Involvement of loop 5 lysine residues and the N-terminal β-hairpin of the ribotoxin hirsutellin A on its insecticidal activity

Ribotoxins are cytotoxic members of the family of fungal extracellular ribonucleases best represented by RNase T1. They share a high degree of sequence identity and a common structural fold, including the geometric arrangement of their active sites. However, ribotoxins are larger,with a well-defined N-terminal β-hairpin, and display longer and positively charged unstructured loops. These structural differences account for their cytotoxic properties.Unexpectedly, the discovery of hirsutellin A (HtA), a ribotoxin produced by the invertebrate pathogen Hirsutella thompsonii, showed how it was possible to accommodate these features into a shorter amino acid sequence. Examination of HtA N-terminal β-hairpin reveals differences in terms of length, charge, and spatial distribution. Consequently,four different HtA mutants were prepared and characterized. One of them was the result of deleting this hairpin [Δ(8-15)] while the other three affected single Lys residues in its close spatial proximity (K115E, K118E, and K123E). The results obtained support the general conclusion that HtA active site would show a high degree of plasticity,being able to accommodate electrostatic and structural changes not suitable for the other previously known larger ribotoxins, as the variants described here only presented small differences in terms of ribonucleolytic activity and cytotoxicity against cultured insect cells.

X-ray absorption study of the ferromagnetic Cu moment at the YBa_(2)Cu_(3)O_(7)/La_(2/3)Ca_(1/3)MnO_(3) interface and variation of its exchange interaction with the Mn moment

With x-ray absorption spectroscopy and polarized neutron reflectometry we studied how the magnetic proximity effect at the interface between the cuprate high-TC superconductor YBa_(2)Cu_(3)O_(7) (YBCO) and the ferromagnet La_(2/3)Ca_(1/3)MnO_(3) (LCMO) is related to the electronic and magnetic properties of the LCMO layers. In particular, we explored how the magnitude of the ferromagnetic Cu moment on the YBCO side depends on the strength of the antiferromagnetic (AF) exchange coupling with the Mn moment on the LCMO side. We found that the Cu moment remains sizable if the AF coupling with the Mn moments is strongly reduced or even entirely suppressed. The ferromagnetic order of the Cu moments thus seems to be intrinsic to the interfacial CuO_(2) planes and related to a weakly ferromagnetic intraplanar exchange interaction. The latter is discussed in terms of the partial occupation of the Cu 3d_(3z^(2)−r^(2)) orbitals, which occurs in the context of the so-called orbital reconstruction of the interfacial Cu ions.

Search for associations containing young stars (SACY). VII. New stellar and substellar candidate members in the young associations

Context. The young associations offer us one of the best opportunities to study the properties of young stellar and substellar objects and to directly image planets thanks to their proximity (<200 pc) and age (≈5−150 Myr). However, many previous works have been limited to identifying the brighter, more active members (≈1 M_⊙) owing to photometric survey sensitivities limiting the detections of lower mass objects. Aims. We search the field of view of 542 previously identified members of the young associations to identify wide or extremely wide (1000−100 000 au in physical separation) companions. Methods. We combined 2MASS near-infrared photometry (J, H, K) with proper motion values (from UCAC4, PPMXL, NOMAD) to identify companions in the field of view of known members. We collated further photometry and spectroscopy from the literature and conducted our own high-resolution spectroscopic observations for a subsample of candidate members. This complementary information allowed us to assess the efficiency of our method. Results. We identified 84 targets (45: 0.2−1.3 M_⊙, 17: 0.08−0.2 M_⊙, 22: <0.08 M_⊙) in our analysis, ten of which have been identified from spectroscopic analysis in previous young association works. For 33 of these 84, we were able to further assess their membership using a variety of properties (X-ray emission, UV excess, Hα, lithium and K I equivalent widths, radial velocities, and CaH indices). We derive a success rate of 76–88% for this technique based on the consistency of these properties. Conclusions. Once confirmed, the targets identified in this work would significantly improve our knowledge of the lower mass end of the young associations. Additionally, these targets would make an ideal new sample for the identification and study of planets around nearby young stars. Given the predicted substellar mass of the majority of these new candidate members and their proximity, high-contrast imaging techniques would facilitate the search for new low-mass planets.

Retinal Macroglial Responses in Health and Disease

Due to their permanent and close proximity to neurons, glial cells perform essential tasks for the normal physiology of the retina. Astrocytes andM¨uller cells (retinal macroglia) provide physical support to neurons and supplement them with several metabolites and growth factors.Macroglia are involved in maintaining the homeostasis of extracellular ions and neurotransmitters, are essential for information processing in neural circuits, participate in retinal glucose metabolism and in removing metabolic waste products, regulate local blood flow, induce the blood-retinal barrier (BRB), play fundamental roles in local immune response, and protect neurons from oxidative damage. In response to polyetiological insults, glia cells react with a process called reactive gliosis, seeking to maintain retinal homeostasis. When malfunctioning, macroglial cells can become primary pathogenic elements. A reactive gliosis has been described in different retinal pathologies, including age-related macular degeneration (AMD), diabetes, glaucoma, retinal detachment, or retinitis pigmentosa. A better understanding of the dual, neuroprotective, or cytotoxic effect of macroglial involvement in retinal pathologies would help in treating the physiopathology of these diseases.The extensive participation of the macroglia in retinal diseases points to these cells as innovative targets for new drug therapies.