Complement activation in leprosy: a retrospective study shows elevated circulating terminal complement complex in reactional leprosy.

Mycobacterium leprae infection gives rise to the immunologically and histopathologically classified spectrum of leprosy. At present, several tools for the stratification of patients are based on acquired immunity markers. However, the role of innate immunity, particularly the complement system, is largely unexplored. The present retrospective study was undertaken to explore whether the systemic levels of complement activation components and regulators can stratify leprosy patients, particularly in reference to the reactional state of the disease. Serum samples from two cohorts were analysed. The cohort from Bangladesh included multi-bacillary (MB) patients with (n = 12) or without (n = 46) reaction (R) at intake and endemic controls (n = 20). The cohort from Ethiopia included pauci-bacillary (PB) (n = 7) and MB (n = 23) patients without reaction and MB (n = 15) patients with reaction. The results showed that the activation products terminal complement complex (TCC) (P ≤ 0·01), C4d (P ≤ 0·05) and iC3b (P ≤ 0·05) were specifically elevated in Bangladeshi patients with reaction at intake compared to endemic controls. In addition, levels of the regulator clusterin (P ≤ 0·001 without R; P < 0·05 with R) were also elevated in MB patients, irrespective of a reaction. Similar analysis of the Ethiopian cohort confirmed that, irrespective of a reaction, serum TCC levels were increased significantly in patients with reactions compared to patients without reactions (P ≤ 0·05). Our findings suggests that serum TCC levels may prove to be a valuable tool in diagnosing patients at risk of developing reactions.

Complement activation and expression during chronic relapsing experimental autoimmune encephalomyelitis in the Biozzi ABH mouse.

Chronic relapsing experimental autoimmune encephalomyelitis (crEAE) in mice recapitulates many of the clinical and histopathological features of human multiple sclerosis (MS), making it a preferred model for the disease. In both, adaptive immunity and anti-myelin T cells responses are thought to be important, while in MS a role for innate immunity and complement has emerged. Here we sought to test whether complement is activated in crEAE and important for disease. Disease was induced in Biozzi ABH mice that were terminated at different stages of the disease to assess complement activation and local complement expression in the central nervous system. Complement activation products were abundant in all spinal cord areas examined in acute disease during relapse and in the progressive phase, but were absent in early disease remission, despite significant residual clinical disease. Local expression of C1q and C3 was increased at all stages of disease, while C9 expression was increased only in acute disease; expression of the complement regulators CD55, complement receptor 1-related gene/protein y (Crry) and CD59a was reduced at all stages of the disease compared to naive controls. These data show that complement is activated in the central nervous system in the model and suggest that it is a suitable candidate for exploring whether anti-complement agents might be of benefit in MS.

Noise-assisted charge pump in elastically deformable molecular junctions.

We study a charge pump realized with an elastically deformable quantum dot whose center of mass follows a nonlinear stochastic dynamics. The interplay of noise, nonlinear effects, dissipation and interaction with an external time-dependent driving on the pumped charge is fully analyzed. The results show that the quantum pumping mechanism not only is not destroyed by the force fluctuations, but it becomes stronger when the forcing signal frequency is tuned close to the resonance of the vibrational mode. The robustness of the quantum pump with temperature is also investigated and an exponential decay of the pumped charge is found when the coupling to the vibrational mode is present. Implications of our results for nanoelectromechanical systems are also discussed.

C6 deficiency does not alter intrinsic regeneration speed after peripheral nerve crush injury.

Peripheral nerve injury leads to Wallerian degeneration, followed by regeneration, in which functionality and morphology of the nerve are restored. We previously described that deficiency for complement component C6, which prevents formation of the membrane attack complex, slows down degeneration and results in an earlier recovery of sensory function after sciatic nerve injury compared to WT animals. In this study, we determine whether C6(-/-) rats have an intrinsic trait that affects sciatic nerve regeneration after injury. To study the contribution of complement activation on degeneration and regeneration with only minimal effect of complement activation, a crush injury model with only modest complement deposition was used. We compared the morphological and functional aspects of crushed nerves during degeneration and regeneration in C6(-/-) and WT animals. Morphological changes of myelin and axons showed similar degeneration and regeneration patterns in WT and C6(-/-) injured nerves. Functional degeneration and regeneration, recorded by ex vivo electrophysiology and in vivo foot flick test, showed that the timeline of the restoration of nerve conduction and sensory recovery also followed similar patterns in WT and C6(-/-) animals. Our findings suggest that C6 deficiency by itself does not alter the regrowth capacity of the peripheral nerve after crush injury.

Innate immunity in the nervous system.

The complement (C) system plays a central role in innate immunity and bridges innate and adaptive immune responses. A fine balance of C activation and regulation mediates the elimination of invading pathogens and the protection of the host from excessive C deposition on healthy tissues. If this delicate balance is disrupted, the C system may cause injury and contribute to the pathogenesis of various diseases, including neurodegenerative disorders and neuropathies. Here we review evidence indicating that C factors and regulators are locally synthesized in the nervous system and we discuss the evidence supporting the protective or detrimental role of C activation in health, injury, and disease of the nerve.

Low-temperature magnetic and transport anisotropy in manganite thin films.

The stability of striped magnetic phases in films of La(1-x)A(x)MnO(3) perovskites is investigated. A variational analysis is developed for different film thicknesses at fixed hole density (x = 0.3) and the competition among magnetic phases as a function of the transfer integral and the temperature is analyzed. The stabilization of an in-plane striped magnetic phase is observed with reducing the film thickness at low temperatures below the metal-insulator transition temperature. Within the adopted variational scheme, treating perturbatively the residual electron-phonon interaction, the dependence of the in-plane resistivity on temperature for different thicknesses is calculated. At low temperatures, due to the striped magnetic phase, the resistivity shows an important in-plane anisotropy. The obtained results are found to be consistent with experiments.

The complement system in the peripheral nerve: friend or foe?

The complement (C) system plays a central role in innate immunity and bridges innate and adaptive immune responses. A fine balance of C activation and regulation mediates the elimination of invading pathogens and the protection of the host from excessive C deposition on healthy tissues. If this delicate balance is disrupted, the C system may cause injury and contribute to the pathogenesis of various diseases, including neuropathies. Here we review evidence indicating that C factors and regulators are locally synthesized in the peripheral nerve and we discuss the evidence supporting the protective or detrimental role of C activation in health, injury and disease of the peripheral nerve.

Rashba quantum wire: exact solution and ballistic transport.

The effect of Rashba spin-orbit interaction in quantum wires with hard-wall boundaries is discussed. The exact wavefunction and eigenvalue equation are worked out, pointing out the mixing between the spin and spatial parts. The spectral properties are also studied within perturbation theory with respect to the strength of the spin-orbit interaction and diagonalization procedure. A comparison is made with the results of a simple model, the two-band model, that takes account only of the first two sub-bands of the wire. Finally, the transport properties within the ballistic regime are analytically calculated for the two-band model and through a tight-binding Green function for the entire system. Single and double interfaces separating regions with different strengths of spin-orbit interaction are analysed by injecting carriers into the first and the second sub-band. It is shown that in the case of a single interface the spin polarization in the Rashba region is different from zero, and in the case of two interfaces the spin polarization shows oscillations due to spin-selective bound states.