Cyclin-dependent kinase 5 (Cdk5) belongs to the family of proline-directed serine/threonine kinases and plays a critical role in neuronal differentiation, migration, synaptogenesis, plasticity, neurotransmission and apoptosis. The deregulation of Cdk5 activity was observed in post mortem analysis of brain tissue of Alzheimer’s disease (AD) patients, suggesting the involvement of Cdk5 in the pathomechanism of this neurodegenerative disease. However, our recent study demonstrated the important function of Cdk5 in regulating inflammatory reaction. Since the role of Cdk5 in regulation of inflammatory signalling in AD is unknown, we investigated the involvement of Cdk5 in neuroinflammation induced by single intracerebroventricular (icv) injection of amyloid beta protein (Aβ) oligomers in mouse. The brain tissue was analysed up to 35 days post injection. Roscovitine (intraperitoneal administration) was used as a potent Cdk5 inhibitor. The experiments were also performed on human neuroblastoma SH-SY5Y as well as mouse BV2 cell lines treated with exogenous oligomeric Aβ. Our results demonstrated that single injection of Aβ oligomers induces long-lasting activation of microglia and astrocytes in the hippocampus. We observed also profound, early inflammatory response in the mice hippocampus, leading to the significant elevation of pro-inflammatory cytokines expression (e.g. TNF-α, IL-1β, IL-6). Moreover, Aβ oligomers elevated the formation of truncated protein p25 in mouse hippocampus and induced overactivation of Cdk5 in neuronal cells. Importantly, administration of roscovitine reduced the inflammatory processes evoked by Aβ in the hippocampus, leading to the significant decrease of cytokines level. These studies clearly show the involvement of Cdk5 in modulation of brain inflammatory response induced by Aβ and may indicate this kinase as a novel target for pharmacological intervention in AD.

The discovery of properties and applications of unknown materials is one of the hottest research areas in materials science. In this work, we navigate a route towards these goals by the development of a new type of graphyne nanostructure. It is synthesised by a Sonogashira cross-coupling reaction of 1,3,5-triethynylbenzene with cyanuric chloride resulting in an extended carbon-based material called TCC. Also, we modify the obtained TCC via fluorination using XeF₂ at various concentrations to investigate the effect of fluorination on the triple bonds and the conjugated structure of graphyne. In this study, we put special emphasis on the determination of the impact of the fluorine content and the type of CF functionalities on the morphology, chemical and electronic structure, biocompatibility, electrical conductivity and possible applicability as anode materials for Li-ion batteries. The obtained results indicate that the character of C–F bonds influences the final properties of fluorinated materials. The polar C–F bonds are preferable for cell proliferation while CF₂ groups are most suitable for battery devices, however, the appearance of PTFE-like units may have a negative impact on battery specific capacitance as well as on cell viability.

The order of Cyanidiales comprises seven acido-thermophilic red microalgal species thriving in hot springs of volcanic origin characterized by extremely low pH, moderately high temperatures and the presence of high concentrations of sulphites and heavy metals that are prohibitive for most other organisms. Little is known about the physiological processes underlying the long-term adaptation of these extremophiles to such hostile environments. Here, we investigated the long-term adaptive responses of a red microalga Cyanidioschyzon merolae, a representative of Cyanidiales, to extremely high nickel concentrations. By the comprehensive physiological, microscopic and elemental analyses we dissected the key physiological processes underlying the long-term adaptation of this model extremophile to high Ni exposure. These include: (i) prevention of significant Ni accumulation inside the cells; (ii) activation of the photoprotective response of non-photochemical quenching; (iii) significant changes of the chloroplast ultrastructure associated with the formation of prolamellar bodies and plastoglobuli together with loosening of the thylakoid membranes; (iv) activation of ROS amelioration machinery; and (v) maintaining the efficient respiratory chain functionality. The dynamically regulated processes identified in this study are discussed in the context of the mechanisms driving the remarkable adaptability of C. merolae to extremely high Ni levels exceeding by several orders of magnitude those found in the natural environment of the microalga. The processes identified in this study provide a solid basis for the future investigation of the specific molecular components and pathways involved in the adaptation of Cyanidiales to the extremely high Ni concentrations.

The correct phagocytic activity of microglia is a prerequisite for maintaining homeostasis in the brain. In the analysis of mechanisms regulating microglial phagocytosis, we focused on the bromodomain and extraterminal domain (BET) proteins: Brd2, Brd3, and Brd4, the acetylation code readers that control gene expression in cooperation with transcription factors. We used pharmacological (JQ1) and genetic (siRNA) inhibition of BET proteins in murine microglial cell line BV2. Inhibition of BET proteins reduced the phagocytic activity of BV2, as determined by using a fluorescent microspheres-based assay and fluorescently labelled amyloid-beta peptides. Gene silencing experiments demonstrated that all brain-existing BET isoforms control phagocytosis in microglia. From a set of 84 phagocytosis-related genes, we have found the attenuation of the expression of 14: Siglec1, Sirpb1a, Cd36, Clec7a, Itgam, Tlr3, Fcgr1, Cd14, Marco, Pld1, Fcgr2b, Anxa1, Tnf, Nod1, upon BET inhibition. Further analysis of the mRNA level of other phagocytosis-related genes which were involved in the pathomechanism of Alzheimer’s disease demonstrated that JQ1 significantly reduced the expression of Cd33, Trem2, and Zyx. Our results indicate the important role of BET proteins in controlling microglial phagocytosis; therefore, targeting BET may be the efficient method of modulating microglial activity.

Core–shell modified nanofiber mats were used as ion-selective membranes for the first time. Keeping the overall macroscopic size of the sensing element the same as for classical plasticized poly(vinyl chloride) membranes, herein the proposed nanofiber based systems resulted in ultrathin (<10 nm) recognition layers with the total area nearly 3 orders of magnitude larger and the surface to volume ratio close to 7.5 × 10⁷. Thus, for the first time close to 2D potentiometric receptors were obtained. Formation of thin and continuous liquid recognition layers on nanofibers was confirmed by XPS studies. The nanofiber based ion-selective mats used in the classical internal-solution arrangement were characterized with analytical parameters – the slope and detection limit well comparable to those for classical plasticized poly(vinyl chloride) based membranes. Despite the novel arrangement of the ion-selective layer and its nanometric thickness, the reproducibility of the recorded potentials, studied for more than 30 days, was high. Using confocal microscopy it was shown that electrolyte transport through porous nanofibers’ mat phase is the rate limiting step in conditioning of the receptor layer. The estimated electrolyte diffusion coefficients for the nanofiber phase are close to 10⁻¹⁰ cm² s⁻¹, and thus are orders of magnitude lower compared to values characterizing ion transport through classical poly(vinyl chloride) based membranes. The truly nanostructural character of nanofiber ion-selective mats is visible in chronoamperometric experiments. It was shown that a core–shell nanofiber mat behaves as an array of nanoelectrodes – individual nanofibers. Thus, the novel nanofiber based architecture of ion-selective mats brings also a new quality to the current based electrochemistry of ion-selective sensors.