Lifeboat Foundation

Recombinant BjADAT2 and BjADAT3 were individually expressed in E. coli and purified, and their enzyme activities were tested by in vitro tRNA deamination assay (Supplementary Fig. 4). Neither BjADAT2 nor BjADAT3 showed any A-to-I editing activity, but BjADAT2, in complex with BjADAT3, could perform A-to-I editing of amphioxus tRNA^Val_(AAC), and the apparent first-order deamination rate constant (k_app) of tRNA deamination was 0.0287 ± 0.00219 min⁻¹. Because the optimal RNA substrate for ADAT2 was the adenosines on the anticodon loop structure of tRNA, we wondered if BjADAT2 could mediate DNA deamination in a structure-specific fashion. Thus, we compared the deamination efficiency of BjADAT2 on DNA hairpin structure substrates (i.e., hpDNA-A and hpDNA-C, containing a single adenosine or cytidine in the loop region, respectively) and single-stranded linear structure substrates (i.e., ssDNA-A and ssDNA-C, containing a single adenosine or cytidine in the substrates, respectively). As shown in Fig. 3, both adenosine deamination of hpDNA-A and cytidine deamination of hpDNA-C were clearly observed under BjADAT2 treatment, and the change of the hairpin substrates to linear substrates resulted in about a threefold decrease in adenosine-and cytidine-deamination ratios. By contrast, no product band was seen in the lane of hpDNA-G or hpDNA-T treated with BjADAT2. Moreover, the BjADAT2-E58A protein purified in the same way as BjADAT2 showed no deamination activity (Supplementary Fig. 5f, g), ruling out the possibility that the observed deamination activity of BjADAT2 arose from a contaminant in the recombinant protein samples. In addition, BjADAT2-mediated adenosine-and cytidine deamination was inhibited by deoxycoformycin (DCF), an adenosine deaminase specific inhibitor, or tetrahydrouridine (THU), a cytidine deaminase specific inhibitor, or 1,10-o-phenanthroline, a zinc chelator. These indicated that BjADAT2 deaminated adenosine and cytidine in a zinc-dependent manner.

The k_app of BjADAT2-induced hpDNA-A deamination (0.00206 ± 0.00019 min⁻¹) was comparable with that of ABE7.10-induced DNA adenosine deamination (0.0010 ± 0.00030 min⁻¹)²². We compared the kinetics of BjADAT2-induced DNA deamination of the hairpin substrates and the linear substrates. The k_app was sixfold higher for the hpDNA-A substrate than for the ssDNA-A substrate (0.00032 ± 0.00004 min⁻¹). Similarly, the k_app was 24-fold higher for hpDNA-C (0.00801 ± 0.00037 min⁻¹) than for ssDNA-C (0.00033 ± 0.000026 min⁻¹) (Fig. 3e). These data together indicated that BjADAT2 preferentially deaminates adenosines and cytidines in the hairpin loop of substrates.

It was known that ADAT3, as a non-catalytic subunit, served a structural role in the adenosine deamination of tRNA^10,23. To date, only trypanosome ADAT2 was shown to be able to deaminate cytosines of DNA in the presence of ADAT3 in vitro⁶, but the specific role of the ADAT3 subunit in this DNA editing reaction was unclear. We demonstrated here that BjADAT3, though lacking catalytic function, could enhance the deamination activity of BjADAT2 toward hairpin structure substrates, including hpDNA-A and hpDNA-C (Fig. 3a, b). This was also supported by the results of kinetic analysis (Fig. 3e), which showed that the k_app of hpDNA-A deamination of BjADAT2/BjADAT3 complex (0.01092 ± 0.00062 min⁻¹) was 5.3-fold higher than that of BjADAT2 alone, and the k_app of hpDNA-C deamination by the complex (0.01066 ± 0.00083 min⁻¹) 1.3-fold higher than that of BjADAT2 alone. On the contrary, the k_app of ssDNA-A deamination of BjADAT2/BjADAT3 complex (0.00016 ± 0.

“For decades Isaac Newton gave us this vision of a universe where space and time is fixed, and every clock across the universe ticks at exactly the same rate. Then Einstein shattered this vision by proposing that time is actually rubbery and relative,” says Geraint Lewis, an astrophysicist at the University of Sydney and lead author of the study. “Now we’ve shown that Einstein was, once again, correct.”

The Einsteinian concept of time running slower in the early universe arose in the late 1920s as astronomers were discovering cosmic expansion. Galaxies in the sky were found to be flying away from the Milky Way at high speed, swept along by the ceaselessly growing void—and the farther off they were, the faster they flew. This not only meant that the universe was once much smaller and denser—arising in a “big bang” from some compact, primordial point—but also that the most distant galaxies visible to us should be receding at close to the speed of light.

According to Einstein’s special and general theories of relativity, both circumstances alter the flow of time. As light from one of those far-distant galaxies travels from the heavier gravitational grip of the deep, dense early cosmos and across the continuously expanding universe, it must traverse increasingly greater expanses of space to reach Earth. Consequently, time becomes stretched in a phenomenon known as time dilation: a clock running 10 billion years ago would tick at a normal rate to an observer from that time, but from the perspective of someone today, it would appear to be ticking much slower.

Researchers have developed an advanced dielectric capacitor using nanosheet technology, providing unprecedented energy storage density and stability. This breakthrough could significantly enhance renewable energy usage and electric vehicle production.

A research group, led by Nagoya University.

Nagoya University, sometimes abbreviated as NU, is a Japanese national research university located in Chikusa-ku, Nagoya. It was the seventh Imperial University in Japan, one of the first five Designated National University and selected as a Top Type university of Top Global University Project by the Japanese government. It is one of the highest ranked higher education institutions in Japan.

We know students learn science concepts better when their learning is embedded in real-world issues. But teachers are currently not well prepared to teach science in this way.

Here, the authors report the realization of WSe2 Schottky junction field-effect transistors with asymmetric multi-layer graphene and WTe2 van der Waals contacts, enabling reconfigurable polarity, low off-state currents, near-ideal rectifying behaviour and bipolar photovoltaic response.

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A trial of donanemab, an experimental drug, found it modestly slowed the worsening of memory and thinking and worked better in patients at earlier stages and those under 75.

In a 2022 predictions tournament, AI experts were far more concerned about AI risks than ‘superforecasters’ were.

To succeed with generative artificial intelligence and extended reality, companies should also harness human creativity, curiosity, and compassion.