Spatial pattern and temporal evolution of glacial terminations of the last 800 ka

The second QUIGS workshop brought together 28 delegates to assess current knowledge and research needs on the spatio-temporal patterns of climate forcing, responses and feedbacks that characterize glacial terminations, i.e. transitions between glacial and interglacial periods

Sea-ice-free Arctic during the Last Interglacial supports fast future loss

The Last Interglacial (LIG), a warmer period 130-116 ka before present, is a potential analog for future climate change. Stronger LIG summertime insolation at high northern latitudes drove Arctic land summer temperatures 4-5 °C higher than the preindustrial era. Climate model simulations have previously failed to capture these elevated temperatures, possibly because they were unable to correctly capture LIG sea-ice changes. Here, we show the latest version of the fully-coupled UK Hadley Center climate model (HadGEM3) simulates a more accurate Arctic LIG climate, including elevated temperatures. Improved model physics, including a sophisticated sea-ice melt-pond scheme, result in a complete simulated loss of Arctic sea ice in summer during the LIG, which has yet to be simulated in past generations of models. This ice-free Arctic yields a compelling solution to the longstanding puzzle of what drove LIG Arctic warmth and supports a fast retreat of future Arctic summer sea ice

Proportions of CD4+ memory T cells are altered in individuals chronically infected with Schistosoma haematobium

Characterisation of protective helminth acquired immunity in humans or experimental models has focused on effector responses with little work conducted on memory responses. Here we show for the first time, that human helminth infection is associated with altered proportions of the CD4+ memory T cells, with an associated alteration of TH1 responses. The reduced CD4+ memory T cell proportions are associated with a significantly lower ratio of schistosome-specific IgE/IgG4 (marker for resistance to infection/re-infection) in uninfected older people. Helminth infection does not affect the CD8+ memory T cell pool. Furthermore, we show for the first time in a helminth infection that the CD4+ memory T cell proportions decline following curative anti-helminthic treatment despite increased CD4+ memory cell replication. Reduced accumulation of the CD4+ memory T cells in schistosome-infected people has implications for the development of natural or vaccine induced schistosome-specific protective immunity as well as for unrelated pathogens

Large-scale features of Last Interglacial climate: Results from evaluating the lig127k simulations for the Coupled Model Intercomparison Project (CMIP6)-Paleoclimate Modeling Intercomparison Project (PMIP4)

Abstract. The modeling of paleoclimate, using physically based tools, is increasingly seen as a strong out-of-sample test of the models that are used for the projection of future climate changes. New to the Coupled Model Intercomparison Project (CMIP6) is the Tier 1 Last Interglacial experiment for 127 000 years ago (lig127k), designed to address the climate responses to stronger orbital forcing than the midHolocene experiment, using the same state-of-the-art models as for the future and following a common experimental protocol. Here we present a first analysis of a multi-model ensemble of 17 climate models, all of which have completed the CMIP6 DECK (Diagnostic, Evaluation and Characterization of Klima) experiments. The equilibrium climate sensitivity (ECS) of these models varies from 1.8 to 5.6 ∘C. The seasonal character of the insolation anomalies results in strong summer warming over the Northern Hemisphere continents in the lig127k ensemble as compared to the CMIP6 piControl and much-reduced minimum sea ice in the Arctic. The multi-model results indicate enhanced summer monsoonal precipitation in the Northern Hemisphere and reductions in the Southern Hemisphere. These responses are greater in the lig127k than the CMIP6 midHolocene simulations as expected from the larger insolation anomalies at 127 than 6 ka. New synthesis for surface temperature and precipitation, targeted for 127 ka, have been developed for comparison to the multi-model ensemble. The lig127k model ensemble and data reconstructions are in good agreement for summer temperature anomalies over Canada, Scandinavia, and the North Atlantic and for precipitation over the Northern Hemisphere continents. The model–data comparisons and mismatches point to further study of the sensitivity of the simulations to uncertainties in the boundary conditions and of the uncertainties and sparse coverage in current proxy reconstructions. The CMIP6–Paleoclimate Modeling Intercomparison Project (PMIP4) lig127k simulations, in combination with the proxy record, improve our confidence in future projections of monsoons, surface temperature, and Arctic sea ice, thus providing a key target for model evaluation and optimization. </jats:p

Different Mechanisms Underlie Post-menarchial Increase in Depression and Weight

Contains fulltext : 99254.pdf (publisher's version ) (Open Access)Background Depression and being overweight are correlated health problems in adulthood. Adolescence is a significant period for the onset and increase of depression and obesity, especially among girls. Pubertal development also occurs with concomitant increases in weight. Thus, it is not yet clear whether the association between depression and being overweight can be explained by pubertal development. Purpose We examined the association between depressive mood, body weight, and pubertal status in adolescent girls. Method The design was cross-sectional. In 962 young adolescent Dutch girls (age range, 11.9-15.9) weight and height measurements were used to calculate height, age, and gender-standardized body weight (zBMI). Questionnaires assessed depressive mood (the Center for Epidemiological Studies-Depression, CES-D, inventory) and menarcheal status (pre or post). Results The correlation between menarcheal status and body weight (r = 0.34, p < 0.001) was not affected by depressive mood, and the correlation between menarcheal status and depressive mood (r = 0.20, p < 0.001) was not affected by body weight. A small correlation between depressive mood and body weight (r = 0.12, p < 0.01) largely disappeared after controlling for menarche. Conclusion Menarcheal status largely explains the association between weight and depression. It is independently associated with both BMI and depression, suggesting that different mechanisms underlie the post-menarcheal increased prevalence of depression and overweight.6 p

Antarctic last interglacial isotope peak in response to sea ice retreat not ice-sheet collapse

Several studies have suggested that sea-level rise during the last interglacial implies retreat of the West Antarctic Ice Sheet (WAIS). The prevalent hypothesis is that the retreat coincided with the peak Antarctic temperature and stable water isotope values from 128,000 years ago (128 ka); very early in the last interglacial. Here, by analysing climate model simulations of last interglacial WAIS loss featuring water isotopes, we show instead that the isotopic response to WAIS loss is in opposition to the isotopic evidence at 128 ka. Instead, a reduction in winter sea ice area of 65±7% fully explains the 128 ka ice core evidence. Our finding of a marked retreat of the sea ice at 128 ka demonstrates the sensitivity of Antarctic sea ice extent to climate warming

APC/C-Mediated Degradation of dsRNA-Binding Protein 4 (DRB4) Involved in RNA Silencing

Background: Selective protein degradation via the ubiquitin-26S proteasome is a major mechanism underlying DNA replication and cell division in all Eukaryotes. In particular, the APC/C (Anaphase Promoting Complex or Cyclosome) is a master ubiquitin protein ligase (E3) that targets regulatory proteins for degradation allowing sister chromatid separation and exit from mitosis. Interestingly, recent work also indicates that the APC/C remains active in differentiated animal and plant cells. However, its role in post-mitotic cells remains elusive and only a few substrates have been characterized. Methodology/Principal Findings: In order to identify novel APC/C substrates, we performed a yeast two-hybrid screen using as the bait Arabidopsis APC10/DOC1, one core subunit of the APC/C, which is required for substrate recruitment. This screen identified DRB4, a double-stranded RNA binding protein involved in the biogenesis of different classes of small RNA (sRNA). This protein interaction was further confirmed in vitro and in plant cells. Moreover, APC10 interacts with DRB4 through the second dsRNA binding motif (dsRBD2) of DRB4, which is also required for its homodimerization and binding to its Dicer partner DCL4. We further showed that DRB4 protein accumulates when the proteasome is inactivated and, most importantly, we found that DRB4 stability depends on APC/C activity. Hence, depletion of Arabidopsis APC/C activity by RNAi leads to a strong accumulation of endogenous DRB4, far beyond its normal level of accumulation. However, we could not detect any defects in sRNA production in lines where DRB4 was overexpressed

Real-Time Monitoring of Tumorigenesis, Dissemination, & Drug Response in a Preclinical Model of Lymphangioleiomyomatosis/Tuberous Sclerosis Complex

Background: TSC2-deficient cells can proliferate in the lungs, kidneys, and other organs causing devastating progressive multisystem disorders such as lymphangioleiomyomatosis (LAM) and tuberous sclerosis complex (TSC). Preclinical models utilizing LAM patient-derived cells have been difficult to establish. We developed a novel animal model system to study the molecular mechanisms of TSC/LAM pathogenesis and tumorigenesis and provide a platform for drug testing. Methods and Findings: TSC2-deficient human cells, derived from the angiomyolipoma of a LAM patient, were engineered to co-express both sodium-iodide symporter (NIS) and green fluorescent protein (GFP). Cells were inoculated intraparenchymally, intravenously, or intratracheally into athymic NCr nu/nu mice and cells were tracked and quantified using single photon emission computed tomography (SPECT) and computed tomography (CT). Surprisingly, TSC2-deficient cells administered intratracheally resulted in rapid dissemination to lymph node basins throughout the body, and histopathological changes in the lung consistent with LAM. Estrogen was found to be permissive for tumor growth and dissemination. Rapamycin inhibited tumor growth, but tumors regrew after the drug treatment was withdrawn. Conclusions: We generated homogeneous NIS/GFP co-expressing TSC2-deficient, patient-derived cells that can proliferate and migrate in vivo after intratracheal instillation. Although the animal model we describe has some limitations, we demonstrate that systemic tumors formed from TSC2-deficient cells can be monitored and quantified noninvasively over time using SPECT/CT, thus providing a much needed model system for in vivo drug testing and mechanistic studies of TSC2-deficient cells and their related clinical syndromes