Slc20a1b is essential for hematopoietic stem/progenitor cell expansion in zebrafish

Science China Life Sciences - Hematopoietic stem and progenitor cells (HSPCs) are able to self-renew and can give rise to all blood lineages throughout their lifetime, yet the mechanisms regulating...     

Transfer RNAs Mediate the Rapid Adaptation of Escherichia coli to Oxidative Stress

Translational systems can respond promptly to sudden environmental changes to provide rapid adaptations to environmental stress. Unlike the well-studied translational responses to oxidative stress in eukaryotic systems, little is known regarding how prokaryotes respond rapidly to oxidative stress in terms of translation. In this study, we measured protein synthesis from the entire Escherichia coli proteome and found that protein synthesis was severely slowed down under oxidative stress. With unchanged translation initiation, this slowdown was caused by decreased translation elongation speed. We further confirmed by tRNA sequencing and qRT-PCR that this deceleration was caused by a global, enzymatic downregulation of almost all tRNA species shortly after exposure to oxidative agents. Elevation in tRNA levels accelerated translation and protected E. coli against oxidative stress caused by hydrogen peroxide and the antibiotic ciprofloxacin. Our results showed that the global regulation of tRNAs mediates the rapid adjustment of the E. coli translation system for prompt adaptation to oxidative stress.     

Antibiofilm activity of an exopolysaccharide from marine bacterium Vibrio sp. QY101

Bacterial exopolysaccharides have always been suggested to play crucial roles in the bacterial initial adhesion and the development of complex architecture in the later stages of bacterial biofilm formation. However, Escherichia coli group II capsular polysaccharide was characterized to exert broad-spectrum biofilm inhibition activity. In this study, we firstly reported that a bacterial exopolysaccharide (A101) not only inhibits biofilm formation of many bacteria but also disrupts established biofilm of some strains. A101 with an average molecular weight of up to 546 KDa, was isolated and purified from the culture supernatant of the marine bacterium Vibrio sp. QY101 by ethanol precipitation, iron-exchange chromatography and gel filtration chromatography. High performance liquid chromatography traces of the hydrolyzed polysaccharides showed that A101 is primarily consisted of galacturonic acid, glucuronic acid, rhamnose and glucosamine. A101 was demonstrated to inhibit biofilm formation by a wide range of Gram-negative and Gram-positive bacteria without antibacterial activity. Furthermore, A101 displayed a significant disruption on the established biofilm produced by Pseudomonas aeruginosa, but not by Staphylococcus aureus. Importantly, A101 increased the aminoglycosides antibiotics' capability of killing P. aeruginosa biofilm. Cell primary attachment to surfaces and intercellular aggregates assays suggested that A101 inhibited cell aggregates of both P. aeruginosa and S. aureus, while the cell-surface interactions inhibition only occurred in S. aureus, and the pre-formed cell aggregates dispersion induced by A101 only occurred in P. aeruginosa. Taken together, these data identify the antibiofilm activity of A101, which may make it potential in the design of new therapeutic strategies for bacterial biofilm-associated infections and limiting biofilm formation on medical indwelling devices. The found of A101 antibiofilm activity may also promote a new recognition about the functions of bacterial exopolysaccharides.     

69 DNA-binding studies of large antiviral polyamides

Polyamides are minor groove DNA-binding agents derived from the natural product distamycin A. PA1 is a large 12 ring polyamide discovered by NanoVir LLC; it is bioactive against the HPV16 virus in cell and tissue culture (Edwards et al., 2011). To better understand the basis of this phenomenon, the interactions of PA1 with the regulatory sequence of the HPV16 genome (7662–122?bp) are being examined. Using affinity cleavage as detected by capillary electrophoresis, with PA1 attached to methyl propyl ethidium iron EDTA, 10 binding sites of PA1 were identified in this part of the HPV genome. Polyamide perfect binding sites were as predicted by recognition rules (Dervan & Edelson, 2003). Quantitative DNaseI footprinting indicates that both perfect and single mismatch sites are bound with K_ds in the low nm range. Interestingly, a wide range of K_ds are observed for double mismatch sites (1–60?nm) and are under examination. This work will permit us to build a map of PA binding to HPV sequences, thus informing mechanisms of in vivo behavior.