Cell-free DNA (cf-DNA)-based liquid biopsy is emerging as a revolutionary new method in individualized cancer treatment and prognosis monitoring, although detecting early-stage cancers using cf-DNA ...remains challenging, partially because of the undefined biological background of cf-DNA.
We investigated somatic mutations in the cf-DNA of 259 cancer-free individuals with a median age of 47 years using an endogenous barcoding duplex method with an ultralow base error rate (2 × 10−7) and compared the variant allele frequencies (VAFs) of these mutations between the cf-DNA and the corresponding blood cell DNA.
Sixty percent (155/259) of the samples showed at least one nonsynonymous mutation on either of two similar target panels covering 508 and 559 cancer-related genes. For individuals older than 50 years of age, the positive rate increased to 76%. Most cf-DNA mutations were also present at similar VAFs in the paired blood cell DNA. The most frequently mutated genes were driver genes of hematologic malignancies, including DNMT3A, TET2, AXSL1, and JAK2. However, the other 58.4% (192/329) of the mutations were likely ‘passenger mutations’ of clonal hematopoiesis, including mutations in NOTCH2, FAT3, EXT2, ERBB4, and ARID2, which are driver genes of solid tumors.
Hematopoietic clone-derived mutations, including ‘driver mutations’ and ‘passenger mutations’, are prevalent in the cf-DNA of both healthy individuals and cancer patients and may be a potential source of false positives in the liquid biopsy. Our results also suggest the ineffectiveness for distinguishing clonal hematopoietic mutations of low VAF (≤0.1%) from tumor-derived mutations using conventional next-generation sequencing of blood cell DNA. However, an error correction model with an ultralow error rate and high coverage depth is required for blood cell DNA sequencing, which is difficult and costly to achieve with current technologies.
The concentrations of lead, zinc, copper and cadmium accumulated by 12 emergent-rooted wetland plant species including different populations of
Leersia hexandra,
Juncus effusus and
Equisetum ...ramosisti were investigated in field conditions of China. The results showed that metal accumulation by wetland plants differed among species, populations and tissues. Populations grown in substrata with elevated metals contained significantly higher metals in plants. Metals accumulated by wetland plants were mostly distributed in root tissues, suggesting that an exclusion strategy for metal tolerance widely exists in them. That some species/populations could accumulate relatively high metal concentrations (far above the toxic concentration to plants) in their shoots indicates that internal detoxification metal tolerance mechanism(s) are also included. The factors affecting metal accumulation by wetland plants include metal concentrations, pH, and nutrient status in substrata. Mostly concentrations of Pb and Cu in both aboveground and underground tissues of the plants were significantly positively related to their total and/or DTPA-extractable fractions in substrata while negatively to soil N and P, respectively. The potential use of these wetland plants in phytoremediation is also discussed.
Molecular collisions in the quantum regime represent a new opportunity to explore chemical reactions. Recently, atom-exchange reactions were observed in a trapped ultracold gas of KRb molecules. In ...an external electric eld, these polar molecules can easily be oriented and the exothermic and barrierless bimolecular reactions, KRb + KRb ! K2 + Rb2, occur at a rate that rises steeply with increasing dipole moment. Here we demonstrate the suppression of the bimolecular chemical reaction rate by nearly two orders of magnitude when we use an optical lattice trap to conne the fermionic polar molecules in a quasi-two-dimensional, pancake-like geometry, with the dipoles oriented along the tight connement direction. With the combination of sufciently tight connement and Fermi statistics of the molecules, two polar molecules can approach each other only in a side-by-side collision under repulsive dipoledipole interactions. The suppression of chemical reactions is a prerequisite for the realization of new molecule-based quantum systems.
A quantum gas of ultracold polar molecules, with long-range and anisotropic interactions, not only would enable explorations of a large class of many-body physics phenomena but also could be used for ...quantum information processing. We report on the creation of an ultracold dense gas of potassium-rubidium (⁴⁰K⁸⁷Rb) polar molecules. Using a single step of STIRAP (stimulated Raman adiabatic passage) with two-frequency laser irradiation, we coherently transfer extremely weakly bound KRb molecules to the rovibrational ground state of either the triplet or the singlet electronic ground molecular potential. The polar molecular gas has a peak density of 10¹² per cubic centimeter and an expansion-determined translational temperature of 350 nanokelvin. The polar molecules have a permanent electric dipole moment, which we measure with Stark spectroscopy to be 0.052(2) Debye (1 Debye = 3.336 x 10⁻³⁰ coulomb-meters) for the triplet rovibrational ground state and 0.566(17) Debye for the singlet rovibrational ground state.
Summary
Activated acid-sensing ion channel 1a (ASIC1a) is involved in acid-induced osteoclastogenesis by regulating activation of the transcription factor NFATc1. These results indicated that ASIC1a ...activation by extracellular acid may cause osteoclast migration and adhesion through Ca
2+
-dependent integrin/Pyk2/Src signaling pathway.
Introduction
Osteoclast adhesion and migration are responsible for osteoporotic bone loss. Acidic conditions promote osteoclastogenesis. ASIC1a in osteoclasts is associated with acid-induced osteoclastogenesis through modulating transcription factor NFATc1 activation. However, the influence and the detailed mechanism of ASIC1a in regulating osteoclast adhesion and migration, in response to extracellular acid, are not well characterized.
Methods
In this study, knockdown of ASIC1a was achieved in bone marrow macrophage cells using small interfering RNA (siRNA). The adhesion and migration abilities of osteoclast precursors and osteoclasts were determined by adhesion and migration assays, in vitro. Bone resorption was performed to measure osteoclast function. Cytoskeletal changes were assessed by F-actin ring formation. αvβ3 integrin expression in osteoclasts was measured by flow cytometry. Western blotting and co-immunoprecipitation were performed to measure alterations in integrin/Pyk2/Src signaling pathway.
Results
Our results showed that blockade of ASIC1a using ASIC1a-siRNA inhibited acid-induced osteoclast precursor migration and adhesion, as well as osteoclast adhesion and bone resorption; we also demonstrated that inhibition of ASIC1a decreased the cell surface αvβ3 integrin and β3 protein expression. Moreover, blocking of ASIC1a inhibited acidosis-induced actin ring formation and reduced Pyk2 and Src phosphorylation in osteoclasts and also inhibited the acid-induced association of the αvβ3 integrin/Src/Pyk2.
Conclusion
Together, these results highlight a key functional role of ASIC1a/αvβ3 integrin/Pyk2/Src signaling pathway in migration and adhesion of osteoclasts.
Ultracold polar molecules offer the possibility of exploring quantum gases with interparticle interactions that are strong, long-range and spatially anisotropic. This is in stark contrast to the much ...studied dilute gases of ultracold atoms, which have isotropic and extremely short-range (or 'contact') interactions. Furthermore, the large electric dipole moment of polar molecules can be tuned using an external electric field; this has a range of applications such as the control of ultracold chemical reactions, the design of a platform for quantum information processing and the realization of novel quantum many-body systems. Despite intense experimental efforts aimed at observing the influence of dipoles on ultracold molecules, only recently have sufficiently high densities been achieved. Here we report the experimental observation of dipolar collisions in an ultracold molecular gas prepared close to quantum degeneracy. For modest values of an applied electric field, we observe a pronounced increase in the loss rate of fermionic potassium-rubidium molecules due to ultracold chemical reactions. We find that the loss rate has a steep power-law dependence on the induced electric dipole moment, and we show that this dependence can be understood in a relatively simple model based on quantum threshold laws for the scattering of fermionic polar molecules. In addition, we directly observe the spatial anisotropy of the dipolar interaction through measurements of the thermodynamics of the dipolar gas. These results demonstrate how the long-range dipolar interaction can be used for electric-field control of chemical reaction rates in an ultracold gas of polar molecules. Furthermore, the large loss rates in an applied electric field suggest that creating a long-lived ensemble of ultracold polar molecules may require confinement in a two-dimensional trap geometry to suppress the influence of the attractive, 'head-to-tail', dipolar interactions.
A nasopharyngeal carcinoma (NPC) mass screening trial using a combination of immunoglobulin A antibodies to Epstein-Barr virus capsid antigen and nuclear antigen-1 by enzyme-linked immunosorbent ...assay in addition to indirect mirror examination in the nasopharynx and/or lymphatic palpation (IMLP) was conducted in southern China. Cantonese aged 30-59 years residing in 2 cities randomly selected by cluster sampling, Sihui and Zhongshan, were invited to participate in this screening from May 2008 through May 2010. Participants were offered fiberoptic endoscopy examination and/or pathologic biopsy if their serologic tests reached our predefined level of high risk or if results from the physical examination indicated possible cancer (i.e., were IMLP positive). A total of 28,688 individuals were voluntarily screened in the initial round. The overall NPC detection rate was 0.14% (41/28,688) with an early diagnosis rate of 68.3% (28/41) during the first year of follow-up. Thirty-eight of 41 cases (92.7%) were detected among the high-risk group, and 7 of 41 cases (17.1%) were detected among the IMLP-positive group. The 2 Epstein-Barr virus serologic tests by enzyme-linked immunosorbent assay could be a feasible alternative for NPC screening in endemic areas. Further follow-up is needed to examine whether screening has an effect on decreasing mortality from NPC in these areas.
How does a chemical reaction proceed at ultralow temperatures? Can simple quantum mechanical rules such as quantum statistics, single partial-wave scattering, and quantum threshold laws provide a ...clear understanding of the molecular reactivity under a vanishing collision energy? Starting with an optically trapped near-quantum-degenerate gas of polar ⁴⁰K⁸⁷Rb molecules prepared in their absolute ground state, we report experimental evidence for exothermic atom-exchange chemical reactions. When these fermionic molecules were prepared in a single quantum state at a temperature of a few hundred nanokelvin, we observed p-wave-dominated quantum threshold collisions arising from tunneling through an angular momentum barrier followed by a short-range chemical reaction with a probability near unity. When these molecules were prepared in two different internal states or when molecules and atoms were brought together, the reaction rates were enhanced by a factor of 10 to 100 as a result of s-wave scattering, which does not have a centrifugal barrier. The measured rates agree with predicted universal loss rates related to the two-body van der Waals length.
Understanding the complex biotic and abiotic interactions invoked by the rice root system in oxygen-depleted soil is an important step in screening genotypes for low toxic metal or metalloid ...accumulation. A hydroponic and a rhizobox experiment have been conducted to explore the effects of varying root oxygen release on chemical changes, As fractionation in rhizosphere soil and Fe plaque formation, As uptake and tolerance by different rice genotypes. The results showed that rice genotypes with higher rates of radial oxygen loss (ROL) and at the bolting stage, tended to have greater effects on rhizosphere Eh, pH, Fe3+/Fe2+ quotients, As fractionation and mobility and also on Fe plaque formation compared to those with lower ROL and at the tillering stage. Genotypes with higher ROL have a strong ability to reduce As accumulation in shoots and increase As tolerance by reducing As mobilization in the rhizosphere and by limiting As translocation.
► We investigate the effects of ROL on As tolerance, uptake, and changes in rhizosphere of rice genotypes and their correlation. ► Indices of As tolerance of genotypes are positively correlated with their rates of ROL. ► Genotypes with higher rates of ROL have greater effects on rhizosphere. ► Genotypes with higher rates of ROL have a strong ability to reduce As uptake by immobilizing As on roots and in rhizosphere.
Rice genotypes with high ROL and at the bolting stage have greater effects on their rhizosphere than others with lower ROL and at tillering stage and also have lower shoot As and higher As tolerance.