Base-J (β-D-glucopyranosyloxymethyluracil) is an unusual kinetoplastid-specific DNA modification, recognized by base-J containing DNA (J-DNA) binding proteins JBP1 and JBP3. Recognition of J-DNA by both JBP1 and JBP3 takes place by a conserved J-DNA binding domain (JDBD). Here we show that JDBD-JBP3 has about 1,000-fold weaker affinity to base-J than JDBD-JBP1 and discriminates between J-DNA and unmodified DNA with a factor ∼5, whereas JDBD-JBP1 discriminates with a factor ∼10,000.
View Article and Find Full Text PDFThe observed temperature record, which combines sea surface temperatures with near-surface air temperatures over land, is crucial for understanding climate variability and change. However, early records of global mean surface temperature are uncertain owing to changes in measurement technology and practice, partial documentation, and incomplete spatial coverage. Here we show that existing estimates of ocean temperatures in the early twentieth century (1900-1930) are too cold, based on independent statistical reconstructions of the global mean surface temperature from either ocean or land data.
View Article and Find Full Text PDFCancers (Basel)
October 2024
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View Article and Find Full Text PDFIn competency-based medical education (CBME), which is being embraced globally, the patient-learner-educator encounter occurs in a highly complex context which contributes to a wide range of assessment outcomes. Current and historical barriers to considering context in assessment include the existing post-positivist epistemological stance that values objectivity and validity evidence over the variability introduced by context. This is most evident in standardized testing.
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