Small molecules are important tools to measure and modulate intracellular signaling pathways. A longstanding limitation for using chemical compounds in complex tissues has been the inability to target bioactive small molecules to a specific cell class. Here, we describe a generalizable esterase-ester pair capable of targeted delivery of small molecules to living cells and tissue with cellular specificity. We used fluorogenic molecules to rapidly identify a small ester masking motif that is stable to endogenous esterases, but is efficiently removed by an exogenous esterase. This strategy allows facile targeting of dyes and drugs in complex biological environments to label specific cell types, illuminate gap junction connectivity, and pharmacologically perturb distinct subsets of cells. We expect this approach to have general utility for the specific delivery of many small molecules to defined cellular populations. cellular imaging | microscopy | enzyme substrates | fluorophores | pharmacological agents C hemical probes are essential tools in biology for measuring and manipulating cellular properties. Optimization of the structural and electronic features of small molecules allows the fine-tuning of molecular recognition specificity for a particular cellular target. Even with high molecular specificity, however, the application of small molecules in complex biological environments is frequently limited by poor cellular specificity. The inability to target small molecules, such as imaging or pharmacological agents, to defined cellular populations can confound the evaluation and control of discrete subsets of cells within a multicellular environment. A general and efficient strategy for cell-specific targeting, combining the molecular specificity of small molecules with the cellular specificity of genetics, would allow intracellular pathways in defined cell types to be selectively probed in complex tissues.An attractive approach for general cell-specific delivery of small molecules employs selective enzyme-substrate pairs. In this strategy, compounds are masked by attachment of a standard, disposable blocking group that is stable to native cellular enzymes, but labile to a specific exogenous enzyme. Expression of such a protein in a genetically defined cell population permits unmasking of the small molecule with cellular specificity. To be useful across experimental paradigms, such a system should utilize an enzyme that unmasks molecules with high efficiency, expresses in different cell types, and exhibits low cellular toxicity. The cognate masking group must be modular, synthetically efficient, and allow molecules to diffuse passively across the cellular membrane, while also exhibiting favorable solubility and stability in aqueous solution.To date only a few enzyme-substrate pairs have been used as targeted delivery systems for small molecules, and none meet all the criteria outlined above. Strategies employing enzymes encoded by common reporter genes (1) have found some success in targeting small molecules (2-4), ...
This study mainly deals with cenosphere-filled phenolic resin-based composite that is prepared using ceramicceramic fiber as reinforcement by traditional hand layup technique. The effect of cenosphere at various percentage is investigated on the mechanical, ablative, and thermal properties of the filled composites. Mechanical investigation revealed that the addition of microsized cenosphere up to 10% concentration increased the tensile strength of the composite. It is also observed that the addition of cenosphere increased the compressive strength and impact resistance of the composites. Thermogravimetric analysis (TGA) and ablative test revealed that the addition of cenosphere not only decreased both linear and mass ablative rates but also increased the upper working temperature of the filled ceramic/phenolic composites.
The importance of hands in the transmission of hospital infections has been well demonstrated and hand hygiene reduces the prevalence of hospital acquired infections. The study was designed to evaluate the knowledge, attitude, practices and satisfaction of the available facilities among Postgraduates and CRRIs and to identify the gaps in hand hygiene practices and to implement an Institutional program on hand hygiene policy. A self-administered questionnaire was used. The study was conducted between September 2018 and November 2018. A total of 275 participants (148 Postgraduates and 127 CRRIs) participated in the study. Data was analyzed using Microsoft excel 2010 software. Pearson chi-square test was used to check for statistically significant differences. A p-value of less than 0.05 was considered significant. Majority had moderate knowledge (90.9%) whereas postgraduates had better knowledge than CRRIs. The study population had moderate attitude (40.7%) and practices (44%). Postgraduates had good attitude and practices than the CRRIs. 73.5% suggested improvement of the available facilities. A need for hand hygiene training program and multifaceted interventional behavioral program particularly for the medical students to improve the compliance.
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