Single­nucleotide polymorphism rs6592645 confers asthma risk through regulating LRRC32 expression.

Asthma is a complex disease, often with evident genetic predisposition; for example, the single-nucleotide polymorphism (SNP) rs7130588 was significantly associated with asthma by genome-wide association study (GWAS). Analysis of 1000 Genomes Project data suggests that there is another SNP, rs6592645, in complete linkage disequilibrium with rs7130588 and should present the same signal in GWAS. However, the causal SNP and the mechanism for the association between rs7130588 and asthma remain to be elucidated. In the presents study, results from dual-luciferase assays indicated that the A/G alleles of rs7130588 failed to present significantly different reporter gene expression. By contrast, A allele of rs6592645 presented a significant increase in relative luciferase activity than G allele, thus suggesting that rs6592645 may be a causal SNP. Using chromosome conformation capture, the enhancer region containing rs6592645 was observed to interact with promoter region of leucine-rich repeat-containing 32 (LRRC32). Gene expression quantification suggested that LRRC32 expression is significantly increased in lung tissue of patients with asthma and is dependent on the genotype of this locus, thus verifying that LRRC32 may be involved in asthma onset and that rs6592645 can regulate LRRC32 expression. Through chromatin immunoprecipitation, transcription factor 3 (TCF3) was identified to bind to rs6592645 surrounding region and the interaction between TCF3 and rs6592645 surrounding region was investigated. Results from the present study may improve our understanding of the mechanism by which the genetic variation in this locus might influence asthma susceptibility.

Convergent Evidence Supports TH2LCRR as a Novel Asthma Susceptibility Gene.

Asthma is a common, complex disease with apparent genetic predispositions, and previous genome-wide association studies suggest that rs1295686 within the IL13 (IL-13) gene is significantly associated with asthma. Analysis of the data provided by the 1,000 Genomes Project indicated an additional four SNPs in nearly complete linkage disequilibrium with rs1295686 in White people. However, the causal SNPs and the associated mechanism remain unclear. To investigate this issue, functional genomics approaches were utilized to analyze the functions of these SNPs. Dual-luciferase assays indicated that the functional SNP is not rs1295686 but a haplotype consisting of three other SNPs: rs1295685, rs848, and rs847. Through chromosome conformation capture, it was found that the enhancer containing the three functional SNPs interacts with the promoter of TH2LCRR (T helper type 2 locus control region associated RNA), a recently identified long noncoding RNA. RNA-seq data analysis indicated that TH2LCRR expression is significantly increased in patients with asthma and is dependent on the genotype at this locus, indicating that TH2LCRR is a novel susceptibility gene for asthma and that these SNPs confer asthma risk by regulating TH2LCRR expression. By chromatin immunoprecipitation, the related transcription factors that bind in the region surrounding these three SNPs were identified, and their interactions were investigated by functional genomics approaches. Our effort identified a novel mechanism through which genetic variations at this locus could influence asthma susceptibility.

Recent Advances in Nanomaterials for Analysis of Trace Heavy Metals.

In an effort to achieve high sensitivity analysis methods for ultra-trace levels of heavy metals, numerous new nanomaterials are explored for the application in preconcentration processes and sensing systems. Nanomaterial-based methods have proven to be effective for selective analysis and speciation of heavy metals in combination with spectrometric techniques. This review outlined the different types of nanomaterials applied in the field of heavy metal analysis, and concentrated on the latest developments in various new materials. In particular, the functionalization of traditional materials and the exploitation of bio-functional materials could increase the specificity to target metals. The hybridization of multiple materials could improve material properties, to build novel sensor system or achieve detection-removal integration. Finally, we discussed the future perspectives of nanomaterials in the heavy metal preconcentration and sensor design, as well as their respective advantages and challenges. Despite impressive progress and widespread attention, the development of new nanomaterials and nanotechnology is still hampered by numerous challenges, particularly in the specificity to the target and the anti-interference performance in complex matrices.

Ensuring high selectivity for preconcentration and detection of ultra-trace cadmium using a phage-functionalized metal-organic framework.

Metal-organic frameworks functionalized with Cd(ii) binding phages were for the first time fabricated for the isolation and preconcentration of ultra-trace cadmium. Highly specific Cd(ii) binding phages were screened through biological panning from a phage display peptide library. Thereafter, chloroauric acid (HAuCl4) was reduced by the phages to provide phage-stabilized gold nanoparticles (AuNPs). The phage-AuNP networks were then assembled onto the metal-organic framework UiO66-NH2 to serve as an affinity probe for the selective recognition and isolation of ultra-trace cadmium. 2.0 µg L-1 Cd2+ was selectively captured by the derived UiO66-NH2@phage composite with an adsorption efficiency of 100%. UiO66-NH2@phage exhibits favorable anti-interference capability against the coexisting species. It ensures highly selective and sensitive quantification of ultra-trace cadmium with detection by graphite furnace atomic absorption spectrometry (GFAAS). An enrichment factor of 17.4 was obtained along with a limit of detection (LOD) of 3.9 ng L-1 within a linear range of 0.01-0.35 µg L-1. The procedure was further validated by analyzing cadmium content in a certified reference material (CRM, simulated water, GBW08608) and a series of environmental water samples. In general, the present study provides a new protocol for the development of novel adsorbents toward the target by biopanning to regulate the selectivity.

Functionalized magnetic composites based on the aptamer serve as novel bio-adsorbent for the separation and preconcentration of trace lead.

A magnetic functionalized bio-sorbent based on aptamer was designed for the selective separation of ultra-trace Pb2+, shortly termed as Fe3O4@Au@DNA. Pb(II) specific aptamer attached to the magnetic solid substrate served as affinity probe to capture and separate trace lead. Oligonucleotides with a polyA block were employed for the immobilization on the surface of AuNPs, with adenine sequences (polyA) as the part of effective anchoring block. The prepared Fe3O4@Au@DNA composites were characterized by FT-IR, SEM and XPS. The binding of lead on Fe3O4@Au@DNA composites surface was pH-dependent, the adsorption follows Langmuir model, and the adsorption dynamic fits the pseudo-second-order kinetics model. Procedure for lead separation and preconcentration was explored and combined with detection of graphite furnace atomic absorption spectrometry (GFAAS). Under the optimum condition, an enrichment factor of 17.73 was obtained with a sample volume of 1.0 mL. The limit of detection (LOD) was 57 ng L-1 along with a relative standard deviation (RSD) of 2.06 (n = 9). The procedure was further validated by a certified reference material GBW08608 and several environmental and blood samples.

Supported carbon dots serve as high-performance adsorbent for the retention of trace cadmium.

Carbon dots were prepared via a one-pot hydrothermal route, and a new solid-phase extraction (SPE) adsorbent was developed by immobilizing the carbon dots on the microcarrier cytopore, shortly termed as C-dots@cytopore. The C-dots@cytopore composites were characterized by means of FT-IR, SEM, XPS and fluorescence spectrometry. The performance of the composites for the adsorption of heavy metals was thoroughly evaluated by using cadmium as a model. The binding of cadmium on C-dots@cytopore fits Langmuir adsorption, and the adsorption dynamic follows pseudo-second-order adsorption kinetics model. The binding of cadmium was pH-dependent, with a maximum adsorption capacity of 2420µgg-1 obtained at pH 4-7. A novel separation and preconcentration procedure was thus developed for trace cadmium using the C-dots@cytopore composites as SPE sorbent. The retained cadmium could be readily eluted and recovered by a 0.1molL-1 HNO3 solution and further quantified with graphite furnace atomic absorption spectrometry (GFAAS). With a sample volume of 1.0mL, an enrichment factor of 17.85 was obtained with a detection limit of 1.8ngL-1 and a RSD value of 2.6% at 0.1µgL-1 (n = 9). The procedure was further validated by analyzing cadmium in certified reference materials and a series of environmental water samples.

A new species of Eostyloceros (Cervidae, Artiodactyla) from the Late Miocene of the Linxia Basin in Gansu, China.

A new species, Eostyloceros hezhengensis sp. nov., is established based on a skull with its cranial appendages collected from the Late Miocene Liushu Formation of the Linxia Basin in Gansu Province, northwestern China. It is a large-sized muntjak with a distinct longitudinal ridge along the lateral margin of the frontal bone that joins the antler pedicle. The pedicle is short, cylindrical, robust, and extends posteriorly from the rear of the orbit. The anterior and posterior branches arise from the burr and diverge at an angle of 30°. The posterior branch is relatively long, and its tip is strongly curved posteriorly. The anterior branch is straight and situated anteromedially from the posterior branch. The posterior branch is lateromedially compressed, and the anterior branch has a circular cross section. The morphological observation together with a cladistic and a principal component analysis indicate that E. hezhengensis is more basal than any known species of the genus Eostyloceros in having shorter pedicles, a lower position of the fork above the burr, more slender anterior branches, and a small angle between the anterior and posterior branches. Its age is the middle Late Miocene, corresponding to the late Bahean.