Dual-action potential of cationic cryptides against infections and cancers.

Cryptides are a subfamily of bioactive peptides embedded latently in their parent proteins and have multiple biological functions. Cationic cryptides could be used as modern drugs in both infectious diseases and cancers because their mechanism of action is less likely to be affected by genetic mutations in the treated cells, therefore addressing a current unmet need in these two areas of medicine. In this review, we present the current understanding of cryptides, methods to mine them sustainably using available online databases and prediction tools, with a particular focus on their antimicrobial and anticancer potential, and their potential applicability in a clinical setting.

An olivine cumulate outcrop on the floor of Jezero crater, Mars.

The geological units on the floor of Jezero crater, Mars, are part of a wider regional stratigraphy of olivine-rich rocks, which extends well beyond the crater. We investigated the petrology of olivine and carbonate-bearing rocks of the Séítah formation in the floor of Jezero. Using multispectral images and x-ray fluorescence data, acquired by the Perseverance rover, we performed a petrographic analysis of the Bastide and Brac outcrops within this unit. We found that these outcrops are composed of igneous rock, moderately altered by aqueous fluid. The igneous rocks are mainly made of coarse-grained olivine, similar to some martian meteorites. We interpret them as an olivine cumulate, formed by settling and enrichment of olivine through multistage cooling of a thick magma body.

Fluvial Depositional Systems of the African Humid Period: An Analog for an Early, Wet Mars in the Eastern Sahara.

A widely hypothesized but complex transition from widespread fluvial activity to predominantly aeolian processes is inferred on Mars based on remote sensing data observations of ancient landforms. However, the lack of analysis of in situ martian fluvial deposits hinders our understanding of the flow regime nature and sustainability of the martian fluvial activity and the hunt for ancient life. Studying analogs from arid zones on Earth is fundamental to quantitatively understanding geomorphic processes and climate drivers that might have dominated during early Mars. Here we investigate the formation and preservation of fluvial depositional systems in the eastern Sahara, where the largest arid region on Earth hosts important repositories of past climatic changes. The fluvial systems are composed of well-preserved single-thread sinuous to branching ridges and fan-shaped deposits interpreted as deltas. The systems' configuration and sedimentary content suggest that ephemeral rivers carved these landforms by sequential intermittent episodes of erosion and deposition active for 10-100s years over ∼10,000 years during the late Quaternary. Subsequently, these landforms were sculpted by a marginal role of rainfall and aeolian processes with minimum erosion rates of 1.1 ± 0.2 mm/yr, supplying ∼96 ± 24 × 1010 m3 of disaggregated sediment to adjacent aeolian dunes. Our results imply that similar martian fluvial systems preserving single-thread, short distance source-to-sink courses may have formed due to transient drainage networks active over short durations. Altogether, this study adds to the growing recognition of the complexity of interpreting climate history from orbital images of landforms.

The Mars Environmental Dynamics Analyzer, MEDA. A Suite of Environmental Sensors for the Mars 2020 Mission.

NASA's Mars 2020 (M2020) rover mission includes a suite of sensors to monitor current environmental conditions near the surface of Mars and to constrain bulk aerosol properties from changes in atmospheric radiation at the surface. The Mars Environmental Dynamics Analyzer (MEDA) consists of a set of meteorological sensors including wind sensor, a barometer, a relative humidity sensor, a set of 5 thermocouples to measure atmospheric temperature at ∼1.5 m and ∼0.5 m above the surface, a set of thermopiles to characterize the thermal IR brightness temperatures of the surface and the lower atmosphere. MEDA adds a radiation and dust sensor to monitor the optical atmospheric properties that can be used to infer bulk aerosol physical properties such as particle size distribution, non-sphericity, and concentration. The MEDA package and its scientific purpose are described in this document as well as how it responded to the calibration tests and how it helps prepare for the human exploration of Mars. A comparison is also presented to previous environmental monitoring payloads landed on Mars on the Viking, Pathfinder, Phoenix, MSL, and InSight spacecraft.

Deposits from giant floods in Gale crater and their implications for the climate of early Mars.

This study reports in-situ sedimentologic evidence of giant floods in Gale crater, Mars, during the Noachian Period. Features indicative of floods are a series of symmetrical, 10 m-high gravel ridges that occur in the Hummocky Plains Unit (HPU). Their regular spacing, internal sedimentary structures, and bedload transport of fragments as large as 20 cm suggest that these ridges are antidunes: a type of sedimentary structure that forms under very strong flows. Their 150 m wavelength indicates that the north-flowing water that deposited them was at least 24 m deep and had a minimum velocity of 10 m/s. Floods waned rapidly, eroding antidune crests, and re-deposited removed sediments as patches on the up-flow limbs and trough areas between these ridges forming the Striated Unit (SU). Each patch of the SU is 50-200 m wide and long and consists of 5-10 m of south-dipping layers. The strike and dip of the SU layers mimic the attitude of the flank of the antidune on which they were deposited. The most likely mechanism that generated flood waters of this magnitude on a planet whose present-day average temperature is - 60 °C was the sudden heat produced by a large impact. The event vaporized frozen reservoirs of water and injected large amounts of CO2 and CH4 from their solid phases into the atmosphere. It temporarily interrupted a cold and dry climate and generated a warm and wet period. Torrential rainfall occurred planetwide some of which entered Gale crater and combined with water roaring down from Mt. Sharp to cause gigantic flash floods that deposited the SU and the HPU on Aeolis Palus. The warm and wet climate persisted even after the flooding ended, but its duration cannot be determined by our study.

Author Correction: Unprecedented rains decimate surface microbial communities in the hyperarid core of the Atacama Desert.

A correction to this article has been published and is linked from the HTML and PDF versions of this paper. The error has not been fixed in the paper.

Unprecedented rains decimate surface microbial communities in the hyperarid core of the Atacama Desert.

The hyperarid core of the Atacama Desert, the driest and oldest desert on Earth, has experienced a number of highly unusual rain events over the past three years, resulting in the formation of previously unrecorded hypersaline lagoons, which have lasted several months. We have systematically analyzed the evolution of the lagoons to provide quantitative field constraints of large-scale impacts of the rains on the local microbial communities. Here we show that the sudden and massive input of water in regions that have remained hyperarid for millions of years is harmful for most of the surface soil microbial species, which are exquisitely adapted to survive with meager amounts of liquid water, and quickly perish from osmotic shock when water becomes suddenly abundant. We found that only a handful of bacteria, remarkably a newly identified species of Halomonas, remain metabolically active and are still able to reproduce in the lagoons, while no archaea or eukaryotes were identified. Our results show that the already low microbial biodiversity of extreme arid regions greatly diminishes when water is supplied quickly and in great volumes. We conclude placing our findings in the context of the astrobiological exploration of Mars, a hyperarid planet that experienced catastrophic floodings in ancient times.

Redox stratification of an ancient lake in Gale crater, Mars.

In 2012, NASA's Curiosity rover landed on Mars to assess its potential as a habitat for past life and investigate the paleoclimate record preserved by sedimentary rocks inside the ~150-kilometer-diameter Gale impact crater. Geological reconstructions from Curiosity rover data have revealed an ancient, habitable lake environment fed by rivers draining into the crater. We synthesize geochemical and mineralogical data from lake-bed mudstones collected during the first 1300 martian solar days of rover operations in Gale. We present evidence for lake redox stratification, established by depth-dependent variations in atmospheric oxidant and dissolved-solute concentrations. Paleoclimate proxy data indicate that a transition from colder to warmer climate conditions is preserved in the stratigraphy. Finally, a late phase of geochemical modification by saline fluids is recognized.

Quantifying Fenton reaction pathways driven by self-generated H2O2 on pyrite surfaces.

Oxidation of pyrite (FeS2) plays a significant role in the redox cycling of iron and sulfur on Earth and is the primary cause of acid mine drainage (AMD). It has been established that this process involves multi-step electron-transfer reactions between surface defects and adsorbed O2 and H2O, releasing sulfoxy species (e.g., S2O32-, SO42-) and ferrous iron (Fe2+) to the solution and also producing intermediate by-products, such as hydrogen peroxide (H2O2) and other reactive oxygen species (ROS), however, our understanding of the kinetics of these transient species is still limited. We investigated the kinetics of H2O2 formation in aqueous suspensions of FeS2 microparticles by monitoring, in real time, the H2O2 and dissolved O2 concentration under oxic and anoxic conditions using amperometric microsensors. Additional spectroscopic and structural analyses were done to track the dependencies between the process of FeS2 dissolution and the degradation of H2O2 through the Fenton reaction. Based on our experimental results, we built a kinetic model which explains the observed trend of H2O2, showing that FeS2 dissolution can act as a natural Fenton reagent, influencing the oxidation of third-party species during the long term evolution of geochemical systems, even in oxygen-limited environments.

Organic molecules in the Sheepbed Mudstone, Gale Crater, Mars.

The Sample Analysis at Mars (SAM) instrument on board the Mars Science Laboratory Curiosity rover is designed to conduct inorganic and organic chemical analyses of the atmosphere and the surface regolith and rocks to help evaluate the past and present habitability potential of Mars at Gale Crater. Central to this task is the development of an inventory of any organic molecules present to elucidate processes associated with their origin, diagenesis, concentration, and long-term preservation. This will guide the future search for biosignatures. Here we report the definitive identification of chlorobenzene (150-300 parts per billion by weight (ppbw)) and C2 to C4 dichloroalkanes (up to 70 ppbw) with the SAM gas chromatograph mass spectrometer (GCMS) and detection of chlorobenzene in the direct evolved gas analysis (EGA) mode, in multiple portions of the fines from the Cumberland drill hole in the Sheepbed mudstone at Yellowknife Bay. When combined with GCMS and EGA data from multiple scooped and drilled samples, blank runs, and supporting laboratory analog studies, the elevated levels of chlorobenzene and the dichloroalkanes cannot be solely explained by instrument background sources known to be present in SAM. We conclude that these chlorinated hydrocarbons are the reaction products of Martian chlorine and organic carbon derived from Martian sources (e.g., igneous, hydrothermal, atmospheric, or biological) or exogenous sources such as meteorites, comets, or interplanetary dust particles. KEY POINTS: First in situ evidence of nonterrestrial organics in Martian surface sediments Chlorinated hydrocarbons identified in the Sheepbed mudstone by SAM Organics preserved in sample exposed to ionizing radiation and oxidative condition.

Ancient aqueous environments at Endeavour crater, Mars.

Opportunity has investigated in detail rocks on the rim of the Noachian age Endeavour crater, where orbital spectral reflectance signatures indicate the presence of Fe(+3)-rich smectites. The signatures are associated with fine-grained, layered rocks containing spherules of diagenetic or impact origin. The layered rocks are overlain by breccias, and both units are cut by calcium sulfate veins precipitated from fluids that circulated after the Endeavour impact. Compositional data for fractures in the layered rocks suggest formation of Al-rich smectites by aqueous leaching. Evidence is thus preserved for water-rock interactions before and after the impact, with aqueous environments of slightly acidic to circum-neutral pH that would have been more favorable for prebiotic chemistry and microorganisms than those recorded by younger sulfate-rich rocks at Meridiani Planum.

Volatile and organic compositions of sedimentary rocks in Yellowknife Bay, Gale crater, Mars.

H2O, CO2, SO2, O2, H2, H2S, HCl, chlorinated hydrocarbons, NO, and other trace gases were evolved during pyrolysis of two mudstone samples acquired by the Curiosity rover at Yellowknife Bay within Gale crater, Mars. H2O/OH-bearing phases included 2:1 phyllosilicate(s), bassanite, akaganeite, and amorphous materials. Thermal decomposition of carbonates and combustion of organic materials are candidate sources for the CO2. Concurrent evolution of O2 and chlorinated hydrocarbons suggests the presence of oxychlorine phase(s). Sulfides are likely sources for sulfur-bearing species. Higher abundances of chlorinated hydrocarbons in the mudstone compared with Rocknest windblown materials previously analyzed by Curiosity suggest that indigenous martian or meteoritic organic carbon sources may be preserved in the mudstone; however, the carbon source for the chlorinated hydrocarbons is not definitively of martian origin.

Non-synaptic dendritic spines in neocortex.

A long-held assumption states that each dendritic spine in the cerebral cortex forms a synapse, although this issue has not been systematically investigated. We performed complete ultrastructural reconstructions of a large (n=144) population of identified spines in adult mouse neocortex finding that only 3.6% of the spines clearly lacked synapses. Nonsynaptic spines were small and had no clear head, resembling dendritic filopodia, and could represent a source of new synaptic connections in the adult cerebral cortex.

Pioneering a golden age of cerebral microcircuits: the births of the combined Golgi-electron microscope methods.

Theodor W. Blackstad devised methods by which the synaptic connectivity of neuron somata and their dendritic and axonal processes in the CNS could be analyzed by the combined use of light and electron microscope techniques. His first publication on that subject dates from 1965 and was contemporary to the independent research by William K. Stell. The Golgi method was an obvious neuronal marker at those times, and Blackstad and Stell showed that the Golgi precipitate is electron-dense and intracellular and, therefore, it could help identify in the electron microscope, with great accuracy, profiles of neurons initially visualized in light microscopy. Besides this convergent research, Blackstad demonstrated for the first time that anterograde axonal degeneration could be combined with the Golgi-electron microscope method, allowing the identification of the neurons whose dendritic or somatic profiles were postsynaptic to the severed axonal afferent projections. Last, but not least, Blackstad pioneered de-impregnation techniques for electron microscopy of Golgi preparations. This had a great impact in the study of synaptic circuitry. The present account is a remembrance of the events that linked these early attempts with the development of a de-impregnation method based on gold toning by Alan Peters and the present author.

Expression and distribution of metabotropic GABA receptor subtypes GABABR1 and GABABR2 during rat neocortical development.

To understand the possible contribution of metabotropic gamma-aminobutyric acid receptors (GABABR) in cortical development, we investigated the expression pattern and the cellular and subcellular localization of the GABABR1 and GABABR2 subtypes in the rat neocortex from embryonic day 14 (E14) to adulthood. At the light microscopic level, both GABABR1 and GABABR2 were detected as early as E14. During prenatal development, both subtypes were expressed highly in the cortical plate. Using double immunofluorescence, GABABR1 colocalized with GABABR2 in neurons of the marginal zone and subplate, indicating that these proteins are coexpressed and could be forming functional GABABRs during prenatal development in vivo. In contrast, only GABABR1 but not GABABR2 was detected in the tangentially migratory cells in the lower intermediate zone. During postnatal development, immunoreactivity for GABABR1 and GABABR2 was distributed mainly in pyramidal cells. Discrete GABABR1-immunopositive cell bodies of interneurons were present throughout the neocortex. In addition, GABABR1 but not GABABR2 was found in identified Cajal-Retzius cells in layer I. At the electron microscopic level, immunoreactivity for GABABR1 and GABABR2 was found in dendritic spines and dendritic shafts at extrasynaptic and perisynaptic sites throughout postnatal development. We further demonstrated the presynaptic localization of GABABR1 and GABABR2, as well as the association of the receptors with asymmetrical synaptic junctions. These results indicate potentially important roles for the GABABRs in the regulation of migratory processes during corticogenesis and in the modulation of synaptic transmission during early development of cortical circuitry.

Differential distribution of group I metabotropic glutamate receptors during rat cortical development.

Neurons in the rat cerebral cortex are enriched in group I metabotropic glutamate receptor (mGluR) subtypes and respond to their activation during development. To understand better the mechanisms by which mGluR1 and mGluR5 mediate these effects, the goal of this study was to elucidate the expression pattern and to determine the cellular and the precise subcellular localization of these two receptor subtypes in the rat neocortex and hippocampus during late prenatal and postnatal development. At the light microscopic level, mGluR1alpha and mGluR5 were first detected in the cerebral cortex with different expression levels at embryonic day E18. Thus, mGluR5 had a moderate expression, whereas mGluR1alpha was detected as a diffuse and weak labeling. mGluR5 was localized in some Cajal- Retzius cells as well as in other cell types, such as pioneer neurons of the marginal zone. During postnatal development, the distribution of the receptors dramatically changed. From P0 to around P10, mGluR1alpha was localized in identified, transient Cajal-Retzius cells of neocortex and hippocampus, until these cells disappear. In addition, a population of interneurons localized the receptor from the second/third postnatal week. In contrast, mGluR5 was localized mainly in pyramidal cells and in some interneurons, with a neuropilar staining throughout the cerebral cortex. At the electron microscopic level, the immunoreactivity for both group I mGluR subtypes was expressed postsynaptically. Using immunogold methods, mGluR1alpha and mGluR5 immunoreactivities were found throughout postnatal development at the edge of postsynaptic specialization of asymmetrical synapses. These results show that the two group I mGluRs have a differential expression pattern in neocortex and hippocampus that may suggest roles for the receptors in the early processing of cortical information and in the control of cortical developmental events.

Cajal-Retzius cells in early postnatal mouse cortex selectively express functional metabotropic glutamate receptors.

Glutamate receptors have been linked to the regulation of several developmental events in the CNS. By using cortical slices of early postnatal mice, we show that in layer I cells, glutamate produces intracellular calcium ([Ca(2+)](i)) elevations mediated by ionotropic and metabotropic glutamate receptors (mGluRs). The contribution of mGluRs to these responses was demonstrated by application of tACPD, an agonist to groups I and II mGluRs, which evoked [Ca(2+)](i) increases that could be reversibly blocked by MCPG, an antagonist to groups I and II mGluRs. In the absence of extracellular Ca(2+), repetitive applications of tACPD or quisqualate, an agonist to group I mGluRs, elicited decreasing [Ca(2+)](i) responses that were restored by refilling a thapsigargin-sensitive Ca(2+) store. The use of specific group I mGluR agonists CHPG and DHPG indicated that the functional mGluR in layer I was of the mGluR1 subtype. Subtype specific antibodies confirmed the presence of mGlur1 alpha, but not mGluR5, in Cajal-Retzius (Reelin-immunoreactive) neurons.

Whole-mount confocal immunofluorescence of mammalian CNS.

Bright-field wholemount labeling techniques applied to the mammalian central nervous system (CNS) offer advantages over conventional methods based on sections since an immediate and three-dimensional view of the stained components is provided. It thereby becomes possible to survey and count large number of cells and fibers in their natural relationships. The ability of confocal laser scanning microscopy to visualize in one focal plane the fluorescence associated with multiple markers could be most valuable by the availability of reliable wholemount fluorescent techniques. Accordingly, based in our previously published bright-field wholemount protocols [Brain Res. Prot. 2 (1998) 165-173], we have devised an effective immmunofluorescence wholemount procedure. We show that reliable wholemount fluorescent staining can be obtained using isolated complete CNS aged up to rat embryonic day 17, with antibodies penetration in the millimeter range. Examples are shown of preparations in which colocalization can be observed in nerve cells of cytoskeletal and calcium-binding proteins.

Cellular mosaics in the rat marginal zone define an early neocortical territorialization.

We describe a novel neuronal group of the neocortical primordium that is formed by the pioneer neurons, unlike the Cajal-Retzius cells and the subplate component of the preplate. These pioneer neurons of the preplate and the marginal zone send transient axonal projections into the nascent internal capsule, preceding the formation of the axonal projection from the subplate neurons. In wholemount preparations, the pioneer neurons of the preplate and the marginal zone cover the prospective neocortical territory from embryonic day (E) 12 to E17. Two subpopulations of pioneer neurons (defined by differential expression of calcium-binding proteins) group into well-defined cell clusters, separated by spaces containing a lower packing density of cells immunoreactive to the corresponding calcium-binding protein. In both cases, cell clustering was concomitant with fasciculation of their axons. Although both subpopulations cohabit in the same areas of the marginal zone, their clustering occurs in specific, well-delineated territories, giving a mosaic appearance to the surface of the neocortical primordium before the arrival of thalamocortical axons. We hypothesize that the fascicles of descending axons arising from defined territories of the marginal zone may intervene in the initial guidance of the subcortical projection from the subplate.