Analysis of Volatile Organic Compounds in the Apollo Next Generation Sample Analysis (ANGSA) 73002 Core Sample

Understanding the organic content of lunar regolith was an early priority upon the return of Apollo samples, with amino acids being of special interest because of their importance to life on Earth and their astrobiological relevance. Many initial studies focused on the detection of amino acids in these samples and attempts to determine the origin of those compounds. Although no consensus on the origin of the amino acids was reached in those early studies, more recent work determined that the detected amino acids originated from both terrestrial contamination and meteoritic or cometary in fall to the lunar surface. A majority of the amino acids in the Apollo samples studied originated from precursor molecules, either indigenous to the lunar samples or contaminants, that reacted during the water extraction and acid hydrolysis process for analysis in the laboratory, but the identities of the amino acid precursors still remain poorly understood. Such precursors could include hydrogen cyanide (HCN) and other volatile organic compounds such as amines, carboxylic acids, or aldehydes and ketones. The identities of these compounds, as well as the effects of years of curation on their abundances in lunar regolith samples stored at ambient temperature under nitrogen gas purge, are not clear. The specially curated samples available through the Apollo Next Generation Sample Analysis (ANGSA) program provide a unique opportunity to use state-of- the-art analytical techniques to examine previously unstudied lunar materials. The ANGSA samples include three types of samples: 1) samples stored frozen since <1 month after Earth arrival; 2) samples stored under helium; and 3) a double drive tube collected by Apollo 17 astronauts, with the bottom portion of the drive tube sealed under vacuum on the Moon and never opened. In contrast to the typically curated Apollo samples that have been kept for decades at room temperature under flowing nitrogen purge that may have significantly reduced the abundance of volatiles, the vacuum-sealed and frozen samples may have enhanced preservation of these volatiles. Our initial investigation examines amino acids and their potential volatile precursors, including hydrogen cyanide (HCN), aldehydes, ketones, amines, and mono-carboxylic acids, in a sample from the top portion of the Apollo 17 double drive tube. These results will aid in understanding the lunar abundances of these molecules and will also be compared to future analyses of other drive tube and frozen ANGSA samples

Inter-observer variation in the assessment of clinical signs in sick Tanzanian children

We assessed the inter-observer agreement in identification of a range of 24 clinical signs associated with disease presentation in 327 children aged 0·41) although there was only fair agreement (Kappa-score 0·21-0·40) in the detection of neck stiffness and chest indrawing and slight agreement in the detection of dehydration (Kappa-score 0·199). All objective neurological signs were less reliably assessed in infants than in older children. The difficulties surrounding the diagnosis of impaired consciousness in young children should increase vigilance in the diagnosis and management of neurological complications of illnesses in infanc

Carbon isotope evidence for the substrates and mechanisms of prebiotic synthesis in the early solar system

Meteorites contain prebiotic, bio-relevant organic compounds including amino acids. Their syntheses could result from diverse sources and mechanisms and provide a window on the conditions and materials present in the early solar system. Here we constrain alanine’s synthetic history in the Murchison meteorite using site-specific ¹³C/¹²C measurements, reported relative to the VPDB standard. The δ¹³C_(VPDB) values of −29 ± 10‰, 142 ± 20‰, and −36 ± 20‰ for the carboxyl, amine-bound, and methyl carbons, respectively, are consistent with Strecker synthesis of interstellar-medium-derived aldehydes, ammonia, and low-δ¹³C nebular or interstellar-medium-derived CN. We report experimentally measured isotope effects associated with Strecker synthesis, and use them to constrain the δ¹³C values of the alanine precursors, which we then use to construct a model that predicts the molecular-average δ¹³C values of 19 other organic compounds of prebiotic significance found in Murchison if they were made by our proposed synthetic network. Most of these predictions agree with previous measurements, suggesting that interstellar-medium-derived aldehydes and nebular and/or pre-solar CN could have served as substrates for synthesis of a wide range of prebiotic compounds in the early solar system

Carbon isotope evidence for the substrates and mechanisms of prebiotic synthesis in the early solar system

Meteorites contain prebiotic, bio-relevant organic compounds including amino acids. Their syntheses could result from diverse sources and mechanisms and provide a window on the conditions and materials present in the early solar system. Here we constrain alanine’s synthetic history in the Murchison meteorite using site-specific ¹³C/¹²C measurements, reported relative to the VPDB standard. The δ¹³C_(VPDB) values of −29 ± 10‰, 142 ± 20‰, and −36 ± 20‰ for the carboxyl, amine-bound, and methyl carbons, respectively, are consistent with Strecker synthesis of interstellar-medium-derived aldehydes, ammonia, and low-δ¹³C nebular or interstellar-medium-derived CN. We report experimentally measured isotope effects associated with Strecker synthesis, and use them to constrain the δ¹³C values of the alanine precursors, which we then use to construct a model that predicts the molecular-average δ¹³C values of 19 other organic compounds of prebiotic significance found in Murchison if they were made by our proposed synthetic network. Most of these predictions agree with previous measurements, suggesting that interstellar-medium-derived aldehydes and nebular and/or pre-solar CN could have served as substrates for synthesis of a wide range of prebiotic compounds in the early solar system

Mutation of a conserved, hydrophobic, cryptic epitope improves manufacturability and immunogenicity of the SARS-CoV-2 RBD

The supply of COVID-19 vaccine doses still lags behind the global demand for first time vaccination and booster doses. Distribution of vaccine doses has been far from equitable across the world given the steep prices and logistical challenges that low- and middle-income countries face. Subunit protein vaccine candidates have now been shown to elicit protective responses against SARS-CoV-2 infection, while providing additional benefits for manufacturing capability and stability requirements compared to many currently approved vaccines. Here we report a second-generation engineered RBD sequence variant with enhanced manufacturability and immunogenicity over the wild-type ancestral RBD and a first-generation engineered variant (RBD-L452K-F490W (RBD-J)). Introducing two additional mutations, S383D and L518D, to a hydrophobic cryptic epitope in the RBD core improved expression titers and biophysical stability compared to RBD-J. These two additional mutations in RBD-S383D-L452K-F490W-L518D (RBD-J6) ablated the interaction of two neutralizing antibodies, CR3022 and EY6A, targeting the class 4 epitope on the RBD core, but the protein is still bound by human convalescent sera. Mice immunized with a Beta sequence variant of RBD-J and RBD-J6 displayed on a virus-like particle were protected against challenges with Alpha and Beta variants of SARS-CoV-2. Sera from mice immunized with three doses of a RBD-J6 β – VLP showed comparable neutralizing activity to several variants of concern compared to two doses of Comirnaty. Please click Download on the upper right corner to see the full abstract

Analysis of Chiral Carboxylic Acids in Meteorites

Homochirality of amino acids in proteins and sugars in DNA and RNA is a critical feature of life on Earth. In the absence of a chiral driving force, however, reactions leading to the synthesis of amino acids and sugars result in racemic mixtures. It is currently unknown whether homochirality was necessary for the origins of life or if it was a product of early life. The observation of enantiomeric excesses of certain amino acids of extraterrestrial origins in meteorites provides evidence to support the hypothesis that there was a mechanism for the preferential synthesis or destruction of a particular amino acid enantiomer [e.g., 1-3]. The cause of the observed chiral excesses is un-clear, although at least in the case of the amino acid isovaline, the degree of aqueous alteration that occurred on the meteorite parent body is correlated to the isovaline L-enantiomeric excess [3, 4]. This suggests that chiral symmetry is broken and/or amplified within the meteorite parent bodies. Besides amino acids, there have been only a few reports of other meteoritic compounds found in enantiomeric excess: sugars and sugar acids [5, 6] and the hydroxy acid lactic acid [7]. Determining whether or not additional types of molecules in meteorites are also present in enantiomeric excesses of extraterrestrial information will provide insights into mechanisms for breaking chiral symmetry. Though the previous measurements (e.g., enantiomeric composition of lactic acid [7], and chiral carboxylic acids [8]) were made by gas chromatography-mass spectrometry, the potential for increased sensitivity of liquid chromatography-mass spectrometry (LC-MS) analyses is important because for many meteorite samples, only small sample masses are available for study. Furthermore, at least in the case of amino acids, many of the largest amino acid enantiomeric excesses were observed in samples that contained lower abundances (tens of ppb) of a given amino acid enantiomer. In the present work, we describe our efforts to develop highly sensitive LC-MS methods for the analysis of chiral carboxylic acids including hydroxy acids

Organic Analysis in the Miller Range 090657 CR2 Chondrite: Part 2 Amino Acid Analyses

Primitive carbonaceous chondrites contain a wide variety of organic material, ranging from soluble discrete molecules to insoluble, unstructured kerogen-like components, as well as structured nano-globules of macromolecular carbon. The relationship between the soluble organic molecules, macromolecular organic material, and host minerals are poorly understood. Due to the differences in extractability of soluble and insoluble organic materials, the analysis methods for each differ and are often performed independently. The combination of soluble and insoluble analyses, when performed concurrently, can provide a wider understanding of spatial distribution, and elemental, structural and isotopic composition of organic material in primitive meteorites. Using macroscale extraction and analysis techniques in combination with in situ microscale observation, we have been studying both insoluble and soluble organic material in the primitive CR2 chondrite Miller Range (MIL) 090657. In accompanying abstracts (Cao et al. and Messenger et al.) we discuss insoluble organic material in the samples. By performing the consortium studies, we aim to improve our understanding of the relationship between the meteorite minerals and the soluble and insoluble organic phases and to delineate which species formed within the meteorite and those that formed in nebular or presolar environments. In this abstract, we present the results of amino acid analyses of MIL 090657 by ultra performance liquid chromatography with fluorescence detection and quadrupole-time of flight mass spectrometry. Amino acids are of interest because they are essential to life on Earth, and because they are present in sufficient structural, enantiomeric and isotopic diversity to allow insights into early solar system chemical processes. Furthermore, these are among the most isotopically anomalous species, yet at least some fraction are thought to have formed by aqueously-mediated processes during parent body alteration

Brightening of 630.0 nm equatorial spread-F airglow depletions

[1] Observations from the Boston University all-sky imaging system at Arecibo, Puerto Rico (18.3°N, 66.7°W, 28°N mag), show an unusual behavior of nighttime 630.0-nm airglow depletions. Associated with equatorial spread-F (ESF), these structures move eastward before reversing their motion and become airglow enhancements. Few other cases have been found, all during December solstices. For the case study presented here, data from the Arecibo incoherent scatter radar and the Republic of China Scientific Satellite (ROCSAT-1) provide supporting information. The radar shows that around local midnight the background zonal and meridional plasma motions reverse to westward and southward, respectively. ROCSAT-1 shows enhanced ion density, i.e., a low-latitude plasma blob, above the bright feature recorded by the all-sky imager, indicating a possible connection between both phenomena. Drifts parallel to the magnetic field are observed only in the region where the enhancement occurs. One possible interpretation of this change in the brightness of the depleted structure involves the influence of northward meridional winds and a reversal in the zonal drift motion, most likely caused by a zonal wind reversal

Safety, Immunogenicity and Duration of Protection of the RTS,S/AS02D Malaria Vaccine: One Year Follow-Up of a Randomized Controlled Phase I/IIb Trial

The RTS,S/AS02(D) vaccine has been shown to have a promising safety profile, to be immunogenic and to confer protection against malaria in children and infants.We did a randomized, controlled, phase I/IIb trial of RTS,S/AS02(D) given at 10, 14 and 18 weeks of age staggered with routine immunization vaccines in 214 Mozambican infants. The study was double-blind until the young child completed 6 months of follow-up over which period vaccine efficacy against new Plasmodium falciparum infections was estimated at 65.9% (95% CI 42.6-79.8, p<0.0001). We now report safety, immunogenicity and estimated efficacy against clinical malaria up to 14 months after study start. Vaccine efficacy was assessed using Cox regression models. The frequency of serious adverse events was 32.7% in the RTS,S/AS02(D) and 31.8% in the control group. The geometric mean titers of anti-circumsporozoite antibodies declined from 199.9 to 7.3 EU/mL from one to 12 months post dose three of RTS,S/AS02(D), remaining 15-fold higher than in the control group. Vaccine efficacy against clinical malaria was 33% (95% CI: -4.3-56.9, p = 0.076) over 14 months of follow-up. The hazard rate of disease per 2-fold increase in anti-CS titters was reduced by 84% (95% CI 35.1-88.2, p = 0.003).The RTS,S/AS02(D) malaria vaccine administered to young infants has a good safety profile and remains efficacious over 14 months. A strong association between anti-CS antibodies and risk of clinical malaria has been described for the first time. The results also suggest a decrease of both anti-CS antibodies and vaccine efficacy over time.ClinicalTrials.gov NCT00197028