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The role of nitric oxide (NO) as a signalling molecule in biological systems has been thoroughly studied in the last decades. More recently, there has been an increasing interest in the one-electron reduction product of NO, namely nitroxyl (HNO/NO−). Some studies suggest that nitroxyl can be produced by nitric oxide synthases under certain conditions, and that distinct pharmacological effects are observed for NO and nitroxyl donors. HNO is capable of react with heme proteins, thiols, molecular oxygen, NO and HNO itself. However, only recently the different reactivity patterns are being thoroughly understood. Heme model compounds offer the opportunity to study the reaction kinetics without the complexity arising from ligand interactions with the protein matrix. In this study we analyzed the reaction between the commonly used nitroxyl donors sodium trioxodinitrate and toluene sulfohydroxamic acid, with the ferric model compounds microperoxidase-11 (MP11) and the cationic metalloporphyrin [FeIIITEPyP]5+ (Tetrakis N-ethylpyridinium-2yl porphyne). Our results show that there are two alternative modes of reactivity for nitroxyl donors towards heme in aqueous solutions. The first one comprises the heme assisted decomposition of the donor, enhancing its decomposition rate more than 100-fold. In the second, the donor produces HNO which subsequently reacts with the porphyrin. The observed rate constants (of about 105 M−1 s−1) are consistent with the estimated data for the HNO reaction with heme proteins, and may be controlled by the leaving water ligand. This rate constant probably represents an upper limit for the bimolecular rate constant of HNO towards these proteins.

Proteins integrated or transiently bound to membranes are subject to strong electric fields. However, the role of these fields on tuning the reactivity of redox proteins is still an open issue. High electric fields are also present in protein-based electrochemical devices. In this work we report DFT calculations of the electric field effects on ligand binding and on the redox potentials of porphyrin models representing the active sites of typical heme proteins such as cytochrome c, cytochrome c oxidase, cytochrome c peroxidase and cytochrome P450.

Microglia play critical roles in tissue homeostasis and can also modulate neuronal function and synaptic connectivity. In contrast to astrocytes and oligodendrocytes, which arise from multiple progenitor pools, microglia arise from yolk sac progenitors and are widely considered to be equivalent throughout the CNS. However, little is known about basic properties of deep brain microglia, such as those within the basal ganglia (BG). Here, we show that microglial anatomical features, lysosome content, membrane properties, and transcriptomes differ significantly across BG nuclei. Region-specific phenotypes of BG microglia emerged during the second postnatal week and were re-established following genetic or pharmacological microglial ablation and repopulation in the adult, indicating that local cues play an ongoing role in shaping microglial diversity. These findings demonstrate that microglia in the healthy brain exhibit a spectrum of distinct functional states and provide a critical foundation for defining microglial contributions to BG circuit function.

X-ray reflectivity was employed as a powerful tool for studying the surface and interface roughness and thickness, as well as density, of TiN/Ti/Si layers. X-ray reflectivity of the as-deposited samples, with nominal thickness of 17.5 nm of Ti and 3.0 nm of TiN, shows uniform oscillations. When the samples are annealed at 710°C, residual strongly attenuated oscillations are still observed, while the 850°C-annealed sample does not show oscillations, indicating high surface and interface roughness of the formed nitride and silicide layers. It is demonstrated that increased interface roughness, even for a layer with a larger average electron density difference, reduces the oscillations in the reflectivity curve very rapidly. For comparison, cross sectional transmission electron microscopy was employed to find the thickness of the surface and interface layers in silicide structures, which are in good agreement with the X-ray reflectivity results. The work was also supported by tapping mode atomic force microscopy observations, where we have observed nearly flat structures for the as-deposited sample surface and needle-like protrusions for the annealed samples. The surface roughness of the top TiN layer was used to obtain simulated X-ray reflectivity spectra in good agreement with the experimental results. Preliminarily, the crystallography of the layers in the samples was determined by the grazing angle X-ray diffraction technique, to acquire knowledge on the Ti and Si compounds formed in the samples after the annealing.