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Abstract Nitrogen (N) doped graphene materials have been synthesized using the sole precursor adenine on the Ir(111) and Ru(0001) surfaces. X-ray photoelectron spectroscopy and scanning tunneling microscopy (STM) have been used to characterize the obtained N-doped graphene materials. Several graphitic and pyridinic N dopants have been identified on the atomic scale by combining STM measurements and STM simulations based on density functional theory calculations. 

The Amazon Basin, which plays a critical role in the carbon and water cycle, is under stress due to changes in climate, agricultural practices, and deforestation. The effects of thermodynamic and microphysical forcing on the strength of thunderstorms in the Basin (75–45°W, 0–15°S) were examined during the pre‐monsoon season (mid‐August through mid‐December), a period with large variations in aerosols, intense convective storms, and plentiful flashes. The analysis used measurements of radar reflectivity, ice water content (IWC), and aerosol type from instruments aboard the CloudSat and CALIPSO satellites, flash rates from the ground‐based Sferics Timing and Ranging Network, and total aerosol optical depth (AOD) from a surface network and a meteorological re‐analysis. After controlling for convective available potential energy (CAPE), it was found that thunderstorms that developed under dirty (high‐AOD) conditions were 1.5 km deeper, had 50% more IWC, and more than two times as many flashes as storms that developed under clean conditions. The sensitivity of flashes to AOD was largest for low values of CAPE where increases of more than a factor of three were observed. The additional ice water indicated that these deeper systems had higher vertical velocities and more condensation nuclei capable of sustaining higher concentrations of water and large hydrometeors in the upper troposphere. Flash rates were also found to be larger during periods when smoke rather than dust was common in the lower troposphere, likely because smoky periods were less stable due to higher values of CAPE and AOD and lower values of mid‐tropospheric relative humidity.

 

Infection with SARS‐CoV‐2 elicits robust antibody responses in some patients, with a majority of the response directed at the receptor binding domain (RBD) of the spike surface glycoprotein. Remarkably, many patient‐derived antibodies that potently inhibit viral infection harbor few to no mutations from the germline, suggesting that naïve antibody libraries are a viable means for discovery of novel SARS‐CoV‐2 neutralizing antibodies. Here, we used a yeast surface‐display library of human naïve antibodies to isolate and characterize three novel neutralizing antibodies that target the RBD: one that blocks interaction with angiotensin‐converting enzyme 2 (ACE2), the human receptor for SARS‐CoV‐2, and two that target other epitopes on the RBD. These three antibodies neutralized SARS‐CoV‐2 spike‐pseudotyped lentivirus with IC₅₀values as low as 60 ng/ml in vitro. Using a biolayer interferometry‐based binding competition assay, we determined that these antibodies have distinct but overlapping epitopes with antibodies elicited during natural COVID‐19 infection. Taken together, these analyses highlight how in vitro selection of naïve antibodies can mimic the humoral response in vivo, yielding neutralizing antibodies and various epitopes that can be effectively targeted on the SARS‐CoV‐2 RBD.

 

Aberrant regulation of metabolic kinases by altered redox homeostasis substantially contributes to aging and various diseases, such as diabetes. We found that the catalytic activity of a conserved family of fructosamine-3-kinases (FN3Ks), which are evolutionarily related to eukaryotic protein kinases, is regulated by redox-sensitive cysteine residues in the kinase domain. The crystal structure of the FN3K homolog fromArabidopsis thalianarevealed that it forms an unexpected strand-exchange dimer in which the ATP-binding P-loop and adjoining β strands are swapped between two chains in the dimer. This dimeric configuration is characterized by strained interchain disulfide bonds that stabilize the P-loop in an extended conformation. Mutational analysis and solution studies confirmed that the strained disulfides function as redox “switches” to reversibly regulate the activity and dimerization of FN3K. Human FN3K, which contains an equivalent P-loop Cys, was also redox sensitive, whereas ancestral bacterial FN3K homologs, which lack a P-loop Cys, were not. Furthermore, CRISPR-mediated knockout of FN3K in human liver cancer cells altered the abundance of redox metabolites, including an increase in glutathione. We propose that redox regulation evolved in FN3K homologs in response to changing cellular redox conditions. Our findings provide insights into the origin and evolution of redox regulation in the protein kinase superfamily and may open new avenues for targeting human FN3K in diabetic complications.