Surface Localization Determinants of Borrelia burgdorferi Lipoproteins

Borrelia spirochetes are the causative agents of Lyme disease and relapsing fever, two common vector-borne diseases. Early experimental evidence, gained from development of genetic tools in the Lyme disease spirochete, Borrelia burgdorferi, emphasized the importance of outer surface lipo-proteins (Osps) during the infectious cycle. Although the functions of these lipoproteins and the complex mechanism of differential regulation is known in increasing detail, it remains to be understood how these virulence factors reach the spirochetal surface. We observed in previous studies that monomeric red fluorescent protein 1 (mRFP1) fused to specifically mutated outer surface protein A (OspA) lipopeptides could be detected by epifluorescence microscopy in both the periplasm and on the bacterial surface. These findings supported the notion that Borrelia spirochetes do not adhere to the +2/+3/+4 sorting rules established in other eubacteria. Rather, borrelial lipoproteins seem to contain a disordered `tether' peptide located at the extreme N-terminus of the mature lipoprotein that influences sorting within the envelope. One facet of this study utilized an N-proximal tandem negative charge (Glu-Asp) that served as an inner membrane retention signal in OspA20:mRFP1 as a target for mutagenesis. A library of random mutants in the two codons was generated and expressed in B. burgdorferi. In situ surface proteolysis combined with fluorescence activated cell sorting (FACS) was then used to screen for viable spirochetes expressing subsurface OspA:mRFP1 fusions. We successfully recovered several mutants that mislocalized the lipo-mRFP1 fusions to the periplasm, adding to our database of peptide sequences that are not permissive for surface export. We then broadened our studies to include the structurally and functionally distinct dimeric OspC-Vsp family lipoproteins and identified their requirements for surface localization. As for OspA, tether sequences influence the localization of OspC-Vsp lipoproteins within the envelope. Interestingly, OspC-Vsp lipoproteins appear to be translocated across the outer membrane as monomers. This suggests that they assume their final oligomeric state only when reaching the spirochetal surface. Additionally, lower molecular weight variants of OspC and Vsp1 were detected indicating cleavage that was exacerbated upon addition of C-terminal epitope tags or mislocalization of the untagged proteins to the periplasm. C-terminal proteolysis of OspC was attributed to a carboxy-terminal protease, CtpA. To date, known substrates of CtpA include the 13-kDa outer membrane porin, P13, and a periplasmic lipoprotein BB0323. C-terminal proteolysis of OspC and Vsp1 suggests CtpA may also function as a periplasmic housekeeping protease. In turn, released C-terminal peptides may play a role in initiation of an envelope stress response. Another aspect of this work examined the subcellular localization pattern of Braun's lipoprotein (Lpp) from E. coli using B. burgdorferi as a surrogate expression host. Surprisingly, Lpp was localized to the B. burgdorferi inner membrane. On the other hand, B. burgdorferi OspA mutants were sorted by E. coli according to E. coli rules. This dataset confirmed that host factors are setting the rules for localization of lipoproteins within the bacterial envelope. Taken together, this work revealed several factors, such as the composition of the lipoprotein tether and the folding state of the lipoprotein, which influences trafficking within the spirochetal cell envelope, and also provided important insights into periplasmic lipoprotein processing of B. burgdorferi. These findings will broaden our understanding of spirochetal lipoprotein transport as well as cell envelope biogenesis. Ultimately, this work may lead to novel treatments and/or vaccination strategies that will be extremely helpful in combating Lyme disease and relapsing fever in the years and decades to come

An Intuitive Automated Modelling Interface for Systems Biology

We introduce a natural language interface for building stochastic pi calculus models of biological systems. In this language, complex constructs describing biochemical events are built from basic primitives of association, dissociation and transformation. This language thus allows us to model biochemical systems modularly by describing their dynamics in a narrative-style language, while making amendments, refinements and extensions on the models easy. We demonstrate the language on a model of Fc-gamma receptor phosphorylation during phagocytosis. We provide a tool implementation of the translation into a stochastic pi calculus language, Microsoft Research's SPiM

Exploring the components of meal-sharing experiences with local foods: A netnography approach

This study aims to explore and ascertain the components of meal-sharing experiences with local foods of international travellers. This study offers insights into the factors influencing local food tourists’ evaluation of destination experiences of a sharing economy platform. A netnography approach is applied to understand the meal-sharing experience and 957 online reviews are examined which were posted on Eatwith by visitors who participated in the meal-sharing economy platform in Rome (Italy) between 2013 and 2020. Findings reveal seven components of meal-sharing experiences with local foods: authenticity, social interaction, local hospitality, awe, local culture, novelty, and servicescape. Findings show that participants can interpret their meal-sharing experience in different ways. To the authors’ knowledge, this is the first research that uses online reviews to explore and understand the meal-sharing experience with local foods. This study has unique theoretical contribution by exploring the components of meal-sharing experience with local foods, as well as practical implications for service providers in order to enhance their service and experience quality

Explicit MBR All-Symbol Locality Codes

Node failures are inevitable in distributed storage systems (DSS). To enable efficient repair when faced with such failures, two main techniques are known: Regenerating codes, i.e., codes that minimize the total repair bandwidth; and codes with locality, which minimize the number of nodes participating in the repair process. This paper focuses on regenerating codes with locality, using pre-coding based on Gabidulin codes, and presents constructions that utilize minimum bandwidth regenerating (MBR) local codes. The constructions achieve maximum resilience (i.e., optimal minimum distance) and have maximum capacity (i.e., maximum rate). Finally, the same pre-coding mechanism can be combined with a subclass of fractional-repetition codes to enable maximum resilience and repair-by-transfer simultaneously

Deep Spin-Glass Hysteresis Area Collapse and Scaling in the d=3d=3 ±J\pm J Ising Model

We investigate the dissipative loss in the $\pm J$ Ising spin glass in three dimensions through the scaling of the hysteresis area, for a maximum magnetic field that is equal to the saturation field. We perform a systematic analysis for the whole range of the bond randomness as a function of the sweep rate, by means of frustration-preserving hard-spin mean field theory. Data collapse within the entirety of the spin-glass phase driven adiabatically (i.e., infinitely-slow field variation) is found, revealing a power-law scaling of the hysteresis area as a function of the antiferromagnetic bond fraction and the temperature. Two dynamic regimes separated by a threshold frequency $\omega_c$ characterize the dependence on the sweep rate of the oscillating field. For $\omega < \omega_c$, the hysteresis area is equal to its value in the adiabatic limit $\omega = 0$, while for $\omega > \omega_c$ it increases with the frequency through another randomness-dependent power law.Comment: 6 pages, 6 figure

Excitation Spectrum Gap and Spin-Wave Stiffness of XXZ Heisenberg Chains: Global Renormalization-Group Calculation

The anisotropic XXZ spin-1/2 Heisenberg chain is studied using renormalization-group theory. The specific heats and nearest-neighbor spin-spin correlations are calculated thoughout the entire temperature and anisotropy ranges in both ferromagnetic and antiferromagnetic regions, obtaining a global description and quantitative results. We obtain, for all anisotropies, the antiferromagnetic spin-liquid spin-wave velocity and the Isinglike ferromagnetic excitation spectrum gap, exhibiting the spin-wave to spinon crossover. A number of characteristics of purely quantum nature are found: The in-plane interaction s_i^x s_j^x + s_i^y s_j^y induces an antiferromagnetic correlation in the out-of-plane s_i^z component, at higher temperatures in the antiferromagnetic XXZ chain, dominantly at low temperatures in the ferromagnetic XXZ chain, and, in-between, at all temperatures in the XY chain. We find that the converse effect also occurs in the antiferromagnetic XXZ chain: an antiferromagnetic s_i^z s_j^z interaction induces a correlation in the s_i^xy component. As another purely quantum effect, (i) in the antiferromagnet, the value of the specific heat peak is insensitive to anisotropy and the temperature of the specific heat peak decreases from the isotropic (Heisenberg) with introduction of either type (Ising or XY) anisotropy; (ii) in complete contrast, in the ferromagnet, the value and temperature of the specific heat peak increase with either type of anisotropy.Comment: New results added to text and figures. 12 pages, 18 figures, 3 tables. Published versio

Inequality and Procedural Justice in Social Dilemmas

This study investigates the influence of resource inequality and the fairness of the allocation procedure of unequal resources on cooperative behavior in social dilemmas. We propose a simple formal behavioral model that incorporates conflicting selfish and social motivations. This model allows us to predict how inequality influences cooperative behavior. Allocation of resources is manipulated by three treatments that vary in terms of procedural justice: allocating resources randomly, based on merit, and based on ascription. As predicted, procedural justice influences cooperation significantly. Moreover, gender is found to be an important factor interacting with the association between procedural justice and cooperative behavior.