Burns and Biofilms: Priority pathogens and in vivo models

Copyright © 2021 The Author(s). Burn wounds can create significant damage to human skin, compromising one of the key barriers to infection. The leading cause of death among burn wound patients is infection. Even in the patients that survive, infections can be notoriously difficult to treat and can cause lasting damage, with delayed healing and prolonged hospital stays. Biofilm formation in the burn wound site is a major contributing factor to the failure of burn treatment regimens and mortality as a result of burn wound infection. Bacteria forming a biofilm or a bacterial community encased in a polysaccharide matrix are more resistant to disinfection, the rigors of the host immune system, and critically, more tolerant to antibiotics. Burn wound-associated biofilms are also thought to act as a launchpad for bacteria to establish deeper, systemic infection and ultimately bacteremia and sepsis. In this review, we discuss some of the leading burn wound pathogens and outline how they regulate biofilm formation in the burn wound microenvironment. We also discuss the new and emerging models that are available to study burn wound biofilm formation in vivo.British Society for Antimicrobial Chemotherapy BSAC-2018-0095; Innovate UK Smart Grant 37800, FRAME, Young European Research University Network Mobility Award, NC3Rs PhD Studentship NC/V001582/1; BBSRC New Investigator Award BB/V007823/1; Academy of Medical Sciences; Wellcome Trust; UK Government Department of Business, Energy and Industrial Strategy; British Heart Foundation/Diabetes UK Springboard Award [SBF006\1040]

Termination Casts: A Flexible Approach to Termination with General Recursion

This paper proposes a type-and-effect system called Teqt, which distinguishes terminating terms and total functions from possibly diverging terms and partial functions, for a lambda calculus with general recursion and equality types. The central idea is to include a primitive type-form "Terminates t", expressing that term t is terminating; and then allow terms t to be coerced from possibly diverging to total, using a proof of Terminates t. We call such coercions termination casts, and show how to implement terminating recursion using them. For the meta-theory of the system, we describe a translation from Teqt to a logical theory of termination for general recursive, simply typed functions. Every typing judgment of Teqt is translated to a theorem expressing the appropriate termination property of the computational part of the Teqt term.Comment: In Proceedings PAR 2010, arXiv:1012.455

Human Pentraxin 3 Binds to the Complement Regulator C4b-Binding Protein

The long pentraxin 3 (PTX3) is a soluble recognition molecule with multiple functions including innate immune defense against certain microbes and the clearance of apoptotic cells. PTX3 interacts with recognition molecules of the classical and lectin complement pathways and thus initiates complement activation. In addition, binding of PTX3 to the alternative complement pathway regulator factor H was shown. Here, we show that PTX3 binds to the classical and lectin pathway regulator C4b-binding protein (C4BP). A PTX3-binding site was identified within short consensus repeats 1–3 of the C4BP α-chain. PTX3 did not interfere with the cofactor activity of C4BP in the fluid phase and C4BP maintained its complement regulatory activity when bound to PTX3 on surfaces. While C4BP and factor H did not compete for PTX3 binding, the interaction of C4BP with PTX3 was inhibited by C1q and by L-ficolin. PTX3 bound to human fibroblast- and endothelial cell-derived extracellular matrices and recruited functionally active C4BP to these surfaces. Whereas PTX3 enhanced the activation of the classical/lectin pathway and caused enhanced C3 deposition on extracellular matrix, deposition of terminal pathway components and the generation of the inflammatory mediator C5a were not increased. Furthermore, PTX3 enhanced the binding of C4BP to late apoptotic cells, which resulted in an increased rate of inactivation of cell surface bound C4b and a reduction in the deposition of C5b-9. Thus, in addition to complement activators, PTX3 interacts with complement inhibitors including C4BP. This balanced interaction on extracellular matrix and on apoptotic cells may prevent excessive local complement activation that would otherwise lead to inflammation and host tissue damage

Critical Enhancement of the In-medium Nucleon-Nucleon Cross Section at low Temperatures

The in-medium nucleon-nucleon cross section is calculated starting from the thermodynamic T-matrix at finite temperatures. The corresponding Bethe-Salpeter-equation is solved using a separable representation of the Paris nucleon-nucleon-potential. The energy-dependent in-medium N-N cross section at a given density shows a strong temperature dependence. Especially at low temperatures and low total momenta, the in-medium cross section is strongly modified by in-medium effects. In particular, with decreasing temperature an enhancement near the Fermi energy is observed. This enhancement can be discussed as a precursor of the superfluid phase transition in nuclear matter.Comment: 10 pages with 4 figures (available on request from the authors), MPG-VT-UR 34/94 accepted for publication in Phys. Rev.

A phenomenological equation of state for isospin asymmetric nuclear matter

A phenomenological momentum-independent (MID) model is constructed to describe the equation of state (EOS) for isospin asymmetric nuclear matter, especially the density dependence of the nuclear symmetry energy $E_{\text{\textrm{sym}}}(\rho)$. This model can reasonably describe the general properties of the EOS for symmetric nuclear matter and the symmetry energy predicted by both the sophisticated isospin and momentum dependent MDI model and the Skyrme-Hartree-Fock approach. We find that there exists a nicely linear correlation between $K_{\mathrm{sym}}$ and $L$ as well as between $J_{0}/K_{0}$ and $K_{0}$, where $L$ and $K_{\mathrm{sym}}$ represent, respectively, the slope and curvature parameters of the symmetry energy at the normal nuclear density $\rho_{0}$ while $K_{0}$ and $J_{0}$ are, respectively, the incompressibility and the third-order derivative parameter of symmetric nuclear matter at $\rho_{0}$. These correlations together with the empirical constraints on $K_{0}$, $L$ and $E_{\text{\textrm{sym}}}(\rho_{0})$ lead to an estimation of -477 MeV $\leq K_{\mathrm{sat,2}}\leq -241$ MeV for the second-order isospin asymmetry expansion coefficient for the incompressibility of asymmetric nuclear matter at the saturation point.Comment: 9 pages, 4 figures, contribution to Special Topic on Large-Scale Scientific Facilities (LSSF) in Science in China Series G: Physics, Mechanics & Astronom

Toward Human-Carnivore Coexistence: Understanding Tolerance for Tigers in Bangladesh

Fostering local community tolerance for endangered carnivores, such as tigers (Panthera tigris), is a core component of many conservation strategies. Identification of antecedents of tolerance will facilitate the development of effective tolerance-building conservation action and secure local community support for, and involvement in, conservation initiatives. We use a stated preference approach for measuring tolerance, based on the ‘Wildlife Stakeholder Acceptance Capacity’ concept, to explore villagers’ tolerance levels for tigers in the Bangladesh Sundarbans, an area where, at the time of the research, human-tiger conflict was severe. We apply structural equation modeling to test an a priori defined theoretical model of tolerance and identify the experiential and psychological basis of tolerance in this community. Our results indicate that beliefs about tigers and about the perceived current tiger population trend are predictors of tolerance for tigers. Positive beliefs about tigers and a belief that the tiger population is not currently increasing are both associated with greater stated tolerance for the species. Contrary to commonly-held notions, negative experiences with tigers do not directly affect tolerance levels; instead, their effect is mediated by villagers’ beliefs about tigers and risk perceptions concerning human-tiger conflict incidents. These findings highlight a need to explore and understand the socio-psychological factors that encourage tolerance towards endangered species. Our research also demonstrates the applicability of this approach to tolerance research to a wide range of socio-economic and cultural contexts and reveals its capacity to enhance carnivore conservation efforts worldwide