Therapeutic Effects of hiPSC-Derived Glial and Neuronal Progenitor Cells-Conditioned Medium in Experimental Ischemic Stroke in Rats

Transplantation of various types of stem cells as a possible therapy for stroke has been tested for years, and the results are promising. Recent investigations have shown that the administration of the conditioned media obtained after stem cell cultivation can also be effective in the therapy of the central nervous system pathology (hypothesis of their paracrine action). The aim of this study was to evaluate the therapeutic effects of the conditioned medium of hiPSC-derived glial and neuronal progenitor cells in the rat middle cerebral artery occlusion model of the ischemic stroke. Secretory activity of the cultured neuronal and glial progenitor cells was evaluated by proteomic and immunosorbent-based approaches. Therapeutic effects were assessed by overall survival, neurologic deficit and infarct volume dynamics, as well as by the end-point values of the apoptosis- and inflammation-related gene expression levels, the extent of microglia/macrophage infiltration and the numbers of formed blood vessels in the affected area of the brain. As a result, 31% of the protein species discovered in glial progenitor cells-conditioned medium and 45% in neuronal progenitor cells-conditioned medium were cell type specific. The glial progenitor cell-conditioned media showed a higher content of neurotrophins (BDNF, GDNF, CNTF and NGF). We showed that intra-arterial administration of glial progenitor cells-conditioned medium promoted a faster decrease in neurological deficit compared to the control group, reduced microglia/macrophage infiltration, reduced expression of pro-apoptotic gene Bax and pro-inflammatory cytokine gene Tnf, increased expression of anti-inflammatory cytokine genes (Il4, Il10, Il13) and promoted the formation of blood vessels within the damaged area. None of these effects were exerted by the neuronal progenitor cell-conditioned media. The results indicate pronounced cytoprotective, anti-inflammatory and angiogenic properties of soluble factors secreted by glial progenitor cells.     

The Formation of Calcified Nanospherites during Micropetrosis Represents a Unique Mineralization Mechanism in Aged Human Bone

Osteocytes—the central regulators of bone remodeling—are enclosed in a network of microcavities (lacunae) and nanocanals (canaliculi) pervading the mineralized bone. In a hitherto obscure process related to aging and disease, local plugs in the lacuno‐canalicular network disrupt cellular communication and impede bone homeostasis. By utilizing a suite of high‐resolution imaging and physics‐based techniques, it is shown here that the local plugs develop by accumulation and fusion of calcified nanospherites in lacunae and canaliculi (micropetrosis). Two distinctive nanospherites phenotypes are found to originate from different osteocytic elements. A substantial deviation in the spherites' composition in comparison to mineralized bone further suggests a mineralization process unlike regular bone mineralization. Clearly, mineralization of osteocyte lacunae qualifies as a strong marker for degrading bone material quality in skeletal aging. The understanding of micropetrosis may guide future therapeutics toward preserving osteocyte viability to maintain mechanical competence and fracture resistance of bone in elderly individuals.     

Deposition welding of hot forging dies using nanoparticle reinforced weld metal

In the application field of forging, the form-giving tool components are subject to process-related severe environmental conditions, such as high mechanical loads acting simultaneously with high tribological and thermal charges. Due to high machine hour rates as well as increasing environmental requirements in terms of energy consumption, wear protection methods and suitable repair measures for forging tools become more and more important. Laser deposition welding represents an established process for the repair of complex shaped surfaces. A new approach is the addition of nano-sized ceramic particles to improve the mechanical properties. The main idea is to reduce the grain size of the cladded layers by adding nano-sized nuclei. A fine grained microstructure will improve strength as well as ductility and fatigue resistance. Furthermore small hard particles can improve the wear resistance without affecting the friction of the surface. After the cladding process the surface has to be finished usually by turning, milling and grinding operations. Within the presented paper the potential of nanoparticle-reinforced deposition welding with regard to increasing the wear resistance of forging dies will be examined. First, the process of nanoparticle-reinforced deposition welding will be presented. Afterwards it will be shown that yttrium oxide, titanium carbide and tungsten carbide nanoparticles in an AISI H10 matrix material will influence the friction coefficient between forging tool and material as well as the wear properties.     

Thermodynamic modeling of oxygen dissolution in uranium mononitride at 900–1400 K

Thermodynamic modeling of oxygen dissolution in uranium mononitride in relation to temperature showed that the solubility limit of oxygen in uranium mononitride monotonically increases from 0.0008 to 0.0092 at. % as the temperature is increased from 900 to 1400 K. The presence of a carbon impurity increases the oxygen solubility in uranium mononitride by a factor of 4–5. The oxygen solubility increases by 20–30% as the stoichiometric coefficient in uranium mononitride containing a carbon impurity is decreased by 0.005.     

Transferrin-Decorated Niosomes with Integrated InP/ZnS Quantum Dots and Magnetic Iron Oxide Nanoparticles: Dual Targeting and Imaging of Glioma

The development of multifunctional nanoscale systems that can mediate efficient tumor targeting, together with high cellular internalization, is crucial for the diagnosis of glioma. The combination of imaging agents into one platform provides dual imaging and allows further surface modification with targeting ligands for specific glioma detection. Herein, transferrin (Tf)-decorated niosomes with integrated magnetic iron oxide nanoparticles (MIONs) and quantum dots (QDs) were formulated (PEGNIO/QDs/MIONs/Tf) for efficient imaging of glioma, supported by magnetic and active targeting. Transmission electron microscopy confirmed the complete co-encapsulation of MIONs and QDs in the niosomes. Flow cytometry analysis demonstrated enhanced cellular uptake of the niosomal formulation by glioma cells. In vitro imaging studies showed that PEGNIO/QDs/MIONs/Tf produces an obvious negative-contrast enhancement effect on glioma cells by magnetic resonance imaging (MRI) and also improved fluorescence intensity under fluorescence microscopy. This novel platform represents the first niosome-based system which combines magnetic nanoparticles and QDs, and has application potential in dual-targeted imaging of glioma.     

Schwarz lemma for driving point impedance functions and its circuit applications

In this paper, a boundary version of the Schwarz lemma is investigated for driving point impedance functions and its circuit applications. It is known that driving point impedance function, Z(s) = 1 + c_p(s − 1)^p + c_{p + 1}(s − 1)^{p + 1} + ..., p > 1, is an analytic function defined on the right half of the s-plane. Two theorems are presented using the modulus of the derivative of driving point impedance function, |Z′(0)|, by assuming the Z(s) function is also analytic at the boundary point s = 0 on the imaginary axis with . In the obtained inequalities, the value of the function at s = 1 and the derivatives with different orders have been used. Finally, the sharpness of the inequalities obtained in the presented theorems is proved. Simple LC circuits are obtained using the obtained driving point impedance functions.     

Aurora Kinase A Is Involved in Controlling the Localization of Aquaporin-2 in Renal Principal Cells

The cAMP-dependent aquaporin-2 (AQP2) redistribution from intracellular vesicles into the plasma membrane of renal collecting duct principal cells induces water reabsorption and fine-tunes body water homeostasis. However, the mechanisms controlling the localization of AQP2 are not understood in detail. Using immortalized mouse medullary collecting duct (MCD4) and primary rat inner medullary collecting duct (IMCD) cells as model systems, we here discovered a key regulatory role of Aurora kinase A (AURKA) in the control of AQP2. The AURKA-selective inhibitor Aurora-A inhibitor I and novel derivatives as well as a structurally different inhibitor, Alisertib, prevented the cAMP-induced redistribution of AQP2. Aurora-A inhibitor I led to a depolymerization of actin stress fibers, which serve as tracks for the translocation of AQP2-bearing vesicles to the plasma membrane. The phosphorylation of cofilin-1 (CFL1) inactivates the actin-depolymerizing function of CFL1. Aurora-A inhibitor I decreased the CFL1 phosphorylation, accounting for the removal of the actin stress fibers and the inhibition of the redistribution of AQP2. Surprisingly, Alisertib caused an increase in actin stress fibers and did not affect CFL1 phosphorylation, indicating that AURKA exerts its control over AQP2 through different mechanisms. An involvement of AURKA and CFL1 in the control of the localization of AQP2 was hitherto unknown.