Silica in a Mars analog environment: Ka'u Desert, Kilauea Volcano, Hawaii

Airborne Visible/Near-Infrared Imaging Spectrometer (AVIRIS) data acquired over the Ka'u Desert are atmospherically corrected to ground reflectance and used to identify the mineralogic components of relatively young basaltic materials, including 250–700 and 200–400 year old lava flows, 1971 and 1974 flows, ash deposits, and solfatara incrustations. To provide context, a geologic surface units map is constructed, verified with field observations, and supported by laboratory analyses. AVIRIS spectral end-members are identified in the visible (0.4 to 1.2 μm) and short wave infrared (2.0 to 2.5 μm) wavelength ranges. Nearly all the spectral variability is controlled by the presence of ferrous and ferric iron in such minerals as pyroxene, olivine, hematite, goethite, and poorly crystalline iron oxides or glass. A broad, nearly ubiquitous absorption feature centered at 2.25 μm is attributed to opaline (amorphous, hydrated) silica and is found to correlate spatially with mapped geologic surface units. Laboratory analyses show the silica to be consistently present as a deposited phase, including incrustations downwind from solfatara vents, cementing agent for ash duricrusts, and thin coatings on the youngest lava flow surfaces. A second, Ti-rich upper coating on young flows also influences spectral behavior. This study demonstrates that secondary silica is mobile in the Ka'u Desert on a variety of time scales and spatial domains. The investigation from remote, field, and laboratory perspectives also mimics exploration of Mars using orbital and landed missions, with important implications for spectral characterization of coated basalts and formation of opaline silica in arid, acidic alteration environments

Potent inhibition of microRNA in vivo without degradation

Chemically modified antisense oligonucleotides (ASOs) are widely used as a tool to functionalize microRNAs (miRNAs). Reduction of miRNA level after ASO inhibition is commonly reported to show efficacy. Whether this is the most relevant endpoint for measuring miRNA inhibition has not been adequately addressed in the field although it has important implications for evaluating miRNA targeting studies. Using a novel approach to quantitate miRNA levels in the presence of excess ASO, we have discovered that the outcome of miRNA inhibition can vary depending on the chemical modification of the ASO. Although some miRNA inhibitors cause a decrease in mature miRNA levels, we have identified a novel 2′-fluoro/2′-methoxyethyl modified ASO motif with dramatically improved in vivo potency which does not. These studies show there are multiple mechanisms of miRNA inhibition by ASOs and that evaluation of secondary endpoints is crucial for interpreting miRNA inhibition studies

TricycloDNA-modified oligo-2′-deoxyribonucleotides reduce scavenger receptor B1 mRNA in hepatic and extra-hepatic tissues—a comparative study of oligonucleotide length, design and chemistry

We report the evaluation of 20-, 18-, 16- and 14-mer phosphorothioate (PS)-modified tricycloDNA (tcDNA) gapmer antisense oligonucleotides (ASOs) in Tm, cell culture and animal experiments and compare them to their gap-matched 20-mer 2′-O-methoxyethyl (MOE) and 14-mer 2′,4′-constrained ethyl (cEt) counterparts. The sequence-matched 20-mer tcDNA and MOE ASOs showed similar Tm and activity in cell culture under free-uptake and cationic lipid-mediated transfection conditions, while the 18-, 16- and 14-mer tcDNA ASOs were moderate to significantly less active. These observations were recapitulated in the animal experiments where the 20-mer tcDNA ASO formulated in saline showed excellent activity (ED50 3.9 mg/kg) for reducing SR-B1 mRNA in liver. The tcDNA 20-mer ASO also showed better activity than the MOE 20-mer in several extra-hepatic tissues such as kidney, heart, diaphragm, lung, fat, gastrocnemius and quadriceps. Interestingly, the 14-mer cEt ASO showed the best activity in the animal experiments despite significantly lower Tm and 5-fold reduced activity in cell culture relative to the 20-mer tcDNA and MOE-modified ASOs. Our experiments establish tcDNA as a useful modification for antisense therapeutics and highlight the role of chemical modifications in influencing ASO pharmacology and pharmacokinetic properties in animal

Identification of hydrated silicate minerals on Mars using MRO-CRISM: Geologic context near Nili Fossae and implications for aqueous alteration

The Noachian terrain west of the Isidis basin hosts a diverse collection of alteration minerals in rocks comprising varied geomorphic units within a 100,000 km2 region in and near the Nili Fossae. Prior investigations in this region by the Observatoire pour l'Minéralogie, l'Eau, les Glaces, et l'Activité (OMEGA) instrument on Mars Express revealed large exposures of both mafic minerals and iron magnesium phyllosilicates in stratigraphic context. Expanding on the discoveries of OMEGA, the Compact Reconnaissance Imaging Spectrometer for Mars (CRISM) aboard the Mars Reconnaissance Orbiter (MRO) has found more spatially widespread and mineralogically diverse alteration minerals than previously realized, which represent multiple aqueous environments. Using CRISM near-infrared spectral data, we detail the basis for identification of iron and magnesium smectites (including both nontronite and more Mg-rich varieties), chlorite, prehnite, serpentine, kaolinite, potassium mica (illite or muscovite), hydrated (opaline) silica, the sodium zeolite analcime, and magnesium carbonate. The detection of serpentine and analcime on Mars is reported here for the first time. We detail the geomorphic context of these minerals using data from high-resolution imagers onboard MRO in conjunction with CRISM. We find that the distribution of alteration minerals is not homogeneous; rather, they occur in provinces with distinctive assemblages of alteration minerals. Key findings are (1) a distinctive stratigraphy, in and around the Nili Fossae, of kaolinite and magnesium carbonate in bedrock units always overlying Fe/Mg smectites and (2) evidence for mineral phases and assemblages indicative of low-grade metamorphic or hydrothermal aqueous alteration in cratered terrains. The alteration minerals around the Nili Fossae are more typical of those resulting from neutral to alkaline conditions rather than acidic conditions, which appear to have dominated much of Mars. Moreover, the mineralogic diversity and geologic context of alteration minerals found in the region around the Nili Fossae indicates several episodes of aqueous activity in multiple distinct environments

Phyllosilicate Diversity and Past Aqueous Activity Revealed at Mawrth Vallis, Mars

Observations by the Mars Reconnaissance Orbiter/Compact Reconnaissance Imaging Spectrometer for Mars in the Mawrth Vallis region show several phyllosilicate species, indicating a wide range of past aqueous activity. Iron/magnesium (Fe/Mg)–smectite is observed in light-toned outcrops that probably formed via aqueous alteration of basalt of the ancient cratered terrain. This unit is overlain by rocks rich in hydrated silica, montmorillonite, and kaolinite that may have formed via subsequent leaching of Fe and Mg through extended aqueous events or a change in aqueous chemistry. A spectral feature attributed to an Fe^(2+) phase is present in many locations in the Mawrth Vallis region at the transition from Fe/Mg-smectite to aluminum/silicon (Al/Si)–rich units. Fe^(2+)-bearing materials in terrestrial sediments are typically associated with microorganisms or changes in pH or cations and could be explained here by hydrothermal activity. The stratigraphy of Fe/Mg-smectite overlain by a ferrous phase, hydrated silica, and then Al-phyllosilicates implies a complex aqueous history

Synthesis of 1-(2-aminopropyl)benzimidazoles, structurally related to the TIBO derivative R82150, with activity against human immunodeficiency virus.

A number of 1-(2-aminopropyl)-2-mercaptobenzimidazoles related to the TIBO derivatives R82150 have been prepared and tested for their activity against human immunodeficiency virus type 1 (HIV-1). These compounds were all modest inhibitors of the cytophatic effects of HIV-1 in vitro, but only very weak inhibitors of HIV-1 reverse transcriptase (RT).A number of 1-(2-aminopropyl)-2-mercaptobenzimidazole derivatives related to the TIBO derivative R82150 have been prepared and tested for their activity against human immunodeficiency virus type 1 (HIV-1). These compounds are all modest inhibitors of the cytopathic effects of HIV-1 in vitro, but were only weak inhibitors of HIV-1 reverse transcriptase (RT).Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/30886/1/0000555.pd

Clay Bearing Units in the Region around Mawrth Vallis: Stratigraphy, Extent, and Possible Alteration Fronts

The largest exposure of phyllosilicates on Mars occurs on the highland plains around Mawrth Vallis. This exposure extends for about 300 km southward from the edge of the dichotomy boundary, covering an area greater than 200 x 300 kilometers over an elevation range of approximately 2000 meters. At least two different types of hydrated phyllosilicates (Fe/Mg-rich and Al-rich phyllosilicates) have been identified in OMEGA data based on absorption bands near 2.3 and 2.2 micrometers, respectively. These clay-bearing units are associated with layered, indurated light-toned units with complex spatial and stratigraphic relationships, and are unconfomably overlain by a darker, indurated, more heavily cratered unit. Ongoing analysis of OMEGA (approximately 1 kilometer/pixel) and CRISM multi-spectral (MSP, 200 meters/pixel) data reveal hydrated minerals with absorptions at approximately 2.2 or 2.3 micrometers in locations up to 300 kilometers away from the borders of the previously identified extent of clay-bearing units. We seek to: 1) further constrain the mineralogy of the hydrated species identified in [5], and 2) understand spatial and stratigraphic relationships between the different hydrated minerals and the cratered plains units in which they are found. In this work we perform mineralogical and stratigraphic comparisons between units to test whether these extended units may be related, in order to establish a broad zone of alteration

Columbus crater and other possible groundwater-fed paleolakes of Terra Sirenum, Mars

Columbus crater in the Terra Sirenum region of the Martian southern highlands contains light-toned layered deposits with interbedded sulfate and phyllosilicate minerals, a rare occurrence on Mars. Here we investigate in detail the morphology, thermophysical properties, mineralogy, and stratigraphy of these deposits; explore their regional context; and interpret the crater's aqueous history. Hydrated mineral-bearing deposits occupy a discrete ring around the walls of Columbus crater and are also exposed beneath younger materials, possibly lava flows, on its floor. Widespread minerals identified in the crater include gypsum, polyhydrated and monohydrated Mg/Fe-sulfates, and kaolinite; localized deposits consistent with montmorillonite, Fe/Mg-phyllosilicates, jarosite, alunite, and crystalline ferric oxide or hydroxide are also detected. Thermal emission spectra suggest abundances of these minerals in the tens of percent range. Other craters in northwest Terra Sirenum also contain layered deposits and Al/Fe/Mg-phyllosilicates, but sulfates have so far been found only in Columbus and Cross craters. The region's intercrater plains contain scattered exposures of Al-phyllosilicates and one isolated mound with opaline silica, in addition to more common Fe/Mg-phyllosilicates with chlorides. A Late Noachian age is estimated for the aqueous deposits in Columbus, coinciding with a period of inferred groundwater upwelling and evaporation, which (according to model results reported here) could have formed evaporites in Columbus and other craters in Terra Sirenum. Hypotheses for the origin of these deposits include groundwater cementation of crater-filling sediments and/or direct precipitation from subaerial springs or in a deep (∼900 m) paleolake. Especially under the deep lake scenario, which we prefer, chemical gradients in Columbus crater may have created a habitable environment at this location on early Mars

A synthesis of Martian aqueous mineralogy after 1 Mars year of observations from the Mars Reconnaissance Orbiter

Martian aqueous mineral deposits have been examined and characterized using data acquired during Mars Reconnaissance Orbiter's (MRO) primary science phase, including Compact Reconnaissance Imaging Spectrometer for Mars hyperspectral images covering the 0.4–3.9 μm wavelength range, coordinated with higher–spatial resolution HiRISE and Context Imager images. MRO's new high-resolution measurements, combined with earlier data from Thermal Emission Spectrometer; Thermal Emission Imaging System; and Observatoire pour la Minéralogie, L'Eau, les Glaces et l'Activitié on Mars Express, indicate that aqueous minerals are both diverse and widespread on the Martian surface. The aqueous minerals occur in 9–10 classes of deposits characterized by distinct mineral assemblages, morphologies, and geologic settings. Phyllosilicates occur in several settings: in compositionally layered blankets hundreds of meters thick, superposed on eroded Noachian terrains; in lower layers of intracrater depositional fans; in layers with potential chlorides in sediments on intercrater plains; and as thousands of deep exposures in craters and escarpments. Carbonate-bearing rocks form a thin unit surrounding the Isidis basin. Hydrated silica occurs with hydrated sulfates in thin stratified deposits surrounding Valles Marineris. Hydrated sulfates also occur together with crystalline ferric minerals in thick, layered deposits in Terra Meridiani and in Valles Marineris and together with kaolinite in deposits that partially infill some highland craters. In this paper we describe each of the classes of deposits, review hypotheses for their origins, identify new questions posed by existing measurements, and consider their implications for ancient habitable environments. On the basis of current data, two to five classes of Noachian-aged deposits containing phyllosilicates and carbonates may have formed in aqueous environments with pH and water activities suitable for life

Competition for RISC binding predicts in vitro potency of siRNA

Short interfering RNAs (siRNA) guide degradation of target RNA by the RNA-induced silencing complex (RISC). The use of siRNA in animals is limited partially due to the short half-life of siRNAs in tissues. Chemically modified siRNAs are necessary that maintain mRNA degradation activity, but are more stable to nucleases. In this study, we utilized alternating 2′-O-methyl and 2′-deoxy-2′-fluoro (OMe/F) chemically modified siRNA targeting PTEN and Eg5. OMe/F-modified siRNA consistently reduced mRNA and protein levels with equal or greater potency and efficacy than unmodified siRNA. We showed that modified siRNAs use the RISC mechanism and lead to cleavage of target mRNA at the same position as unmodified siRNA. We further demonstrated that siRNAs can compete with each other, where highly potent siRNAs can compete with less potent siRNAs, thus limiting the ability of siRNAs with lower potency to mediate mRNA degradation. In contrast, a siRNA with low potency cannot compete with a highly efficient siRNA. We established a correlation between siRNA potency and ability to compete with other siRNAs. Thus, siRNAs that are more potent inhibitors for mRNA destruction have the potential to out-compete less potent siRNAs indicating that the amount of a cellular component, perhaps RISC, limits siRNA activity