A large discontinuity in the mid-twentieth century in observed global-mean surface temperature

Data sets used to monitor the Earth's climate indicate that the surface of the Earth warmed from approximately 1910 to 1940, cooled slightly from approximately 1940 to 1970, and then warmed markedly from approximately 1970 onward. The weak cooling apparent in the middle part of the century has been interpreted in the context of a variety of physical factors, such as atmosphere-ocean interactions and anthropogenic emissions of sulphate aerosols. Here we call attention to a previously overlooked discontinuity in the record at 1945, which is a prominent feature of the cooling trend in the mid-twentieth century. The discontinuity is evident in published versions of the global-mean temperature time series, but stands out more clearly after the data are filtered for the effects of internal climate variability. We argue that the abrupt temperature drop of approximately 0.3 degrees C in 1945 is the apparent result of uncorrected instrumental biases in the sea surface temperature record. Corrections for the discontinuity are expected to alter the character of mid-twentieth century temperature variability but not estimates of the century-long trend in global-mean temperatures.     

LNA-mediated microRNA silencing in non-human primates

microRNAs (miRNAs) are small regulatory RNAs that are important in development and disease and therefore represent a potential new class of targets for therapeutic intervention. Despite recent progress in silencing of miRNAs in rodents, the development of effective and safe approaches for sequence-specific antagonism of miRNAs in vivo remains a significant scientific and therapeutic challenge. Moreover, there are no reports of miRNA antagonism in primates. Here we show that the simple systemic delivery of a unconjugated, PBS-formulated locked-nucleic-acid-modified oligonucleotide (LNA-antimiR) effectively antagonizes the liver-expressed miR-122 in non-human primates. Acute administration by intravenous injections of 3 or 10 mg kg(-1) LNA-antimiR to African green monkeys resulted in uptake of the LNA-antimiR in the cytoplasm of primate hepatocytes and formation of stable heteroduplexes between the LNA-antimiR and miR-122. This was accompanied by depletion of mature miR-122 and dose-dependent lowering of plasma cholesterol. Efficient silencing of miR-122 was achieved in primates by three doses of 10 mg kg(-1) LNA-antimiR, leading to a long-lasting and reversible decrease in total plasma cholesterol without any evidence for LNA-associated toxicities or histopathological changes in the study animals. Our findings demonstrate the utility of systemically administered LNA-antimiRs in exploring miRNA function in rodents and primates, and support the potential of these compounds as a new class of therapeutics for disease-associated miRNAs.