Persistence of full glacial conditions in the central Pacific until 15,000 years ago

The magnitude of atmospheric cooling during the Last Glacial Maximum and the timing of the transition into the current interglacial period remain poorly constrained in tropical regions, partly because of a lack of suitable climate records. Glacial moraines provide a method of reconstructing past temperatures, but they are relatively rare in the tropics. Here we present a reconstruction of atmospheric temperatures in the central Pacific during the last deglaciation on the basis of cosmogenic ^3He ages of moraines and numerical modelling of the ice cap on Mauna Kea volcano, Hawaii—the only highland in the central Pacific on which moraines that formed during the last glacial period are preserved. Our reconstruction indicates that the Last Glacial Maximum occurred between 19,000 and 16,000 years ago in this region and that temperatures at high elevations were about 7 °C lower than today during this interval. Glacial retreat began about 16,000 years ago, but temperatures were still about 6.5 °C lower than today until 15,000 years ago. When combined with estimates of sea surface temperatures in the central Pacific Ocean, our reconstruction indicates that the lapse rate during the Last Glacial Maximum was higher than at present, which is consistent with the proposal that the atmosphere was drier at that time. Furthermore, the persistence of full glacial conditions until 15,000 years ago is consistent with the relatively late and abrupt transition to warmer temperatures in Greenland5, indicating that there may have been an atmospheric teleconnection between the central Pacific and North Atlantic regions during the last deglaciation

Lag and mixing during sediment transfer across the Tian Shan piedmont caused by climate-driven aggradation-incision cycles

Transient sediment storage and mixing of deposits of various ages during transport across alluvial piedmonts alter the clastic sedimentary record. We quantify buffering and mixing during cycles of aggradation–incision in the north piedmont of the Eastern Tian Shan. We complement existing chronologic data with 20 new luminescence ages and one cosmogenic radionuclide age of terrace abandonment and alluvial aggradation. Over the last 0.5 Myr, the piedmont deeply incised and aggraded many times per 100 kyr. Aggradation is driven by an increased flux of glacial sediment accumulated in the high range and flushed onto the piedmont by greater water discharge at stadial–interstadial transitions. After this sediment is evacuated from the high range, the reduced input sediment flux results in fluvial incision of the piedmont as fast as 9 cm year−1 and to depths up to 330 m. The timing of incision onset is different in each river and does not directly reflect climate forcing but the necessary time for the evacuation of glacial sediment from the high range. A significant fraction of sediments evacuated from the high range is temporarily stored on the piedmont before a later incision phase delivers it to the basin. Coarse sediments arrive in the basin with a lag of at least 7–14 kyrs between the first evacuation from the mountain and later basinward transport. The modern output flux of coarse sediments from the piedmont contains a significant amount of recycled material that was deposited on the piedmont as early as the Middle Pleistocene. Variations in temperature and moisture delivered by the Westerlies are the likely cause of repeated aggradation–incision cycles in the north piedmont instead of monsoonal precipitation. The arrival of the gravel front into the proximal basin is delayed relative to the fine-grained load and both are separated by a hiatus. This work shows, based on field observations and data, how sedimentary systems respond to climatic perturbations, and how sediment recycling and mixing can ensue

Byrd ice core debris constrains the sediment provenance signature of central West Antarctica

Provenance records from sediments deposited offshore of the West Antarctic Ice Sheet (WAIS) can help identify past major ice retreat, thus constraining ice-sheet models projecting future sea-level rise. Interpretations from such records are, however, hampered by the ice obscuring Antarctica's geology. Here, we explore central West Antarctica's subglacial geology using basal debris from within the Byrd ice core, drilled to the bed in 1968. Sand grain microtextures and a high kaolinite content (∼38–42%) reveal the debris consists predominantly of eroded sedimentary detritus, likely deposited initially in a warm, pre-Oligocene, subaerial environment. Detrital hornblende 40Ar/39Ar ages suggest proximal late Cenozoic subglacial volcanism. The debris has a distinct provenance signature, with: common Permian-Early Jurassic mineral grains; absent early Ross Orogeny grains; a high kaolinite content; and high 143Nd/144Nd and low 87Sr/86Sr ratios. Detecting this “fingerprint” in Antarctic sedimentary records could imply major WAIS retreat, revealing the WAIS's sensitivity to future warming

Implicating Calpain in Tau-Mediated Toxicity In Vivo

Alzheimer's disease and other related neurodegenerative disorders known as tauopathies are characterized by the accumulation of abnormally phosphorylated and aggregated forms of the microtubule-associated protein tau. Several laboratories have identified a 17 kD proteolytic fragment of tau in degenerating neurons and in numerous cell culture models that is generated by calpain cleavage and speculated to contribute to tau toxicity. In the current study, we employed a Drosophila tauopathy model to investigate the importance of calpain-mediated tau proteolysis in contributing to tau neurotoxicity in an animal model of human neurodegenerative disease. We found that mutations that disrupted endogenous calpainA or calpainB activity in transgenic flies suppressed tau toxicity. Expression of a calpain-resistant form of tau in Drosophila revealed that mutating the putative calpain cleavage sites that produce the 17 kD fragment was sufficient to abrogate tau toxicity in vivo. Furthermore, we found significant toxicity in the fly retina associated with expression of only the 17 kD tau fragment. Collectively, our data implicate calpain-mediated proteolysis of tau as an important pathway mediating tau neurotoxicity in vivo

Uncoupling neuronal death and dysfunction in Drosophila models of neurodegenerative disease

Common neurodegenerative proteinopathies, such as Alzheimer’s disease (AD) and Parkinson’s disease (PD), are characterized by the misfolding and aggregation of toxic protein species, including the amyloid beta (Aß) peptide, microtubule-associated protein Tau (Tau), and alpha-synuclein (αSyn) protein. These factors also show toxicity in Drosophila; however, potential limitations of prior studies include poor discrimination between effects on the adult versus developing nervous system and neuronal versus glial cell types. In addition, variable expression paradigms and outcomes hinder systematic comparison of toxicity profiles. Using standardized conditions and medium-throughput assays, we express human Tau, Aß or αSyn selectively in neurons of the adult Drosophila retina and monitor age-dependent changes in both structure and function, based on tissue histology and recordings of the electroretinogram (ERG), respectively. We find that each protein causes a unique profile of neurodegenerative pathology, demonstrating distinct and separable impacts on neuronal death and dysfunction. Strikingly, expression of Tau leads to progressive loss of ERG responses whereas retinal architecture and neuronal numbers are largely preserved. By contrast, Aß induces modest, age-dependent neuronal loss without degrading the retinal ERG. αSyn expression, using a codon-optimized transgene, is characterized by marked retinal vacuolar change, progressive photoreceptor cell death, and delayed-onset but modest ERG changes. Lastly, to address potential mechanisms, we perform transmission electron microscopy (TEM) to reveal potential degenerative changes at the ultrastructural level. Surprisingly, Tau and αSyn each cause prominent but distinct synaptotoxic profiles, including disorganization or enlargement of photoreceptor terminals, respectively. Our findings highlight variable and dynamic properties of neurodegeneration triggered by these disease-relevant proteins in vivo, and suggest that Drosophila may be useful for revealing determinants of neuronal dysfunction that precede cell loss, including synaptic changes, in the adult nervous system

Predicting major bleeding in patients with noncardioembolic stroke on antiplatelets

Objective: To develop and externally validate a prediction model for major bleeding in patients with a TIA or ischemic stroke on antiplatelet agents. Methods: We combined individual patient data from 6 randomized clinical trials (CAPRIE, ESPS-2, MATCH, CHARISMA, ESPRIT, and PRoFESS) investigating antiplatelet therapy after TIA or ischemic stroke. Cox regression analyses stratified by trial were performed to study the association between predictors and major bleeding. A risk prediction model was derived and validated in the PERFORM trial. Performance was assessed with the c statistic and calibration plots. Results: Major bleeding occurred in 1,530 of the 43,112 patients during 94,833 person-years of follow-up. The observed 3-year risk of major bleeding was 4.6% (95% confidence interval [CI] 4.4%–4.9%). Predictors were male sex, smoking, type of antiplatelet agents (aspirin-clopidogrel), outcome on modified Rankin Scale ≥3, prior stroke, high blood pressure, lower body mass index, elderly, Asian ethnicity, and diabetes (S2TOP-BLEED). The S2TOP-BLEED score had a c statistic of 0.63 (95% CI 0.60–0.64) and showed good calibration in the development data. Major bleeding risk ranged from 2% in patients aged 45–54 years without additional risk factors to more than 10% in patients aged 75–84 years with multiple risk factors. In external validation, the model had a c statistic of 0.61 (95% CI 0.59–0.63) and slightly underestimated major bleeding risk. Conclusions: The S2TOP-BLEED score can be used to estimate 3-year major bleeding risk in patients with a TIA or ischemic stroke who use antiplatelet agents, based on readily available characteristics. The discriminatory performance may be improved by identifying stronger predictors of major bleeding

Les isotopes cosmogéniques 3He et 10Be dans les minéraux mafiques : développements analytiques, calibration et nouvelles applications

Improving precision and accuracy of the techniques based on cosmogenic nuclides requires new analytical protocols, amelioration of existing routines and precise calibration of production rates. Specific tests allowed improving the standard technique for the analysis of cosmogenic 3Hec (3Hec) in olivines and clinopyroxenes, by evidencing a 3Hec loss during the preliminary crushing step. Similarly, a new chemical treatment has been developed for the measurement of in situ 10Bec in mafic minerals. Using these refined methods on natural phenocrysts, new reference production rates of 128±5 at.g-1.yr- 1 and 4.4±0.6 at.g-1.yr-1 are proposed for 3Hec in olivines and 10Bec in clinopyroxenes, respectively. These rates have been yielded from natural calibration on basaltic lava flows from Mt Etna (Sicily, 38°N), Mauna Loa and Mauna Kea (Hawaii, 19°N) independently dated by K-Ar or 14C between 1.47±0.05 and 149±23 ka. The accuracy of the 3Hec dating method allowed a precise chronology of the last glacial retreat of Mauna Kea (Hawaii) to be established. The age of the local last glacial maximum (LGM) has been constrained between 16 and 19 ka. Numerical simulations moreover allowed paleoclimatic conditions to be reconstructed. The amplitude of high altitude (> 3000 m) cooling was thus 7±1°C during the LGM. The subsequent post glacial warming occurred ~15 ka. Such result confirms the behaviour of this zone is disconnected from the other Pacific regions. Finally, it has been demonstrated that geological objects that have experienced ancient (or fossil) exposure episodes are able to quantify a great variety of parameters, such as paleoaltitudes, paleo-erosion rates, or lava flow emission rates. The uncertainties and limitations of these new methods have been assessed both by numerical simulations and testing on geological targets.L'amélioration de la précision et de la justesse des techniques basées sur les isotopes cosmogéniques passe par la mise au point de nouveaux protocoles analytiques, l'affinement des méthodes existantes et la calibration de leurs taux de production. Des tests spécifiques ont ainsi permis d'améliorer la technique standard d'analyse du 3He cosmogénique (3Hec) dans les olivines et les pyroxènes, grâce à l'identification d'une perte de 3Hec lors de l'étape préliminaire de broyage. De même, un nouveau protocole de traitement chimique a été mis au point pour la mesure du 10Bec in situ dans ces minéraux. L'utilisation de ces méthodes affinées sur des phénocristaux naturels conduit à proposer de nouveaux taux de production de 128±5 at.g-1.a-1 pour le 3Hec dans les olivines et de 4.4±0.6 at.g-1.a-1 pour le 10Bec dans les clinopyroxènes. Ces valeurs sont obtenues par calibration sur des coulées basaltiques du Mt Etna (Sicile, 38°N), du Mauna Loa et du Mauna Kea (Hawaii, 19°N) qui ont été datées par K-Ar ou 14C entre 1.47±0.05 et 149±23 ka. La fiabilité de la méthode de datation par 3Hec a été mise à profit pour établir avec précision la chronologie du dernier retrait glaciaire du Mauna Kea (Hawaii). L'âge du dernier maximum glaciaire (DMG) local a été contraint entre 19 et 16 ka. Ces datations ont de plus été valorisées par simulation numérique des conditions paléoclimatiques. Il a ainsi été établi que le refroidissement en haute altitude (> 3000 m) du Pacifique Central était de l'ordre de 7±1°C au DMG. Le réchauffement post glaciaire n'a été significatif qu'à partir de ~15 ka, ce résultat confirmant le comportement isolé de cette zone par rapport au reste du Pacifique. Enfin, il a été montré que les objets géologiques ayant enregistrés des expositions anciennes (ou fossiles) ont le potentiel pour quantifier des paramètres aussi variés que la mesure de paléoaltitudes, de paléo-taux d'érosion ou la vitesse d'émission des grandes provinces volcaniques. Les incertitudes et les limites de ces nouvelles méthodes ont été à la fois évaluées par simulation numérique et testées sur des objets géologiques