Aura Microwave Limb Sounder Observations of Dynamics and Transport During the Record-Breaking 2009 Arctic Stratospheric Major Warming

A major stratospheric sudden warming (SSW) in January 2009 was the strongest and most prolonged on record. Aura Microwave Limb Sounder (MLS) observations are used to provide an overview of dynamics and transport during the 2009 SSW, and to compare with the intense, long-lasting SSW in January 2006. The Arctic polar vortex split during the 2009 SSW, whereas the 2006 SSW was a vortex displacement event. Winds reversed to easterly more rapidly and reverted to westerly more slowly in 2009 than in 2006. More mixing of trace gases out of the vortex during the decay of the vortex fragments, and less before the fulfillment of major SSW criteria, was seen in 2009 than in 2006; persistent well-defined fragments of vortex and anticyclone air were more prevalent in 2009. The 2009 SSW had a more profound impact on the lower stratosphere than any previously observed SSW, with no significant recovery of the vortex in that region. The stratopause breakdown and subsequent reformation at very high altitude, accompanied by enhanced descent into a rapidly strengthening upper stratospheric vortex, were similar in 2009 and 2006. Many differences between 2006 and 2009 appear to be related to the different character of the SSWs in the two years

The Evolution of the Stratopause During the 2006 Major Warming: Satellite Data and Assimilated Meteorological Analyses

Microwave Limb Sounder and Sounding of the Atmosphere with Broadband Emission Radiometry data show the polar stratopause, usually higher than and separated from that at midlatitudes, dropping from <55-60 to near 30 km, and cooling dramatically in January 2006 during a major stratospheric sudden warming (SSW). After a nearly isothermal period, a cool stratopause reforms near 75 km in early February, then drops to <55 km and warms. The stratopause is separated in longitude as well as latitude, with lowest temperatures in the transition regions between higher and lower stratopauses. Operational assimilated meteorological analyses, which are not constrained by data at stratopause altitude, do not capture a secondary temperature maximum that overlies the stratopause or the very high stratopause that reforms after the SSW; they underestimate the stratopause altitude variation during the SSW. High-quality daily satellite temperature measurements are invaluable in improving our understanding of stratopause evolution and its representation in models and assimilation systems

APP metabolism regulates tau proteostasis in human cerebral cortex neurons.

Accumulation of Aβ peptide fragments of the APP protein and neurofibrillary tangles of the microtubule-associated protein tau are the cellular hallmarks of Alzheimer's disease (AD). To investigate the relationship between APP metabolism and tau protein levels and phosphorylation, we studied human-stem-cell-derived forebrain neurons with genetic forms of AD, all of which increase the release of pathogenic Aβ peptides. We identified marked increases in intracellular tau in genetic forms of AD that either mutated APP or increased its dosage, suggesting that APP metabolism is coupled to changes in tau proteostasis. Manipulating APP metabolism by β-secretase and γ-secretase inhibition, as well as γ-secretase modulation, results in specific increases and decreases in tau protein levels. These data demonstrate that APP metabolism regulates tau proteostasis and suggest that the relationship between APP processing and tau is not mediated solely through extracellular Aβ signaling to neurons.This research was supported by grants from Alzheimer’s Research UK and the Wellcome Trust (to F.J.L.) and core funding to the Gurdon Trust from the Wellcome Trust and Cancer Research UK. N.S. was supported by a Woolf-Fisher Trust (NZ) PhD studentship. H.Z. was supported by the Wolfson Centre at UCL, and the UCLH Dementia BRU provided financial support for the collection of patient materials. F.J.L. is a Wellcome Trust Senior Investigator, K.B. is a Torsten So¨ derberg Academy Professor, and H.Z. is a Wallenberg Academy Fellow.This is the final version. It was first published by Elsevier at http://www.sciencedirect.com/science/article/pii/S2211124715003599

Solar Occultation Satellite Data and Derived Meteorological Products: Sampling Issues and Comparisons with Aura MLS

Derived Meteorological Products (DMPs, including potential temperature (theta), potential vorticity, equivalent latitude (EqL), horizontal winds and tropopause locations) have been produced for the locations and times of measurements by several solar occultation (SO) instruments and the Aura Microwave Limb Sounder (MLS). DMPs are calculated from several meteorological analyses for the Atmospheric Chemistry Experiment-Fourier Transform Spectrometer, Stratospheric Aerosol and Gas Experiment II and III, Halogen Occultation Experiment, and Polar Ozone and Aerosol Measurement II and III SO instruments and MLS. Time-series comparisons of MLS version 1.5 and SO data using DMPs show good qualitative agreement in time evolution of O3, N2O, H20, CO, HNO3, HCl and temperature; quantitative agreement is good in most cases. EqL-coordinate comparisons of MLS version 2.2 and SO data show good quantitative agreement throughout the stratosphere for most of these species, with significant biases for a few species in localized regions. Comparisons in EqL coordinates of MLS and SO data, and of SO data with geographically coincident MLS data provide insight into where and how sampling effects are important in interpretation of the sparse SO data, thus assisting in fully utilizing the SO data in scientific studies and comparisons with other sparse datasets. The DMPs are valuable for scientific studies and to facilitate validation of non-coincident measurements

Extracellular Forms of A? and Tau from iPSC Models of Alzheimer\u27s Disease Disrupt Synaptic Plasticity

The early stages of Alzheimer?s disease are associated with synaptic dysfunction prior to overt loss of neurons. To identify extracellular molecules that impair synaptic plasticity in the brain, we studied the secretomes of human iPSC-derived neuronal models of Alzheimer?s disease. When introduced into the rat brain, secretomes from human neurons with either a presenilin-1 mutation, amyloid precursor protein duplication, or trisomy of chromosome 21 all strongly inhibit hippocampal long-term potentiation. Synaptic dysfunction caused by presenilin-1 mutant and amyloid precusor protein duplication secretomes is mediated by A? peptides, whereas trisomy of chromosome 21 (trisomy 21) neuronal secretomes induce dysfunction through extracellular tau. In all cases, synaptotoxicity is relieved by antibody blockade of cellular prion protein. These data indicate that human models of Alzheimer?s disease generate distinct proteins that converge at the level of cellular prion protein to induce synaptic dysfunction in vivo

APP Metabolism Regulates Tau Proteostasis in Human Cerebral Cortex Neurons

Accumulation of Aβ peptide fragments of the APP protein and neurofibrillary tangles of the microtubule-associated protein tau are the cellular hallmarks of Alzheimer’s disease (AD). To investigate the relationship between APP metabolism and tau protein levels and phosphorylation, we studied human-stem-cell-derived forebrain neurons with genetic forms of AD, all of which increase the release of pathogenic Aβ peptides. We identified marked increases in intracellular tau in genetic forms of AD that either mutated APP or increased its dosage, suggesting that APP metabolism is coupled to changes in tau proteostasis. Manipulating APP metabolism by β-secretase and γ-secretase inhibition, as well as γ-secretase modulation, results in specific increases and decreases in tau protein levels. These data demonstrate that APP metabolism regulates tau proteostasis and suggest that the relationship between APP processing and tau is not mediated solely through extracellular Aβ signaling to neurons