Multidrug-resistant (MDR) gram-negative bacteria have increased the prevalence of fatal sepsis in modern times. Colistin is a cationic antimicrobial peptide (CAMP) antibiotic that permeabilizes the bacterial outer membrane (OM) and has been used to treat these infections. The OM outer leaflet is comprised of endotoxin containing lipid A, which can be modified to increase resistance to CAMPs and prevent clearance by the innate immune response. One type of lipid A modification involves the addition of phosphoethanolamine to the 1 and 4′ headgroup positions by phosphoethanolamine transferases. Previous structural work on a truncated form of this enzyme suggested that the full-length protein was required for correct lipid substrate binding and catalysis. We now report the crystal structure of a full-length lipid A phosphoethanolamine transferase from Neisseria meningitidis, determined to 2.75-Å resolution. The structure reveals a previously uncharacterized helical membrane domain and a periplasmic facing soluble domain. The domains are linked by a helix that runs along the membrane surface interacting with the phospholipid head groups. Two helices located in a periplasmic loop between two transmembrane helices contain conserved charged residues and are implicated in substrate binding. Intrinsic fluorescence, limited proteolysis, and molecular dynamics studies suggest the protein may sample different conformational states to enable the binding of two very different-sized lipid substrates. These results provide insights into the mechanism of endotoxin modification and will aid a structure-guided rational drug design approach to treating multidrug-resistant bacterial infections.lipid modification | multidrug resistance | molecular dynamics | Neisseria | membrane protein structure

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This paper argues for the regular testing of people in groups that are more likely to be exposed to SARS-CoV-2, to reduce the spread of COVID-19 and resume economic activity. We call this ‘stratified periodic testing’. It is ‘stratified’ as it is based on at-risk groups, and ‘periodic’ as everyone in the group is tested at regular intervals. We argue that this is a better use of scarce testing resources than ‘universal random testing’, as has been recently discussed globally. We find that, under reasonable assumptions and allowing for false negative results 30 per cent of the time, 17 per cent of a subgroup would need to be tested each day to lower the effective reproduction number R from 2.5 to 0.75, under stratified periodic testing. Using the same assumptions the universal random testing rate would need to be 27 per cent (as opposed to 7 per cent as argued by Romer (2020b)). We obtain this rate of testing using a corrected method for calculating the impact of an infectious person on others, and allowing for asymptomatic cases. We also find that the effect of one day’s delay between testing positive and self-isolating is similar to having a test that is 30 per cent less accurate.

Do oil booms reduce poverty and inequality?To study this we propose a new measure of rural poverty: counting people that live in darkness at night. We do this by combining high-resolution satellite data on night-time lights and population globally from 2000-2013. This measure accurately identifies up to 83% of households as above or below the poverty line when compared to over 600,000 surveys. We find that both high oil prices and new discoveries increase illumination and GDP nationally, but promote inequality because the increases are limited to towns and cities with no evidence that they benefit the rural poor.

Inequality is important, both for its own sake and for its political, social, and economic implications. However, measuring inequality is not straightforward, as it requires decisions to be made on the variable, population, and distributional characteristics of interest. These decisions will naturally influence the conclusions that are drawn so they must be closely linked to an underlying purpose, which is ultimately defined by a social welfare function. This paper outlines important considerations when making each of these decisions, before surveying recent advances in measuring inequality and suggesting avenues for future work.

The α--acetylgalactosaminidase from the probiotic bacterium (NagBb) belongs to the glycoside hydrolase family 129 and hydrolyzes the glycosidic bond of Tn-antigen (GalNAcα1-Ser/Thr). NagBb is involved in assimilation of-glycans on mucin glycoproteins by in the human gastrointestinal tract, but its catalytic mechanism has remained elusive because of a lack of sequence homology around putative catalytic residues and of other structural information. Here we report the X-ray crystal structure of NagBb, representing the first GH129 family structure, solved by the single-wavelength anomalous dispersion method based on sulfur atoms of the native protein. We determined ligand-free, GalNAc, and inhibitor complex forms of NagBb and found that Asp-435 and Glu-478 are located in the catalytic domain at appropriate positions for direct nucleophilic attack at the anomeric carbon and proton donation for the glycosidic bond oxygen, respectively. A highly conserved Asp-330 forms a hydrogen bond with the O4 hydroxyl of GalNAc in the -1 subsite, and Trp-398 provides a stacking platform for the GalNAc pyranose ring. Interestingly, a metal ion, presumably Ca, is involved in the recognition of the GalNAc -acetyl group. Mutations at Asp-435, Glu-478, Asp-330, and Trp-398 and residues involved in metal coordination (including an all-Ala quadruple mutant) significantly reduced the activity, indicating that these residues and the metal ion play important roles in substrate recognition and catalysis. Interestingly, NagBb exhibited some structural similarities to the GH101 endo-α--acetylgalactosaminidases, but several critical differences in substrate recognition and reaction mechanism account for the different activities of these two enzymes.

This paper studies how monetary policy should respond to news about an oil discovery, using a workhorse New Keynesian model. Good news about future production can create a recession today under exchange rate pegs and a simple Taylor rule, as seen in practice. This is explained by forward-looking inflation. Recession is avoided by a Taylor rule that accommodates changes in the natural level of output, which closely approximates optimal policy. Central banks have an incentive to exploit oil revenues by appreciating the terms of trade, creating "Dutch disease" and a deflationary bias which is overcome by committing to future policy.