81 research outputs found
Defective CFTR Expression and Function Are Detectable in Blood Monocytes: Development of a New Blood Test for Cystic Fibrosis
BACKGROUND: Evaluation of cystic fibrosis transmembrane conductance regulator (CFTR) functional activity to assess new therapies and define diagnosis of cystic fibrosis (CF) is cumbersome. It is known that leukocytes express detectable levels of CFTR but the molecule has not been characterized in these cells. In this study we aim at setting up and validating a blood test to evaluate CFTR expression and function in leukocytes. DESCRIPTION: Western blot, PCR, immunofluorescence and cell membrane depolarization analysis by single-cell fluorescence imaging, using the potential-sensitive DiSBAC(2)(3) probe were utilized. Expression of PKA phosphorylated, cell membrane-localized CFTR was detected in non-CF monocytes, being undetectable or present in truncated form in monocytes derived from CF patients presenting with nonsense mutations. CFTR agonist administration induced membrane depolarization in monocytes isolated from non-CF donors (31 subjects) and, to a lesser extent, obligate CFTR heterozygous carriers (HTZ: 15 subjects), but it failed in monocytes from CF patients (44 subjects). We propose an index, which values in CF patients are significantly (p<0.001) lower than in the other two groups. Nasal Potential Difference, measured in selected subjects had concordant results with monocytes assay (Kappa statistic 0.93, 95%CI: 0.80-1.00). RESULTS AND SIGNIFICANCE: CFTR is detectable and is functional in human monocytes. We also showed that CFTR-associated activity can be evaluated in 5 ml of peripheral blood and devise an index potentially applicable for diagnostic purposes and both basic and translational research: from drug development to evaluation of functional outcomes in clinical trials
How Many Varieties of Capitalism? Comparing the Comparative Institutional Analyses of Capitalist Diversity
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 suggest the presence of oxychlorine phase(s). Sulfides are likely sources for S-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 C sources may be preserved in the mudstone; however, the C source for the chlorinated hydrocarbons is not definitively of martian origin
A Habitable Fluvio-Lacustrine Environment at Yellowknife Bay, Gale Crater, Mars
The Curiosity rover discovered fine-grained sedimentary rocks, inferred to represent an ancient lake, preserve evidence of an environment that would have been suited to support a Martian biosphere founded on chemolithoautotrophy. This aqueous environment was characterized by neutral pH, low salinity, and variable redox states of both iron and sulfur species. C, H, O, S, N, and P were measured directly as key biogenic elements, and by inference N and P are assumed to have been available. The environment likely had a minimum duration of hundreds to tens of thousands of years. These results highlight the biological viability of fluvial-lacustrine environments in the post-Noachian history of Mars
Mineralogy of a Mudstone at Yellowknife Bay, Gale Crater, Mars
Sedimentary rocks at Yellowknife Bay (Gale Crater) on Mars include mudstone sampled by the Curiosity rover. The samples, John Klein and Cumberland, contain detrital basaltic minerals, Ca-sulfates, Fe oxide/hydroxides, Fe-sulfides, amorphous material, and trioctahedral smectites. The John Klein smectite has basal spacing of ~10 Å indicating little interlayer hydration. The Cumberland smectite has basal spacing at ~13.2 Å as well as ~10 Å. The ~13.2 Å spacing suggests a partially chloritized interlayer or interlayer Mg or Ca facilitating H_2O retention. Basaltic minerals in the mudstone are similar to those in nearby eolian deposits. However, the mudstone has far less Fe-forsterite, possibly lost with formation of smectite plus magnetite. Late Noachian/Early Hesperian or younger age indicates that clay mineral formation on Mars extended beyond Noachian time
The Petrochemistry of Jake_M: A Martian Mugearite
“Jake_M,” the first rock analyzed by the Alpha Particle X-ray Spectrometer instrument on the
Curiosity rover, differs substantially in chemical composition from other known martian igneous
rocks: It is alkaline (>15% normative nepheline) and relatively fractionated. Jake_M is
compositionally similar to terrestrial mugearites, a rock type typically found at ocean islands and
continental rifts. By analogy with these comparable terrestrial rocks, Jake_M could have been
produced by extensive fractional crystallization of a primary alkaline or transitional magma at
elevated pressure, with or without elevated water contents. The discovery of Jake_M suggests that
alkaline magmas may be more abundant on Mars than on Earth and that Curiosity could encounter
even more fractionated alkaline rocks (for example, phonolites and trachytes)
X-ray Diffraction Results from Mars Science Laboratory: Mineralogy of Rocknest at Gale Crater
The Mars Science Laboratory rover Curiosity scooped samples of soil from the Rocknest aeolian
bedform in Gale crater. Analysis of the soil with the Chemistry and Mineralogy (CheMin) x-ray
diffraction (XRD) instrument revealed plagioclase (~An57), forsteritic olivine (~Fo62), augite,
and pigeonite, with minor K-feldspar, magnetite, quartz, anhydrite, hematite, and ilmenite.
The minor phases are present at, or near, detection limits. The soil also contains 27 ± 14 weight
percent x-ray amorphous material, likely containing multiple Fe^(3+)- and volatile-bearing phases,
including possibly a substance resembling hisingerite. The crystalline component is similar to
the normative mineralogy of certain basaltic rocks from Gusev crater on Mars and of martian
basaltic meteorites. The amorphous component is similar to that found on Earth in places
such as soils on the Mauna Kea volcano, Hawaii
Elemental Geochemistry of Sedimentary Rocks at Yellowknife Bay, Gale Crater, Mars
Sedimentary rocks examined by the Curiosity rover at Yellowknife Bay, Mars, were derived from sources that evolved from approximately average Martian crustal composition to one influenced by alkaline basalts. No evidence of chemical weathering is preserved indicating arid, possibly cold, paleoclimates and rapid erosion/deposition. Absence of predicted geochemical variations indicates that magnetite and phyllosilicates formed by diagenesis under low temperature, circum-neutral pH, rock-dominated aqueous conditions. High spatial resolution analyses of diagenetic features, including concretions, raised ridges and fractures, indicate they are composed of iron- and halogen-rich components, magnesium-iron-chlorine-rich components and hydrated calcium-sulfates, respectively. Composition of a cross-cutting dike-like feature is consistent with sedimentary intrusion. Geochemistry of these sedimentary rocks provides further evidence for diverse depositional and diagenetic sedimentary environments during the early
history of Mars
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