Doppler weather radar imaging enabled the rapid recovery of the Sutter's Mill meteorite after a rare 4-kiloton of TNT-equivalent asteroid impact over the foothills of the Sierra Nevada in northern California. The recovered meteorites survived a record high-speed entry of 28.6 kilometers per second from an orbit close to that of Jupiter-family comets (Tisserand's parameter = 2.8 ± 0.3). Sutter's Mill is a regolith breccia composed of CM (Mighei)-type carbonaceous chondrite and highly reduced xenolithic materials. It exhibits considerable diversity of mineralogy, petrography, and isotope and organic chemistry, resulting from a complex formation history of the parent body surface. That diversity is quickly masked by alteration once in the terrestrial environment but will need to be considered when samples returned by missions to C-class asteroids are interpreted.
Emerging therapeutic treatments based on the production of proteins by delivering mRNA have become increasingly important in recent times. While lipid nanoparticles (LNPs) are approved vehicles for small interfering RNA delivery, there are still challenges to use this formulation for mRNA delivery. LNPs are typically a mixture of a cationic lipid, distearoylphosphatidylcholine (DSPC), cholesterol, and a PEG-lipid. The structural characterization of mRNA-containing LNPs (mRNA-LNPs) is crucial for a full understanding of the way in which they function, but this information alone is not enough to predict their fate upon entering the bloodstream. The biodistribution and cellular uptake of LNPs are affected by their surface composition as well as by the extracellular proteins present at the site of LNP administration, e.g., apolipoproteinE (ApoE). ApoE, being responsible for fat transport in the body, plays a key role in the LNP’s plasma circulation time. In this work, we use small-angle neutron scattering, together with selective lipid, cholesterol, and solvent deuteration, to elucidate the structure of the LNP and the distribution of the lipid components in the absence and the presence of ApoE. While DSPC and cholesterol are found to be enriched at the surface of the LNPs in buffer, binding of ApoE induces a redistribution of the lipids at the shell and the core, which also impacts the LNP internal structure, causing release of mRNA. The rearrangement of LNP components upon ApoE incubation is discussed in terms of potential relevance to LNP endosomal escape.
[1] We have carried out nuclear resonant scattering measurements on 57 Fe-enriched Fe 3 C between 1 bar and 50 GPa at 300 K. Synchrotron Mössbauer spectra reveal a pressure-induced magnetic transition in Fe 3 C between 4.3 and 6.5 GPa. On the basis of our nuclear resonant inelastic X-ray scattering spectra and existing equation-of-state data, we have derived the compressional wave velocity V P and shear wave velocity V S for the high-pressure nonmagnetic phase, which can be expressed as functions of density (r):) and V S (km/s) = 1.45 + 0.24r(g/cm 3
Ribonucleotide reductase (RNR) catalyzes the only known de-novo pathway for production of all four deoxyribonucleotides required for DNA synthesis1,2. It is essential for all organisms with DNA as genetic material and a current drug target3,4. Since the discovery that iron is required for function in the aerobic, class I RNR found in all eukaryotes and many bacteria, a di-nuclear metal site has been viewed as a requirement for generating and stabilizing a catalytic radical, essential for RNR activity5,6,7. Here, we describe a new group of RNR proteins in Mollicutes, including Mycoplasma pathogens, which possesses a metal-independent stable radical residing on a modified tyrosyl residue. Structural, biochemical and spectroscopic characterization reveal an unprecedented stable DOPA radical species that directly supports ribonucleotide reduction in vitro and in vivo. This observation overturns the presumed requirement of a dinuclear metal site in aerobic RNR. The metal-independent radical compels completely novel mechanisms for radical generation and stabilization, processes that are targeted by RNR inhibitors. Conceivably, this RNR variant provides an advantage under metal starvation induced by the immune system. Organisms encoding this type of RNR are involved in diseases of the respiratory, urinary and genital tracts, some with developing resistance to antibiotics. Further characterization of this novel RNR family and its mechanism for cofactor generation will provide insight into new enzymatic chemistry and be of value to devise strategies to combat the pathogens that utilize it. We propose that the new RNR subclass is denoted class Ie.
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