Equilibrium climate sensitivity, the global surface temperature response to CO 2 doubling, has been persistently uncertain. Recent consensus places it likely within 1.5–4.5 K. Global climate models (GCMs), which attempt to represent all relevant physical processes, provide the most direct means of estimating climate sensitivity via CO 2 quadrupling experiments. Here we show that the closely related effective climate sensitivity has increased substantially in Coupled Model Intercomparison Project phase 6 (CMIP6), with values spanning 1.8–5.6 K across 27 GCMs and exceeding 4.5 K in 10 of them. This (statistically insignificant) increase is primarily due to stronger positive cloud feedbacks from decreasing extratropical low cloud coverage and albedo. Both of these are tied to the physical representation of clouds which in CMIP6 models lead to weaker responses of extratropical low cloud cover and water content to unforced variations in surface temperature. Establishing the plausibility of these higher sensitivity models is imperative given their implied societal ramifications.

Dyskeratosis congenita (DC) is a genetic disorder of defective tissue maintenance and cancer predisposition caused by short telomeres and impaired stem cell function. Telomerase mutations are thought to precipitate DC by reducing either the catalytic activity or the overall levels of the telomerase complex. However, the underlying genetic mutations and the mechanisms of telomere shortening remain unknown for as many as 50% of DC patients, who lack mutations in genes controlling telomere homeostasis. Here, we show that disruption of telomerase trafficking accounts for unknown cases of DC. We identify DC patients with missense mutations in TCAB1, a telomerase holoenzyme protein that facilitates trafficking of telomerase to Cajal bodies. Compound heterozygous mutations in TCAB1 disrupt telomerase localization to Cajal bodies, resulting in misdirection of telomerase RNA to nucleoli, which prevents telomerase from elongating telomeres. Our findings establish telomerase mislocalization as a novel cause of DC, and suggest that telomerase trafficking defects may contribute more broadly to the pathogenesis of telomere-related disease.

Genomic research involving human genetics and evolutionary biology relies heavily on linkage disequilibrium (LD) to investigate population-specific genetic structure, functionally map regions of disease susceptibility and uncover evolutionary history. Interactive and powerful tools are needed to calculate population-specific LD estimates for integrative genomics research. LDlink is an interactive suite of web-based tools developed to query germline variants in 1000 Genomes Project population groups of interest and generate interactive tables and plots of LD estimates. As an expansion to this resource, we have developed an R package, LDlinkR, designed to rapidly calculate statistics for large lists of variants and LD attributes that eliminates the time needed to perform repetitive requests from the web-based LDlink tool. LDlinkR accelerates genomic research by providing efficient and user-friendly functions to programmatically interrogate and download pairwise LD estimates from expansive lists of genetic variants. LDlinkR is a free and publicly available R package that can be installed from the Comprehensive R Archive Network (CRAN) or downloaded from https://github.com/ CBIIT/LDlinkR.

Conventional wisdom suggests that subsidence favors the presence of marine stratus and stratocumulus because regions of enhanced boundary layer cloudiness are observed to climatologically co-occur with regions of enhanced subsidence. Here it is argued that the climatological positive correlation between subsidence and cloudiness is not the result of a direct physical mechanism connecting the two. Instead, it arises because enhanced subsidence is typically associated with stronger temperature inversions capping the marine boundary layer, and stronger temperature inversions favor greater cloudiness. Through statistical analysis of satellite cloud data and meteorological reanalyses for the subsidence regime over tropical (308S-308N) oceans, it is shown that enhanced subsidence promotes reduced cloudiness for the same value of inversion strength and that a stronger inversion favors greater cloudiness for the same value of subsidence. Using a simple conceptual model, it is argued that enhanced subsidence leads to reduced cloud thickness, liquid water path, and cloud fraction by pushing down the top of the marine boundary layer. Moreover, a stronger inversion reduces entrainment drying and warming, thus leading to a more humid boundary layer and greater cloud thickness, liquid water path, and cloud fraction. These two mechanisms typically oppose each other for geographical and seasonal cloud variability because enhanced subsidence is usually associated with stronger inversions. If global warming results in stronger inversions but weaker subsidence, the two mechanisms could both favor increased subtropical low-level cloudiness.