From small molecules to polymeric probes: recent advancements of formaldehyde sensors.

Formaldehyde is a well-known industrial material regularly used in fishery, vegetable markets, and fruit shops for maintaining their freshness. But due to its carcinogenic nature and other toxic effects, it is very important to detect it in very low concentrations. In recent years, amine-containing fluorescent probes have gained significant attention for designing formaldehyde sensors. However, the major drawbacks of these small molecular probes are low sensitivity and long exposure time, which limits their real-life applications. In this regard, polymeric probes have gained significant attention to overcome the aforementioned problems. Several polymeric probes have been utilized as a coating material, nanoparticle, quartz crystal microbalance (QCM), etc., for the selective and sensitive detection of formaldehyde. The main objective of this review article is to comprehensively describe the recent advancements in formaldehyde sensors based on small molecules and polymers, and their successful applications in various fields, especially in situ formaldehyde sensing in biological systems.

In Vitro Selection of Short DNA Aptamers that Can Inhibit or Alleviate Cocaine and MK-801 Inhibition of Muscle-Type Nicotinic Acetylcholine Receptors.

Ligands of high specificity and selectivity have been selected for biological molecules of interest including nicotinic acetylcholine receptor (nAChR) using combinatorial libraries of nucleic acids. The nAChR belongs to a group of structurally related proteins that regulate signal transmission between ~ 1012 cells of the mammalian nervous system. It is inhibited by both therapeutic agents and abused drugs, including cocaine. A mechanism-based approach to alleviating noncompetitive inhibition of the mucle-type nAChR, including Torpedo, resulted in the selection of very short DNA aptamers only seven nucleotides long. By transient kinetic measurements, these DNA aptamers, which displaced cocaine from its binding site on the muscle-type nAChR, were classified into two groups based on their effects on the nAChR: Class I aptamers inhibit agonist-induced current in the muscle-type nAChR and Class II molecules alleviate inhibition by MK-801 [(+)-dizocilpine] without affecting the receptor function. The most potent Class I DNA aptamer, which inhibits the muscle-type nAChR, has an apparent dissociation constant (KIapt) of 5 µM, while the most efficient Class II DNA aptamer, which alleviates MK-801-induced inhibition, has an apparent dissociation constant (KApt) of 1.8 µM. An innovative aspect of the work is the identification of very short DNA aptamers with these properties that makes them attractive for therapeutic and diagnostic applications.

Minimal RNA aptamer sequences that can inhibit or alleviate noncompetitive inhibition of the muscle-type nicotinic acetylcholine receptor.

Combinatorially synthesized nucleotide polymers have been used during the last decade to find ligands that bind to specific sites on biological molecules, including membrane-bound proteins such as the nicotinic acetylcholine receptors (nAChRs). The neurotransmitter receptors belong to a group of four structurally related proteins that regulate signal transmission between ~10(11) neurons of the mammalian nervous system. The nAChRs are inhibited by compounds such as the anticonvulsant MK-801 [(+)-dizocilpine] and abused drugs such as cocaine. Based on predictions arising from the mechanism of receptor inhibition by MK-801 and cocaine, we developed two classes of RNA aptamers: class I members, which inhibit the nAChR, and class II members, which alleviate inhibition of the receptor by MK-801 and cocaine. The systematic evolution of ligands by the exponential enrichment (SELEX) method was used to obtain these compounds. Here, we report that we have truncated RNA aptamers in each class to determine the minimal nucleic acid sequence that retains the characteristic function for which the aptamer was originally selected. We demonstrate that a truncated class I aptamer containing a sequence of seven nucleotides inhibits the nAChR and that a truncated class II aptamer containing a sequence of only four nucleotides can alleviate MK-801 inhibition.

Physical characterization of dibasic calcium phosphate dihydrate and anhydrate.

The dehydration of different commercial brands of dibasic calcium phosphate dihydrate (DCPD; CaHPO(4).2H(2)O) was examined over a range of temperatures and water vapor pressures. To determine the main factors affecting the physical stability of DCPD, the baseline characterization of DCPD and dibasic calcium phosphate anhydrate (DCPA; CaHPO(4)) was conducted by thermogravimetric analysis, differential scanning calorimetry and X-ray diffractometry. The surface area and the DCPA content (present as an impurity) depended on the commercial source of DCPD. The larger particles contained a higher concentration of DCPA and the anhydrate exhibited a concentration-dependent acceleratory effect on the dehydration of DCPD. Unlike DCPD, DCPA is physically stable and resisted hydration even when dispersed in water for over 7 months in the temperature range of 4-50 degrees C. In dosage forms containing DCPD, there is a potential for phase transformation to DCPA, while the reverse transition, that is, DCPA --> DCPD appears to be extremely unlikely. Thus, the risk of physical transformation can be minimized by using DCPA in formulations.

Molecular properties of local anesthetics as predictors of affinity for nicotinic acetylcholine receptors.

In spinal anesthesia, the effects of local anesthetics (LAs) are not completely explained by sodium channel inhibition. Other targets include neuronal nicotinic acetylcholine receptors (nAChRs). LA affinities for the Torpedo californica nAChR were measured by inhibition of [(3)H]TCP binding and correlated with molecular volume, surface area, molecular weight, and log of the octanol-water partition coefficients (P and D). To understand the molecular determinants important for interaction with the nAChR, ester and amide LAs were compared separately. Also, correlations with the aromatic/linker half and the hydrophilic half of the LA molecules were considered individually. The IC(50)s of the ester LAs correlated better with the molecular volume, surface area, molecular weight, and log P of the aromatic/linker half of the molecules; whereas the IC(50)s for amide LAs correlated better with the four parameters based on the hydrophilic half. These correlations were used to predict the IC(50) of various LAs (including several not studied here) and to compare these values with the published values. The predicted values of IC(50) correlated well with the published results both for neuronal and for electroplaque-desensitized nAChR, suggesting that the results can be generalized to include neuronal nAChRs.

Towards a unifying hypothesis of Alzheimer's disease: cholinergic system linked to plaques, tangles and neuroinflammation.

The central role of cholinergic system in Alzheimer's disease (AD) pathway is becoming increasingly significant as reports linking the various components of cholinergic neurotransmission with the other pathological hallmarks emerge. This review, while addressing the molecular mechanisms associated with the pathological hallmarks of the disease and their close interactions, also makes an attempt to address the critical question that evades an answer: Given the significant role played by cholinergic system in AD pathway, why do the cholinergic-mechanism-based drugs are not successful in reversing or arresting the disease progress? Further, as molecules of diverse structural features were shown to inhibit amyloid aggregation, an understanding of the generic pathway of amyloid aggregation slowly emerges. For the first time, a coherent view of amyloid aggregation is presented in this review. The possible role of neuroinflammatory response in the events leading to the degeneration of cholinergic neurons is also discussed.