The lithospheric-to-lower-mantle carbon cycle recorded in superdeep diamonds.

The transport of carbon into Earth's mantle is a critical pathway in Earth's carbon cycle, affecting both the climate and the redox conditions of the surface and mantle. The largest unconstrained variables in this cycle are the depths to which carbon in sediments and altered oceanic crust can be subducted and the relative contributions of these reservoirs to the sequestration of carbon in the deep mantle1. Mineral inclusions in sublithospheric, or 'superdeep', diamonds (derived from depths greater than 250 kilometres) can be used to constrain these variables. Here we present oxygen isotope measurements of mineral inclusions within diamonds from Kankan, Guinea that are derived from depths extending from the lithosphere to the lower mantle (greater than 660 kilometres). These data, combined with the carbon and nitrogen isotope contents of the diamonds, indicate that carbonated igneous oceanic crust, not sediment, is the primary carbon-bearing reservoir in slabs subducted to deep-lithospheric and transition-zone depths (less than 660 kilometres). Within this depth regime, sublithospheric inclusions are distinctly enriched in 18O relative to eclogitic lithospheric inclusions derived from crustal protoliths. The increased 18O content of these sublithospheric inclusions results from their crystallization from melts of carbonate-rich subducted oceanic crust. In contrast, lower-mantle mineral inclusions and their host diamonds (deeper than 660 kilometres) have a narrow range of isotopic values that are typical of mantle that has experienced little or no crustal interaction. Because carbon is hosted in metals, rather than in diamond, in the reduced, volatile-poor lower mantle2, carbon must be mobilized and concentrated to form lower-mantle diamonds. Our data support a model in which the hydration of the uppermost lower mantle by subducted oceanic lithosphere destabilizes carbon-bearing metals to form diamond, without disturbing the ambient-mantle stable-isotope signatures. This transition from carbonate slab melting in the transition zone to slab dehydration in the lower mantle supports a lower-mantle barrier for carbon subduction.

The upper limb of Paranthropus boisei from Ileret, Kenya.

Paranthropus boisei was first described in 1959 based on fossils from the Olduvai Gorge and now includes many fossils from Ethiopia to Malawi. Knowledge about its postcranial anatomy has remained elusive because, until recently, no postcranial remains could be reliably attributed to this taxon. Here, we report the first associated hand and upper limb skeleton (KNM-ER 47000) of P. boisei from 1.51 to 1.53 Ma sediments at Ileret, Kenya. While the fossils show a combination of primitive and derived traits, the overall anatomy is characterized by primitive traits that resemble those found in Australopithecus, including an oblique scapular spine, relatively long and curved ulna, lack of third metacarpal styloid process, gracile thumb metacarpal, and curved manual phalanges. Very thick cortical bone throughout the upper limb shows that P. boisei had great upper limb strength, supporting hypotheses that this species spent time climbing trees, although probably to a lesser extent than earlier australopiths. Hand anatomy shows that P. boisei, like earlier australopiths, was capable of the manual dexterity needed to create and use stone tools, but lacked the robust thumb of Homo erectus, which arguably reflects adaptations to the intensification of precision grips and tool use. KNM-ER 47000 provides conclusive evidence that early Pleistocene hominins diverged in postcranial and craniodental anatomy, supporting hypotheses of competitive displacement among these contemporaneous hominins.

Electron-ion equilibration in ultrafast heated graphite.

We have employed fast electrons produced by intense laser illumination to isochorically heat thermal electrons in solid density carbon to temperatures of ∼10,000 K. Using time-resolved x-ray diffraction, the temperature evolution of the lattice ions is obtained through the Debye-Waller effect, and this directly relates to the electron-ion equilibration rate. This is shown to be considerably lower than predicted from ideal plasma models. We attribute this to strong ion coupling screening the electron-ion interaction.

Orbital-free density-functional theory simulations of the dynamic structure factor of warm dense aluminum.

Here, we report orbital-free density-functional theory (OF DFT) molecular dynamics simulations of the dynamic ion structure factor of warm solid density aluminum at T=0.5 eV and T=5 eV. We validate the OF DFT method in the warm dense matter regime through comparison of the static and thermodynamic properties with the more complete Kohn-Sham DFT. This extension of OF DFT to dynamic properties indicates that previously used models based on classical molecular dynamics may be inadequate to capture fully the low frequency dynamics of the response function.

Observations of the effect of ionization-potential depression in hot dense plasma.

The newly commissioned Orion laser system has been used to study dense plasmas created by a combination of short pulse laser heating and compression by laser driven shocks. Thus the plasma density was systematically varied between 1 and 10 g/cc by using aluminum samples buried in plastic foils or diamond sheets. The aluminum was heated to electron temperatures between 500 and 700 eV allowing the plasma conditions to be diagnosed by K-shell emission spectroscopy. The K-shell spectra show the effect of the ionization potential depression as a function of density. The data are compared to simulated spectra which account for the change in the ionization potential by the commonly used Stewart and Pyatt prescription and an alternative due to Ecker and Kröll suggested by recent x-ray free-electron laser experiments. The experimental data are in closer agreement with simulations using the model of Stewart and Pyatt.

Mass distribution and shape influence the perceived weight of objects.

Research suggests that the rotational dynamics of an object underpins our perception of its weight. We examine the generalisability of that account using a more ecologically valid way of manipulating an object's mass distribution (mass concentrated either at the top, bottom, centre, near the edges or evenly distributed throughout the object), shape (cube or sphere), and lifting approach (lifting directly by the hand or indirectly using a handle or string). The results were in line with our predictions. An interaction effect was found where the mass distribution and lifting approach both associated with the lowest rotational dynamics made the stimulus appear lighter compared to other combinations. These findings demonstrate rotational dynamic effects in a more run-of-the-mill experience of weight perception than what has been demonstrated before using cumbersome stimuli.

The role of line-orientation processing in the production of the Poggendorff illusion: A dual-task study.

Using a dual-task paradigm, the present investigation examined whether processes related to line orientation play a critical role in the production of the Poggendorff illusion. In Experiment 1, we assessed the magnitude of the Poggendorff illusion under three different task conditions. In the single-task condition, participants were asked to report how they perceive the alignment of transversal lines in the Poggendorff figure. In two different dual-task conditions, the participants were asked to read aloud the time displayed on a digital or analogue clock while also performing the Poggendorff perception task. The method of constant stimuli was used to calculate the point of subjective equality (PSE) and bistability width values, which represent illusion strength and perceptual uncertainty, respectively. PSEs indicated that the magnitude of the illusion did not vary between single, dual-analogue, and dual-digital task conditions, which suggests that the additional demands placed by the dual tasks had no effect on the illusion strength. Perceptual uncertainty and clock-reading errors were greater in the dual-analogue task condition. Experiment 2 revealed that the analogue clockface was more difficult to read than the digital clockface. Based on these results, we conclude that having participants perform a secondary task does not influence the magnitude of the Poggendorff illusion.

Social immunity in honeybees (Apis mellifera): transcriptome analysis of varroa-hygienic behaviour.

Honeybees have evolved a social immunity consisting of the cooperation of individuals to decrease disease in the hive. We identified a set of genes involved in this social immunity by analysing the brain transcriptome of highly varroa-hygienic bees, who efficiently detect and remove brood infected with the Varroa destructor mite. The function of these candidate genes does not seem to support a higher olfactory sensitivity in hygienic bees, as previously hypothesized. However, comparing their genomic profile with those from other behaviours suggests a link with brood care and the highly varroa-hygienic Africanized honeybees. These results represent a first step toward the identification of genes involved in social immunity and thus provide first insights into the evolution of social immunity.

Early archaeological sites, hominid remains and traces of fire from Chesowanja, Kenya.

Recent investigations of Lower Pleistocene sites at Chesowanja have yielded in situ Oldowan and Oldowan-like stone artefacts, evidence of fire and a fragmentary 'robust' australopithecine cranium. Burnt clay found at one artefact locality dated to >1.42±0.07 Myr is the earliest known evidence of fire associated with a hominid occupation site.

Primordial and recycled helium isotope signatures in the mantle transition zone.

Isotope compositions of basalts provide information about the chemical reservoirs in Earth's interior and play a critical role in defining models of Earth's structure. However, the helium isotope signature of the mantle below depths of a few hundred kilometers has been difficult to measure directly. This information is a vital baseline for understanding helium isotopes in erupted basalts. We measured He-Sr-Pb isotope ratios in superdeep diamond fluid inclusions from the transition zone (depth of 410 to 660 kilometers) unaffected by degassing and shallow crustal contamination. We found extreme He-C-Pb-Sr isotope variability, with high 3He/4He ratios related to higher helium concentrations. This indicates that a less degassed, high-3He/4He deep mantle source infiltrates the transition zone, where it interacts with recycled material, creating the diverse compositions recorded in ocean island basalts.

Modulation of erlotinib pharmacokinetics in mice by a novel cytochrome P450 3A4 inhibitor, BAS 100.

Administration of BAS 100, a novel mechanism-based CYP3A4 inhibitor isolated from grapefruit juice, resulted in a 2.1-fold increase in erlotinib exposure following oral administration to wild-type and humanized CYP3A4 transgenic mice. This study illustrates the potential of BAS 100 to increase the low and variable oral bioavailability of erlotinib in cancer patients.

OSIRIS-REx Contamination Control Strategy and Implementation.

OSIRIS-REx will return pristine samples of carbonaceous asteroid Bennu. This article describes how pristine was defined based on expectations of Bennu and on a realistic understanding of what is achievable with a constrained schedule and budget, and how that definition flowed to requirements and implementation. To return a pristine sample, the OSIRIS-REx spacecraft sampling hardware was maintained at level 100 A/2 and <180 ng/cm2 of amino acids and hydrazine on the sampler head through precision cleaning, control of materials, and vigilance. Contamination is further characterized via witness material exposed to the spacecraft assembly and testing environment as well as in space. This characterization provided knowledge of the expected background and will be used in conjunction with archived spacecraft components for comparison with the samples when they are delivered to Earth for analysis. Most of all, the cleanliness of the OSIRIS-REx spacecraft was achieved through communication among scientists, engineers, managers, and technicians.

Effects of Tumor-like assay conditions, lonizing radiation, and hyperthermia on immune lysis of tumor cells by cytotoxic T-lymphocytes.

Cytotoxic T-lymphocytes (CTL's) harvested from mixed splenic lymphocyte cultures (DBA/2 + C57BL) were tested for their ability to lyse allogeneic P815 mastocytoma cells under various tumor-like assay conditions, with or without previous exposure to ionizing radiation or hyperthermia (43 degrees). There was little or no decrease of immune cytolysis when CTL's were assayed by 51Cr release under tumor-like conditions (plateau-phase target cells, low pH, or anoxia) or after irradiation, but cytolytic activity was greatly reduced when CTL's were exposed to heat; 45 min of hyperthermic treatment decreased activity by greater than or equal to 99% while reducing the apparent cell viability (as indicated by trypan blue exclusion) by only 30%. When the P815 target cells rather than the CTL's were exposed to heat their susceptibility to immune lysis was not affected even after treatment times that were lethal to the tumor cells. Despite the dissimilar heat sensitivities of CTL and P815 cells, the dose-response curves for inhibition of protein synthesis by heat, as indicated by [3H]leucine incorporation, were similar for both cell types: neither the depression of protein synthesis in heated CTL's nor the decreased cytolytic ability of these cells was reversed within 3 hr. When irradiated or heated P815 cells were incubated with CTL's, the resulting survival curves were always additive, indicating that neither irradiation nor heat treatment affected the susceptibility of the tumor cells to immune attack. The extreme heat sensitivity of cytotoxic T-lymphocytes raises important questions about the possible effects of hyperthermic treatment on the immune competence of cancer patients.

Effects of extreme hypoxia on the growth and viability of EMT6/SF mouse tumor cells in vitro.

The purpose of this study was to characterize a model system in which to study hypoxic cell biology in vitro as a function of time under extremely hypoxic conditions. EMT6/SF cells that were maintained at 37 degrees under hypoxic conditions showed no increase in cell number for up to 70 hr. The mitotic index of hypoxic cultures was less than 0.1%, compared to 2.3 to 3.0% in aerated cultures. The plating efficiency of hypoxic cells decreased with time to 20 to 30% of control values by 70 hr. Aerated cultures consumed glucose more rapidly than did hypoxic ones, due to increasing cell number in air. But, on a per cell basis, hypoxic and aerated cells consumed glucose at equal rates (congruent to 1.2 X 10(-4) micrograms/cell/hr). Virtually 100% of the glucose consumed was converted into lactic acid in both aerated and hypoxic cultures. The labeling index and rate of incorporation of [3H]thymidine decreased exponentially with time in hypoxia. However, the percentage of cells with S-phase DNA content remained nearly constant for up to 72 hr. The rate of protein synthesis was suppressed in hypoxic cultures to between 20 and 50% of control (aerated) rates. When cultures were reaerated following 45 hr of hypoxia, congruent to 12 hr was required for resumption of DNA synthesis and cell division. The application of this system to further study of hypoxic cell biology is discussed.

Cellular glutathione, thermal sensitivity, and thermotolerance in Chinese hamster fibroblasts and their heat-resistant variants.

HA-1 Chinese hamster fibroblasts and two heat-resistant variants, designated 2242 and 3012. have been investigated to determine the role that glutathione (GSH) plays in intrinsic cellular resistance to heat and in the development of thermotolerance. The constitutive levels of GSH did not correlate with intrinsic heat sensitivities, but depletion of GSH sensitized all three cell lines to thermal stress. After heating (43.5 degrees C/2 h), surviving fractions were 1 X 10(-3), 1 X 10(-2), and 8 X 10(-3) for HA-1, 2242, and 3012 cells, respectively. Depletion of cellular GSH with L-buthionine-S, R-sulfoximine to less than 10% of control values sensitized such that the thermal responses of these three cell lines were nearly indistinguishable at 43.5 degrees C. Surviving fractions were 2 X 10(-4), 1 X 10(-4), and 1 X 10(-4) for L-buthionine-S,R-sulfoximine-treated HA-1, 2242, and 3012 cells, respectively, following heating at 43.5 degrees C for 2 h. The development of thermotolerance in HA-1 cells following heat shock (45 degrees C/15 min) was unaffected by the inhibition of GSH synthesis. On the other hand, when GSH levels were maintained at extremely low levels, the development of thermotolerance was inhibited. In addition, following heat shock, cellular GSH was decreased and remained below control levels during the development of thermotolerance.

The role of adenosine triphosphate, chalones, and specific proteins in controlling tumor growth fraction.

During growth of Ehrlich ascites tumor cells in vivo, the proportion of cells in the S phase of the proliferative cell cycle decreases in a manner analogous to the decreasing growth fraction often associated with the growth of solid tumors. An examination of biochemical parameters that might regulate the growth fraction of Ehrlich ascites tumors by causing accumulation of cells in G1-G0 shows that (a) the tumor progresses from an aerobic to an anerobic state as it approaches the plateau phase of growth, as indicated by lactate dehydrogenase content, but cellular adenosine triphosphate content remains constant; (b) tumor-specific growth inhibitors (chalones) are not detectable in cell-free ascites fluid from plateau-phase tumors; (c) electrophoretically identifiable soluble proteins isolated from tumor cells that have been exposed to labeled amino acids in vivo are qualitatively identical during early and late tumor growth; and (d) ornithine decarboxylase activity increases in a bimodal fashion in the first 10 hr after transplantation of 10(7) cells and then declines rapidly during the first few days of growth. The second (and larger) of the two ornithine decarboxylase increases coincides with the surge of cells from G1-G0 into S phase, suggesting that this enzyme, or the polyamines that it synthesizes, may play a role in controlling the growth fraction of this cell population.

Selective biotransformation of taxol to 6 alpha-hydroxytaxol by human cytochrome P450 2C8.

The principal taxol biotransformation reaction of humans and of human hepatic in vitro preparations is 6 alpha-hydroxylation of the taxane ring, but a separate, minor hydroxylation pathway (metabolite B formation) also exists. Taxol metabolism was studied using membrane fractions from Hep G2 cells infected with recombinant vaccinia viruses that contain complementary DNAs encoding several human cytochrome P450 enzymes. Only P450 2C8 formed detectable 6 alpha-hydroxytaxol. Metabolite B formation was catalyzed by complementary DNA-expressed 3A3 and 3A4, but not by 3A5. Each P450 3A preparation catalyzed felodipine oxidation. The apparent Km and Vmax values for taxol 6 alpha-hydroxylation were 5.4 +/- 1.0 microM and 30 +/- 1.5 nmol/min/nmol P450, respectively, for complementary DNA-expressed P450 2C8; the values were 4.0 +/- 1.0 microM and 0.87 +/- 0.06 nmol/min/mg protein, respectively, for human hepatic microsomes. The inhibition of 6 alpha-hydroxytaxol formation by quercetin was competitive with an apparent Ki of 1.3 or 1.1 microM with 2C8 or hepatic microsomes, respectively; retinoic acid was inhibitory, showing an apparent Ki of 27 microM with hepatic microsomes; inhibition by tolbutamide was complex, weak, and unlikely to be clinically relevant. The correlation between hepatic 2C8 protein content and 6 alpha-hydroxytaxol formation was high (r2 = 0.82), while the correlation with 2C9 content was low (r2 = 0.38). These data show that human biotransformation routes of taxol result from catalysis by specific enzymes of two P450 families and that taxol 6 alpha-hydroxylation is a useful indicator of P450 2C8 activity in human hepatic microsomes.

Metabolism of taxol by human hepatic microsomes and liver slices: participation of cytochrome P450 3A4 and an unknown P450 enzyme.

Incubation of taxol with human hepatic microsomal fractions or freshly isolated human liver slices yields three metabolite high performance liquid chromatography peaks, metabolite A, metabolite B, and 6 alpha-hydroxytaxol. These metabolites are formed in patients given taxol, with 6 alpha-hydroxytaxol formation representing the principal biotransformation pathway. Metabolite B and 6 alpha-hydroxytaxol are shown to be products of different, highly regioselective cytochrome P-450 (P450) enzymes, while metabolite A results from stepwise metabolism by each of these enzymes. Correlation of metabolite B formation with P450 3A markers was good (r2 = 0.91-0.94), but the correlation of 6 alpha-hydroxytaxol formation with markers for several P450 enzymes was poor. Chemical inhibitors that selectively inhibited metabolite B formation (troleandomycin, cyclosporine), that selectively inhibited 6 alpha-hydroxytaxol formation (naringenin, quercetin), or that nonselectively inhibited both pathways (felodipine, ketoconazole) were found. Metabolite B formation was selectively reduced by anti-P450 3A4 antibodies. Expressed human P450 3A4 preparations were efficient catalysts of metabolite B formation; no expressed P450 preparation tested showed a capacity for catalyzing taxane 6 alpha-hydroxylation reactions. The combined results of several experimental approaches show that P450 3A4 is the major catalyst of metabolite B formation and that the identity of the P450 enzyme or enzymes responsible for 6 alpha-hydroxytaxol formation cannot be assigned with certainty.

Calcium-dependent inhibition of the erythrocyte Ca2+ translocating ATPase by carbodiimides.

The ATP hydrolytic activity of the solubilized and purified Ca2+-translocating ATPase from human erythrocyte plasma membrane was strongly inhibited by the nonpolar compound, N,N'-dicyclohexylcarbodiimide, both in the presence and in the absence of calmodulin. However, the more water-soluble carbodiimides, 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide and 1-cyclohexyl-3-(2-morpholinoethyl)carbodiimide had little inhibitory effect on the enzyme. The inhibitory effect of N,N'-dicyclohexylcarbodiimide was most pronounced at acid pH, and declined sharply at alkaline pH values. In addition, the optimum pH for the enzyme activity also shifted to more alkaline values in the presence of the carbodiimide. Calcium ion appears to favor the inhibition induced by the carbodiimide, in contrast to the observed protection by Ca2+ in the sarcoplasmic reticulum Ca2+-translocating ATPase. N,N'-Dicyclohexylcarbodiimide also dramatically decreased the stimulatory effect of calmodulin on the activity of the enzyme.

Rheologic behavior of deoxyhemoglobin S gels.

The physical properties of deoxyhemoglobin S gels formed from solutions at concentrations and temperatures approaching those in vivo have been characterized by stress relaxation using a rotational rheometer. Gels were annealed in the rheometer and then subjected to a constant shear strain; thereafter the stress sustained was followed with time. Gels with solid-like behavior held stress indefinitely, and were characterized by yield temperature (the temperature at which stress decreased). Gels with less solid behavior were unable to hold target stress, and were characterized by yield stress (maximum stress attained) and equilibrium stress (final stress held). The samples were ultracentrifuged to calculate pellet and polymer masses. The solidity of the gels, as measured by yield temperature or yield stress, was related to the initial hemoglobin concentration, pellet and polymer masses, shear history, temperature, and the temperature and time of annealing. Solidity increased significantly with time when gels were annealed at 37 degrees C, whereas, when annealed at 25 degrees C, no or minimal increases in solidity were noted. Studies suggest that polymerization occurs rapidly and is completed early in or before the gel annealing period and that the increase in solidity with time of annealing is mainly due to factors other than polymer mass, i.e. alignment, increasing bond strength, water loss. The chemical activity of deoxyhemoglobin S did not affect the solidity of the formed gels. When the resultant polymer masses were comparable, gels formed from samples with albumin present (higher initial total protein concentration, but lower initial deoxyhemoglobin S concentration), had the same behavior as gels formed from solutions with higher initial hemoglobin S concentration. These findings demonstrate that gel annealing conditions must be standardized when comparing the rheologic behaviors of deoxyhemoglobin S gels and indicate that the gel's physical properties (influenced by polymer mass, shear history, annealing time) must be considered in understanding pathophysiology of sickling disorders.