Brine-driven destruction of clay minerals in Gale crater, Mars.

Mars' sedimentary rock record preserves information on geological (and potential astrobiological) processes that occurred on the planet billions of years ago. The Curiosity rover is exploring the lower reaches of Mount Sharp, in Gale crater on Mars. A traverse from Vera Rubin ridge to Glen Torridon has allowed Curiosity to examine a lateral transect of rock strata laid down in a martian lake ~3.5 billion years ago. We report spatial differences in the mineralogy of time-equivalent sedimentary rocks <400 meters apart. These differences indicate localized infiltration of silica-poor brines, generated during deposition of overlying magnesium sulfate-bearing strata. We propose that destabilization of silicate minerals driven by silica-poor brines (rarely observed on Earth) was widespread on ancient Mars, because sulfate deposits are globally distributed.

Evidence for Multiple Diagenetic Episodes in Ancient Fluvial-Lacustrine Sedimentary Rocks in Gale Crater, Mars.

The Curiosity rover's exploration of rocks and soils in Gale crater has provided diverse geochemical and mineralogical data sets, underscoring the complex geological history of the region. We report the crystalline, clay mineral, and amorphous phase distributions of four Gale crater rocks from an 80-m stratigraphic interval. The mineralogy of the four samples is strongly influenced by aqueous alteration processes, including variations in water chemistries, redox, pH, and temperature. Localized hydrothermal events are evidenced by gray hematite and maturation of amorphous SiO2 to opal-CT. Low-temperature diagenetic events are associated with fluctuating lake levels, evaporative events, and groundwater infiltration. Among all mudstones analyzed in Gale crater, the diversity in diagenetic processes is primarily captured by the mineralogy and X-ray amorphous chemistry of the drilled rocks. Variations indicate a transition from magnetite to hematite and an increase in matrix-associated sulfates suggesting intensifying influence from oxic, diagenetic fluids upsection. Furthermore, diagenetic fluid pathways are shown to be strongly affected by unconformities and sedimentary transitions, as evidenced by the intensity of alteration inferred from the mineralogy of sediments sampled adjacent to stratigraphic contacts.

An actualistic perspective into Archean worlds - (cyano-)bacterially induced sedimentary structures in the siliciclastic Nhlazatse Section, 2.9 Ga Pongola Supergroup, South Africa.

Extensive microbial mats colonize sandy tidal flats that form along the coasts of today's Earth. The microbenthos (mainly cyanobacteria) respond to the prevailing physical sediment dynamics by biostabilization, baffling and trapping, as well as binding. This biotic-physical interaction gives rise to characteristic microbially induced sedimentary structures (MISS) that differ greatly from both purely physical structures and from stromatolites. Actualistic studies of the MISS on modern tidal flats have been shown to be the key for understanding equivalent fossil structures that occur in tidal and shelf sandstones of all Earth ages. However, until now the fossil record of Archean MISS has been poor, and relatively few specimens have been found. This paper describes a study location that displays a unique assemblage with a multitude of exceptionally preserved MISS in the 2.9-Ga-old Pongola Supergroup, South Africa. The 'Nhlazatse Section' includes structures such as 'erosional remnants and pockets', 'multidirected ripple marks', 'polygonal oscillation cracks', and 'gas domes'. Optical and geochemical analyses support the biogenicity of microscopic textures such as filamentous laminae or 'orientated grains'. Textures resembling filaments are lined by iron oxide and hydroxides, as well as clay minerals. They contain organic matter, whose isotope composition is consistent with carbon of biological origin. The ancient tidal flats of the Nhlazatse Section record four microbial mat facies that occur in modern tidal settings as well. We distinguish endobenthic and epibenthic microbial mats, including planar, tufted, and spongy subtypes. Each microbial mat facies is characterized by a distinct set of MISS, and relates to a typical tidal zone. The microbial mat structures are preserved in situ, and are consistent with similar features constructed today by benthic cyanobacteria. However, other mat-constructing microorganisms also could have formed the structures in the Archean tidal flats.

In vitro development of resistance to human immunodeficiency virus protease inhibitor GW640385.

Development of in vitro resistance to GW640385, a new human immunodeficiency virus type 1 protease inhibitor, was studied. Variants characterized included one with <4-fold resistance and amino acid substitutions Q58E/A71V (protease) and P452K (Gag) and one with >50-fold resistance and amino acid substitutions L10F/G16E/E21K/A28S/M46I/F53L/A71V (protease) and L449F/P453T (Gag). The A28S substitution substantially reduced replication capacity.

2-Amino-6-arylsulfonylbenzonitriles as non-nucleoside reverse transcriptase inhibitors of HIV-1.

A series of 2-amino-5-arylthiobenzonitriles (1) was found to be active against HIV-1. Structural modifications led to the sulfoxides (2) and sulfones (3). The sulfoxides generally showed antiviral activity against HIV-1 similar to that of 1. The sulfones, however, were the most potent series of analogues, a number having activity against HIV-1 in the nanomolar range. Structural-activity relationship (SAR) studies suggested that a meta substituent, particularly a meta methyl substituent, invariably increased antiviral activities. However, optimal antiviral activities were manifested by compounds where both meta groups in the arylsulfonyl moiety were substituted and one of the substituents was a methyl group. Such a disubstitution led to compounds 3v, 3w, 3x, and 3y having IC50 values against HIV-1 in the low nanomolar range. When gauged for their broad-spectrum antiviral activity against key non-nucleoside reverse transcriptase inhibitor (NNRTI) related mutants, all the di-meta-substituted sulfones 3u-z and the 2-naphthyl analogue 3ee generally showed single-digit nanomolar activity against the V106A and P236L strains and submicromolar to low nanomolar activity against strains E138K, V108I, and Y188C. However, they showed a lack of activity against the K103N and Y181C mutant viruses. The elucidation of the X-ray crystal structure of the complex of 3v (739W94) in HIV-1 reverse transcriptase showed an overlap in the binding domain when compared with the complex of nevirapine in HIV-1 reverse transcriptase. The X-ray structure allowed for the rationalization of SAR data and potencies of the compounds against the mutants.

Selective adsorption of L- and D-amino acids on calcite: Implications for biochemical homochirality.

The emergence of biochemical homochirality was a key step in the origin of life, yet prebiotic mechanisms for chiral separation are not well constrained. Here we demonstrate a geochemically plausible scenario for chiral separation of amino acids by adsorption on mineral surfaces. Crystals of the common rock-forming mineral calcite (CaCO(3)), when immersed in a racemic aspartic acid solution, display significant adsorption and chiral selectivity of d- and l-enantiomers on pairs of mirror-related crystal-growth surfaces. This selective adsorption is greater on crystals with terraced surface textures, which indicates that d- and l-aspartic acid concentrate along step-like linear growth features. Thus, selective adsorption of linear arrays of d- and l-amino acids on calcite, with subsequent condensation polymerization, represents a plausible geochemical mechanism for the production of homochiral polypeptides on the prebiotic Earth.

Nondestructive, in situ, cellular-scale mapping of elemental abundances including organic carbon in permineralized fossils.

The electron microprobe allows elemental abundances to be mapped at the microm scale, but until now high resolution mapping of light elements has been challenging. Modifications of electron microprobe procedure permit fine-scale mapping of carbon. When applied to permineralized fossils, this technique allows simultaneous mapping of organic material, major matrix-forming elements, and trace elements with microm-scale resolution. The resulting data make it possible to test taphonomic hypotheses for the formation of anatomically preserved silicified fossils, including the role of trace elements in the initiation of silica precipitation and in the prevention of organic degradation. The technique allows one to understand the localization of preserved organic matter before undertaking destructive chemical analyses and, because it is nondestructive, offers a potentially important tool for astrobiological investigations of samples returned from Mars or other solar system bodies.

Perceived versus measured height. Which is the stronger predictor of psychosocial functioning?

The relationship between perceptions versus measured height and children's psychosocial adaptation in a sample of medically referred youth with short stature was investigated. All children referred for a growth evaluation to one regional pediatric endocrinology clinic received a psychosocial screening assessment as a routine component of their initial visit. Data were collected for patients ages 4-18 years (n = 620) with heights ranging from -4.0 to -1.1 SD for age- and gender-adjusted population norms. Patients (8 years and older) and in all cases a parent/guardian served as informant through paper-and-pencil questionnaires. Both children and parents overestimated the child's height. Overestimations of height were associated with greater patient and parent satisfaction with stature. Perceived height was more strongly associated with psychosocial adaptation than was measured height. Clinical management decisions designed to enhance patient quality of life by increasing projected adult height through hormonal interventions should take into account both measured and perceived patient height.

Primordial carbonylated iron-sulfur compounds and the synthesis of pyruvate.

Experiments exploring the potential catalytic role of iron sulfide at 250 degrees C and elevated pressures (50, 100, and 200 megapascals) revealed a facile, pressure-enhanced synthesis of organometallic phases formed through the reaction of alkyl thiols and carbon monoxide with iron sulfide. A suite of organometallic compounds were characterized with ultraviolet-visible and Raman spectroscopy. The natural synthesis of such compounds is anticipated in present-day and ancient environments wherever reduced hydrothermal fluids pass through iron sulfide-containing crust. Here, pyruvic acid was synthesized in the presence of such organometallic phases. These compounds could have provided the prebiotic Earth with critical biochemical functionality.

Novel inhibitors of HIV protease: design, synthesis and biological evaluation of picomolar inhibitors containing cyclic P1/P2 scaffolds.

A novel series of HIV protease inhibitors containing cyclic P1/P2 scaffolds has been synthesized and evaluated for biological activity. The trans 3,5-dibenzyl-2-oxo pyrrolidinone ring system resulted in a 50 pM enzyme inhibitor against HIV protease in vitro when combined with an indanolamine derived P'-backbone. This compound also shows comparable activity to currently marketed drugs in the MT-4 cell-based antiviral assay.

A bone quality-based implant system: first year of prosthetic loading.

This interim report presents the data from a prospective study of BioHorizons, a bone quality-based implant system, with four implant designs. The surgical survival of 975 implants was 99.4%, with the survival 100% for D4 bone. Three critical phases of crestal bone loss have been identified: bone remodeling from stage I to stage II surgery; stage II uncovery to prosthesis delivery (transition period); and prosthesis delivery up to the first year of loading (early loading bone loss). The stage I to stage II uncovery crestal bone remodeling resulted in a mean vertical bone loss of 0.21 mm to 0.36 mm (SD = 0.90 mm), dependent on whether the implant became exposed in the oral cavity during osseous healing. No statistically significant difference was found among the four implant designs, diameter, bone density, or location. The stage II to prosthesis delivery mean vertical bone loss ranged from 0.12 mm to 0.20 mm. One hundred three consecutive patients (partially and totally edentulous) were restored, with 360 implants and 105 prostheses in function for a period of 12 to 26 months. No early loading implant failure occurred, and all patients with implants are in satisfactory to optimum health according to the Misch Implant Quality Scale. The mean early loading bone loss was 0.29 mm (SD = 0.99 mm). Past clinical reports in the literature indicate most failures or crestal bone loss occur by the first year of loading. This study suggests the bone quality based dental implant design minimizes overall implant failure and crestal bone loss, regardless of bone density.

Abiotic nitrogen reduction on the early Earth.

The production of organic precursors to life depends critically on the form of the reactants. In particular, an environment dominated by N2 is far less efficient in synthesizing nitrogen-bearing organics than a reducing environment rich in ammonia. Relatively reducing lithospheric conditions on the early Earth have been presumed to favour the generation of an ammonia-rich atmosphere, but this hypothesis has not been studied experimentally. Here we demonstrate mineral-catalysed reduction of N2, NO2- and NO3- to ammonia at temperatures between 300 and 800 degrees C and pressures of 0.1-0.4 GPa-conditions typical of crustal and oceanic hydrothermal systems. We also show that only N2 is stable above 800 degrees C, thus precluding significant atmospheric ammonia formation during hot accretion. We conclude that mineral-catalysed N2 reduction might have provided a significant source of ammonia to the Hadean ocean. These results also suggest that, whereas nitrogen in the Earth's early atmosphere was present predominantly as N2, exchange with oceanic, hydrothermally derived ammonia could have provided a significant amount of the atmospheric ammonia necessary to resolve the early-faint-Sun paradox.

A bone quality-based implant system: a preliminary report of stage I & stage II.

A system is introduced in which dental implants are specifically designed for containment within four different categories of bone densities. The sizes and the textured surfaces that accompany the gradations of lengths and diameters are standardized for each bone type. A modified thread design focuses on compression of bone rather than on shear, and the geometry of the entire implant body reflects features that are concurrent with a "platform effect." Having been tested by means of finite element analysis and initial animal studies, the results are provided herein for the placement of 364 consecutive implants in five clinical centers on human patients, with surgical survival results of 98.9 percent overall. The initial clinical report of these implants indicates that all bone densities may have similar initial survival rates.

Inhibitors of human immunodeficiency virus type 1 derived from gp41 transmembrane protein: structure--activity studies.

We synthesized analogues of gp41 (553-590), 1, and evaluated them for their inhibitory activity against HIV-1 in MT4 cell assay (IC50(1) = 2.7 microM). (The numbering scheme for gp41 (e.g., gp41(553-590) for 1) adapted throughout the text is from ref 6.) Gradual truncation of either the N- or C-terminal end of gp41 (553-590) resulted in a substantial loss of inhibitory properties of resulting compounds. Unexpectedly, simultaneous truncations of both N- and C-termini of gp41(553-590) resulted in a potent heptadecamer, 13, IC50 = 10.4 microM. Coupling of a racemic alpha-aminotetradecanoic acid (Atd) to gp41 fragments afforded diastereomeric conjugates, most of which were chromatographically separable. In this series, pentadecamer 27 had an IC50 of 8.9 microM, while its Atd diastereomer 28 was much less inhibitory. This finding is consistent with relative inhibitory potencies of other Atd-containing diastereomeric pairs and could reflect a chiral sense of Atd residue interacting with the receptor. Compounds 13 and 27, which are practically equipotent to 1, represent minimalistic fragments of the leucine-zipper region of gp41 and constitute a basis for design of a second generation of gp41-based inhibitors. Circular dichroism studies suggested that compounds in this series are likely to inhibit HIV-1 replication by virtue of their alpha-helical character. The observed structure-activity relationship supports impairment of viral gp41 as a possible mechanism of action of 1.

Antiviral, metabolic, and pharmacokinetic properties of the isomeric dideoxynucleoside 4(S)-(6-amino-9H-purin-9-yl)tetrahydro-2(S)-furanmethanol.

4(S)-(6-Amino-9H-purin-9-yl)tetrahydro-2(S)-furanmethanol (IsoddA) is the most antivirally active member of a novel class of optically active isomeric dideoxynucleosides in which the base has been transposed from the natural 1' position to the 2' position and the absolute configuration is (S,S). IsoddA was active against human immunodeficiency virus type 1 (HIV-1) (strain IIIB), HIV-2 (strain ZY), and HIV-1 clinical isolates. Combinations of the compound with zidovudine (3'-azido-3'-deoxythymidine), 2',3'-dideoxyinosine, or 5-fluoro-2'-deoxy-3'-thiacytidine showed synergistic inhibition of HIV. A moderate reduction of activity was observed with clinical isolates resistant to zidovudine. An IsoddA-resistant virus (eightfold-increased 50% inhibitory concentration) was selected in vitro by repeated passage of HIV-1 (HXB2) in the presence of increasing concentrations of IsoddA. The reverse transcriptase-coding region of the mutant virus contained a single base change resulting in a change at codon 184 from Met to Val. IsoddA was also active against hepatitis B virus (HBV) in vitro; however, it lacked substantial selective activity in an in vivo HBV model. IsoddA was inefficiently phosphorylated in CEM cells; however, the half-life of the triphosphate was 9.4 h, and IsoddATP was a potent inhibitor of HIV-1 reverse transcriptase, with a Ki of 16 nM. The cytotoxicity 50% inhibitory concentrations of IsoddA were greater than 100 microM for CEM, MOLT-4, IM9, and the HepG2-derived HBV-infected 2.2.15 (subclone P5A) cell lines but were 12 and 11 microM for human granulocyte-macrophage (CFU-GM) and erythroid (BFU-E) progenitor cells, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

The extractability of Cr(VI) from contaminated soil in synthetic sweat.

Hexavalent chromium is a common skin irritant that can cause contact dermatitis in sensitized individuals. Soil samples from two chromium waste sites having different Cr(VI) concentrations were extracted in synthetic sweat solutions over a pH range of 4 to 8 and analyzed for Cr(VI). These extractions were performed to determine the potential availability of Cr(VI) from contaminated soils upon contact with human sweat. The samples were also extracted using the EPA Method 3060 alkaline digestion. Overall, hexavalent chromium was readily extractable from both samples in the solutions tested. One of the samples contained Cr(VI) crystals, known as blooms, and had a Cr(VI) concentration approximately 40 times greater than the sample without blooms. The pH of the synthetic sweat solution had little effect on the Cr(VI) concentration determined for the sample containing blooms, whereas the Cr(VI) concentration determined for the sample without blooms increased with increasing pH. The Cr(VI) extracted in the synthetic sweat solutions was consistently lower than the amount extracted by the EPA 3060 alkaline extraction.