Strategies against nonsense: oxadiazoles as translational readthrough-inducing drugs (TRIDs)

This review focuses on the use of oxadiazoles as translational readthrough-inducing drugs (TRIDs) to rescue the functional full-length protein expression in mendelian genetic diseases caused by nonsense mutations. These mutations in specific genes generate premature termination codons (PTCs) responsible for the translation of truncated proteins. After a brief introduction on nonsense mutations and their pathological effects, the features of various classes of TRIDs will be described discussing differences or similarities in their mechanisms of action. Strategies to correct the PTCs will be presented, particularly focusing on a new class of Ataluren-like oxadiazole derivatives in comparison to aminoglycosides. Additionally, recent results on the efficiency of new candidate TRIDs in restoring the production of the cystic fibrosis transmembrane regulator (CFTR) protein will be presented. Finally, a prospectus on complementary strategies to enhance the effect of TRIDs will be illustrated together with a conclusive paragraph about perspectives, opportunities, and caveats in developing small molecules as TRIDs

A Probit Model of NLRB Bargaining Order Cases in the Appellate Courts

This study examines NLRB bargaining orders that have gone to appeals courts and ascertains what factors influence whether or not the order is enforced and to what degree these factors influence the likelihood of enforcement. Substantial information has been collected from each reported appellate decision that reviewed NLRB bargaining orders issued over a four-year period. A probit regression model is employed to examine whether factors related to an employer\u27s unfair labor practice campaign are involved in the circuit court\u27s enforcement decisions or if more weight is given to unrelated factors, such as the circuit in which the appeal is heard or the amount of judicial delay involved in the appeals process

A Probit Model of NLRB Bargaining Order Cases in the Appellate Courts

This study examines NLRB bargaining orders that have gone to appeals courts and ascertains what factors influence whether or not the order is enforced and to what degree these factors influence the likelihood of enforcement. Substantial information has been collected from each reported appellate decision that reviewed NLRB bargaining orders issued over a four-year period. A probit regression model is employed to examine whether factors related to an employer\u27s unfair labor practice campaign are involved in the circuit court\u27s enforcement decisions or if more weight is given to unrelated factors, such as the circuit in which the appeal is heard or the amount of judicial delay involved in the appeals process

A new approach to mass spectrometer measurements of thermospheric density

The gas sampling problem in satellite and high velocity probes was investigated by applying the theory of a drifting Maxwellian gas. A lens system using a free stream ion source was developed and experimentally evaluated over the pressure range of 0.00001 to 0.01 N/m sq (approx. 10 to the minus 7th power to 0.0001 torr). The source has high beam transparency, which minimizes gas-surface collisions within, or near, the ionization volume. It is shown that for high ion energy (60 eV), the extracted ion beam has an on-axis energy spread of less than 4 eV, and that 90 percent of the ions are within 2.5 deg of the beam axis. It is concluded that the molecular beam mass spectrometer concept, developed for gas density measurements in the upper atmosphere, substantially reduces gas-surface scattering and gas-surface reactions in the sample, and preserves the integrity of the gas sample during the analysis process. Studies show that both the Scout and Delta launch vehicles have adequate volume, control, velocity, and data acquisition capability necessary to obtain thermospheric number density in real time

Genomic and Non-genomic Action of Neurosteroids in the Peripheral Nervous System

Since the former evidence of biologic actions of neurosteroids in the central nervous system, also the peripheral nervous system (PNS) was reported as a structure affected by these substances. Indeed, neurosteroids are synthesized and active in the PNS, exerting many important actions on the different cell types of this system. PNS is a target for neurosteroids, in their native form or as metabolites. In particular, old and recent evidence indicates that the progesterone metabolite allopregnanolone possesses important functions in the PNS, thus contributing to its physiologic processes. In this review, we will survey the more recent findings on the genomic and non-genomic actions of neurosteroids in nerves, ganglia, and cells forming the PNS, focusing on the mechanisms regulating the peripheral neuron-glial crosstalk. Then, we will refer to the physiopathological significance of the neurosteroid signaling disturbances in the PNS, in to identify new molecular targets for promising pharmacotherapeutic approaches