Hydrazides and hydrazones as versatile Michael-Donors for iminium-catalyzed conjugate addition reactions

396 : il., graf.

Asymmetric organocatalytic cascade reactions

302 p. : gráf.

Phosphorylation of the carboxy-terminal domain of histone H1: effects on secondary structure and DNA condensation

Linker histone H1 plays an important role in chromatin folding. Phosphorylation by cyclin-dependent kinases is the main post-translational modification of histone H1. We studied the effects of phosphorylation on the secondary structure of the DNA-bound H1 carboxy-terminal domain (CTD), which contains most of the phosphorylation sites of the molecule. The effects of phosphorylation on the secondary structure of the DNA-bound CTD were site-specific and depended on the number of phosphate groups. Full phosphorylation significantly increased the proportion of -structure and decreased that of -helix. Partial phosphorylation increased the amount of undefined structure and decreased that of -helix without a significant increase in -structure. Phosphorylation had a moderate effect on the affinity of the CTD for the DNA, which was proportional to the number of phosphate groups. Partial phosphorylation drastically reduced the aggregation of DNA fragments by the CTD, but full phosphorylation restored to a large extent the aggregation capacity of the unphosphorylated domain. These results support the involvement of H1 hyperphosphorylation in metaphase chromatin condensation and of H1 partial phosphorylation in interphase chromatin relaxation. More generally, our results suggest that the effects of phosphorylation are mediated by specific structural changes and are not simply a consequence of the net charge.

Prediction of Multi-Target Networks of Neuroprotective Compounds with Entropy Indices and Synthesis, Assay, and Theoretical Study of New Asymmetric 1,2-Rasagiline Carbamates

In a multi-target complex network, the links (L-ij) represent the interactions between the drug (d(i)) and the target (t(j)), characterized by different experimental measures (K-i, K-m, IC50, etc.) obtained in pharmacological assays under diverse boundary conditions (c(j)). In this work, we handle Shannon entropy measures for developing a model encompassing a multi-target network of neuroprotective/neurotoxic compounds reported in the CHEMBL database. The model predicts correctly >8300 experimental outcomes with Accuracy, Specificity, and Sensitivity above 80%-90% on training and external validation series. Indeed, the model can calculate different outcomes for >30 experimental measures in >400 different experimental protocolsin relation with >150 molecular and cellular targets on 11 different organisms (including human). Hereafter, we reported by the first time the synthesis, characterization, and experimental assays of a new series of chiral 1,2-rasagiline carbamate derivatives not reported in previous works. The experimental tests included: (1) assay in absence of neurotoxic agents; (2) in the presence of glutamate; and (3) in the presence of H2O2. Lastly, we used the new Assessing Links with Moving Averages (ALMA)-entropy model to predict possible outcomes for the new compounds in a high number of pharmacological tests not carried out experimentally.

Mugilid Fish Are Sentinels of Exposure to Endocrine Disrupting Compounds in Coastal and Estuarine Environments

Effects on fish reproduction can result from a variety of toxicity mechanisms first operating at the molecular level. Notably, the presence in the environment of some compounds termed endocrine disrupting chemicals (EDCs) can cause adverse effects on reproduction by interfering with the endocrine system. In some cases, exposure to EDCs leads to the animal feminization and male fish may develop oocytes in testis (intersex condition). Mugilid fish are well suited sentinel organisms to study the effects of reproductive EDCs in the monitoring of estuarine/marine environments. Up-regulation of aromatases and vitellogenins in males and juveniles and the presence of intersex individuals have been described in a wide array of mullet species worldwide. There is a need to develop new molecular markers to identify early feminization responses and intersex condition in fish populations, studying mechanisms that regulate gonad differentiation under exposure to xenoestrogens. Interestingly, an electrophoresis of gonad RNA, shows a strong expression of 5S rRNA in oocytes, indicating the potential of 5S rRNA and its regulating proteins to become useful molecular makers of oocyte presence in testis. Therefore, the use of these oocyte markers to sex and identify intersex mullets could constitute powerful molecular biomarkers to assess xenoestrogenicity in field conditions.

Reutilización de escoria negra de acería como soporte en biofiltros para la eliminación de H2S del biogás.

[EN]Due to the limitations associated with fossil fuels it is necessary to promote energy sources that are renewable as well as eco-friendly, such as biogas generated in anaerobic digesters. The biogas, composed principally of methane and CO2, is the result of the biodegradation of organic matter under anaerobic conditions. Its use as fuel is limited by the presence of minority compounds such as hydrogen sulphide (H2S); therefore, its pre-treatment is necessary. Currently there are various technologies for the removal of H2S from a gas stream, but most of them are based on physic-chemical treatments which have a number of drawbacks as reactive consumption, generation of secondary flows, etc. Biofiltration has been used as an efficient and low cost alternative to conventional purification processes, and excellent results for the degradation of H2S have been obtained. However process can be limited due to the progressive ageing of the support material, along with the loss of nutrients and other specific characteristics necessary for the good development of biomass. The purpose of this project is to develop a mixed support consisting of a mixture of an organic material and an inorganic support for its application in the removal of the H2S from biogas. This support material helps to optimize the characteristics of the bed and extend its lifespan. The development of such material will contribute to the implementation of biofiltration for treating biogas from anaerobic digesters for its use as biofuel. The inorganic material used is electric arc furnace (EAF) black slag, a by-product generated in large quantities in the production of steel in the Basque Country. Although traditionally the slag has been used in civil engineering, its physicochemical characteristics make it suitable for reuse as a filter medium in biofiltration. The main conclusion drawn from the experimental results is that EAF black slag is a suitable co-packing material in organic biofilters treating H2S-polluted gaseous streams. High pollutant removal rates have been achieved during the whole experimental period. The removal capacity recorded in biofilters with less inorganic material was higher than in those with higher slag portion. Nevertheless, all the biofilters have shown a satisfactory response even at high inlet loads (48 g·m-3·h-1), where the RE has not decreased over 82%.

Exploring new labelling strategies for boronated compounds: towards fast development and efficient assessment of BNCT drug candidates

208 p.