Proteomic Adaptation of Streptococcus pneumoniae to the Human Antimicrobial Peptide LL-37

Secreted antimicrobial peptides (AMPs) are an important part of the human innate immune system and prevent local and systemic infections by inhibiting bacterial growth in a concentration-dependent manner. In the respiratory tract, the cationic peptide LL-37 is one of the most abundant AMPs and capable of building pore complexes in usually negatively charged bacterial membranes, leading to the destruction of bacteria. However, the adaptation mechanisms of several pathogens to LL-37 are already described and are known to weaken the antimicrobial effect of the AMP, for instance, by repulsion, export or degradation of the peptide. This study examines proteome-wide changes in Streptococcus pneumoniae D39, the leading cause of bacterial pneumonia, in response to physiological concentrations of LL-37 by high-resolution mass spectrometry. Our data indicate that pneumococci may use some of the known adaptation mechanisms to reduce the effect of LL-37 on their physiology, too. Additionally, several proteins seem to be involved in resistance to AMPs which have not been related to this process before, such as the teichoic acid flippase TacF (SPD_1128). Understanding colonization- and infection-relevant adaptations of the pneumococcus to AMPs, especially LL-37, could finally uncover new drug targets to weaken the burden of this widespread pathogen

The k-Point Random Matrix Kernels Obtained from One-Point Supermatrix Models

The k-point correlation functions of the Gaussian Random Matrix Ensembles are certain determinants of functions which depend on only two arguments. They are referred to as kernels, since they are the building blocks of all correlations. We show that the kernels are obtained, for arbitrary level number, directly from supermatrix models for one-point functions. More precisely, the generating functions of the one-point functions are equivalent to the kernels. This is surprising, because it implies that already the one-point generating function holds essential information about the k-point correlations. This also establishes a link to the averaged ratios of spectral determinants, i.e. of characteristic polynomials

Two-resonator circuit QED: Dissipative Theory

We present a theoretical treatment for the dissipative two-resonator circuit quantum electrodynamics setup referred to as quantum switch. There, switchable coupling between two superconducting resonators is mediated by a superconducting qubit operating in the dispersive regime, where the qubit transition frequency is far detuned from those of the resonators. We derive an effective Hamiltonian for the quantum switch beyond the rotating wave approximation and study the dissipative dynamics within a Bloch-Redfield quantum master equation approach. We derive analytically how the qubit affects the quantum switch even if the qubit has no dynamics, and we estimate the strength of this influence. The analytical results are corroborated by numerical calculations, where coherent oscillations between the resonators, the decay of coherent and Fock states, and the decay of resonator-resonator entanglement are studied. Finally, we suggest an experimental protocol for extracting the damping constants of qubit and resonators by measuring the quadratures of the resonator fields.Comment: 17 pages, 9 figure

Exact Coupling Coefficient Distribution in the Doorway Mechanism

In many--body and other systems, the physics situation often allows one to interpret certain, distinct states by means of a simple picture. In this interpretation, the distinct states are not eigenstates of the full Hamiltonian. Hence, there is an interaction which makes the distinct states act as doorways into background states which are modeled statistically. The crucial quantities are the overlaps between the eigenstates of the full Hamiltonian and the doorway states, that is, the coupling coefficients occuring in the expansion of true eigenstates in the simple model basis. Recently, the distribution of the maximum coupling coefficients was introduced as a new, highly sensitive statistical observable. In the particularly important regime of weak interactions, this distribution is very well approximated by the fidelity distribution, defined as the distribution of the overlap between the doorway states with interaction and without interaction. Using a random matrix model, we calculate the latter distribution exactly for regular and chaotic background states in the cases of preserved and fully broken time--reversal invariance. We also perform numerical simulations and find excellent agreement with our analytical results.Comment: 22 pages, 4 figure

The Process of Organ Donation from Non-Living Donors: A Case-Based Journey from Potential Donor Identification to Organ Procurement

Each year, thousands of people worldwide succumb to end-organ failure while awaiting life-saving transplantation procedures. The shortage of organs continues with no signs of easing in the foreseeable future. The availability of organs from living donors continues to be constrained. At the same time, the cumulative knowledge of organ preservation is advancing steadily resulting in an enhanced ability to utilize a growing number of previously unsuitable tissue and organ gifts. Our ability to procure and preserve more organs is accompanied by the increasing use of so-called “expanded criteria” donors, or those whose organs may not have been suitable without modern advances in organ preservation science. Within the overall context of organ donation from non-living donors, the importance of physiologic and end-organ optimization cannot be understated. This chapter discusses our current state of understanding of optimized organ procurement approaches derived from practical experiences and “lessons learned” at a high-performing, community-based tertiary referral hospital

The type-2 Streptococcus canis M protein SCM-2 binds fibrinogen and facilitates antiphagocytic properties

Streptococcus canis is a zoonotic agent that causes severe invasive diseases in domestic animals and humans, but little is known about its pathogenesis and virulence mechanisms so far. SCM, the M-like protein expressed by S. canis, is considered one of the major virulence determinants. Here, we report on the two distinct groups of SCM. SCM-1 proteins were already described to interact with its ligands IgG and plasminogen as well as with itself and confer antiphagocytic capability of SCM-1 expressing bacterial isolates. In contrast, the function of SCM-2 type remained unclear to date. Using whole-genome sequencing and subsequent bioinformatics, FACS analysis, fluorescence microscopy and surface plasmon resonance spectrometry, we demonstrate that, although different in amino acid sequence, a selection of diverse SCM-2-type S. canis isolates, phylogenetically representing the full breadth of SCM-2 sequences, were able to bind fibrinogen. Using targeted mutagenesis of an SCM-2 isolate, we further demonstrated that this strain was significantly less able to survive in canine blood. With respect to similar studies showing a correlation between fibrinogen binding and survival in whole blood, we hypothesize that SCM-2 has an important contribution to the pathogenesis of S. canis in the host

Floquet-Markov description of the parametrically driven, dissipative harmonic quantum oscillator

Using the parametrically driven harmonic oscillator as a working example, we study two different Markovian approaches to the quantum dynamics of a periodically driven system with dissipation. In the simpler approach, the driving enters the master equation for the reduced density operator only in the Hamiltonian term. An improved master equation is achieved by treating the entire driven system within the Floquet formalism and coupling it to the reservoir as a whole. The different ensuing evolution equations are compared in various representations, particularly as Fokker-Planck equations for the Wigner function. On all levels of approximation, these evolution equations retain the periodicity of the driving, so that their solutions have Floquet form and represent eigenfunctions of a non-unitary propagator over a single period of the driving. We discuss asymptotic states in the long-time limit as well as the conservative and the high-temperature limits. Numerical results obtained within the different Markov approximations are compared with the exact path-integral solution. The application of the improved Floquet-Markov scheme becomes increasingly important when considering stronger driving and lower temperatures.Comment: 29 pages, 7 figure

Abnormalities in autonomic function in obese boys at-risk for insulin resistance and obstructive sleep apnea.

Study objectivesCurrent evidence in adults suggests that, independent of obesity, obstructive sleep apnea (OSA) can lead to autonomic dysfunction and impaired glucose metabolism, but these relationships are less clear in children. The purpose of this study was to investigate the associations among OSA, glucose metabolism, and daytime autonomic function in obese pediatric subjects.MethodsTwenty-three obese boys participated in: overnight polysomnography; a frequently sampled intravenous glucose tolerance test; and recordings of spontaneous cardiorespiratory data in both the supine (baseline) and standing (sympathetic stimulus) postures.ResultsBaseline systolic blood pressure and reactivity of low-frequency heart rate variability to postural stress correlated with insulin resistance, increased fasting glucose, and reduced beta-cell function, but not OSA severity. Baroreflex sensitivity reactivity was reduced with sleep fragmentation, but only for subjects with low insulin sensitivity and/or low first-phase insulin response to glucose.ConclusionsThese findings suggest that vascular sympathetic activity impairment is more strongly affected by metabolic dysfunction than by OSA severity, while blunted vagal autonomic function associated with sleep fragmentation in OSA is enhanced when metabolic dysfunction is also present

Folding-competent and folding-defective forms of Ricin A chain have different fates following retrotranslocation from the endoplasmic reticulum

We report that a toxic polypeptide retaining the potential to refold upon dislocation from the endoplasmic reticulum (ER) to the cytosol (ricin A chain; RTA) and a misfolded version that cannot (termed RTAΔ), follow ER-associated degradation (ERAD) pathways in Saccharomyces cerevisiae that substantially diverge in the cytosol. Both polypeptides are dislocated in a step mediated by the transmembrane Hrd1p ubiquitin ligase complex and subsequently degraded. Canonical polyubiquitylation is not a prerequisite for this interaction because a catalytically inactive Hrd1p E3 ubiquitin ligase retains the ability to retrotranslocate RTA, and variants lacking one or both endogenous lysyl residues also require the Hrd1p complex. In the case of native RTA, we established that dislocation also depends on other components of the classical ERAD-L pathway as well as an ongoing ER–Golgi transport. However, the dislocation pathways deviate strikingly upon entry into the cytosol. Here, the CDC48 complex is required only for RTAΔ, although the involvement of individual ATPases (Rpt proteins) in the 19S regulatory particle (RP) of the proteasome, and the 20S catalytic chamber itself, is very different for the two RTA variants. We conclude that cytosolic ERAD components, particularly the proteasome RP, can discriminate between structural features of the same substrate