The impact of crystal phase transition on the hardness and structure of kidney stones.

Calcium oxalate kidney stones, the most prevalent type of kidney stones, undergo a multi-step process of crystal nucleation, growth, aggregation, and secondary transition. The secondary transition has been rather overlooked, and thus, the effects on the disease and the underlying mechanism remain unclear. Here, we show, by periodic micro-CT images of human kidney stones in an ex vivo incubation experiment, that the growth of porous aggregates of calcium oxalate dihydrate (COD) crystals triggers the hardening of the kidney stones that causes difficulty in lithotripsy of kidney stone disease in the secondary transition. This hardening was caused by the internal nucleation and growth of precise calcium oxalate monohydrate (COM) crystals from isolated urine in which the calcium oxalate concentrations decreased by the growth of COD in closed grain boundaries of COD aggregate kidney stones. Reducing the calcium oxalate concentrations in urine is regarded as a typical approach for avoiding the recurrence. However, our results revealed that the decrease of the concentrations in closed microenvironments conversely promotes the transition of the COD aggregates into hard COM aggregates. We anticipate that the suppression of the secondary transition has the potential to manage the deterioration of kidney stone disease.

Atmospheric formaldehyde production on early Mars leading to a potential formation of bio-important molecules.

Formaldehyde (H2CO) is a critical precursor for the abiotic formation of biomolecules, including amino acids and sugars, which are the building blocks of proteins and RNA. Geomorphological and geochemical evidence on Mars indicates a temperate environment compatible with the existence of surface liquid water during its early history at 3.8-3.6 billion years ago (Ga), which was maintained by the warming effect of reducing gases, such as H2. However, it remains uncertain whether such a temperate and weakly reducing surface environment on early Mars was suitable for producing H2CO. In this study, we investigated the atmospheric production of H2CO on early Mars using a 1-D photochemical model assuming a thick CO2-dominated atmosphere with H2 and CO. Our results show that a continuous supply of atmospheric H2CO can be used to form various organic compounds, including amino acids and sugars. This could be a possible origin for the organic matter observed on the Martian surface. Given the previously reported conversion rate from H2CO into ribose, the calculated H2CO deposition flux suggests a continuous supply of bio-important sugars on early Mars, particularly during the Noachian and early Hesperian periods.

Hexose phosphorylation for a non-enzymatic glycolysis and pentose phosphate pathway on early Earth.

Glycolysis and pentose phosphate pathways play essential roles in cellular processes and are assumed to be among the most ancient metabolic pathways. Non-enzymatic metabolism-like reactions might have occurred on the prebiotic Earth and been inherited by the biological reactions. Previous research has identified a part of the non-enzymatic glycolysis and the non-enzymatic pentose phosphate pathway from glucose 6-phosphate and 6-phosphogluconate, which are intermediates of these reactions. However, how these phosphorylated molecules were formed on the prebiotic Earth remains unclear. Herein, we demonstrate the synthesis of glucose and gluconate from simple aldehydes in alkaline solutions and the formation of glucose 6-phosphate and 6-phosphogluconate with borate using thermal evaporation. These results imply that the initial stages of glycolysis-like and pentose phosphate pathway-like reactions were achieved in borate-rich evaporative environments on prebiotic Earth, suggesting that non-enzymatic metabolism provided biomolecules and their precursors on prebiotic Earth.

Reassigning CI chondrite parent bodies based on reflectance spectroscopy of samples from carbonaceous asteroid Ryugu and meteorites.

The carbonaceous asteroid Ryugu has been explored by the Hayabusa2 spacecraft to elucidate the actual nature of hydrous asteroids. Laboratory analyses revealed that the samples from Ryugu are comparable to unheated CI carbonaceous chondrites; however, reflectance spectra of Ryugu samples and CIs do not coincide. Here, we demonstrate that Ryugu sample spectra are reproduced by heating Orgueil CI chondrite at 300°C under reducing conditions, which caused dehydration of terrestrial weathering products and reduction of iron in phyllosilicates. Terrestrial weathering of CIs accounts for the spectral differences between Ryugu sample and CIs, which is more severe than space weathering that likely explains those between asteroid Ryugu and the collected samples. Previous assignments of CI chondrite parent bodies, i.e., chemically most primitive objects in the solar system, are based on the spectra of CI chondrites. This study indicates that actual spectra of CI parent bodies are much darker and flatter at ultraviolet to visible wavelengths than the spectra of CI chondrites.

Boron-assisted abiotic polypeptide synthesis.

The emergence of proteins and their interactions with RNAs were a key step in the origin and early evolution of life. The abiotic synthesis of peptides has been limited in short amino acid length and is favored in highly alkaline evaporitic conditions in which RNAs are unstable. This environment is also inconsistent with estimated Hadean Earth. Prebiotic environments rich in boron are reportedly ideal for abiotic RNA synthesis. However, the effects of boron on amino acid polymerization are unclear. We report that boric acid enables the polymerization of amino acids at acidic and near-neutral pH levels based on simple heating experiments of amino acid solutions containing borate/boric acid at various pH levels. Our study provides evidence for the boron-assisted synthesis of polypeptides in prebiotically plausible environments, where the same conditions would allow for the formation of RNAs and interactions of primordial proteins and RNAs that could be inherited by RNA-dependent protein synthesis during the evolution of life.

Distributions of CHN compounds in meteorites record organic syntheses in the early solar system.

Carbonaceous meteorites contain diverse soluble organic compounds. These compounds formed in the early solar system from volatiles accreted on tiny dust particles. However, the difference in the organic synthesis on respective dust particles in the early solar system remains unclear. We found micrometer-scale heterogeneous distributions of diverse CHN1-2 and CHN1-2O compounds in two primitive meteorites: the Murchison and NWA 801, using a surface-assisted laser desorption/ionization system connected to a high mass resolution mass spectrometer. These compounds contained mutual relationships of ± H2, ± CH2, ± H2O, and ± CH2O and showed highly similar distributions, indicating that they are the products of series reactions. The heterogeneity was caused by the micro-scale difference in the abundance of these compounds and the extent of the series reactions, indicating that these compounds formed on respective dust particles before asteroid accretion. The results of the present study provide evidence of heterogeneous volatile compositions and the extent of organic reactions among the dust particles that formed carbonaceous asteroids. The compositions of diverse small organic compounds associated with respective dust particles in meteorites are useful to understand different histories of volatile evolution in the early solar system.

Quantitative analysis of calcium oxalate monohydrate and dihydrate for elucidating the formation mechanism of calcium oxalate kidney stones.

We sought to identify and quantitatively analyze calcium oxalate (CaOx) kidney stones on the order of micrometers, with a focus on the quantitative identification of calcium oxalate monohydrate (COM) and dihydrate (COD). We performed Fourier transform infrared (FTIR) spectroscopy, powder X-ray diffraction (PXRD), and microfocus X-ray computed tomography measurements (microfocus X-ray CT) and compared their results. An extended analysis of the FTIR spectrum focusing on the 780 cm-1 peak made it possible to achieve a reliable analysis of the COM/COD ratio. We succeeded in the quantitative analysis of COM/COD in 50-µm2 areas by applying microscopic FTIR for thin sections of kidney stones, and by applying microfocus X-ray CT system for bulk samples. The analysis results based on the PXRD measurements with micro-sampling, the microscopic FTIR analysis of thin sections, and the microfocus X-ray CT system observation of a bulk kidney stone sample showed roughly consistent results, indicating that all three methods can be used complementarily. This quantitative analysis method evaluates the detailed CaOx composition on the preserved stone surface and provides information on the stone formation processes. This information clarifies where and which crystal phase nucleates, how the crystals grow, and how the transition from the metastable phase to the stable phase proceeds. The phase transition affects the growth rate and hardness of kidney stones and thus provides crucial clues to the kidney stone formation process.

Soluble organic molecules in samples of the carbonaceous asteroid (162173) Ryugu.

The Hayabusa2 spacecraft collected samples from the surface of the carbonaceous near-Earth asteroid (162173) Ryugu and brought them to Earth. The samples were expected to contain organic molecules, which record processes that occurred in the early Solar System. We analyzed organic molecules extracted from the Ryugu surface samples. We identified a variety of molecules containing the atoms CHNOS, formed by methylation, hydration, hydroxylation, and sulfurization reactions. Amino acids, aliphatic amines, carboxylic acids, polycyclic aromatic hydrocarbons, and nitrogen-heterocyclic compounds were detected, which had properties consistent with an abiotic origin. These compounds likely arose from an aqueous reaction on Ryugu's parent body and are similar to the organics in Ivuna-type meteorites. These molecules can survive on the surfaces of asteroids and be transported throughout the Solar System.

Borate-guided ribose phosphorylation for prebiotic nucleotide synthesis.

Polymers of ribonucleotides (RNAs) are considered to store genetic information and promote biocatalytic reactions for the proto life on chemical evolution. Abiotic synthesis of ribonucleotide was successful in past experiments; nucleoside synthesis occurred first, followed by phosphorylation. These abiotic syntheses are far from biotic reactions and have difficulties as a prebiotic reaction in reacting chemicals in a specific order and purifying intermediates from other molecules in multi-steps of reactions. Another reaction, ribose phosphorylation followed by nucleobase synthesis or nucleobase addition, is close to the biotic reactions of nucleotide synthesis. However, the synthesis of ribose 5'-phosphate under prebiotically plausible conditions remains unclear. Here, we report a high-yield regioselective one-pot synthesis of ribose 5'-phosphate from an aqueous solution containing ribose, phosphate, urea, and borate by simple thermal evaporation. Of note, phosphorylation of ribose before the nucleoside formation differs from the traditional prebiotic nucleotide syntheses and is also consistent with biological nucleotide synthesis. Phosphorylation occurred to the greatest extent in ribose compared to other aldopentoses, only in the presence of borate. Borate is known to improve the stability of ribose preferentially. Geological evidence suggests the presence of borate-rich settings on the early Earth. Therefore, borate-rich evaporitic environments could have facilitated preferential synthesis of ribonucleotide coupled with enhanced stability of ribose on the early Earth.

Identifying the wide diversity of extraterrestrial purine and pyrimidine nucleobases in carbonaceous meteorites.

The lack of pyrimidine diversity in meteorites remains a mystery since prebiotic chemical models and laboratory experiments have predicted that these compounds can also be produced from chemical precursors found in meteorites. Here we report the detection of nucleobases in three carbonaceous meteorites using state-of-the-art analytical techniques optimized for small-scale quantification of nucleobases down to the range of parts per trillion (ppt). In addition to previously detected purine nucleobases in meteorites such as guanine and adenine, we identify various pyrimidine nucleobases such as cytosine, uracil, and thymine, and their structural isomers such as isocytosine, imidazole-4-carboxylic acid, and 6-methyluracil, respectively. Given the similarity in the molecular distribution of pyrimidines in meteorites and those in photon-processed interstellar ice analogues, some of these derivatives could have been generated by photochemical reactions prevailing in the interstellar medium and later incorporated into asteroids during solar system formation. This study demonstrates that a diversity of meteoritic nucleobases could serve as building blocks of DNA and RNA on the early Earth.

Analytical protocols for Phobos regolith samples returned by the Martian Moons eXploration (MMX) mission.

Japan Aerospace Exploration Agency (JAXA) will launch a spacecraft in 2024 for a sample return mission from Phobos (Martian Moons eXploration: MMX). Touchdown operations are planned to be performed twice at different landing sites on the Phobos surface to collect > 10 g of the Phobos surface materials with coring and pneumatic sampling systems on board. The Sample Analysis Working Team (SAWT) of MMX is now designing analytical protocols of the returned Phobos samples to shed light on the origin of the Martian moons as well as the evolution of the Mars-moon system. Observations of petrology and mineralogy, and measurements of bulk chemical compositions and stable isotopic ratios of, e.g., O, Cr, Ti, and Zn can provide crucial information about the origin of Phobos. If Phobos is a captured asteroid composed of primitive chondritic materials, as inferred from its reflectance spectra, geochemical data including the nature of organic matter as well as bulk H and N isotopic compositions characterize the volatile materials in the samples and constrain the type of the captured asteroid. Cosmogenic and solar wind components, most pronounced in noble gas isotopic compositions, can reveal surface processes on Phobos. Long- and short-lived radionuclide chronometry such as 53Mn-53Cr and 87Rb-87Sr systematics can date pivotal events like impacts, thermal metamorphism, and aqueous alteration on Phobos. It should be noted that the Phobos regolith is expected to contain a small amount of materials delivered from Mars, which may be physically and chemically different from any Martian meteorites in our collection and thus are particularly precious. The analysis plan will be designed to detect such Martian materials, if any, from the returned samples dominated by the endogenous Phobos materials in curation procedures at JAXA before they are processed for further analyses.

Multicolor imaging of calcium-binding proteins in human kidney stones for elucidating the effects of proteins on crystal growth.

The pathogenesis of kidney stone formation includes multi-step processes involving complex interactions between mineral components and protein matrix. Calcium-binding proteins in kidney stones have great influences on the stone formation. The spatial distributions of these proteins in kidney stones are essential for evaluating the in vivo effects of proteins on the stone formation, although the actual distribution of these proteins is still unclear. We reveal micro-scale distributions of three different proteins, namely osteopontin (OPN), renal prothrombin fragment 1 (RPTF-1), and calgranulin A (Cal-A), in human kidney stones retaining original mineral phases and textures: calcium oxalate monohydrate (COM) and calcium oxalate dihydrate (COD). OPN and RPTF-1 were distributed inside of both COM and COD crystals, whereas Cal-A was distributed outside of crystals. OPN and RPTF-1 showed homogeneous distributions in COM crystals with mosaic texture, and periodically distributions parallel to specific crystal faces in COD crystals. The unique distributions of these proteins enable us to interpret the different in vivo effects of each protein on CaOx crystal growth based on their physico-chemical properties and the complex physical environment changes of each protein. This method will further allow us to elucidate in vivo effects of different proteins on kidney stone formation.

Synthesis of 13C-enriched amino acids with 13C-depleted insoluble organic matter in a formose-type reaction in the early solar system.

Solvent-soluble organic matter (SOM) in meteorites, which includes life's building molecules, is suspected to originate from the cold region of the early solar system, on the basis of 13C enrichment in the molecules. Here, we demonstrate that the isotopic characteristics are reproducible in amino acid synthesis associated with a formose-type reaction in a heated aqueous solution. Both thermochemically driven formose-type reaction and photochemically driven formose-type reaction likely occurred in asteroids and ice-dust grains in the early solar system. Thus, the present results suggest that the formation of 13C-enriched SOM was not specific to the cold outer protosolar disk or the molecular cloud but occurred more widely in the early solar system.

Experimental Investigation of the Formation of Formaldehyde by Hadean and Noachian Impacts.

Formaldehyde (FA) is an important precursor in the abiotic synthesis of major biomolecules including amino acids, sugars, and nucleobases. Thus, spontaneous formation of prebiotic FA must have been crucial for the chemical origin of life. The frequent impacts of meteorites and asteroids on Hadean Earth have been considered one of the abiotic synthetic processes of organic compounds. However, the impact-induced formation of FA from CO2 as the major atmospheric constituent has not been confirmed yet. This study investigated the formation of FA in impact-induced reactions among meteoritic minerals, bicarbonate, gaseous nitrogen, and water to simulate the abiotic process experimentally. Products were analyzed with ultra-high-performance liquid chromatography/tandem mass spectrometry and powder X-ray diffraction techniques. The results show the formation of FA and oxidation of metallic iron to siderite in the impact shock experiments. This indicates that this important prebiotic molecule was also synthesized by impacts of iron-bearing meteorites/asteroids on the Hadean oceans. The impact events might have generated spatially and temporally FA-enriched localized environments. Moreover, the impact-induced synthesis of FA may have also occurred on Noachian Mars given the presence of liquid water and a CO2-N2-rich atmosphere on the planet.

Extraterrestrial hexamethylenetetramine in meteorites-a precursor of prebiotic chemistry in the inner solar system.

Despite extensive studies on the formation of organic molecules in various extraterrestrial environments, it still remains under debate when, where, and how such molecules were abiotically formed. A key molecule to solve the problem, hexamethylenetetramine (HMT) has not been confirmed in extraterrestrial materials despite extensive laboratory experimental evidence that it can be produced in interstellar or cometary environments. Here we report the first detection of HMT and functionalized HMT species in the carbonaceous chondrites Murchison, Murray, and Tagish Lake. While the part-per-billion level concentration of HMT in Murchison and Tagish Lake is comparable to other related soluble organic molecules like amino acids, these compounds may have eluded detection in previous studies due to the loss of HMT during the extraction processes. HMT, which can yield important molecules for prebiotic chemistry such as formaldehyde and ammonia upon degradation, is a likely precursor of meteoritic organic compounds of astrochemical and astrophysical interest.

Impact-induced amino acid formation on Hadean Earth and Noachian Mars.

Abiotic synthesis of biomolecules is an essential step for the chemical origin of life. Many attempts have succeeded in synthesizing biomolecules, including amino acids and nucleobases (e.g., via spark discharge, impact shock, and hydrothermal heating), from reduced compounds that may have been limited in their availabilities on Hadean Earth and Noachian Mars. On the other hand, formation of amino-acids and nucleobases from CO2 and N2 (i.e., the most abundant C and N sources on Earth during the Hadean) has been limited via spark discharge. Here, we demonstrate the synthesis of amino acids by laboratory impact-induced reactions among simple inorganic mixtures: Fe, Ni, Mg2SiO4, H2O, CO2, and N2, by coupling the reduction of CO2, N2, and H2O with the oxidation of metallic Fe and Ni. These chemical processes simulated the possible reactions at impacts of Fe-bearing meteorites/asteroids on oceans with a CO2 and N2 atmosphere. The results indicate that hypervelocity impact was a source of amino acids on the Earth during the Hadean and potentially on Mars during the Noachian. Amino acids formed during such events could more readily polymerize in the next step of the chemical evolution, as impact events locally form amino acids at the impact sites.

Extraterrestrial ribose and other sugars in primitive meteorites.

Sugars are essential molecules for all terrestrial biota working in many biological processes. Ribose is particularly essential as a building block of RNA, which could have both stored information and catalyzed reactions in primitive life on Earth. Meteorites contain a number of organic compounds including key building blocks of life, i.e., amino acids, nucleobases, and phosphate. An amino acid has also been identified in a cometary sample. However, the presence of extraterrestrial bioimportant sugars remains unclear. We analyzed sugars in 3 carbonaceous chondrites and show evidence of extraterrestrial ribose and other bioessential sugars in primitive meteorites. The 13C-enriched stable carbon isotope compositions (δ13C vs.VPDB) of the detected sugars show that the sugars are of extraterrestrial origin. We also conducted a laboratory simulation experiment of a potential sugar formation reaction in space. The compositions of pentoses in meteorites and the composition of the products of the laboratory simulation suggest that meteoritic sugars were formed by formose-like processes. The mineral compositions of these meteorites further suggest the formation of these sugars both before and after the accretion of their parent asteroids. Meteorites were carriers of prebiotic organic molecules to the early Earth; thus, the detection of extraterrestrial sugars in meteorites establishes the existence of natural geological routes to make and preserve them as well as raising the possibility that extraterrestrial sugars contributed to forming functional biopolymers like RNA on the early Earth or other primitive worlds.

Racemization of Valine by Impact-Induced Heating.

Homochirality plays an important role in all living organisms but its origin remains unclear. It also remains unclear whether such chiral molecules survived terrestrial heavy impact events. Impacts of extraterrestrial objects on early oceans were frequent and could have affected the chirality of oceanic amino acids when such amino acids accumulated during impacts. This study investigated the effects of shock-induced heating on enantiomeric change of valine with minerals such as olivine ([Mg0.9, Fe0.1]2SiO4), hematite (Fe2O3), and calcite (CaCO3). With a shock wave generated by an impact at ~0.8 km/s, both D- and L-enriched valine were significantly decomposed and partially racemized under all experimental conditions. Different minerals had different shock impedances; therefore, they provided different P-T conditions for identical impacts. Furthermore, the high pH of calcite promoted the racemization of valine. The results indicate that in natural hypervelocity impacts, amino acids in shocked oceanic water would have decomposed completely, since impact velocity and the duration of shock compression and heating are typically greater in hypervelocity impact events than those in experiments. Even with the shock wave by the impact of small and decelerated projectiles in which amino acids survive, the shock heating may generate sufficient heat for significant racemization in shocked oceanic water. However, the duration of shock induced heating by small projectiles is limited and the population of such decelerated projectiles would be limited. Therefore, even though impacts of asteroids and meteorites were frequent on the prebiotic Earth, impact events would not have significantly changed the ee of proteinogenic amino acids accumulated in the entire ocean.

Temperature-induced oligomerization of polycyclic aromatic hydrocarbons at ambient and high pressures.

Temperature-induced oligomerization of polycyclic aromatic hydrocarbons (PAHs) was found at 500-773 K and ambient and high (3.5 GPa) pressures. The most intensive oligomerization at 1 bar and 3.5 GPa occurs at 740-823 K. PAH carbonization at high pressure is the final stage of oligomerization and occurs as a result of sequential oligomerization and polymerization of the starting material, caused by overlapping of π-orbitals, a decrease of intermolecular distances, and finally the dehydrogenation and polycondensation of benzene rings. Being important for building blocks of life, PAHs and their oligomers can be formed in the interior of the terrestrial planets with radii less than 2270 km.

Adsorption of RNA on mineral surfaces and mineral precipitates.

The prebiotic significance of laboratory experiments that study the interactions between oligomeric RNA and mineral species is difficult to know. Natural exemplars of specific minerals can differ widely depending on their provenance. While laboratory-generated samples of synthetic minerals can have controlled compositions, they are often viewed as "unnatural". Here, we show how trends in the interaction of RNA with natural mineral specimens, synthetic mineral specimens, and co-precipitated pairs of synthetic minerals, can make a persuasive case that the observed interactions reflect the composition of the minerals themselves, rather than their being simply examples of large molecules associating nonspecifically with large surfaces. Using this approach, we have discovered Periodic Table trends in the binding of oligomeric RNA to alkaline earth carbonate minerals and alkaline earth sulfate minerals, where those trends are the same when measured in natural and synthetic minerals. They are also validated by comparison of co-precipitated synthetic minerals. We also show differential binding of RNA to polymorphic forms of calcium carbonate, and the stabilization of bound RNA on aragonite. These have relevance to the prebiotic stabilization of RNA, where such carbonate minerals are expected to have been abundant, as they appear to be today on Mars.