MoS2 pixel arrays for real-time photoluminescence imaging of redox molecules.

Measuring the behavior of redox-active molecules in space and time is crucial for understanding chemical and biological systems and for developing new technologies. Optical schemes are noninvasive and scalable, but usually have a slow response compared to electrical detection methods. Furthermore, many fluorescent molecules for redox detection degrade in brightness over long exposure times. Here, we show that the photoluminescence of "pixel" arrays of monolayer MoS2 can image spatial and temporal changes in redox molecule concentration. Because of the strong dependence of MoS2 photoluminescence on doping, changes in the local chemical potential substantially modulate the photoluminescence of MoS2, with a sensitivity of 0.9 mV / Hz on a 5 µm × 5 µm pixel, corresponding to better than parts-per-hundred changes in redox molecule concentration down to nanomolar concentrations at 100-ms frame rates. This provides a new strategy for visualizing chemical reactions and biomolecules with a two-dimensional material screen.

Valproate and neuroendocrine changes in relation to women treated for epilepsy and bipolar disorder: a review.

Valproic acid (2-n-propylpentanoic acid, VPA) is well-established as a mood-stabilizer for bipolar disorder, in addition to its application as a treatment in neurological disorders such as epilepsy, migraine headaches, and chronic neuropathic pain. Its mechanisms of actions in any of the disorders have not yet been fully elucidated but currently include GABA-ergic inhibitory effects, the suppression of NMDA-mediated excitatory neurotransmission, and possibly effects on monoamines and cerebral glucose metabolism. Given the rising use of VPA by women of reproductive age for various conditions it is increasingly important to understand how VPA affects reproductive and metabolic function in women, yet a number of key issues regarding VPA use in women of reproductive age remain unclear. These include the question of whether VPA use is associated with the development of polycystic ovary syndrome (PCOS)-like features (such as elevated androgen concentrations and/or chronic anovulation). The metabolic effects of VPA use, particularly on insulin sensitivity and weight gain, are also important to understand. Lastly, questions of VPA use during pregnancy and lactation require continued attention. This article reviews the current understanding of VPA's mechanisms of action, effects on the reproductive and metabolic system, and teratogenic qualities, highlighting important future areas of study.

Electronic absorption, EPR, and resonance raman spectroscopy of CooA, a CO-sensing transcription activator from R. rubrum, reveals a five-coordinate NO-heme.

Electronic absorption, EPR, and resonance Raman spectroscopies revealed that CooA, the CO-sensing transcriptional regulator from Rhodospirillum rubrum, reacts with NO to form a five-coordinate NO-heme. NO must therefore displace both of the heme ligands from six-coordinate, low-spin Fe(II)CooA in forming five-coordinate Fe(II)CooA(NO). CO, in contrast, displaces a single heme ligand from Fe(II)CooA to form six-coordinate Fe(II)CooA(CO). Of a series of common heme-binding ligands, only CO and NO were able to bind to the heme of wild-type CooA; imidazole, azide anion, and cyanide anion had no effect on the heme absorption spectrum. Although NO binds to the heme and displaces the endogenous ligands, NO was not able to induce CooA to bind to its target DNA. The mechanism of CO-dependent activation of CooA is thus more complex than simple displacement of a ligand from the heme iron since NO does not trigger DNA binding. These observations suggest that the CooA heme site discriminates between NO and the biologically relevant signal, CO.

Identification of two important heme site residues (cysteine 75 and histidine 77) in CooA, the CO-sensing transcription factor of Rhodospirillum rubrum.

The CO-sensing mechanism of the transcription factor CooA from Rhodospirillum rubrum was studied through a systematic mutational analysis of potential heme ligands. Previous electron paramagnetic resonance (EPR) spectroscopic studies on wild-type CooA suggested that oxidized (FeIII) CooA contains a low-spin heme with a thiolate ligand, presumably a cysteine, bound to its heme iron. In the present report, electronic absorption and EPR analysis of various substitutions at Cys residues establish that Cys75 is a heme ligand in FeIII CooA. However, characterization of heme stability and electronic properties of purified C75S CooA suggest that Cys75 is not a ligand in FeII CooA. Mutational analysis of all CooA His residues showed that His77 is critical for CO-stimulated transcription. On the basis of findings that H77Y CooA is perturbed in its FeII electronic properties and is unable to bind DNA in a site-specific manner in response to CO, His77 appears to be an axial ligand to FeII CooA. These results imply a ligand switch from Cys75 to His77 upon reduction of CooA. In addition, an interaction has been identified between Cys75 and His77 in FeIII CooA that may be involved in the CO-sensing mechanism. Finally, His77 is necessary for the proper conformational change of CooA upon CO binding.