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The emergence of multi-drug resistant (MDR) microbes leads to urgent demands for novel antibiotics exploration. We demonstrated a cDNA from amphioxus Branchiostoma japonicum, designated Bjamp1, encoded a protein with features typical of antimicrobial peptides (AMPs), which is not homologous to any AMPs currently discovered. It was found that Bjamp1 was expressed in distinct tissues, and its expression was remarkably up-regulated following challenge with LPS and LTA. Moreover, the synthesized putative mature AMP, mBjAMP1, underwent a coil-to-helix transition in the presence of TFE or SDS, agreeing well with the expectation that BjAMP1 was a potential AMP. Functional assays showed that mBjAMP1 inhibited the growth of all the bacteria tested, and induced membrane/cytoplasmic damage. ELISA indicated that mBjAMP1 was a pattern recognition molecule capable of identifying LPS and LTA. Importantly, mBjAMP1 disrupted the bacterial membranes by a membranolytic mechanism. Additionally, mBjAMP1 was non-cytotoxic to mammalian cells. Collectively, these data indicate that mBjAMP1 is a new AMP with a high bacterial membrane selectivity, rendering it a promising template for the design of novel peptide antibiotics against MDR microbes. It also shows for the first time that use of signal conserved sequence of AMPs is effective identifying potential AMPs across different animal classes.

Major histocompatibility Complex class I (MHC I) molecules are ubiquitously expressed, being found in most nucleated cells, where they are central mediators of both the adaptive and innate immune responses. Recent studies have shown that MHC I are also expressed in the developing brain where they participate in synapse elimination and plasticity. Up‐regulation of MHC I within the developing brain has been reported, however, the mechanism(s) regulating this developmental up‐regulation of neuronal MHC I remains unknown. Here, we show NLR family CARD domain containing 5 (NLRC5), a newly identified member of the NLR family, is widely expressed in hippocampal neurons, and the expression pattern of NLRC5 coincides with increased MHC I mRNA in the developing hippocampus. Using a luciferase assay in Neuro‐2a cells we demonstrate that NLRC5 can induce the activation of MHC I and this induction requires the W/S‐X‐Y motif. Further studies show that transcription factors regulatory factor X (RFX) and CREB1, which bind to X1 and X2 box, are crucial for NLRC5‐mediated induction. Moreover immunoprecipitation experiments reveal that NLRC5 interacts with RFX subunits RFX5 and RFXANK. Knockout of Nlrc5 dramatically impairs basal expression of MHC I in mouse hippocampus. Taken together, our findings identify NLRC5 as a key regulator of MHC I up‐regulation in the developing hippocampus and suggest an important role for NLRC5 in neurons. Cover Image for this issue: doi: .

No abstract

Aging asymmetry is the observation that different tissues age in different ways and at different rates. This has not been assessed in a single organism using multiple biomarkers of aging. Here we clearly demonstrated that the levels of protein oxidation and lipid peroxidation as well as CAT, SOD and GPX activities all showed a tissue-dependent change with advancing age; and DNA repair ability, as revealed by the expression of ercc1 and its protein levels, also exhibited a tissue-specific variation with age. We also found that protein oxidation and lipid peroxidation levels remained relatively stable in the liver, intestine, skin and testis as well as in the brain, eye and heart of young, adult and aged fishes; SOD and GPX activities displayed little variation in the intestine, eye and skin as well as in the brain and skin of young, adult and aged fishes; and low and stable expression of ercc1 was observed in the spleen, eye and heart of young, adult and aged fishes. Collectively, these results indicate that aging is tissue specific and asymmetric in N. guentheri. The observation of aging asymmetry may have practical implications for the application of non-intrusion intervention approaches to prolong lifespan.