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  • Walker Mollerup posted an update 3 months, 2 weeks ago

    Recent studies suggest midkine (MDK) is involved in the development and regeneration of the zebrafish retina. We investigate the expression patterns of MDK and related factors, roles in neuronal survival, and influence upon the formation of Müller glia-derived progenitor cells (MGPCs) in chick and mouse model systems. By using single-cell RNA-sequencing, we find that MDK and pleiotrophin (PTN), a MDK-related cytokine, are upregulated by Müller glia (MG) during later stages of development in chick. While PTN is downregulated, MDK is dramatically upregulated in mature MG after retinal damage or FGF2 and insulin treatment. By comparison, MDK and PTN are downregulated by MG in damaged mouse retinas. In both chick and mouse retinas, exogenous MDK induces expression of cFos and pS6 in MG. In the chick, MDK significantly decreases numbers dying neurons, reactive microglia, and proliferating MGPCs, whereas PTN has no effect. Inhibition of MDK-signaling with Na3 VO4 blocks neuroprotective effects with an increase in the number of dying cells and negates the pro-proliferative effects on MGPCs in damaged retinas. selleck chemicals llc Inhibitors of PP2A and Pak1, which are associated with MDK-signaling through integrin β1, suppressed the formation of MGPCs in damaged chick retinas. In mice, MDK promotes a small but significant increase in proliferating MGPCs in damaged retinas and potently decreases the number of dying cells. We conclude that MDK expression is dynamically regulated in Müller glia during embryonic maturation, following retinal injury, and during reprogramming into MGPCs. MDK mediates glial activity, neuronal survival, and the re-programming of Müller glia into proliferating MGPCs.There is emerging evidence that the performance of risk assessment instruments is weaker when used for clinical decision-making than for research purposes. For instance, research has found lower agreement between evaluators when the risk assessments are conducted during routine practice. We examined the field interrater reliability of the Short-Term Assessment of Risk and Treatability Adolescent Version (STARTAV). Clinicians in a Dutch secure youth care facility completed STARTAV assessments as part of the treatment routine. Consistent with previous literature, interrater reliability of the items and total scores was lower than previously reported in non-field studies. Nevertheless, moderate to good interrater reliability was found for final risk judgments on most adverse outcomes. Field studies provide insights into the actual performance of structured risk assessment in real-world settings, exposing factors that affect reliability. This information is relevant for those who wish to implement structured risk assessment with a level of reliability that is defensible considering the high stakes.The trifluoromethyl group represents one of the most functional and widely used fluoroalkyl groups in drug design and screening, while the drug candidates containing chiral trifluoromethyl-bearing carbons are still few due to the lack of efficient methods for the asymmetric introduction of trifluoromethyl group into organic molecules. Herein, we described a nickel-catalyzed asymmetric trifluoroalkylation of aryl iodides, for the first time, by utilizing reductive cross-coupling in enantioselective fluoroalkylation. This novel method has demonstrated high efficiency, mild conditions, and excellent functional group tolerance, especially for substrates containing diverse pharmaceutical and bioactive molecules moieties. This strategy provided an efficient and facile way for diversity-oriented synthesis of chiral trifluoromethylated alkanes.Li metal holds great promise to be the ultimate anode choice owing to its high specific capacity and low redox potential. However, processing Li metal into thin-film anode with high electrochemical performance and good safety to match commercial cathodes remains challenging. Herein, a new method is reported to prepare ultrathin, flexible, and high-performance Li-Sn alloy anodes with various shapes on a number of substrates by directly stamping a molten metal solution. The printed anode is as thin as 15 µm, corresponding to an areal capacity of ≈3 mAh cm-2 that matches most commercial cathode materials. The incorporation of Sn provides the nucleation center for Li, thereby mitigating Li dendrites as well as decreasing the overpotential during Li stripping/plating (e.g., less then 10 mV at 0.25 mA cm-2 ). As a proof-of-concept, a flexible Li-ion battery using the ultrathin Li-Sn alloy anode and a commercial NMC cathode demonstrates good electrochemical performance and reliable cell operation even after repetitive deformation. The approach can be extended to other metal/alloy anodes such as Na, K, and Mg. This study opens a new door toward the future development of high-performance ultrathin alloy-based anodes for next-generation batteries.Sample injection in microchip-based capillary zone electrophoresis (CZE) frequently rely on the use of electric fields which can introduce differences in the injected volume for the various analytes depending on their electrophoretic mobilities and molecular diffusivities. While such injection biases may be minimized by employing hydrodynamic flows during the injection process, this approach typically requires excellent dynamic control over the pressure gradients applied within a microfluidic network. The current article describes a microchip device that offers this needed control by generating pressure gradients on-chip via electrokinetic means to minimize the dead volume in the system. In order to realize the desired pressure-generation capability, an electric field was applied across two channel segments of different depths to produce a mismatch in the electroosmotic flow rate at their junction. The resulting pressure-driven flow was then utilized to introduce sample zones into a CZE channel with minimal injection bias. The reported injection strategy allowed the introduction of narrow sample plugs with spatial standard deviations down to about 45 μm. This injection technique was later integrated to a capillary zone electrophoresis process for analyzing amino acid samples yielding separation resolutions of about 4-6 for the analyte peaks in a 3 cm long analysis channel.

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