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G-quadruplex (G4) DNA is a type of quadruple helix structure formed by a continuous guanine-rich DNA sequence. Emerging evidence in recent years authenticated that G4 DNA structures exist both in cell-free and cellular systems, and function in different diseases, especially in various cancers, aging, neurological diseases, and have been considered novel promising targets for drug design. In this review, we summarize the detection method and the structure of G4, highlighting some non-canonical G4 DNA structures, such as G4 with a bulge, a vacancy, or a hairpin. Subsequently, the functions of G4 DNA in physiological processes are discussed, especially their regulation of DNA replication, transcription of disease-related genes (c-MYC, BCL-2, KRAS, c-KIT et al.), telomere maintenance, and epigenetic regulation. Typical G4 ligands that target promoters and telomeres for drug design are also reviewed, including ellipticine derivatives, quinoxaline analogs, telomestatin analogs, berberine derivatives, and CX-5461, which is currently in advanced phase I/II clinical trials for patients with hematologic cancer and BRCA1/2-deficient tumors. Furthermore, since the long-term stable existence of G4 DNA structures could result in genomic instability, we summarized the G4 unfolding mechanisms emerged recently by multiple G4-specific DNA helicases, such as Pif1, RecQ family helicases, FANCJ, and DHX36. This review aims to present a general overview of the field of G-quadruplex DNA that has progressed in recent years and provides potential strategies for drug design and disease treatment. [ABSTRACT FROM AUTHOR]

Cratonic lamproites bear extreme Sr−Nd−Pb isotopic compositions widely known as enriched mantle I (EMI), yet the origin of the EMI reservoir remains controversial. Here, we explore this issue by examining Mg−Sr−Nd−Pb isotopic compositions of lamproites from Leucite Hills, Wyoming, USA. The δ26Mg values vary from the range of the normal mantle to lower values (− 0.43 to − 0.18 ‰), correlating with indices of the degree of carbonate metasomatism, an observation that can be best explained through mantle metasomatism by subducted carbonate-bearing sediments. With increasing extent of carbonate metasomatism, these samples display less extreme EMI Sr−Nd−Pb isotopic signatures, arguing for at least two metasomatic events that occurred in their mantle sources. The early metasomatic event associated with subducted continent-derived siliciclastic sediments led to the formation of the EMI Sr−Nd−Pb isotopic signatures while the recent carbonate metasomatism produced the light Mg isotopic signature but diluted the EMI Sr−Nd−Pb isotopic signatures. Our study indicates that a combination of Mg and Sr−Nd−Pb isotopes could be an effective tool in deciphering multiple-stage metasomatic events in mantle sources and places new constraints on the generation of enriched mantle reservoirs. [ABSTRACT FROM AUTHOR]

Earth's habitability is closely tied to its late-stage accretion, during which impactors delivered the majority of life-essential volatiles. However, the nature of these final building blocks remains poorly constrained. Nickel (Ni) can be a useful tracer in characterizing this accretion as most Ni in the bulk silicate Earth (BSE) comes from the late-stage impactors. Here, we apply Ni stable isotope analysis to a large number of meteorites and terrestrial rocks, and find that the BSE has a lighter Ni isotopic composition compared to chondrites. Using first-principles calculations based on density functional theory, we show that core-mantle differentiation cannot produce the observed light Ni isotopic composition of the BSE. Rather, the sub-chondritic Ni isotopic signature was established during Earth's late-stage accretion, probably through the Moon-forming giant impact. We propose that a highly reduced sulfide-rich, Mercury-like body, whose mantle is characterized by light Ni isotopic composition, collided with and merged into the proto-Earth during the Moon-forming giant impact, producing the sub-chondritic Ni isotopic signature of the BSE, while delivering sulfur and probably other volatiles to the Earth. Based on Nickel isotope analysis of meteorites and terrestrial rocks, the authors suggest that the Bulk Silicate Earth has a sub-chondritic Nickel isotope composition. This signature is thought to result from the impact and accretion of a Mercury-like impactor which originated from the innermost Solar System. [ABSTRACT FROM AUTHOR]

The Liulin Spring catchment in Shanxi Province has abundant karst groundwater resources that play a supporting role in the economic and social development of the Lvliang region. Research on the factors controlling the chemical evolution of karst groundwater can be of great significance for the sustainable utilization and effective protection of groundwater resources in the basin. In this study, the major ions of karst groundwater have been studied to identify the hydrogeochemical processes and regional evolution using 29 samples that were collected in 2014 from the recharge area, throughflow area, discharge area and stagnant area of the catchment. The results showed that the temperature and the concentrations of Na+, Ca2+, Mg2+, Cl−, HCO3− and SO42− increased with the increasing distance from the recharge area to the throughflow area, to the discharge area and then to the stagnant area. The chemical composition of karst groundwater in both recharge area and throughflow area was mainly derived from carbonate dissolution, while it was largely controlled by the weathering of silicate minerals in the discharge area, and dominated by the dissolution of both silicates and gypsum in the stagnant areas. The K+, Na+ and Cl− were mainly sourced from the dissolution of salt rock, while the Ca2+, Mg2+, HCO3−, and SO42− were mainly derived from the dissolution of calcite, dolomite, and gypsum. The hydrochemical types of karst groundwater changed from HCO3-Ca • Mg type in the recharge area to HCO3 • SO4-Ca • Mg type in the throughflow area and to HCO3 • SO4-Ca • Na • Mg type in the discharge area, and finally evolved into Cl • HCO3-Na • Ca, Cl • HCO3-Na type and Cl-Na • Ca type in the stagnant area. The results of this study will be useful to effectively guide the sustainable utilization and the integrated planning of water resources in the Liulin Spring catchment. [ABSTRACT FROM AUTHOR]

The large equilibrium Mg isotope fractionation between clinopyroxene and garnet observed in eclogites makes it a potential high-precision geothermometer, but calibration of this thermometer by natural samples is still limited. Here, we report Mg isotopic compositions of eclogite whole rocks as well as Mg and O isotopic compositions of clinopyroxene and garnet separates from 16 eclogites that formed at different temperatures from the Dabie orogen, China. The whole-rock δMg values vary from −1.20 to +0.10 ‰. Among them, 11 samples display limited δMg variations from −0.36 to −0.17 ‰, similar to those of their protoliths. The mineral separates exhibit very different δMg values, from −0.39 to +0.39 ‰ for clinopyroxenes and from −1.94 to −0.81 ‰ for garnets. The clinopyroxene-garnet Mg isotope fractionation (ΔMg = δMg-δMg) varies from 1.05 to 2.15 ‰. The clinopyroxene-garnet O isotope fractionation (ΔO = δO-δO) varies from −1.01 to +0.98 ‰. Equilibrium Mg isotope fractionation between clinopyroxene and garnet in the investigated samples is selected based on both the δMg versus δMg plot and the state of O isotope equilibrium between clinopyroxene and garnet. The equilibrium ΔMg and corresponding temperature data obtained in this study, together with those available so far in literatures for natural eclogites, are used to calibrate the clinopyroxene-garnet Mg isotope thermometer. This yields a function of ΔMg = (0.99 ± 0.06) × 10/ T, where T is temperature in Kelvin. The refined function not only provides the best empirically calibrated clinopyroxene-garnet Mg isotope thermometer for precise constraints of temperatures of clinopyroxene- and garnet-bearing rocks, but also has potential applications in high-temperature Mg isotope geochemistry. [ABSTRACT FROM AUTHOR]

In animals, heme oxygenase (HO), a rate-limiting enzyme responsible for carbon monoxide (CO) production, was regarded as a protective system maintaining cellular homeostasis. It was also established that metal ions are powerful HO-inducing agents and cobalt chloride (CoCl) was the first metal ion identified with an inducing property. Previous study suggests that CoCl stimulates adventitious root formation in tomato and cucumber cuttings. In this test, we discover that both CoCl and an inducer of HO-1, hemin, could lead to the promotion of lateral root development, as well as the induction of HO-1 protein expression, HO activity, or LeHO- 1/2 transcripts, in lateral root initiation zone of tomato seedlings. The effect is specific for HO since the potent HO-1 inhibitor zinc protoporphyrin IX (ZnPPIX) blocked the above actions of CoCl, and the inhibitory effect was reversed partially when 50% CO aqueous solution was added. However, the addition of ascorbic acid (AsA), a well-known antioxidant, exhibited no obvious effect on lateral root formation. Molecular evidence further showed that CoCl-induced the up-regulation of target genes responsible for lateral root formation, including LeCDKA1, LeCYCA2;1, and LeCYCA3;1, was suppressed differentially by ZnPPIX. And these decreases were reversed further by the addition of CO. All together, these results suggest a novel role for HO in the CoCl-induced tomato lateral root formation. [ABSTRACT FROM AUTHOR]

The purpose of this study is to investigate if the EGFR-Stat3 signal pathway contributes to the carcinogenesis of hepatoma in rats. Hepatoma was induced in rats by 3′Me-DAB as a model. EGFR, TGFα, Stat3, p-Stat3 in different stages of carcinogenesis were detected by immunohistochemistry and Western blot. In situ hybridization was applied to investigate the expression of Stat3 mRNA. The expressions of signal molecules were assessed by KS400 Image Analysis system. The data were statistically evaluated. EGFR, TGFα, Stat3 were highly expressed in the stages of liver necrosis and repairment. All hepatocellular carcinoma cases revealed elevated expression of EGFR, TGFα. Elevation of Stat3 mRNA and protein levels were identified, increase of activation of Stat3 was also observed. In HCC, there was positive correlation between p-Stat3 level and the expression of TGFα and PCNA. Increased expression of Bcl-2 ( P < 0.05) coincided with elevated level of p-Stat3. Therefore, the EGFR-Stat3 signal pathway was related to the development of hepatoma in rats. TGFα-EGFR autocrine ring formation may lead to the activation of Stat3 and in turn, promote proliferation and regulate the transcription of genes regulating cell apoptosis and cell cycle. [ABSTRACT FROM AUTHOR]

A series of methods was developed for targeted mutagenesis in enterococci. First, a transposon mutagenesis system, miniγδ-200 (mγδ), which was used previously to make insertion mutants in streptococci, was shown to be useful for generation of mutants in enterococci. After mutagenesis of cosmid clones carrying enterococcal DNA inserts in Escherichia coli with mγδ, we were able to isolate the mutants by phenotype or to screen for them by immunoblotting or comparison of restriction digestion patterns. Clones with mγδ insertions in targeted enterococcal genes were then introduced into enterococci by electroporation to generate targeted disruption mutations. Allelic replacement en masse, that is, electroporation of enterococci with DNA from a pool of mutagenized cosmid clones, was shown to be an efficient method to obtain mutations in genes with detectable phenotypes in enterococci. We next constructed a vector for mutagenesis using small intragenic fragments of enterococcal genes to disrupt targeted genes. This vector was modified from pBluescript SK (−) by cloning the kanamycin resistance determinant from mγδ into the ScaI site internal to the ampicillin resistance gene. It was then used to generate insertion mutants in Enterococcus faecalis with an intragenic fragment as small as about 500 bp. A third method, based on the conjugation system reported by Trieu-Cuot et al. [1], was developed in order to circumvent difficulties in the electroporation of some enterococcal strains and to improve the efficiency with which targeted mutations can be generated in enterococci. This system was capable of mobilizing both small plasmids and large cosmids into enterococci by conjugation, and produced disruption mutations by homologous recombination. [ABSTRACT FROM AUTHOR]

The oceanic magnesium cycle is largely controlled by continental weathering and marine authigenic mineral formation, which are intimately linked to long-term climate. Uncertainties in the magnesium cycle propagate into other chemical budgets, and into interpretations of paleo-oceanographic reconstructions of seawater δ26Mg and Mg/Ca ratios. Here, we produce a detailed global map of the flux of dissolved magnesium from the ocean into deeper marine sediments (greater than ∼1 meter below seafloor), and quantify the global flux and associated isotopic fractionation. We find that this flux accounts for 15–20% of the output of magnesium from the ocean, with a flux-weighted fractionation factor of ∼0.9994 acting to increase the magnesium isotopic ratio in the ocean. Our analysis provides the best constraints to date on the sources and sinks that define the oceanic magnesium cycle, including new constraints on the output flux of magnesium and isotopic fractionation during low-temperature ridge flank hydrothermal circulation. The oceanic magnesium cycle is closely linked to Earth's carbon cycle and long-term climate change, due to processes such as continental weathering and authigenic mineral formation. Here, the authors update the global oceanic magnesium budget by quantifying the flux of magnesium from oceans to marine sediments and the associated isotopic fractionation. [ABSTRACT FROM AUTHOR]

This study presents high-precision analyses of stable potassium (K) isotope ratio using the recently-developed, collision-cell multi-collector inductively coupled plasma mass spectrometry (CC-MC-ICP-MS, Nu Sapphire). The accuracy of our analyses is confirmed by measuring well-characterized geostandards (including rocks and seawater). Our results are consistent with literature values and a precision of 0.04‰ (2SD) has been achieved based on multiple measurements of BCR-2 geostandard over a six-month period. We also evaluate factors that may lead to artificial isotope fractionations, including the mismatches in K concentration and acid molarity between samples and bracketing standards, as well as potential matrices. As the K adsorption capacity of AGW50-X8 (200–400 mesh) is reduced with an increasing amount of matrix elements, less than 150 µg K was loaded during the column chemistry. To evaluate the potential use of K isotopes as an archive of paleo seawater composition, δ41K values of an international seawater standard (IAPSO), a Mn-nodule (NOD-P-1), and two iron formation standards (FeR-2 and FeR-4) are reported. The δ41K value of IAPSO is consistent with other seawater samples reported previously, further substantiating a homogeneous K isotopic distribution in modern global oceans. The K isotopes in Mn-nodule (NOD-P-1: −0.121±0.013‰) and iron formation samples (FeR-2: −0.538±0.009‰; FeR-4: −0.401±0.008‰) seem to be an effective tracer of their formation genesis and compositional changes of ancient seawater. Our results suggest that high-precision measurements of stable K isotopes can be routinely obtained and open up a large variety of geological applications, such as continental weathering, hydrothermal circulation and alteration of oceanic crust. [ABSTRACT FROM AUTHOR]