Sequencing and de novo assembly of 150 genomes from Denmark as a population reference.

Hundreds of thousands of human genomes are now being sequenced to characterize genetic variation and use this information to augment association mapping studies of complex disorders and other phenotypic traits. Genetic variation is identified mainly by mapping short reads to the reference genome or by performing local assembly. However, these approaches are biased against discovery of structural variants and variation in the more complex parts of the genome. Hence, large-scale de novo assembly is needed. Here we show that it is possible to construct excellent de novo assemblies from high-coverage sequencing with mate-pair libraries extending up to 20 kilobases. We report de novo assemblies of 150 individuals (50 trios) from the GenomeDenmark project. The quality of these assemblies is similar to those obtained using the more expensive long-read technology. We use the assemblies to identify a rich set of structural variants including many novel insertions and demonstrate how this variant catalogue enables further deciphering of known association mapping signals. We leverage the assemblies to provide 100 completely resolved major histocompatibility complex haplotypes and to resolve major parts of the Y chromosome. Our study provides a regional reference genome that we expect will improve the power of future association mapping studies and hence pave the way for precision medicine initiatives, which now are being launched in many countries including Denmark.

Diabetic oxidative stress-induced telomere damage aggravates periodontal bone loss in periodontitis.

Periodontitis, one of the most common oral complications of diabetes mellitus (DM), causes a reduction in alveolar bone height and loss of alveolar bone mass. It has been shown that DM aggravates the progression of periodontitis, but the mechanism remains inconclusive. The hyperglycemic environment of DM has been proven to generate reactive oxygen species (ROS). Since telomeres, guanine-rich repeats, are highly susceptible to oxidative attack, we speculate that the excessive accumulation of ROS in DM could induce telomere damage resulting in dysfunction of periodontal ligament cells, especially periodontal ligament stem cells (PDLSCs), which reduces the ability of tissue repair and reconstruction in diabetic periodontitis. In this study, our current data revealed that oxidative telomere damage occurred in the periodontal ligaments of diabetic mice. And Micro-CT scans showed reduced alveolar bone height and impaired alveolar bone mass in a diabetic periodontitis model. Next, cultured mouse PDLSCs (mPDLSCs) were treated with the oxidant tert-butyl hydroperoxide (t-BHP) in vitro, as we expected telomere damage was observed and resulted in cellular senescence and dysfunction. Taken together, oxidative stress in DM causes telomere dysfunction and PDLSCs senescence, which influences periodontal bone tissue regeneration and reconstruction and ultimately exacerbates bone loss in periodontitis.

Highly sensitive detection of carbendazim in juices based on mung bean-derived porous carbon@chitosan composite modified electrochemical sensor.

We reported a simple and scalable strategy for the preparation of mung bean-derived porous carbon@chitosan (MBC@CTS) composite, which was used to optimize the glassy carbon electrode (GCE). The MBC@CTS/GCE sensor was applied for the carbendazim (CBZ) detection. For the MBC@CTS composite, MBC with three-dimensional hierarchical structure presented large specific surface area, good adsorbability, and high electrical conductivity, while CTS had good film-forming property, hydrophilicity performance, and adhesion capacity. The MBC@CTS/GCE sensor exhibited wonderful electrochemical detection performance towards CBZ. Under the optimized conditions, the MBC@CTS/GCE sensor showed a linear concentration range from 0.1 to 20 µM with relatively low limit of detection (LOD) of 20 nM. In addition, the fabricated sensor with good reproducibility, stability, and selectivity were successfully applied for the CBZ detection in apple and tomato juices with low relative standard deviation of 2.4 %-4.2% and satisfactory recoveries of 98.8-103.2%.

A novel electrochemical sensor based on ß-cyclodextrin functionalized carbon nanosheets@carbon nanotubes for sensitive detection of bactericide carbendazim in apple juice.

Carbendazim (CBZ) abuse always causes the over-standard of pesticide residues in agricultural products, which has adverse effects on human health. Herein, a novel electrochemical sensor was firstly fabricated based on the ß-cyclodextrin (ß-CD) functionalized carbon nanosheets@carbon nanotubes (CNS@CNT) for the CBZ determination. CNS@CNT combined large surface area of CNS and excellent electrical conductivity of CNT, which significantly enhanced the electrocatalytic performance. Moreover, ß-CD possessed excellent host-gest supramolecular recognition ability, which could improve the selective recognition and enrichment capability of CBZ. Thanks to the synergistic interaction of CNS@CNT and ß-CD, the ß-CD/CNS@CNT/GCE sensor exhibited a low limit of detection of 9.4 nM in the linear CBZ concentration range of 0.03-30 µM. The fabricated sensor presented favorable stability, high sensitivity (30.86 µA µM-1 cm-2), and reliable reproducibility (RSD = 3.6%). Especially, the ß-CD/CNS@CNT/GCE sensor could show pretty practical feasibility for the detection of CBZ in apple juice with recoveries of 97.1%-99.4%.

Three-dimensional hierarchical porous carbon coupled with chitosan based electrochemical sensor for sensitive determination of niclosamide.

Herein, a simple, low-cost, environment-friendly strategy was proposed to prepare the composite of three-dimensional hierarchical porous carbon and chitosan, which was applied to modify the glass carbon electrode to fabricate an electrochemical sensor for the determination of niclosamide. The three-dimensional porous carbon with interconnected conductive network, high surface area, and self-generated oxygen-containing functional groups was prepared by salt-templating method with glucose as carbon source and eutectic mixture of LiBr/KBr as both activating and pore-forming agent. During the subsequent ultrasonic process, chitosan with excellent filming property, strong adsorption ability, and good dispersibility was successfully decorated on the obtained porous carbon to further enhance the determination performance of niclosamide. Benefitting from the multi-functional integration of three-dimensional hierarchical porous carbon and chitosan, the fabricated sensor presented a low limit of detection (6.7 nM) in the linear concentration range from 0.01 to 10 µM. Moreover, the fabricated sensor could show good repeatability, reproducibility, stability, and selectivity. Most important, the decent practicability for the detection of niclosamide was obtained in different food samples with low relative standard deviation and satisfactory recoveries. This work provides a very valuable reference for the sensitive determination of niclosamide in food samples.

Ultrasonic-assisted preparation of halloysite nanotubes/zirconia/carbon black nanocomposite for the highly sensitive determination of methyl parathion.

Herein, a cost-effective and scalable ultrasound assisted approach was proposed to prepare the nanocomposite of halloysite nanotubes/zirconia/carbon black (Hal/ZrO2/CB), which was used to fabricate a novel electrochemical sensor for the highly sensitive determination of methyl parathion (MP). In the Hal/ZrO2/CB nanocomposite, Hal with large specific surface area and numerous active sites could enhance the adsorption capacity and accelerate the redox reaction of MP; ZrO2 nanoparticles with high affinity toward the phosphate group could contribute to good recognition performance for MP; CB nanoparticles with good dispersibility formed an interconnected pearl-chain-like conductive network. Benefitting from the synergistic effect of the three components, the Hal/ZrO2/CB/GCE (glassy carbon electrode) sensor showed a remarkably low detection limit of 5.23 nM in a good linear MP detection range of 0.01-10 µM. The Hal/ZrO2/CB/GCE sensor possessed a pretty decent practicality with satisfactory RSD and recovery results for the determination of MP in peach, pear, and apple juices. Therefore, the Hal/ZrO2/CB/GCE sensor has important implication on the quite sensitive detection of MP.

Facile synthesis of Vulcan XC-72 nanoparticles-decorated halloysite nanotubes for the highly sensitive electrochemical determination of niclosamide.

We report a scalable and controllable ultrasound-assisted strategy for the preparation of Vulcan XC-72 nanoparticles-decorated halloysite nanotubes (HNTs@VXC-72), which was applied to modify glassy carbon electrode (GCE) for the highly sensitive electrochemical determination of niclosamide (NA). For the HNTs@VXC-72 nanocomposite, VXC-72 nanoparticles with excellent electrical conductivity and good dispersing property contributed to the formation of the interconnected conductive network; HNTs possessed good adsorption performance and promoted the electrochemical redox reaction. The research results showed that the combination of VXC-72 nanoparticles and HNTs produced the effect of synergistic enhancement. The HNTs@VXC-72/GCE sensor could show a relatively low detection limit of 3.28 nM in the great linear NA concentration range of 0.01-1 µM. When used for the NA determination in food samples, the HNTs@VXC-72/GCE sensor exhibited good practical feasibility with low RSD and acceptable recoveries, which provided a promising NA determination approach to ensure food safety.

The genome of a Mongolian individual reveals the genetic imprints of Mongolians on modern human populations.

Mongolians have played a significant role in modern human evolution, especially after the rise of Genghis Khan (1162[?]-1227). Although the social cultural impacts of Genghis Khan and the Mongolian population have been well documented, explorations of their genome structure and genetic imprints on other human populations have been lacking. We here present the genome of a Mongolian male individual. The genome was de novo assembled using a total of 130.8-fold genomic data produced from massively parallel whole-genome sequencing. We identified high-confidence variation sets, including 3.7 million single nucleotide polymorphisms (SNPs) and 756,234 short insertions and deletions. Functional SNP analysis predicted that the individual has a pathogenic risk for carnitine deficiency. We located the patrilineal inheritance of the Mongolian genome to the lineage D3a through Y haplogroup analysis and inferred that the individual has a common patrilineal ancestor with Tibeto-Burman populations and is likely to be the progeny of the earliest settlers in East Asia. We finally investigated the genetic imprints of Mongolians on other human populations using different approaches. We found varying degrees of gene flows between Mongolians and populations living in Europe, South/Central Asia, and the Indian subcontinent. The analyses demonstrate that the genetic impacts of Mongolians likely resulted from the expansion of the Mongolian Empire in the 13th century. The genome will be of great help in further explorations of modern human evolution and genetic causes of diseases/traits specific to Mongolians.