Finishing the euchromatic sequence of the human genome

The sequence of the human genome encodes the genetic instructions for human physiology, as well as rich information about human evolution. In 2001, the International Human Genome Sequencing Consortium reported a draft sequence of the euchromatic portion of the human genome. Since then, the international collaboration has worked to convert this draft into a genome sequence with high accuracy and nearly complete coverage. Here, we report the result of this finishing process. The current genome sequence (Build 35) contains 2.85 billion nucleotides interrupted by only 341 gaps. It covers ∼99% of the euchromatic genome and is accurate to an error rate of ∼1 event per 100,000 bases. Many of the remaining euchromatic gaps are associated with segmental duplications and will require focused work with new methods. The near-complete sequence, the first for a vertebrate, greatly improves the precision of biological analyses of the human genome including studies of gene number, birth and death. Notably, the human enome seems to encode only 20,000-25,000 protein-coding genes. The genome sequence reported here should serve as a firm foundation for biomedical research in the decades ahead

Formation of anodic TiO₂ nanotube arrays with bimodal pore size distribution

It is revealed that TiO2 nanotube arrays fabricated by anodization of the widely used polycrystalline hexagonal Ti foils have a bimodal pore size distribution rather than the commonly believed monomodal distribution manner. As characterized by X-ray diffraction (XRD), scanning electron microscopy (SEM) and transmission electron microscopy (TEM), it is shown that nanotubes grown on the Ti (0001) plane have thinner barrier thickness, smaller pore size, shorter tube length and better crystallinity than those grown on other planes, due to the enhanced electron transfer reaction and lower oxide formation efficiency on the Ti (0001) plane. When (0001) oriented Ti thin films deposited by RF magnetron sputtering are anodized, the pore sizes of the grown anodic TiO2 nanotubes distribute monomodally and are close to the smaller pore size of the bimodally distributed TiO2 nanotubes grown on polycrystalline Ti foils under the same conditions. Keywords: TiO2 nanotubes, Pore size distribution, Electrochemical anodization, Crystallographic orientatio

Formation of anodic TiO₂ nanotube arrays with bimodal pore size distribution

It is revealed that TiO2 nanotube arrays fabricated by anodization of the widely used polycrystalline hexagonal Ti foils have a bimodal pore size distribution rather than the commonly believed monomodal distribution manner. As characterized by X-ray diffraction (XRD), scanning electron microscopy (SEM) and transmission electron microscopy (TEM), it is shown that nanotubes grown on the Ti (0001) plane have thinner barrier thickness, smaller pore size, shorter tube length and better crystallinity than those grown on other planes, due to the enhanced electron transfer reaction and lower oxide formation efficiency on the Ti (0001) plane. When (0001) oriented Ti thin films deposited by RF magnetron sputtering are anodized, the pore sizes of the grown anodic TiO2 nanotubes distribute monomodally and are close to the smaller pore size of the bimodally distributed TiO2 nanotubes grown on polycrystalline Ti foils under the same conditions. (c) 2013 Elsevier B.V. All rights reserved.</p

Therapeutic Effect of Subunit Vaccine AEC/BC02 on <i>Mycobacterium tuberculosis</i> Post-Chemotherapy Relapse Using a Latent Infection Murine Model

Tuberculosis (TB), caused by the human pathogen Mycobacterium tuberculosis (Mtb), is an infectious disease that presents a major threat to human health. Bacillus Calmette-Guérin (BCG), the only licensed TB vaccine, is ineffective against latent TB infection, necessitating the development of further TB drugs or therapeutic vaccines. Herein, we evaluated the therapeutic effect of a novel subunit vaccine AEC/BC02 after chemotherapy in a spontaneous Mtb relapse model. Immunotherapy followed 4 weeks of treatment with isoniazid and rifapentine, and bacterial loads in organs, pathological changes, and adaptive immune characteristics were investigated. The results showed slowly increased bacterial loads in the spleen and lungs of mice inoculated with AEC/BC02 with significantly lower loads than those of the control groups. Pathological scores for the liver, spleen, and lungs decreased accordingly. Moreover, AEC/BC02 induced antigen-specific IFN-γ-secreting or IL-2-secreting cellular immune responses, which decreased with the number of immunizations and times. Obvious Ag85b- and EC-specific IgG were observed in mice following the treatment with AEC/BC02, indicating a significant Th1-biased response. Taken together, these data suggest that AEC/BC02 immunotherapy post-chemotherapy may shorten future TB treatment

Organic molecular evidence of seafloor hydrocarbon seepage in sedimentary intervals down a core in the northern South China Sea

The hydrocarbons in sedimentary organic matter (OM) at Site 4B in the Pearl River Mouth Basin (PRMB), northern South China Sea (SCS) were analyzed. The odd/even predominance (OEP) of long chain n-alkanes (> n-C-24) with CPI (carbon preference index) values from 1.62 to 3.80 and n-C-29/n-C-31 being the two most abundant in most of the samples are strongly indicative of a terrestrial higher plant source, and the even/odd predominance (EOP) distribution of mid-chain n-alkanes (n-C16-22) suggests a marine bacterial input, probably chemical autotrophic bacteria. However, the biomarker distributions at the 65-70 cm, 80-85 cm and 85-90 cm intervals show a similar to those of crude oils, which were characterized by a dominance of an unresolved complex mixture (UCM) in the n-C20+ region, low CPI values ( 9) of total tricyclic terpanes/alpha beta-C-30 hopane. These features are typical characteristics of mature OM that has experienced catagenesis and metagenesis, suggesting that outside hydrocarbons migrated into these three intervals. In terms of petroleum systems developed in the PRMB, hydrocarbon seepage from deep source rocks via a diaper structure and fault system is proposed to be responsible for the occurrence of this mature OM

The Subunit AEC/BC02 Vaccine Combined with Antibiotics Provides Protection in Mycobacterium tuberculosis-Infected Guinea Pigs

A latent tuberculosis infection (LTBI) is a major source of active tuberculosis, and addressing an LTBI is crucial for the elimination of tuberculosis. The treatment of tuberculosis often requires a 6-month course of multidrug therapy, and for drug-resistant tuberculosis, a longer course of multidrug therapy is needed, which has many drawbacks. At present, vaccines are proposed as an adjunct to chemotherapy to protect populations with an LTBI and delay its recurrence. In this study, we analyzed the protective effect of a novel subunit vaccine, AEC/BC02, in a guinea pig latent infection model. Through the optimization of different chemotherapy durations and immunization times, it was found that 4 weeks of administration of isoniazid&ndash;rifampin tablets combined with three or six injections of the vaccine could significantly reduce the gross pathological score and bacterial load in organs and improve the pathological lesions. This treatment regimen had a better protective effect than the other administration methods. Furthermore, no drug resistance of Mycobacterium tuberculosis was detected after 2 or 4 weeks of administration of the isoniazid&ndash;rifampin tablets, indicating a low risk of developing drug-resistant bacteria during short-term chemotherapy. The above results provided the foundation for an AEC/BC02 clinical protocol

Self-Consistent Thermodynamic Parameters of Diopside at High Temperatures and High Pressures: Implications for the Adiabatic Geotherm of an Eclogitic Upper Mantle

Using an iterative numerical approach, we have obtained the self-consistent thermal expansion, heat capacity, and Grüneisen parameters of diopside (MgCaSi2O6) over wide pressure and temperature ranges based on experimental data from the literature. Our results agree well with the published experimental and theoretical data. The determined thermodynamic parameters exhibit nonlinear dependences with increasing pressure. Compared with other minerals in the upper mantle, we found that the adiabatic temperature gradient obtained using the thermodynamic data of diopside is larger than that of garnet while lower than that of olivine, when ignoring the Fe incorporation. Combining our results with thermodynamic parameters of garnet obtained in previous studies, we have estimated the adiabatic temperature gradient and geotherm of an eclogitic upper mantle in a depth range of 200–450 km. The results show that the estimated adiabatic temperature gradient of the eclogite model is ~16% and ~3% lower than that of the pyrolite model at a depth of 200 km and 410 km, respectively. However, the high mantle potential temperature of the eclogite model leads to a similar temperature as the pyrolite model in a depth range of 200–410 km

Characterization of human enterovirus71 virus-like particles used for vaccine antigens.

Human enterovirus 71 (EV71) is a major causative pathogen of hand, foot and mouth disease (HFMD) and has caused outbreaks with significant mortality among young children in the Asia-Pacific region in recent years. Towards developing a vaccine for this disease, we have expressed and purified EV71 virus-like particles (VLPs), which resemble the authentic virus in appearance, capsid structure and protein sequence, from insect cells (Sf9) using a multistep chromatography process. We demonstrated intracellular localization of the VLPs in host cells by in situ immunogold detection, electron microscopy and immunofluorescence. Characteristics of these EV71 VLPs were studied using a variety of immunological and physicochemical techniques, which aimed to reveal that the purified EV71 VLPs have good morphology and structure consistent with natural EV71 empty capsids. Results of the amino acid analysis, SDS-PAGE, Western blotting and high-performance liquid chromatography confirmed the high purity of the EV71 VLPs. However the sedimentation coefficient of the VLPs showed that they were smaller than that of secreted EV71 VLPs purified by discontinuous cesium chloride density gradients, they were similar to the empty capsids of natural EV71 virions reported previously. Combined with the previous study that EV71 VLPs purified by a multistep chromatography process were able to elicit strong humoral immune responses in mice, our results further supported the conclusion that our EV71 VLPs had well-preserved molecular and structural characteristics. The EV71 VLPs produced from the baculovirus expression system and purified by a multistep chromatography process displayed key structural and immunological features, which would contribute to their efficacy as a HFMD vaccine