Structural basis for hemoglobin capture by Staphylococcus aureus cell-surface protein, IsdH

Pathogens must steal iron from their hosts to establish infection. In mammals, hemoglobin (Hb) represents the largest reservoir of iron, and pathogens express Hb-binding proteins to access this source. Here, we show how one of the commonest and most significant human pathogens, Staphylococcus aureus, captures Hb as the first step of an iron-scavenging pathway. The x-ray crystal structure of Hb bound to a domain from the Isd (iron-regulated surface determinant) protein, IsdH, is the first structure of a Hb capture complex to be determined. Surface mutations in Hb that reduce binding to the Hb-receptor limit the capacity of S. aureus to utilize Hb as an iron source, suggesting that Hb sequence is a factor in host susceptibility to infection. The demonstration that pathogens make highly specific recognition complexes with Hb raises the possibility of developing inhibitors of Hb binding as antibacterial agents. © 2011 by The American Society for Biochemistry and Molecular Biology, Inc

Intraoperative hyperspectral label-free imaging: from system design to first-in-patient translation.

Despite advances in intraoperative surgical imaging, reliable discrimination of critical tissue during surgery remains challenging. As a result, decisions with potentially life-changing consequences for patients are still based on the surgeon's subjective visual assessment. Hyperspectral imaging (HSI) provides a promising solution for objective intraoperative tissue characterisation, with the advantages of being non-contact, non-ionising and non-invasive. However, while its potential to aid surgical decision-making has been investigated for a range of applications, to date no real-time intraoperative HSI (iHSI) system has been presented that follows critical design considerations to ensure a satisfactory integration into the surgical workflow. By establishing functional and technical requirements of an intraoperative system for surgery, we present an iHSI system design that allows for real-time wide-field HSI and responsive surgical guidance in a highly constrained operating theatre. Two systems exploiting state-of-the-art industrial HSI cameras, respectively using linescan and snapshot imaging technology, were designed and investigated by performing assessments against established design criteria and ex vivo tissue experiments. Finally, we report the use of our real-time iHSI system in a clinical feasibility case study as part of a spinal fusion surgery. Our results demonstrate seamless integration into existing surgical workflows

Direct Type I IFN but Not MDA5/TLR3 Activation of Dendritic Cells Is Required for Maturation and Metabolic Shift to Glycolysis after Poly IC Stimulation

We thank the Rockefeller University Center for Clinical and Translational Science (UL1 TR000043 NCATS, NIH) for technical support

Impact of Climate Change on Voltinism and Prospective Diapause Induction of a Global Pest Insect – Cydia pomonella (L.)

Global warming will lead to earlier beginnings and prolongation of growing seasons in temperate regions and will have pronounced effects on phenology and life-history adaptation in many species. These changes were not easy to simulate for actual phenologies because of the rudimentary temporal (season) and spatial (regional) resolution of climate model projections. We investigate the effect of climate change on the regional incidence of a pest insect with nearly worldwide distribution and very high potential for adaptation to season length and temperature – the Codling Moth, Cydia pomonella. Seasonal and regional climate change signals were downscaled to the hourly temporal scale of a pest phenology model and the spatial scale of pest habitats using a stochastic weather generator operating at daily scale in combination with a re-sampling approach for simulation of hourly weather data. Under future conditions of increased temperatures (2045–2074), the present risk of below 20% for a pronounced second generation (peak larval emergence) in Switzerland will increase to 70–100%. The risk of an additional third generation will increase from presently 0–2% to 100%. We identified a significant two-week shift to earlier dates in phenological stages, such as overwintering adult flight. The relative extent (magnitude) of first generation pupae and all later stages will significantly increase. The presence of first generation pupae and later stages will be prolonged. A significant decrease in the length of overlap of first and second generation larval emergence was identified. Such shifts in phenology may induce changes in life-history traits regulating the life cycle. An accordingly life-history adaptation in photoperiodic diapause induction to shorter day-length is expected and would thereby even more increase the risk of an additional generation. With respect to Codling Moth management, the shifts in phenology and voltinism projected here will require adaptations of plant protection strategies to maintain their sustainability

Engineered hexavalent Fc proteins with enhanced Fc-gamma receptor avidity provide insights into immune-complex interactions

Tania Rowley et al. present multivalent Fc molecules with enhanced avidity for Fc gamma receptors in order to improve the treatment of autoantibody-mediated human diseases. They found several key amino acids involved in Fc receptor binding interactions

Structure of the hemoglobin-isdh complex reveals the molecular basis of iron capture by staphylococcus aureus

Background: IsdB and IsdH proteins from Staphylococcus aureus strip heme iron from human hemoglobin. Results: The IsdH·hemoglobin complex shows how globin-binding and heme-binding NEAT domains of IsdH cooperate to remove heme from both chains of hemoglobin. Conclusion: The supradomain architecture of IsdH confers activity by precisely positioning the heme acceptor domain. Significance: Multiple IsdH·hemoglobin interfaces may be targets for new antibiotics. © 2014 by The American Society for Biochemistry and Molecular Biology, Inc