Mammalian cells from both sexes typically contain one active X chromosome but two sets of autosomes. It has previously been hypothesized that X-linked genes are expressed at twice the level of autosomal genes per active allele to balance the gene dose between the X chromosome and autosomes (termed 'Ohno's hypothesis'). This hypothesis was supported by the observation that microarray-based gene expression levels were indistinguishable between one X chromosome and two autosomes (the X to two autosomes ratio (X:AA) ~1). Here we show that RNA sequencing (RNA-Seq) is more sensitive than microarray and that RNA-Seq data reveal an X:AA ratio of ~0.5 in human and mouse. In Caenorhabditis elegans hermaphrodites, the X:AA ratio reduces progressively from ~1 in larvae to ~0.5 in adults. Proteomic data are consistent with the RNA-Seq results and further suggest the lack of X upregulation at the protein level. Together, our findings reject Ohno’s hypothesis, necessitating a major revision of the current model of dosage compensation in the evolution of sex chromosomes.
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Overoxidized polypyrrole films templated with L-glutamate have been utilized for enantioselective detection of L- and D-glutamic acid. Various important fabrication factors controlling the performance of the overoxidized polypyrrole films have been investigated using fluorescence spectrometry in conjugation with the electrochemical quartz crystal microbalance technique. The measured fluorescence intensity was related to the concentration of glutamate taken up into the films. It was found that L-glutamate was inserted approximately 30 times higher into the film than D-glutamate. Several key parameters such as applied potential and pH of amino acid solution were varied to achieve the optimum sensor response. The sensor templated with L-glutamic acid also exhibited excellent selectivity over several other L- and D-amino acids. Higher enantioselectivity of overoxidized polypyrrole film than that for previously reported imprinted polymers can be attributed to the potential-induced uptake/release of targeted molecules.
It is unknown how the composition and structure of DNA within the cell affect spontaneous mutations. Theory suggests that in eukaryotic genomes, nucleosomal DNA undergoes fewer C→T mutations because of suppressed cytosine hydrolytic deamination relative to nucleosome-depleted DNA. Comparative genomic analyses and a mutation accumulation experiment showed that nucleosome occupancy nearly eliminated cytosine deamination, resulting in an ~50% decrease of the C→T mutation rate in nucleosomal DNA. Furthermore, the rates of G→T and A→T mutations were also about twofold suppressed by nucleosomes. On the basis of these results, we conclude that nucleosome-dependent mutation spectra affect eukaryotic genome structure and evolution and may have implications for understanding the origin of mutations in cancers and in induced pluripotent stem cells.
Infections caused by multidrug-resistant (MDR) bacteria pose a threat to human health worldwide, making new effective antibacterial agents urgently desired. To date, it is still a great challenge to develop new antibiotics for MDR bacteria with clear antibacterial mechanisms. Herein, a novel alternative antibacterial copper clusters (CuCs) molecule is precisely synthesized utilizing an artificially designed theanine peptide. The prepared CuCs exhibit excellent broad-spectrum antibacterial activity in vitro, including gram-positive bacteria (methicillin-resistant Staphylococcus aureus [MRSA], Staphylococcus aureus, and Staphylococcus epidermidis) and gram-negative bacteria (Escherichia coli and Pseudomonas aeruginosa). The robust antibacterial effect is due to its ability to not only destroy the bacterial wall structure, but also regulate the ratio of GSH/GSSG by inhibiting the activity of glutathione reductase, thus causing the outbreak of reactive oxygen species and ultimately leading to bacterial death. In addition, in vivo studies demonstrate that CuCs can significantly rescue skin wound infections and sepsis in mice caused by MRSA, and has the same therapeutic efficacy as mupirocin ointment and first-line clinically anchored anti-MRSA drug vancomycin. Moreover, CuCs exhibit extremely low cytotoxicity to normal mammalian cells compared to silver and platinum clusters. With further development and optimization, CuCs has great potential as a new class of antibacterial agents to fight antibiotic-resistant pathogens.
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