Climate sensitivity increases under higher CO₂ levels due to feedback temperature dependence

Equilibrium climate sensitivity‐the equilibrium warming per CO2 doubling‐increases with CO2 concentration for 13 of 14 coupled general circulation models for 0.5–8 times the preindustrial concentration. In particular, the abrupt 4 × CO2 equilibrium warming is more than twice the 2 × CO2 warming. We identify three potential causes: nonlogarithmic forcing, feedback CO2 dependence, and feedback temperature dependence. Feedback temperature dependence explains at least half of the sensitivity increase, while feedback CO2 dependence explains a smaller share, and nonlogarithmic forcing decreases sensitivity in as many models as it increases it. Feedback temperature dependence is positive for 10 out of 14 models, primarily due to the longwave clear‐sky feedback, while cloud feedbacks drive particularly large sensitivity increases. Feedback temperature dependence increases the risk of extreme or runaway warming, and is estimated to cause six models to warm at least an additional 3K under 8 × CO2

Mutation Detection in Patients with Retinal Dystrophies Using Targeted Next Generation Sequencing

Retinal dystrophies (RD) constitute a group of blinding diseases that are characterized by clinical variability and pronounced genetic heterogeneity. The different nonsyndromic and syndromic forms of RD can be attributed to mutations in more than 200 genes. Consequently, next generation sequencing (NGS) technologies are among the most promising approaches to identify mutations in RD. We screened a large cohort of patients comprising 89 independent cases and families with various subforms of RD applying different NGS platforms. While mutation screening in 50 cases was performed using a RD gene capture panel, 47 cases were analyzed using whole exome sequencing. One family was analyzed using whole genome sequencing. A detection rate of 61% was achieved including mutations in 34 known and two novel RD genes. A total of 69 distinct mutations were identified, including 39 novel mutations. Notably, genetic findings in several families were not consistent with the initial clinical diagnosis. Clinical reassessment resulted in refinement of the clinical diagnosis in some of these families and confirmed the broad clinical spectrum associated with mutations in RD genes

On simple representations of the climate response to external radiative forcing

Global warming in response to external radiative forcing is determined by the feedback of the climate system. Recent studies have suggested that simple mathematical models incorporating a radiative response which is related to upper- and deep-ocean disequilibrium (ocean heat uptake efficacy), inhomogeneous patterns of surface warming and radiative feedbacks (pattern effect), or an explicit dependence of the strength of radiative feedbacks on surface temperature change (feedback temperature dependence) may explain the climate response in atmosphere-ocean coupled general circulation models (AOGCMs) or can be useful for interpreting the instrumental record. We analyze a two-layer model with an ocean heat transport efficacy, a two-region model with region specific heat capacities and radiative responses; a one-layer model with a temperature dependent feedback; and a model which combines elements of the two-layer/region models and the state-dependent feedback parameter. We show that, from the perspective of the globally averaged surface temperature and radiative imbalance, the two-region and two-layer models are equivalent. State-dependence of the feedback parameter introduces a nonlinearity in the system which makes the adjustment timescales forcing-dependent. Neither the linear two-region/layer models, nor the state-dependent feedback model adequately describes the behavior of complex climate models. The model which combines elements of both can adequately describe the response of more comprehensive models but may require more experimental input than is available from single forcing realizations

Mutations in the CEP290 (NPHP6) Gene Are a Frequent Cause of Leber Congenital Amaurosis

Leber congenital amaurosis (LCA) is one of the main causes of childhood blindness. To date, mutations in eight genes have been described, which together account for ∼45% of LCA cases. We localized the genetic defect in a consanguineous LCA-affected family from Quebec and identified a splice defect in a gene encoding a centrosomal protein (CEP290). The defect is caused by an intronic mutation (c.2991+1655A→G) that creates a strong splice-donor site and inserts a cryptic exon in the CEP290 messenger RNA. This mutation was detected in 16 (21%) of 76 unrelated patients with LCA, either homozygously or in combination with a second deleterious mutation on the other allele. CEP290 mutations therefore represent one of the most frequent causes of LCA identified so far