“Salus Populi Suprema Lex”: Considerations on the Initial Response of the United Kingdom to the SARS-CoV-2 Pandemic

In several countries worldwide, the initial response to coronavirus disease 2019 (COVID-19) has been heavily criticized by general public, media, and healthcare professionals, as well as being an acrimonious topic in the political debate. The present article elaborates on some aspects of the United Kingdom (UK) primary reaction to SARS-CoV-2 pandemic; specifically, from February to July 2020. The fact that the UK showed the highest mortality rate in Western Europe following the first wave of COVID-19 certainly has many contributing causes; each deserves an accurate analysis. We focused on three specific points that have been insofar not fully discussed in the UK and not very well known outside the British border: clinical governance, access to hospital care or intensive care unit, and implementation of non-pharmaceutical interventions. The considerations herein presented on these fundamental matters will likely contribute to a wider and positive discussion on public health, in the context of an unprecedented crisis.

The phosphatidylglycerol phosphate synthase PgsA utilizes a trifurcated amphipathic cavity for catalysis at the membrane-cytosol interface

Phosphatidylglycerol is a crucial phospholipid found ubiquitously in biological membranes of prokaryotic and eukaryotic cells. The phosphatidylglycerol phosphate (PGP) synthase (PgsA), a membrane-embedded enzyme, catalyzes the primary reaction of phosphatidylglycerol biosynthesis. Mutations in pgsA frequently correlate with daptomycin resistance in Staphylococcus aureus and other prevalent infectious pathogens. Here we report the structures of S. aureus PgsA (SaPgsA) captured at two distinct states of the catalytic process, with lipid substrate (cytidine diphosphate-diacylglycerol, CDP-DAG) or product (PGP) bound to the active site within a trifurcated amphipathic cavity. The hydrophilic head groups of CDP-DAG and PGP occupy two different pockets in the cavity, inducing local conformational changes. An elongated membrane-exposed surface groove accommodates the fatty acyl chains of CDP-DAG/PGP and opens a lateral portal for lipid entry/release. Remarkably, the daptomycin resistance-related mutations mostly cluster around the active site, causing reduction of enzymatic activity. Our results provide detailed mechanistic insights into the dynamic catalytic process of PgsA and structural frameworks beneficial for development of antimicrobial agents targeting PgsA from pathogenic bacteria.

The primary photolysis dynamics of oxalate in aqueous solution: decarboxylation

We study the primary reaction dynamics of aqueous oxalate following photo-excitation of the nO -> πCO* transition at λ = 200 nm. After the excitation, part of the oxalate molecules...

A novel approach to medical radioisotope production using inverse kinematics

The inverse kinematics methodology using a gas target has been applied to produce medically important radionuclides at the Cyclotron Institute at Texas A&M University. The production of the theranostic radionuclide 67Cu (T1/2 = 62 h) through the reaction of a 70Zn beam at 15 MeV/nucleon with a hydrogen gas target was performed. The activities at end of irradiation and the thick target yield were obtained for 67Cu. A test using the forward-focused neutrons from the primary reaction to irradiate natZn to produce 67Cu is also presented.

Noncanonical transnitrosylation network contributes to synapse loss in Alzheimer’s disease

We describe mechanistically-distinct enzymes, i.e., a kinase, a guanosine triphosphatase and a ubiquitin protein hydrolase, which function in disparate biochemical pathways, that can also act in concert to mediate a series of redox reactions. Each enzyme manifests a second, noncanonical function – transnitrosylation – triggering a pathological biochemical cascade in Alzheimer’s disease (AD). The resulting series of transnitrosylation reactions contributes to synapse loss, the major pathological correlate to cognitive decline in AD. We conclude that enzymes with distinct primary reaction mechanisms can form a completely separate network for aberrant transnitrosylation. This network operates in the post-reproductive period, so natural selection against such abnormal activity may be decreased.

Selective Oxidation of Citronellol over Titanosilicate Catalysts

Citronellol is one of the most widely used fragrances for bouquetting purposes and it is a starting material for synthesis of several other terpenoids. Nevertheless, few data have been reported on citronellol selective oxidation. Accordingly, we report our findings on the selective oxidation of citronellol with hydrogen peroxide using a set of titanosilicate catalysts with different morphologies and textural properties—conventional titanium silicalite 1 (TS-1), mesoporous TS-1, layered TS-1 and silica-titania pillared TS-1 and also studying the effect of the solvent used. Epoxidation of C6=C7 double bond was the main primary reaction in this system and trace signals of C5 allylic oxidation products were observed without formation of citronellal. Due to the presence of post-synthesis introduced additional Ti sites, the silica-titania pillared TS-1 (TS-1-PITi) provided the highest conversion among the tested catalysts; nevertheless, citronellol was oxidized over all the studied catalysts including conventional TS-1; therefore, showing that it penetrates even into MFI micropores (0.55 nm in diameter). When using acetonitrile as a solvent, the conversion was proportional to the titanium content of the catalyst. When studying the effect of the solvent, acetonitrile provided the highest epoxide selectivity (55%) while in methanol, 2-propanol and 1,4-dioxane, ring opening reactions caused epoxide decomposition.