Ring Vibrations to Sense Anionic Ibuprofen in Aqueous Solution as Revealed by Resonance Raman

We unravel the potentialities of resonance Raman spectroscopy to detect ibuprofen in diluted aqueous solutions. In particular, we exploit a fully polarizable quantum mechanics/molecular mechanics (QM/MM) methodology based on fluctuating charges coupled to molecular dynamics (MD) in order to take into account the dynamical aspects of the solvation phenomenon. Our findings, which are discussed in light of a natural bond orbital (NBO) analysis, reveal that a selective enhancement of the Raman signal due to the normal mode associated with the C–C stretching in the ring, νC=C, can be achieved by properly tuning the incident wavelength, thus facilitating the recognition of ibuprofen in water samples.

2-Oxoglutarate derivatives can selectively enhance or inhibit the activity of human oxygenases

Abstract2-Oxoglutarate (2OG) oxygenases are validated agrochemical and human drug targets. The potential for modulating their activity with 2OG derivatives has not been explored, possibly due to concerns regarding selectivity. We report proof-of-principle studies demonstrating selective enhancement or inhibition of 2OG oxygenase activity by 2-oxo acids. The human 2OG oxygenases studied, factor inhibiting hypoxia-inducible transcription factor HIF-α (FIH) and aspartate/asparagine-β-hydroxylase (AspH), catalyze C3 hydroxylations of Asp/Asn-residues. Of 35 tested 2OG derivatives, 10 enhance and 17 inhibit FIH activity. Comparison with results for AspH reveals that 2OG derivatives selectively enhance or inhibit FIH or AspH. Comparison of FIH structures complexed with 2OG derivatives to those for AspH provides insight into the basis of the observed selectivity. 2-Oxo acid derivatives have potential as drugs, for use in biomimetic catalysis, and in functional studies. The results suggest that the in vivo activity of 2OG oxygenases may be regulated by natural 2-oxo acids other than 2OG.

Acetylcholine prioritises direct synaptic inputs from entorhinal cortex to CA1 by differential modulation of feedforward inhibitory circuits

Acetylcholine release in the hippocampus plays a central role in the formation of new memory representations. An influential but largely untested theory proposes that memory formation requires acetylcholine to enhance responses in CA1 to new sensory information from entorhinal cortex whilst depressing inputs from previously encoded representations in CA3. Here, we show that excitatory inputs from entorhinal cortex and CA3 are depressed equally by synaptic release of acetylcholine in CA1. However, feedforward inhibition from entorhinal cortex exhibits greater depression than CA3 resulting in a selective enhancement of excitatory-inhibitory balance and CA1 activation by entorhinal inputs. Entorhinal and CA3 pathways engage different feedforward interneuron subpopulations and cholinergic modulation of presynaptic function is mediated differentially by muscarinic M3 and M4 receptors, respectively. Thus, our data support a role and mechanisms for acetylcholine to prioritise novel information inputs to CA1 during memory formation.

The Role of Endoplasmic Reticulum in the Differential Endurance against Redox Stress in Cortical and Spinal Astrocytes from the Newborn SOD1G93A Mouse Model of Amyotrophic Lateral Sclerosis

Recent studies reported that the uptake of [18F]-fluorodeoxyglucose (FDG) is increased in the spinal cord (SC) and decreased in the motor cortex (MC) of patients with ALS, suggesting that the disease might differently affect the two nervous districts with different time sequence or with different mechanisms. Here we show that MC and SC astrocytes harvested from newborn B6SJL-Tg (SOD1G93A) 1Gur mice could play different roles in the pathogenesis of the disease. Spectrophotometric and cytofluorimetric analyses showed an increase in redox stress, a decrease in antioxidant capacity and a relative mitochondria respiratory uncoupling in MC SOD1G93A astrocytes. By contrast, SC mutated cells showed a higher endurance against oxidative damage, through the increase in antioxidant defense, and a preserved respiratory function. FDG uptake reproduced the metabolic response observed in ALS patients: SOD1G93A mutation caused a selective enhancement in tracer retention only in mutated SC astrocytes, matching the activity of the reticular pentose phosphate pathway and, thus, of hexose-6P dehydrogenase. Finally, both MC and SC mutated astrocytes were characterized by an impressive ultrastructural enlargement of the endoplasmic reticulum (ER) and impairment in ER–mitochondria networking, more evident in mutated MC than in SC cells. Thus, SOD1G93A mutation differently impaired MC and SC astrocyte biology in a very early stage of life.

Surface-enhanced Raman scattering of water in aqueous dispersions of silver nanoparticles

The resonance Raman effect (RRE) is a phenomenon which results in a strong selective enhancement of Raman signals from the samples. Previous studies showed that the RRE in liquid water directly corresponds to its supramolecular structure. It was also reported that the electric-field-induced orientation of water molecules on the electrode surface results in the surface-enhanced Raman scattering (SERS) effect. In this work, we show the SERS effect for water molecules in the dispersion of silver nanoparticles (AgNPs) without any external electrical field. An enhancement factor was estimated to be (4.8 ± 0.8) × 106 for an excitation wavelength of 514.5 nm and for AgNPs with an average size of 34 ± 14 nm. The temperature experiment results showed a higher enhancement with temperature increase. Performed simulation studies revealed a slowdown of the mobility of the water molecules close to the surface of AgNPs.