A mechanochemical synthesis of submicron-sized Li2S and a mesoporous Li2S/C hybrid for high performance lithium/sulfur battery cathodes

Lithium sulfide, Li2S, is a promising cathode material for lithium–sulfur batteries (LSBs), with a high theoretical capacity of 1166 mA h g−1. However, it suffers from low cycling stability, low-rate capability and high initial activation potential. In addition, commercially available Li2S is of high cost and of large size, over ten microns, which further exacerbate its shortcomings as a sulfur cathode. Exploring new approaches to fabricate small-sized Li2S of low cost and to achieve Li2S cathodes of high electrochemical performance is highly desired. This work reports a novel mechanochemical method for synthesizing Li2S of high purity and submicron size by ball-milling LiH with sulfur in an Ar atmosphere at room temperature. By further milling the as-synthesized Li2S with polyacrylonitrile (PAN) followed by carbonization of PAN at 1000 °C, a Li2S/C hybrid with nano-sized Li2S embedded in a mesoporous carbon matrix is achieved. The hybrid with Li2S as high as 74 wt% shows a high initial capacity of 971 mA h g−1 at 0.1C and retains a capacity of 570 mA h g−1 after 200 cycles as a cathode material for LSBs. A capacity of 610 mA h g−1 is obtained at 1C. The synthesis method of Li2S is facile, environmentally benign, and of high output and low cost. The present work opens a new route for the scalable fabrication of submicron-sized Li2S and for the development of high performance Li2S-based cathodes

A Recalibrated Molecular Clock and Independent Origins for the Cholera Pandemic Clones

Cholera, caused by Vibrio cholerae, erupted globally from South Asia in 7 pandemics, but there were also local outbreaks between the 6th (1899–1923) and 7th (1961–present) pandemics. All the above are serotype O1, whereas environmental or invertebrate isolates are antigenically diverse. The pre 7th pandemic isolates mentioned above, and other minor pathogenic clones, are related to the 7th pandemic clone, while the 6th pandemic clone is in the same lineage but more distantly related, and non-pathogenic isolates show no clonal structure. To understand the origins and relationships of the pandemic clones, we sequenced the genomes of a 1937 prepandemic strain and a 6th pandemic isolate, and compared them with the published 7th pandemic genome. We distinguished mutational and recombinational events, and allocated these and other events, to specific branches in the evolutionary tree. There were more mutational than recombinational events, but more genes, and 44 times more base pairs, changed by recombination. We used the mutational single-nucleotide polymorphisms and known isolation dates of the prepandemic and 7th pandemic isolates to estimate the mutation rate, and found it to be 100 fold higher than usually assumed. We then used this to estimate the divergence date of the 6th and 7th pandemic clones to be about 1880. While there is a large margin of error, this is far more realistic than the 10,000–50,000 years ago estimated using the usual assumptions. We conclude that the 2 pandemic clones gained pandemic potential independently, and overall there were 29 insertions or deletions of one or more genes. There were also substantial changes in the major integron, attributed to gain of individual cassettes including copying from within, or loss of blocks of cassettes. The approaches used open up new avenues for analysing the origin and history of other important pathogens

Transcription and splicing regulation in human umbilical vein endothelial cells under hypoxic stress conditions by exon array

<p>Abstract</p> <p>Background</p> <p>The balance between endothelial cell survival and apoptosis during stress is an important cellular process for vessel integrity and vascular homeostasis, and it is also pivotal in angiogenesis during the development of many vascular diseases. However, the underlying molecular mechanisms remain largely unknown. Although both transcription and alternative splicing are important in regulating gene expression in endothelial cells under stress, the regulatory mechanisms underlying this state and their interactions have not yet been studied on a genome-wide basis.</p> <p>Results</p> <p>Human umbilical vein endothelial cells (HUVECs) were treated with cobalt chloride (CoCl₂) both to mimic hypoxia and to induce cell apoptosis and alternative splicing responses. Cell apoptosis rate analysis indicated that HUVECs exposed to 300 μM CoCl₂for 24 hrs were initially counterbalancing apoptosis with cell survival. We therefore used the Affymetrix exon array system to determine genome-wide transcript- and exon-level differential expression. Other than 1583 differentially expressed transcripts, 342 alternatively spliced exons were detected and classified by different splicing types. Sixteen alternatively spliced exons were validated by RT-PCR. Furthermore, direct evidence for the ongoing balance between HUVEC survival and apoptosis was provided by Gene Ontology (GO) and protein function, as well as protein domain and pathway enrichment analyses of the differentially expressed transcripts. Importantly, a novel molecular module, in which the heat shock protein (HSP) families play a significant role, was found to be activated under mimicked hypoxia conditions. In addition, 46% of the transcripts containing stress-modulated exons were differentially expressed, indicating the possibility of combinatorial regulation of transcription and splicing.</p> <p>Conclusion</p> <p>The exon array system effectively profiles gene expression and splicing on the genome-wide scale. Based on this approach, our data suggest that transcription and splicing not only regulate gene expression, but also carry out combinational regulation of the balance between survival and apoptosis of HUVECs under mimicked hypoxia conditions. Since cell survival following the apoptotic challenge is pivotal in angiogenesis during the development of many vascular diseases, our results may advance the knowledge of multilevel gene regulation in endothelial cells under physiological and pathological conditions.</p

AN INTEGRATED BIOINFORMATIC/EXPERIMENTAL APPROACH FOR DISCOVERING NOVEL TYPE II POLYKETIDES ENCODED IN ACTINOBACTERIAL GENOMES

Discovery of new natural products (NPs) is critical both for diseases treatment and crops protection. Numerous NP biosynthetic gene clusters (BGCs) in sequenced microbial genomes allow identification of new NPs through genome mining. Developing an integrated bioinformatic/experimental approach for discovering novel type II polyketides (PK-IIs) facilitates investigation of this family of NPs in an efficient, systematic way. Here, we developed an approach to analyze ketosynthase α/β (KSα/β) gene sequences to predict PK-II core structures, allowing us to target novel PK-II BGCs either from isolated genomic DNA or genomes from the NCBI databank, and to isolate novel PK-IIs produced by these BGCs. First, new degenerate primers were designed to amplify the region containing key “fingerprint residues” used as predictive indicators of the KSα/β gene product novelty. This work resulted in identification of several BGCs encoding potentially novel PK-IIs in the genomes of 54 Actinobacteria, including 38 unique environmental strains. Next, complete PK-II BGCs were obtained through whole genome sequencing of 5 strains of high priority. Through combined core structure prediction and bioinformatic analysis, Alloactinosynnema sp. L-07 was chosen for compound isolation. By optimizing fermentation conditions, we purified 3.8 mg of sample to elucidate the structure of this compound, a pentangular PK-II which we named alloactinomicin. In another route, we bioinformatically identified over 500 PK-II BGCs from the NCBI databank, and selected 28 of these predicted to produce structurally novel PK-IIs for experimental characterization by a combined genetic/metabolic approach. As a proof of concept, the CRISPR/Cas9-based genome editing was utilized to achieve KSα gene inactivation in two Streptomyces PK-II BGCs. Comparison of wild-type and mutant metabolite profiles led to identification of new putative PK-IIs and correlation of genotype to chemotype for the PK-II BGC being characterized. Finally, we purified one of the metabolites identified and obtained uv-visible and mass spectral evidences consistent with an angucycline-type PK-II, which we named flavochromycin. This work demonstrates two routes for discovery of novel PK-IIs using genomics-driven bioinformatic/experimental approaches. Results from both routes have laid the foundation for more targeted and efficient ways to discover novel NPs for drug and agrochemical development