Elucidating the cellular dynamics of the brain with single-cell RNA sequencing

Single-cell RNA-sequencing (scRNA-seq) has emerged in recent years as a breakthrough technology to understand RNA metabolism at cellular resolution. In addition to allowing new cell types and states to be identified, scRNA-seq can permit cell-type specific differential gene expression changes, pre-mRNA processing events, gene regulatory networks and single-cell developmental trajectories to be uncovered. More recently, a new wave of multi-omic adaptations and complementary spatial transcriptomics workflows have been developed that facilitate the collection of even more holistic information from individual cells. These developments have unprecedented potential to provide penetrating new insights into the basic neural cell dynamics and molecular mechanisms relevant to the nervous system in both health and disease. In this review we discuss this maturation of single-cell RNA-sequencing over the past decade, and review the different adaptations of the technology that can now be applied both at different scales and for different purposes. We conclude by highlighting how these methods have already led to many exciting discoveries across neuroscience that have furthered our cellular understanding of the neurological disease

Can Mg isotopes be used to trace cyanobacteria-mediated magnesium carbonate precipitation in alkaline lakes?

The fractionation of Mg isotopes was determined during the cyanobacterial mediated precipitation of hydrous magnesium carbonate precipitation in both natural environments and in the laboratory. Natural samples were obtained from Lake Salda (SE Turkey), one of the few modern environments on the Earth's surface where hydrous Mg-carbonates are the dominant precipitating minerals. This precipitation was associated with cyanobacterial stromatolites which were abundant in this aquatic ecosystem. Mg isotope analyses were performed on samples of incoming streams, groundwaters, lake waters, stromatolites, and hydromagnesite-rich sediments. Laboratory Mg carbonate precipitation experiments were conducted in the presence of purified Synechococcus sp cyanobacteria that were isolated from the lake water and stromatolites. The hydrous magnesium carbonates nesquehonite (MgCO3·3H2O) and dypingite (Mg5(CO3)4(OH)25(H2O)) were precipitated in these batch reactor experiments from aqueous solutions containing either synthetic NaHCO3/MgCl2 mixtures or natural Lake Salda water, in the presence and absence of live photosynthesizing Synechococcus sp. Bulk precipitation rates were not to affected by the presence of bacteria when air was bubbled through the system. In the stirred non-bubbled reactors, conditions similar to natural settings, bacterial photosynthesis provoked nesquehonite precipitation, whilst no precipitation occurred in bacteria-free systems in the absence of air bubbling, despite the fluids achieving a similar or higher degree of supersaturation. The extent of Mg isotope fractionation (?26Mgsolid-solution) between the mineral and solution in the abiotic experiments was found to be identical, within uncertainty, to that measured in cyanobacteria-bearing experiments, and ranges from ?1.4 to ?0.7 ‰. This similarity refutes the use of Mg isotopes to validate microbial mediated precipitation of hydrous Mg carbonate

Tracing olivine carbonation and serpentinization in CO2-rich fluids via magnesium exchange and isotopic fractionation

Chemical exchange between seawater and the oceanic crust is thought to play a significant role in the regulation of the global magnesium (Mg) cycle, yet relatively little is known about the rates and mechanisms of Mg exchange in these crustal environments. In this study we experimentally characterize the extent, and nature, of Mg isotope fractionation during the carbonation and serpentinization of olivine (one of the principal minerals found in ultramafic rocks) under hydrothermal conditions. Olivine alteration was found to be incongruent, with the reactant fluid composition varying according to the extent of olivine dissolution and the precipitation of secondary minerals. In mildly acid water (pH ∼ 6.5), olivine dissolved to form Mg-Fe carbonate solid solutions and minor chrysotile. Upon carbonation and a decrease of CO2 in the water, the pH increased to >8, with chrysotile and brucite becoming the dominant alteration minerals. The Mg-rich carbonates preferentially incorporated lighter Mg isotopes, resulting in a ∼0.5‰ increase of the δ26Mg composition of the fluid relative to olivine during the initial carbonation and serpentinization reactions. This was followed by a decrease in δ26Mg under higher pH conditions associated with the formation of brucite. Our experimental and modeling results therefore demonstrate that the δ26Mg composition of fluids involved in olivine alteration reflect the type and quantity of secondary Mg minerals formed, which in turn depend on the pH and CO2 concentration of the water. Comparison of these results with natural groundwaters and geothermal waters from basaltic terrains indicate that the δ26Mg composition of natural waters are likely to also be controlled by mafic rock dissolution and the preferential incorporation of isotopically light Mg into carbonates and isotopically heavy Mg into Mg-Si minerals. Together, these findings improve our understanding of Mg isotope systematics during water-rock interaction, and suggest that δ26Mg may be a useful tool for tracing reactions that are critical to geological CO2 sequestration

The efficient long-term inhibition of forsterite dissolution by common soil bacteria and fungi at earth surface conditions

San Carlos forsterite was dissolved in initially pure H2O in a batch reactor in contact with the atmosphere for five years. The reactive fluid aqueous pH remained relatively stable at pH 6.7 throughout the experiment. Aqueous Mg concentration maximized after approximately two years time at 3x10-5 mol/kg, whereas aqueous Si concentrations increased continuously with time, reaching 2x10-5 mol/kg after 5 years. Element release rates closely matched those determined on this same forsterite sample during short-term abiotic open system experiments for the first 10 days, then slowed substantially such that the Mg and Si release rates are approximately an order of magnitude slower than that calculated from the short-term abiotic experiments. Post-experiment analysis reveals that secondary hematite, a substantial biotic community, and minor amorphous silica formed on the dissolving forsterite during the experiment. The biotic community included bacteria, dominated by Rhizobiales (Alphaproteobacteria), and fungi, dominated by Trichocomaceae, that grew in a carbon and nutrient-limited media on the dissolving forsterite. The Mg isotope composition of the reactive fluid was near constant after 2 years but 0.25‰ heavier in δ26Mg than the dissolving forsterite. Together these results suggest long-term forsterite dissolution in natural Earth surface systems maybe substantially slower that estimated from short-term abiotic experiments due to the growth of biotic communities on their surfaces

The response of Li and Mg isotopes to rain events in a highly-weathered catchment

Storms are responsible for up to ~50% of total annual rainfall on tropical islands and result in rapid increases in discharge from rivers. Storm events are, however, notoriously under-sampled and their effects on weathering rates and processes are poorly constrained. To address this, we have undertaken high-frequency sampling of Quiock Creek catchment, a Critical Zone Observatory located in Guadeloupe, over a period of 21 days, encompassing several storm events. Chemical and isotopic (Li and Mg) analyses of different critical zone reservoirs (throughfall, soil pore water, groundwater and river water) were used to assess the interactions between rock, water and secondary minerals. The Li concentrations and δ7Li values of these different reservoirs range from 14 to 95 nmol/kg and 1.8 to 16.8‰, respectively. After several rain events, the average δ7Li value (13.3‰) of soil solutions from the lower part of the soil profile (>~150 cm below the surface) was unchanged, whereas in the upper part of the profile δ7Li values increased by ~2–4‰ due to increased contribution from throughfall. By contrast, the δ26Mg value of soil waters in the upper part of the soil profile were not significantly affected by the rain events with an average value of −0.90‰. The δ26Mg values of the different fluid reservoirs were generally close to the value of throughfall (~−0.90‰), but higher δ26Mg values (up to −0.58‰) were measured in the deeper parts of the soil profile, whereas groundwaters that have a long residence time had lower δ26Mg values (down to −1.48‰). These higher and lower values are attributed to, respectively, adsorption/desorption of light Mg isotopes on/from the surface of clay minerals. The δ7Li value of the river waters was ~9.3‰, with a Li concentration of 60 μmol/kg, but during a storm these values decreased to, respectively, 7.8‰ and 40 μmol/kg. This change in δ7Li is consistent with an increased contribution of Li from the soil solution. Thus, even in highly weathered catchments, changes in hydrological conditions can have a significant impact on weathering processes and therefore the composition of river waters delivered to the ocean

Behaviour of chromium isotopes in the eastern sub-tropical Atlantic Oxygen Minimum Zone

Constraints on the variability of chromium (Cr) isotopic compositions in the modern ocean are required to validate the use of Cr isotopic signatures in ancient authigenic marine sediments for reconstructing past levels of atmospheric and ocean oxygenation. This study presents dissolved Cr concentrations (CrT, where CrT = Cr(VI) + Cr(III)) and Cr isotope data (δ53Cr) for shelf, slope and open ocean waters within the oxygen minimum zone (OMZ) of the eastern sub-tropical Atlantic Ocean. Although dissolved oxygen concentrations were as low as 44–90 μmol kg−1 in the core of the OMZ, there was no evidence for removal of Cr(VI). Nonetheless, there was significant variability in seawater δ53Cr, with values ranging from 1.08 to 1.72‰. Shelf CrT concentrations were slightly lower (2.21 ± 0.07 nmol kg−1) than in open ocean waters at the same water depth (between 0 and 160 m, 2.48 ± 0.07 nmol kg−1). The shelf waters also had higher δ53Cr values (1.41 ± 0.14‰ compared to 1.18 ± 0.05‰ for open ocean waters shallower than 160 m). This is consistent with partial reduction of Cr(VI) to Cr(III), with subsequent removal of isotopically light Cr(III) onto biogenic particles. We also provide evidence for input of relatively isotopically heavy Cr from sediments on the shelf. Intermediate and deep water masses (AAIW and NADW) show a rather limited range of δ53Cr values (1.19 ± 0.09‰) and inputs of Cr from remineralisation of organic material or re-oxidation of Cr(III) appear to be minimal. Authigenic marine precipitates deposited in deep water in the open ocean therefore have the potential to faithfully record seawater δ53Cr, whereas archives of seawater δ53Cr derived from shelf sediments must be interpreted with caution

Stable and radiogenic strontium isotope fractionation during hydrothermal seawater-basalt interaction

The fluid-rock interactions occurring in hydrothermal systems at or near mid-oceanic ridges (MOR) were studied experimentally by reacting crystalline and glassy basalt with seawater at 250 °C and 290 °C while monitoring the liquid phase Sr isotopic evolution (87Sr/86Sr and δ88/86Sr). The results indicate that seawater Sr was incorporated into anhydrite during the early stages of seawater-basalt interaction. Liquid 87Sr/86Sr values trend towards the basaltic signature as non-stoichiometric basalt dissolution became the dominant process. This suggests that the interplay between fast Sr incorporation into secondary sulfates versus slow and continuous Sr liberation due to basalt dissolution at intermediate temperatures could partly explain previously identified discrepancies between MOR heat budget constraints and the marine 87Sr/86Sr budget. Late-stage anhydrite re-dissolution, likely caused by the liquid phase becoming more reducing through further basalt dissolution, as well as by quenching of the experiments, represents a potential explanation for the low amounts of anhydrite found in naturally altered oceanic basalt samples. Relatively strong decreases in liquid δ88/86Sr values in experiments with crystalline basalt suggest that isotopically light Sr was preferentially released due to non-stoichiometric dissolution. A slight preference of anhydrite for isotopically heavy Sr (‰εAnhydrite-Liquid88/86=0.034±0.019‰) is indicated by the data, suggesting that changes in MOR spreading rates and Sr removal could be recorded in the isotope compositions of authigenic, sedimentary Sr phases. Such insights will help to constrain the influence of hydrothermal systems on the oceanic stable Sr cycle

A diagnostic autoantibody signature for primary cutaneous melanoma

Melanoma is an aggressive form of skin cancer that is curable by surgical excision in the majority of cases, if detected at an early stage. To improve early stage melanoma detection, the development of a highly sensitive diagnostic test is of utmost importance. Here we aimed to identify antibodies to a panel of tumour associated antigens that can differentiate primary melanoma patients and healthy individuals. A total of 245 sera from primary melanoma patients and healthy volunteers were screened against a high-throughput microarray platform containing 1627 functional proteins. Following rigorous statistical analysis, we identified a combination of 10 autoantibody biomarkers that, as a panel, displays a sensitivity of 79%, specificity of 84% and an AUC of 0.828 for primary melanoma detection. This melanoma autoantibody signature may prove valuable for the development of a diagnostic blood test for routine population screening that, when used in conjunction with current melanoma diagnostic techniques, could improve the early diagnosis of this malignancy and ultimately decrease the mortality rate of patients

Seawater redox variations during the deposition of the Kimmeridge Clay Formation, United Kingdom (Upper Jurassic): evidence from molybdenum isotopes and trace metal ratios

The Kimmeridge Clay Formation (KCF) and its equivalents worldwide represent one of the most prolonged periods of organic carbon accumulation of the Mesozoic. In this study, we use the molybdenum (Mo) stable isotope system in conjunction with a range of trace metal paleoredox proxies to assess how seawater redox varied both locally and globally during the deposition of the KCF. Facies with lower organic carbon contents (TOC 1–7 wt %) were deposited under mildly reducing (suboxic) conditions, while organic-rich facies (TOC >7 wt %) accumulated under more strongly reducing (anoxic or euxinic) local conditions. Trace metal abundances are closely linked to TOC content, suggesting that the intensity of reducing conditions varied repeatedly during the deposition of the KCF and may have been related to orbitally controlled climate changes. Long-term variations in ?98/95Mo are associated with the formation of organic-rich intervals and are related to third-order fluctuations in relative sea level. Differences in the mean ?98/95Mo composition of the organic-rich intervals suggest that the global distribution of reducing conditions was more extensive during the deposition of the Pectinatites wheatleyensis and lower Pectinatites hudlestoni zones than during the deposition of the upper Pectinatites hudlestoni and Pectinatites pectinatus zones. The global extent of reducing conditions during the Kimmerigidan was greater than today but was less widespread than during the Toarcian (Early Jurassic) oceanic anoxic event. This study also demonstrates that the Mo isotope system in Jurassic seawater responded to changes in redox conditions in a manner consistent with its behavior in present-day sedimentary environment

Field-induced canting of magnetic moments in GdCo5 at finite temperature : first-principles calculations and high-field measurements

We present calculations and experimental measurements of the temperature-dependent magnetization of a single crystal of GdCo5 in magnetic fields of order 60 T. At zero temperature the calculations, based on density-functional theory in the disordered-local-moment picture, predict a field-induced transition from an antiferromagnetic to a canted alignment of Gd and Co moments at 46.1 T. At higher temperatures the calculations find this critical field to increase along with the zerofield magnetization. The experimental measurements observe this transition to occur between 44–48 T at 1.4 K. Up to temperatures of at least 100 K, the experiments continue to observe the transition; however, at variance with the calculations, no strong temperature dependence of the critical field is apparent. We assign this difference to the inaccurate description of the zero-field magnetization of the calculations at low temperatures, due to the use of classical statistical mechanics. Correcting for this effect, we recover a consistent description of the high-field magnetization of GdCo5 from theory and experiment