The Third Pole (TP) is experiencing rapid warming and is currently in its warmest period in the past 2,000 years. This paper reviews the latest development in multidisciplinary TP research associated with this warming. The rapid warming facilitates intense and broad glacier melt over most of the TP, although some glaciers in the northwest are advancing. By heating the atmosphere and reducing snow/ice albedo, aerosols also contribute to the glaciers melting. Glacier melt is accompanied by lake expansion and intensification of the water cycle over the TP. Precipitation has increased over the eastern and northwestern TP. Meanwhile, the TP is greening and most regions are experiencing advancing phenological trends, although over the southwest there is a spring phenological delay mainly in response to the recent decline in spring precipitation. Atmospheric and terrestrial thermal and dynamical processes over the TP affect the Asian monsoon at different scales. Recent evidence indicates substantial roles that mesoscale convective systems play in the TP’s precipitation as well as an association between soil moisture anomalies in the TP and the Indian monsoon. Moreover, an increase in geohazard events has been associated with recent environmental changes, some of which have had catastrophic consequences caused by glacial lake outbursts and landslides. Active debris flows are growing in both frequency of occurrences and spatial scale. Meanwhile, new types of disasters, such as the twin ice avalanches in Ali in 2016, are now appearing in the region. Adaptation and mitigation measures should be taken to help societies’ preparation for future environmental challenges. Some key issues for future TP studies are also discussed.
PML/RARalpha is of crucial importance in acute promyelocytic leukemia (APL) both pathologically and therapeutically. Using a genome-wide approach, we identified in vivo PML/RARalpha binding sites in a PML/RARalpha-inducible cell model. Of the 2979 targeted regions, >62% contained canonical PU.1 motifs and >84% of these PU.1 motifs coexisted with one or more RARE half (RAREh) sites in nearby regions. Promoters with such PU.1-RAREh binding sites were transactivated by PU.1. PU.1-mediated transactivation was repressed by PML/RARalpha and restored by the addition of all-trans retinoic acid (ATRA). Genes containing such promoters were significantly represented by genes transcriptionally suppressed in APL and/or reactivated upon treatment with ATRA. Thus, selective targeting of PU.1-regulated genes by PML/RARalpha is a critical mechanism for the pathogenesis of APL.
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