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Microbes are present as communities in the environment. However, the importance of minor populations has not been well studied experimentally. In this study, we evaluated the role of Bacillus subtilis with a 1% population and its effect on co-incubated Enterococcus faecalis with a 99% population. Here we used an azo dye-decolorizing Enterococcus faecalis strain T6a1 and non-dye-decolorizing Bacillus subtilis strain S4ga. The dye decolorization assay enabled the investigation of the effects of B. subtilis S4ga on the activity of E. faecalis T6a1, even when B. subtilis S4ga was present at only 1% relative abundance or lower. We found that non-decolorizing B. subtilis S4ga enhanced the dye decolorization activity of E. faecalis T6a1, shortened the lag time of E. faecalis T6a1 to start decreasing the dye concentration, and increased the time for E. faecalis T6a1 to continue dye decolorization. These effects were correlated with redox potential values. We compared the extracellular amino acids between each incubation culture of E. faecalis T6a1 and B. subtilis S4ga, which revealed their mutual relationship by cross-feeding of specific amino acids. We also compared the intracellular primary metabolites between co-incubation and sole incubation of E. faecalis T6a1. The arginine deiminase (ADI) pathway in the co-incubated E. faecalis T6a1 was activated compared to that of E. faecalis T6a1 incubated solely. These findings explained that co-incubation with B. subtilis S4ga promoted ATP production in E. faecalis T6a1 cells to a greater extent and enhanced dye-decolorization activity.IMPORTANCEThis study highlights the importance of minor bacterial populations and their effects on major populations. We used Enterococcus faecalis as the major population and Bacillus subtilis as the minor population. Both species are becoming increasingly important. Some strains of E. faecalis are antibiotic-resistant pathogens, show probiotic effects, or are applicable for textile wastewater treatment. Some strains of B. subtilis are known to produce antimicrobial agents, reduce intestinal inflammation, or restore gut microbiota. We demonstrated that a low abundance of B. subtilis with 1% population increased the amount of energy produced by E. faecalis with 99% population, which appeared as enhanced dye decolorization activity of dye-decolorizing E. faecalis. Metabolomic analysis suggested that E. faecalis and B. subtilis had a mutual relationship by feeding specific amino acids to each other. These results provide new insights into co-existing minor populations in microbial communities and will improve our understanding of bacterial control.Graphical abstract

Chemical modifications of histones, such as lysine acetylation and ubiquitination, play pivotal roles in epigenetic regulation of gene expression. Methods to alter the epigenome thus hold promise as tools for elucidating epigenetic mechanisms and as therapeutics. However, an entirely chemical method to introduce histone modifications in living cells without genetic manipulation is unprecedented. Here, we developed a chemical catalyst, PEG-LANA-DSSMe 11, that binds with nucleosome’s acidic patch and promotes regioselective, synthetic histone acetylation at H2BK120 in living cells. The size of polyethylene glycol in the catalyst was a critical determinant for its in-cell metabolic stability, binding affinity to histones, and high activity. The synthetic acetylation promoted by 11 without genetic manipulation competed with and suppressed physiological H2B ubiquitination, a mark regulating chromatin functions, such as transcription and DNA damage response. Thus, the chemical catalyst will be a useful tool to manipulate epigenome for unraveling epigenetic mechanisms in living cells.

The neuromuscular junction (NMJ) is the synapse between a motor neuron and skeletal muscle. Defects in NMJ transmission cause muscle weakness, termed myasthenia. The muscle protein Dok-7 is essential for activation of the receptor kinase MuSK, which governs NMJ formation, and DOK7 mutations underlie familial limb-girdle myasthenia (DOK7 myasthenia), a neuromuscular disease characterized by small NMJs. Here, we show in a mouse model of DOK7 myasthenia that therapeutic administration of an adeno-associated virus (AAV) vector encoding the human DOK7 gene resulted in an enlargement of NMJs and substantial increases in muscle strength and life span. When applied to model mice of another neuromuscular disorder, autosomal dominant Emery-Dreifuss muscular dystrophy, DOK7 gene therapy likewise resulted in enlargement of NMJs as well as positive effects on motor activity and life span. These results suggest that therapies aimed at enlarging the NMJ may be useful for a range of neuromuscular disorders.

Chimpanzees rarely capture an animal without eating it, but this puzzling pattern occurs in both nature and captivity, mostly by youngsters1-6. At Bossou in Guinea, chimpanzees rarely hunt for meat; their home range presents few suitable prey7. From 1976 to 2008, only one bird (West African wood-owl, Ciccaba woodfordi) capture was recorded, and it was consumed7. In 2009, we saw two captures of this species, which were not followed by consumption. Instead, both raptors were used as toys, as previously observed at Bossou with tree hyrax, Dendrohyrax dorsalis3. Here we describe the captures and discuss the implications of this behavior from an evolutionary perspective.

Skeletal muscle contraction is controlled by motor neurons, which contact the muscle at the neuromuscular junction (NMJ). The formation and maintenance of the NMJ, which includes the aggregation of densely packed clusters of acetylcholine receptor (AChR) opposite the motor nerve terminal, is orchestrated by muscle-specific receptor tyrosine kinase, MuSK. Recently, a MuSK-interacting cytoplasmic adaptor-like protein Dok-7 was identified and its localization at the postsynaptic region of the NMJ was revealed. Mice lacking Dok-7 have a phenotype indistinguishable from MuSK-deficient mice, and fail to form both AChR clusters and NMJs. In cultured myotubes, Dok-7 is required for MuSK activation and AChR clustering. Thus, Dok-7 is essential for neuromuscular synaptogenesis and it appears that the regulatory interaction of Dok-7 with MuSK is integrally involved in this process. In humans there are both autoimmune and genetic causes of defective neuromuscular transmission that gives rise to the fatigable muscle weakness known as myasthenia. DOK7 has been found to be a major locus for mutations that underlie a genetic form of myasthenia with a characteristic 'limb girdle' pattern of muscle weakness (DOK7 CMS). Patients with DOK7 CMS have small, simplified NMJs but normal AChR function. The most common mutation causes a COOH-terminal truncation, which greatly impairs Dok-7's ability to activate MuSK. Recently, a series of differing DOK7 mutations have been identified, which affect not only the COOH-terminal region but also the NH2-terminal moiety. The study of these mutations may help understand the underlying pathogenic mechanism of DOK7 CMS.