Subtle atomic group discrimination in the RNA minor groove

As a problem in molecular recognition and for drug discovery, great interest has developed around the possibility that RNA structures could be discriminated by peptides and other small molecules. Although small peptides have been shown to have the capacity to discriminate specific bulges and loops in RNA molecules, discrimination of double helical regions by a peptide binder has not been reported. Indeed, the most accessible part of an RNA helix is the minor groove, and fundamental stereochemical considerations have suggested that discrimination of at least some base pairs would be difficult in the minor groove. Here we report the design and isolation of a peptide binder that manifests the most subtle kind of discrimination of base pair differences in the RNA minor groove. Functional discrimination of a single atomic group is demonstrated as well as the difference between two different angular orientations of the same group. This report of RNA helix discrimination by a peptide binder suggests a richer potential for RNA minor groove recognition than previously thought.

Sex differences in selection of pacemakers: retrospective observational study

Objective: To evaluate the effect of patients’ sex on selection of pacemakers.

Kinetic discrimination in T-cell activation.

We propose a quantitative model for T-cell activation in which the rate of dissociation of ligand from T-cell receptors determines the agonist and antagonist properties of the ligand. The ligands are molecular complexes between antigenic peptides and proteins of the major histocompatibility complex on the surfaces of antigen-presenting cells. Binding of ligand to receptor triggers a series of biochemical reactions in the T cell. If the ligand dissociates after these reactions are complete, the T cell receives a positive activation signal. However, dissociation of ligand after completion of the first reaction but prior to generation of the final products results in partial T-cell activation, which acts to suppress a positive response. Such a negative signal is brought about by T-cell ligands containing the variants of antigenic peptides referred to as T-cell receptor antagonists. Results of recent experiments with altered peptide ligands compare favorably with T-cell responses predicted by this model.

From the boom to the crisis: changes in employment conditions of immigrants in Spain and their effects on mental health

Background: Migrant workers have been one of the groups most affected by the economic crisis. This study evaluates the influence of changes in employment conditions on the incidence of poor mental health of immigrant workers in Spain, after a period of 3 years, in context of economic crisis. Methods: Follow-up survey was conducted at two time points, 2008 and 2011, with a reference population of 318 workers from Colombia, Ecuador, Morocco and Romania residing in Spain. Individuals from this population who reported good mental health in the 2008 survey (n = 214) were interviewed again in 2011 to evaluate their mental health status and the effects of their different employment situations since 2008 by calculating crude and adjusted odds ratios (aORs) for sociodemographic and employment characteristics. Findings: There was an increased risk of poor mental health in workers who lost their jobs (aOR = 3.62, 95%CI: 1.64–7.96), whose number of working hours increased (aOR = 2.35, 95%CI: 1.02–5.44), whose monthly income decreased (aOR = 2.75, 95%CI: 1.08–7.00) or who remained within the low-income bracket. This was also the case for people whose legal status (permission for working and residing in Spain) was temporary or permanent compared with those with Spanish nationality (aOR = 3.32, 95%CI: 1.15–9.58) or illegal (aOR = 17.34, 95%CI: 1.96–153.23). In contrast, a decreased risk was observed among those who attained their registration under Spanish Social Security system (aOR = 0.10, 95%CI: 0.02–0.48). Conclusion: There was an increase in poor mental health among immigrant workers who experienced deterioration in their employment conditions, probably influenced by the economic crisis.