Synthesis and two-photon photolysis of 6-(ortho-nitroveratryl)-caged IP3 in living cells

The synthesis of a photolabile derivative of inositol-1,4,5-trisphosphate (IP3) is described. This new caged second messenger (6-ortho-nitroveratryl)-IP3 (6-NV-IP3) has an extinction coefficient of 5000 M(-1) cm(-1) at 350 nm, and a quantum yield of photolysis of 0.12. Therefore, 6-NV-IP3 is photolyzed with UV light about three times more efficiently than the widely used P(4(5))-1-(2-nitrophenyl)ethyl-caged IP3 (NPE-IP3). 6-NV-IP3 has a two-photon cross-section of about 0.035 GM at 730 nm. This absorbance is sufficiently large for effective two-photon excitation in living cells at modest power levels. Using near-IR light (5 mW, 710 nm, 80 MHz, pulse-width 70 fs), we produced focal bursts of IP3 in HeLa cells, as revealed by laser-scanning confocal imaging of intracellular Ca2+ concentrations. Therefore, 6-NV-IP3 can be used for efficient, subcellular photorelease of IP3, not only in cultured cells but also, potentially, in vivo. It is in the latter situation that two-photon photolysis should reveal its true forte.

Anticancer activity of natural cytokinins: a structure-activity relationship study

Cytokinin ribosides (N(6)-substituted adenosine derivatives) have been shown to have anticancer activity both in vitro and in vivo. This study presents the first systematic analysis of the relationship between the chemical structure of cytokinins and their cytotoxic effects against a panel of human cancer cell lines with diverse histopathological origins. The results confirm the cytotoxic activity of N(6)-isopentenyladenosine, kinetin riboside, and N(6)-benzyladenosine and show that the spectrum of cell lines that are sensitive to these compounds and their tissues of origin are wider than previously reported. The first evidence that the hydroxylated aromatic cytokinins (ortho-, meta-, para-topolin riboside) and the isoprenoid cytokinin cis-zeatin riboside have cytotoxic activities is presented. Most cell lines in the panel showed greatest sensitivity to ortho-topolin riboside (IC(50)=0.5-11.6 microM). Cytokinin nucleotides, some synthesized for the first time in this study, were usually active in a similar concentration range to the corresponding ribosides. However, cytokinin free bases, 2-methylthio derivatives and both O- and N-glucosides showed little or no toxicity. Overall the study shows that structural requirements for cytotoxic activity of cytokinins against human cancer cell lines differ from the requirements for their activity in plant bioassays. The potent anticancer activity of ortho-topolin riboside (GI(50)=0.07-84.60 microM, 1st quartile=0.33 microM, median=0.65 microM, 3rd quartile=1.94 microM) was confirmed using NCI(60), a standard panel of 59 cell lines, originating from nine different tissues. Further, the activity pattern of oTR was distinctly different from those of standard anticancer drugs, suggesting that it has a unique mechanism of activity. In comparison with standard drugs, oTR showed exceptional cytotoxic activity against NCI(60) cell lines with a mutated p53 tumour suppressor gene. oTR also exhibited significant anticancer activity against several tumour models in in vivo hollow fibre assays.

In vitro efficacy of nitro- and bromo-thiazolyl-salicylamide compounds (thiazolides) against Besnoitia besnoiti infection in Vero cells

Nitazoxanide (NTZ) and its deacetylated metabolite tizoxanide (TIZ) exhibit considerable in vitro activity against Besnoitia besnoiti tachyzoites grown in Vero cells. Real-time-PCR was used to assess B. besnoiti tachyzoite adhesion, invasion, and intracellular proliferation in vitro. A number of NTZ-derivatives, including Rm4822 and Rm4803, were generated, in which the thiazole-ring-associated nitro-group was replaced by a bromo-moiety. We here show that replacement of the nitro-group on the thiazole ring with a bromo (as it occurs in Rm4822) does not impair the efficacy of the drug, but methylation of the salicylate ring at the ortho-position in a bromo-derivative (Rm4803) results in complete abrogation of the antiparasitic activity. Treatment of extracellular B. besnoiti tachyzoites with NTZ has an inhibitory effect on host cell invasion, while treatments with TIZ, Rm4822 do not. TEM demonstrates that the effects of Rm4822 treatment upon the parasites are similar to the damage induced by NTZ. This includes increased vacuolization of the parasite cytoplasm, and loss of the structural integrity of the parasitophorous vacuole and its membrane. Thus, Rm4822, due to the absence of a potentially mutagenic nitro-group, may represent an important potential addition to the anti-parasitic arsenal for food animal production, especially in cattle.

Deciphering High-Pressure metamorphism in collisional context using microprobe-mapping methods : application to the Stak eclogitic massif (NW Himalaya)

The Stak massif, northern Pakistan, is a newly recognized occurrence of eclogite formed by the subduction of the northern margin of the Indian continent in the northwest Himalaya. Although this unit was extensively retrogressed during the Himalayan collision, records of the high-pressure (HP) event as well as a continuous pressure-temperature (P-T) path were assessed from a single thin section using a new multiequilibrium method. This method uses microprobe X-ray compositional maps of garnet and omphacitic pyroxene followed by calculations of ∼200,000 P-T estimates using appropriate thermobarometers. The Stak eclogite underwent prograde metamorphism, increasing from 650 °C and 2.4 GPa to the peak conditions of 750 °C and 2.5 GPa, then retrogressed to 700–650 °C and 1.6–0.9 GPa under amphibolite-facies conditions. The estimated peak metamorphic conditions and P-T path are similar to those of the Kaghan and Tso Morari high- to ultrahigh-pressure (HP-UHP) massifs. We propose that these three massifs define a large HP to UHP province in the northwest Himalaya, comparable to the Dabie-Sulu province in China and the Western Gneiss Region in Norway.

From stellar nebula to planets: The refractory components

Context. To date, calculations of planet formation have mainly focused on dynamics, and only a few have considered the chemical composition of refractory elements and compounds in the planetary bodies. While many studies have been concentrating on the chemical composition of volatile compounds (such as H2O, CO, CO2) incorporated in planets, only a few have considered the refractory materials as well, although they are of great importance for the formation of rocky planets. Aims. We computed the abundance of refractory elements in planetary bodies formed in stellar systems with a solar chemical composition by combining models of chemical composition and planet formation. We also considered the formation of refractory organic compounds, which have been ignored in previous studies on this topic. Methods. We used the commercial software package HSC Chemistry to compute the condensation sequence and chemical composition of refractory minerals incorporated into planets. The problem of refractory organic material is approached with two distinct model calculations: the first considers that the fraction of atoms used in the formation of organic compounds is removed from the system (i.e., organic compounds are formed in the gas phase and are non-reactive); and the second assumes that organic compounds are formed by the reaction between different compounds that had previously condensed from the gas phase. Results. Results show that refractory material represents more than 50 wt % of the mass of solids accreted by the simulated planets with up to 30 wt % of the total mass composed of refractory organic compounds. Carbide and silicate abundances are consistent with C/O and Mg/Si elemental ratios of 0.5 and 1.02 for the Sun. Less than 1 wt % of carbides are present in the planets, and pyroxene and olivine are formed in similar quantities. The model predicts planets that are similar in composition to those of the solar system. Starting from a common initial nebula composition, it also shows that a wide variety of chemically different planets can form, which means that the differences in planetary compositions are due to differences in the planetary formation process. Conclusions. We show that a model in which refractory organic material is absent from the system is more compatible with observations. The use of a planet formation model is essential to form a wide diversity of planets in a consistent way.

Olfactory function after transsphenoidal pituitary surgery

Pituitary surgery remains mainly performed trough a transnasal, transseptal and transsphenoidal way. This surgical approach can damage intranasal structures and, in particular, may impede olfactory function. Our study investigates olfactory function in 67 patients undergoing this type of surgery before and 3 months after surgery. Mean olfactory scores were identical pre- and postoperatively. However, on an individual bases seven percent of the patients showed a clear decrease in olfactory function. In conclusion, transnasal, transseptal and transsphenoidal surgery is relativelv safe with regards to olfactory function

The Synthesis of Functionalised Diaryltetraynes and Their Transport Properties in Single-Molecule Junctions

The synthesis and characterisation is described of six diaryltetrayne derivatives [Ar-(C[TRIPLE BOND]C)4-Ar] with Ar=4-NO2-C6H4- (NO24), 4-NH(Me)C6H4- (NHMe4), 4-NMe2C6H4- (NMe24), 4-NH2-(2,6-dimethyl)C6H4- (DMeNH24), 5-indolyl (IN4) and 5-benzothienyl (BTh4). X-ray molecular structures are reported for NO24, NHMe4, DMeNH24, IN4 and BTh4. The stability of the tetraynes has been assessed under ambient laboratory conditions (20 °C, daylight and in air): NO24 and BTh4 are stable for at least six months without observable decomposition, whereas NHMe4, NMe24, DMeNH24 and IN4 decompose within a few hours or days. The derivative DMeNH24, with ortho-methyl groups partially shielding the tetrayne backbone, is considerably more stable than the parent compound with Ar=4-NH2C6H4 (NH24). The ability of the stable tetraynes to anchor in Au|molecule|Au junctions is reported. Scanning-tunnelling-microscopy break junction (STM-BJ) and mechanically controllable break junction (MCBJ) techniques are employed to investigate single-molecule conductance characteristics.

Magnetic anisotropy in clinopyroxene and orthopyroxene single crystals

Pyroxenes constitute an important component in mafic igneous and metamorphic rocks. They often possess a prismatic habit, and their long axis, the crystallographic c axis, helps define a lineation in a textured rock. Anisotropy of magnetic susceptibility (AMS) serves as a fabric indicator in igneous and metamorphic rocks. If a rock’s AMS is carried by pyroxenes, it can be related to their crystallographic preferred orientation and degree of alignment. This requires knowing the intrinsic AMS of pyroxene single crystals. This study provides a comprehensive low-field and high-field AMS investigation of chemically diverse orthopyroxene and clinopyroxene crystals in relation to crystal structure, chemical composition, oxidation state of Fe, and the possible presence of ferromagnetic inclusions. The paramagnetic anisotropy, extracted from high-field data, shows clear relationships to crystallographic directions and Fe concentration both in clinopyroxene and orthopyroxene. In the diopside-augite series, the intermediate susceptibility is parallel to b, and the maximum is at 45° to the c axis. In aegirine, the intermediate axis remains parallel to b, while the maximum susceptibility is parallel to c. The AMS of spodumene depends on Fe concentration. In enstatite, the maximum susceptibility aligns with c and the minimum with b, and in the case of hypersthene, the maximum susceptibility is normal to the exsolution lamellae. Magnetite inclusions within augite possess a ferromagnetic anisotropy with consistent orientation of the principal susceptibilities, which dominates the low-field anisotropy. These results provide better understanding of magnetic anisotropy in pyroxenes and form a solid basis for interpretation of magnetic fabrics in pyroxene-bearing rocks.

Magnetic anisotropy in natural amphibole crystals

Anisotropy of magnetic susceptibility (AMS) is often used as a proxy for mineral fabric in deformed rocks. To do so quantitatively, it is necessary to quantify the intrinsic magnetic anisotropy of single crystals of rock-forming minerals. Amphiboles are common in mafic igneous and metamorphic rocks and often define rock texture due to their general prismatic crystal habits. Amphiboles may dominate the magnetic anisotropy in intermediate to felsic igneous rocks and in some metamorphic rock types, because they have a high Fe concentration and they can develop a strong crystallographic preferred orientation. In this study, the AMS is characterized in 28 single crystals and I crystal aggregate of compositionally diverse clino- and ortho-amphiboles. High-field methods were used to isolate the paramagnetic component of the anisotropy, which is unaffected by ferromagnetic inclusions that often occur in amphibole crystals. Laue imaging, laser ablation-inductively coupled plasma-mass spectrometry, and Mossbauer spectroscopy were performed to relate the magnetic anisotropy to crystal structure and Fe concentration. The minimum susceptibility is parallel to the crystallographic a*-axis and the maximum susceptibility is generally parallel to the crystallographic b-axis in tremolite, actinolite, and hornblende. Gedrite has its minimum susceptibility along the a-axis, and maximum susceptibility aligned with c. In richterite, however, the intermediate susceptibility is parallel to the b-axis and the minimum and maximum susceptibility directions are distributed in the a-c plane. The degree of anisotropy, k', increases generally with Fe concentration, following a linear trend: k' = 1.61 x 10(-9) Fe - 1.17 x 10(-9) m(3)/kg. Additionally, it may depend on the Fe2+/Fe3+ ratio. For most samples, the degree of anisotropy increases by a factor of approximately 8 upon cooling from room temperature to 77 K. Fen-oactinolite, one pargasite crystal and riebeckite show a larger increase, which is related to the onset of local ferromagnetic (s.l.) interactions below about 100 K. This comprehensive data set increases our understanding of the magnetic structure of amphiboles, and it is central to interpreting magnetic fabrics of rocks whose AMS is controlled by amphibole minerals.

Is Vesta an intact and pristine protoplanet?

It is difficult to find a Vesta model of iron core, pyroxene and olivine-rich mantle, and HED crust that can match the joint constraints of (a) Vesta's density and core size as reported by the Dawn spacecraft team; (b) the chemical trends of the HED meteorites, including the depletion of sodium, the FeO abundance, and the trace element enrichments; and (c) the absence of exposed mantle material on Vesta's surface, among Vestoid asteroids, or in our collection of basaltic meteorites. These conclusions are based entirely on mass-balance and density arguments, independent of any particular formation scenario for the HED meteorites themselves. We suggest that Vesta either formed from source material with non-chondritic composition or underwent after its formation a radical physical alteration, possibly caused by collisional processes, that affected its global composition and interior structure. (C) 2015 Elsevier Inc. All rights reserved.

Characterization of OSIRIS NAC filters for the interpretation of multispectral data of comet 67P/Churyumov-Gerasimenko

Context. We interpret multicolor data from OSIRIS NAC for the remote-sensing exploration of comet 67P/Churyumov-Gerasimenko. Aims. We determine the most meaningful definition of color maps for the characterization of surface variegation with filters available on OSIRIS NAC. Methods. We analyzed laboratory spectra of selected minerals and olivine-pyroxene mixtures seen through OSIRIS NAC filters, with spectral methods existing in the literature: reflectance ratios, minimum band wavelength, spectral slopes, band tilt, band curvature, and visible tilt. Results. We emphasize the importance of reflectance ratios and particularly the relation of visible tilt vs. band tilt. This technique provides a reliable diagnostic of the presence of silicates. Color maps constructed by red-green-blue colors defined with the green, orange, red, IR, and Fe2O3 filters let us define regions that may significantly differ in composition.

Long term low latitude and high elevation cosmogenic 3He production rate inferred from a 107 ka-old lava flow in northern Chile; 22°S-3400 m a.s.l

Available geological calibration sites used to estimate the rate at which cosmogenic 3He is produced at the Earth’s surface are mostly clustered in medium to high latitudes. Moreover, most of them have exposure histories shorter than tens of thousands of years. This lack of sites prevents a qualitative assessment of available production models used to convert cosmogenic 3He concentrations into exposure ages and/or denudation rates. It thus limits our ability to take into account the atmospheric, geomagnetic and solar modulation conditions that might have affected the production of cosmogenic nuclides in the past for longer exposure histories and in low latitude regions. We present the cosmogenic 3He production rate inferred from a new geological calibration site located in northern Chile. Five samples were collected on the surface of the largest and best-preserved lava flow of the San Pedro volcano (21.934°S-68.510°W- 3390 m a.s.l), which displays pristine crease-structure features. 40Ar/39Ar dating yield a reliable plateau age of 107±12 ka for the eruption of this lava flow. Eight pyroxene aliquots separated from the surface samples yield a weighted average cosmogenic 3He concentration of 99.3±1.2 Mat.g-1 from which a local cosmogenic 3He production rate of 928±101 at.g-1.yr-1 is calculated. The local production rate is then scaled to a sea level high latitude (SLHL) reference position using different combinations of geographic spatialization schemes, atmosphere models and geomagnetic field reconstructions, yielding SLHL production rates between 103±11 and 130±14 at.g-1.yr-1 consistent with the most recent estimates available from the literature. Finally, we use the same scaling frameworks to re-evaluate the mean global-scale cosmogenic 3He production rate in olivine and pyroxene minerals at 120±16 at.g-1.yr-1 from the compilation of previously published calibration datasets.