the diagnosis. Predictive markers for a diagnostic 18F-FDG-PET/CT were age over 50 years (p=0.019), C-reactive protein (CRP) level over 30 mg/L (p=0.002) and absence of fever (p=0.001). CONCLUSION: 18F-FDG-PET/CT scanning is helpful in ascertaining the correct diagnosis in more than 50% of the cases presenting with FUO and IUO. Absence of intermittent fever, higher age and elevated CRP level increase the likelihood for a diagnostic 18F-FDG-PET/CT.

68Ga-PSMA-11 PET/CT-derived metabolic parameters for determination of whole-body tumor burden and treatment response in prostate cancer.

PURPOSE: We aimed at evaluating the role of 68Ga-PSMA-11 PET/CT-derived metabolic parameters for assessment of whole-body tumor burden and its capability to determine therapeutic response in patients with prostate cancer. METHODS: A total of 142 patients with biochemical recurrence of prostate cancer underwent PET/CT with [68Ga]Ga-PSMA-HBED-CC (68Ga-PSMA-11). Quantitative assessment of all 641 68Ga-PSMA-11-positive lesions in the field of view was performed to calculate PSMA-derived parameters, including whole-body PSMA tumor volume (PSMA-TV) and whole-body total lesion PSMA (TL-PSMA), as well as the established SUVmax and SUVmean values. All PET-derived parameters were tested for correlation with serum PSA levels and for association with Gleason scores. In 23 patients who underwent 68Ga-PSMA-11 PET/CT before and after therapy with either external beam radiation, androgen deprivation, or docetaxel chemotherapy, SUVmax and TL-PSMA were compared to radiographic response assessment of CT images based on RECIST 1.1 criteria and to biochemical response determined by changes of serum PSA levels. RESULTS: PSMA-TV and TL-PSMA demonstrated a significant correlation with serum PSA levels (P < 0.0001) and TL-PSMA was significantly different for different Gleason scores. The agreement rate between TL-PSMA derived from PET and biochemical response was 87% (95% confidence interval, 0.66-0.97; Cohen's κ = 0.78; P < 0.01) and, thus, higher than for SUVmax, which was 74% (95% CI, 0.52-0.90; κ = 0.55; P < 0.01). Furthermore, agreement with PSA was higher for TL-PSMA and SUVmax than for CT-based response evaluation. Discordant findings between PET and CT were most likely due to limitations of CT and RECIST in rating small lymph nodes as metastases, as well as bone involvement, which was sometimes not detectable in CT. CONCLUSION: 68Ga-PSMA-11 PET/CT-derived metabolic tumor parameters showed promising results for evaluation of treatment response. Especially, TL-PSMA demonstrated higher agreement rates with biochemical response compared to SUVmax. Larger, ideally prospective trials are needed to help to reveal the full potential of metabolic parameters derived from PET imaging with 68Ga-PSMA-11.

Repeating of local therapy of distant metastases increases overall survival in patients with synchronous metastasized rectal cancer-a monocentric analysis.

PURPOSE: The aim was to evaluate the outcome of treatment-naive patients with synchronous metastatic rectal cancer after chemotherapy with FOLFOXIRI followed by local therapeutic procedures of all tumor lesions as complete as possible. METHODS: We reviewed data of 30 patients with synchronous distant metastatic rectal cancer who underwent chemotherapy with FOLFOXIRI and subsequent local therapy in our institution. RESULTS: Median follow-up was 28 months (range: 8; 74). Cumulative overall survival (OS) and progression-free survival (PFS) was 93.3, 76.9, 55.6% and 46.2, 29.7, 29.7% after 1, 2, 4 years. Non-response to chemotherapy with FOLFOXIRI was associated with a highly significant decreased OS (p < 0.0001). The consistent use of local ablative procedures led to a statistically significant increase in OS (p < 0.0001), but not in PFS (p = 0.635). Patients with ≤ 4 distant metastases showed a better OS (p = 0.033). CONCLUSIONS: Response to intensified first-line chemotherapy with FOLFOXIRI, treatment of the primary rectal tumor, and repeated thorough local ablative procedures in patients with synchronous metastasized rectal cancer may lead to long-term survival, even in a subset of patients with unresectable disease at initial diagnosis.

Strategies in times of crisis-insights into the benthic foraminiferal record of the Palaeocene-Eocene Thermal Maximum.

Climate change is predicted to alter temperature, carbonate chemistry and oxygen availability in the oceans, which will affect individuals, populations and ecosystems. We use the fossil record of benthic foraminifers to assess developmental impacts in response to environmental changes during the Palaeocene-Eocene Thermal Maximum (PETM). Using an unprecedented number of µ-computed tomography scans, we determine the size of the proloculus (first chamber), the number of chambers and the final size of two benthic foraminiferal species which survived the extinction at sites 690 (Atlantic sector, Southern Ocean, palaeodepth 1900 m), 1210 (central equatorial Pacific, palaeodepth 2100 m) and 1135 (Indian Ocean sector, Southern Ocean, palaeodepth 600-1000 m). The population at the shallowest site, 1135, does not show a clear response to the PETM, whereas those at the other sites record reductions in diameter or proloculus size. Temperature was similar at all sites, thus it is not likely to be the reason for differences between sites. At site 1210, small size coincided with higher chamber numbers during the peak event, and may have been caused by a combination of low carbonate ion concentrations and low food supply. Dwarfing at site 690 occurred at lower chamber numbers, and may have been caused by decreasing carbonate saturation at sufficient food levels to reproduce. Proloculus size varied strongly between sites and through time, suggesting a large influence of environment on both microspheric and megalospheric forms without clear bimodality. The effect of the environmental changes during the PETM was more pronounced at deeper sites, possibly implicating carbonate saturation.This article is part of a discussion meeting issue 'Hyperthermals: rapid and extreme global warming in our geological past'.

Ontogenetic constraints on foraminiferal test construction.

Developmental processes represent one of the main constraints on the generation of adult form. Determining how constructional and energetic demands operate throughout growth is es-sential to understanding fundamental growth rules and trade-offs that define the framework within which new species originate. In organisms producing spiral shells, coiling patterns can inform on the constructional constraints acting throughout development that dictated the diversification of forms within a group. Here, we use Synchrotron radiation X-Ray tomographic microscopy (SRXTM) reconstructions of eight planktic foraminifera repre-sentative of the major morphotypic groups to determine disparity of coiling patterns by measuring Raupian parameters. The results show that foraminifera are a morphologically highly conservative group, exploiting a limited range of poten-tial coiling patterns. Very similar coiling patterns during early ontogeny, regardless of species, point toward strong constraints in early ontogeny and to common develop-mental processes acting across all morphogroups. Dispersion and lateral displacement of taxa in morphospace are limited to the adult stage. Accretion with low translation down the coiling axis in juveniles may maximize lateral growth and metabolic efficiency in light of costly calcification. Increased translation in the adult stages allows growth to accommo-date new chamber shapes, mediated by changes in aperture location and the site of accretion over ontogeny. These constructional constraints, and the accretion of a small number of discrete chambers, limit the potential for novel forms within the foraminifera compared to other groups of coiling organisms and may explain the repeated evolution of similar morphotypes throughout the evolutionary history of the group.

Modelling the climatic niche of turtles: a deep-time perspective.

Ectotherms have close physiological ties with the thermal environment; consequently, the impact of future climate change on their biogeographic distributions is of major interest. Here, we use the modern and deep-time fossil record of testudines (turtles, tortoises, and terrapins) to provide the first test of climate on the niche limits of both extant and extinct (Late Cretaceous, Maastrichtian) taxa. Ecological niche models are used to assess niche overlap in model projections for key testudine ecotypes and families. An ordination framework is applied to quantify metrics of niche change (stability, expansion, and unfilling) between the Maastrichtian and present day. Results indicate that niche stability over evolutionary timescales varies between testudine clades. Groups that originated in the Early Cretaceous show climatic niche stability, whereas those diversifying towards the end of the Cretaceous display larger niche expansion towards the modern. Temperature is the dominant driver of modern and past distributions, whereas precipitation is important for freshwater turtle ranges. Our findings demonstrate that testudines were able to occupy warmer climates than present day in the geological record. However, the projected rate and magnitude of future environmental change, in concert with other conservation threats, presents challenges for acclimation or adaptation.

Computing autocatalytic sets to unravel inconsistencies in metabolic network reconstructions.

MOTIVATION: Genome-scale metabolic network reconstructions have been established as a powerful tool for the prediction of cellular phenotypes and metabolic capabilities of organisms. In recent years, the number of network reconstructions has been constantly increasing, mostly because of the availability of novel (semi-)automated procedures, which enabled the reconstruction of metabolic models based on individual genomes and their annotation. The resulting models are widely used in numerous applications. However, the accuracy and predictive power of network reconstructions are commonly limited by inherent inconsistencies and gaps. RESULTS: Here we present a novel method to validate metabolic network reconstructions based on the concept of autocatalytic sets. Autocatalytic sets correspond to collections of metabolites that, besides enzymes and a growth medium, are required to produce all biomass components in a metabolic model. These autocatalytic sets are well-conserved across all domains of life, and their identification in specific genome-scale reconstructions allows us to draw conclusions about potential inconsistencies in these models. The method is capable of detecting inconsistencies, which are neglected by other gap-finding methods. We tested our method on the Model SEED, which is the largest repository for automatically generated genome-scale network reconstructions. In this way, we were able to identify a significant number of missing pathways in several of these reconstructions. Hence, the method we report represents a powerful tool to identify inconsistencies in large-scale metabolic networks. AVAILABILITY AND IMPLEMENTATION: The method is available as source code on http://users.minet.uni-jena.de/∼m3kach/ASBIG/ASBIG.zip. CONTACT: christoph.kaleta@uni-jena.de SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.

Surviving rapid climate change in the deep sea during the Paleogene hyperthermals.

Predicting the impact of ongoing anthropogenic CO2 emissions on calcifying marine organisms is complex, owing to the synergy between direct changes (acidification) and indirect changes through climate change (e.g., warming, changes in ocean circulation, and deoxygenation). Laboratory experiments, particularly on longer-lived organisms, tend to be too short to reveal the potential of organisms to acclimatize, adapt, or evolve and usually do not incorporate multiple stressors. We studied two examples of rapid carbon release in the geological record, Eocene Thermal Maximum 2 (∼53.2 Ma) and the Paleocene Eocene Thermal Maximum (PETM, ∼55.5 Ma), the best analogs over the last 65 Ma for future ocean acidification related to high atmospheric CO2 levels. We use benthic foraminifers, which suffered severe extinction during the PETM, as a model group. Using synchrotron radiation X-ray tomographic microscopy, we reconstruct the calcification response of survivor species and find, contrary to expectations, that calcification significantly increased during the PETM. In contrast, there was no significant response to the smaller Eocene Thermal Maximum 2, which was associated with a minor change in diversity only. These observations suggest that there is a response threshold for extinction and calcification response, while highlighting the utility of the geological record in helping constrain the sensitivity of biotic response to environmental change.