Recognition of hemi-methylated DNA by the SRA protein UHRF1 by a base-flipping mechanism

DNA methylation of CpG dinucleotides is an important epigenetic modification of mammalian genomes and is essential for the regulation of chromatin structure, of gene expression and of genome stability. Differences in DNA methylation patterns underlie a wide range of biological processes, such as genomic imprinting, inactivation of the X chromosome, embryogenesis, and carcinogenesis. Inheritance of the epigenetic methylation pattern is mediated by the enzyme DNA methyltransferase 1 (Dnmt1), which methylates newly synthesized CpG sequences during DNA replication, depending on the methylation status of the template strands. The protein UHRF1 (also known as Np95 and ICBP90) recognizes hemi-methylation sites via a SET and RING-associated (SRA) domain and directs Dnmt1 to these sites. Here we report the crystal structures of the SRA domain in free and hemi-methylated DNA-bound states. The SRA domain folds into a globular structure with a basic concave surface formed by highly conserved residues. Binding of DNA to the concave surface causes a loop and an amino-terminal tail of the SRA domain to fold into DNA interfaces at the major and minor grooves of the methylation site. In contrast to fully methylated CpG sites recognized by the methyl-CpG-binding domain, the methylcytosine base at the hemi-methylated site is flipped out of the DNA helix in the SRA-DNA complex and fits tightly into a protein pocket on the concave surface. The complex structure suggests that the successive flip out of the pre-existing methylated cytosine and the target cytosine to be methylated is associated with the coordinated transfer of the hemi-methylated CpG site from UHRF1 to Dnmt1.     

Distinct parasitoid communities associated with host races of the leaf-mining moth Acrocercops transecta on distantly related host plants (Juglandaceae and Ericaceae)

Differences in host-plant species may affect the structure of parasitoid communities of phytophagous insects. Phytophagous insect species often consist of host races, and comparisons between host races enable us to infer the effects of host-plant differences on parasitoid communities. Here, we compare the parasitoid fauna of two host races of the leaf-mining moth Acrocercops transecta, which are associated with either Juglandaceae or Lyonia ovalifolia (Ericaceae). Field collection and subsequent laboratory rearing revealed a significantly higher parasitization ratio in the Juglandaceae race than in the Lyonia race. In the Juglandaceae race the majority of parasitoids were Braconidae, whereas in the Lyonia race the majority were Eulophidae. Furthermore, even within the same host race the most abundant parasitoid species differed between populations with different host associations. Hence, the present results strongly indicate that different host-plant taxa affect the structure of parasitoid communities even within a single phytophagous insect species.     

Perceptual learning without perception.

The brain is able to adapt rapidly and continually to the surrounding environment, becoming increasingly sensitive to important and frequently encountered stimuli. It is often claimed that this adaptive learning is highly task-specific, that is, we become more sensitive to the critical signals in the tasks we attend to. Here, we show a new type of perceptual learning, which occurs without attention, without awareness and without any task relevance. Subjects were repeatedly presented with a background motion signal so weak that its direction was not visible; the invisible motion was an irrelevant background to the central task that engaged the subject's attention. Despite being below the threshold of visibility and being irrelevant to the central task, the repetitive exposure improved performance specifically for the direction of the exposed motion when tested in a subsequent suprathreshold test. These results suggest that a frequently presented feature sensitizes the visual system merely owing to its frequency, not its relevance or salience.     

Sulphur isotope evidence for an oxic Archaean atmosphere

The presence of mass-independently fractionated sulphur isotopes (MIF-S) in many sedimentary rocks older than approximately 2.4 billion years (Gyr), and the absence of MIF-S in younger rocks, has been considered the best evidence for a dramatic change from an anoxic to oxic atmosphere around 2.4 Gyr ago. This is because the only mechanism known to produce MIF-S has been ultraviolet photolysis of volcanic sulphur dioxide gas in an oxygen-poor atmosphere. Here we report the absence of MIF-S throughout approximately 100-m sections of 2.76-Gyr-old lake sediments and 2.92-Gyr-old marine shales in the Pilbara Craton, Western Australia. We propose three possible interpretations of the MIF-S geologic record: (1) the level of atmospheric oxygen fluctuated greatly during the Archaean era; (2) the atmosphere has remained oxic since approximately 3.8 Gyr ago, and MIF-S in sedimentary rocks represents times and regions of violent volcanic eruptions that ejected large volumes of sulphur dioxide into the stratosphere; or (3) MIF-S in rocks was mostly created by non-photochemical reactions during sediment diagenesis, and thus is not linked to atmospheric chemistry.     

Diurnal variations in serum and liver zinc levels throughout the 4-day estrous cycle of the hamster

Summary Diurnal variations of serum zinc level and liver zinc level of the golden hamster were found throughout the 4-day estrous cycle, and on the different days of the cycle, the patterns of fluctuation differed.     

Specific inhibition of a calcium dependent activation of brain cyclic AMP phosphodiesterase activity by vinblastine

Summary Vinblastine selectively inhibits the activation of brain cyclic AMP phosphodiesterase activity by Ca⁺⁺-protein activator (50% inhibition by 2×10^–5 M). This inhibitory effect was reversed by excessive amounts of the activator, whereas large quantities of Ca⁺⁺ caused only a slight suppression of the vinblastine effect. This result of vinblastine suggests a new site of its action and also suggests the possible role of protein activator, phosphodiesterase proteins or cyclic nucleotides in the previously known effects of vinblastine in vivo and in vitro.Our thanks to Drs A. R. Rhoads, C. B. Klee and R. A. Fergusson for analyzing PA preparations by gel electrophoresis and gel electrofocusing, and to Drs A. A. Suran and D. Soifer for their valuable critiques to this work. This work was partly supported by Biochemical Research Support Grant No. 5SO7RRO5361 to K.W. and Graduate Training Grant No. 5TO2GMO500002 to W.L.W. from NIH.