Synthesis and pharmacological evaluation of new 16-methyl pregnane derivatives

The pharmacological activity of several new pregnane derivatives 15-19 were determined on gonadectomized male hamster flank organs, seminal vesicles and in vitro conversion of testosterone (T) to dihydrotestosterone (DHT) as 5alpha-reductase inhibitors. Steroids 15-19 decreased the diameter of the pigmented spot in the flank organs as compared to the T treated animals; in this model, steroids 16 and 19 showed a higher activity than the commercially available finasteride 3. Injection of T increased the weight of the seminal vesicles. Compounds 15-19 when injected together with T decreased the weight of the seminal vesicles thus showing an antiandrogenic effect. The trienone 19 exhibited a considerably higher activity than finasteride. Steroids 15-19 inhibited the in vitro metabolism of [3H]T to [3H]DHT in seminal vesicles homogenates of gonadectomized male hamsters. Compounds 18 and 19 showed a much higher antiandrogenic effect than finasteride. This enhancement of the biological activity could probably be attributed to the coplanarity of the steroidal skeleton as previously observed by our group. The high antiandrogenic activity of the epoxy compound 16 is probably the result of the ring opening of the oxiran ring with the nucleophilic part of the enzyme 5alpha-reductase thus leading to a stable adduct with concomitant deactivation of this enzyme.     

Human Y‐chromosome SNP characterization by multiplex amplified product‐length polymorphism analysis

We designed an allele‐specific amplification protocol to optimize Y‐chromosome SNP typing, which is an unavoidable step for defining the phylogenetic status of paternal lineages. It allows the simultaneous highly specific definition of up to six mutations in a single reaction by amplification fragment length polymorphism (AFLP) without the need of specialized equipment, at a considerably lower cost than that based on single‐base primer extension (SNaPshot?) technology or PCR‐RFLP systems, requiring as little as 0.5 ng DNA and compatible with the small fragments characteristic of low‐quality DNA. By designation of two primers recognizing the derived and ancestral state for each SNP, which can be differentiated by size by the addition of a noncomplementary nucleotide tail, we could define major Y clades E, F, K, R, Q, and subhaplogroups R1, R1a, R1b, R1b1b, R1b1c, J1, J2, G1, G2, I1, Q1a3, and Q1a3a1 through amplification fragments that ranged between 60 and 158bp.     

Fluorescence lifetime enhancement of organic chromophores attached to gold nanoparticles

We present for the first time experimental evidence of fluorescence lifetime enhancement of organic chromophores attached to metal nanospheres via radiative decay engineering. The hybrid system (HS) was a modified "diconjugated" molecular probe, 4-acetamido-4'-maleimidylstilbene-2,2'-dithiol (AMDT), covalently bound to the surface of 5-nm-diameter Au nanospheres by its two sulfur atoms, at a distance d < 1 nm and with its molecular axis parallel to the surface of the nanoparticle surface. We measured a fluorescence lifetime increase of a factor of 2 at room temperature (tau(AMDT) = (4.32 +/- 0.10) ns and tau(HS) = (8.73 +/- 0.23) ns) and a factor of 3.4 at 4.2 K (tau(AMDT) = (2.64 +/- 0.07) ns and tau(HS) = (7.96 +/- 0.14) ns). We also found that the fluorescence quantum yield of this hybrid system is not reduced, proof of a weak energy transfer between the molecular probe and the nanoparticle. These results demonstrate that a molecular dipole oriented parallel to the metal surface tends to be reduced by the coupling with its image.     

Peptoids bearing tertiary amino residues in the n-alkyl side chains: synthesis of a potent inhibitor of Semaphorin 3A

A study on the preparation of N-alkylglycines (peptoids) that contain tertiary amino residues on the N-alkyl side chains is reported. The appropriate combination of the submonomer strategy with N-alkylglycine monomer couplings depending upon the structure of the N-alkyl side chain that must be incorporated into the peptoid is determinant for the efficiency of the synthetic pathway. The application of this strategy to the preparation of SICHI, an N-alkyglycine trimer containing tertiary amino residues in the three N-alkyl branches, and that has been identified as a potent Semaphorin 3A inhibitor, is presented.     

Evaluation of isotope-coded protein labeling (ICPL) in the quantitative analysis of complex proteomes

An evaluation of the ICPL (isotope-coded protein labeling) non-isobaric labeling technique was performed using two different biological models. Two samples containing phage T4 capsids were mixed in a 1:1 ratio after being labeled with the light or heavy versions of the ICPL reagent. The analysis of this proteome demonstrated the feasibility of this approach for differential quantitative proteomics and was employed to optimize the experimental parameters of the ICPL workflow. ICPL-mediated analysis of two more complex proteomes, those of a Salmonella enterica serovar Typhimurium virulent strain and an isogenic attenuated mutant, and its comparison with the results obtained in a 2D-PAGE “classical” approach confirmed that ICPL is a valuable alternative to other labeling techniques currently in use. In addition, our results suggest that labeling at the peptide level instead of following the standard ICPL workflow should increase both the number of proteins quantified and the reliability of the quantification.     

Early error detection: an action-research experience teaching vector calculus

This paper describes an action-research experience carried out with second year students at the School of Engineering of the National University of Entre Ríos, Argentina. Vector calculus students played an active role in their own learning process. They were required to present weekly reports, in both oral and written forms, on the topics studied, instead of merely sitting and watching as the teacher solved problems on the blackboard. The students were also asked to perform computer assignments, and their learning process was continuously monitored. Among many benefits, this methodology has allowed students and teachers to identify errors and misconceptions that might have gone unnoticed under a more passive approach.     

Determination of natural uranium by various analytical techniques in soils of Zacatecas State (Mexico)

Journal of Radioanalytical and Nuclear Chemistry - 238U is a radionuclide present in the earth’s crust that provides 65.9% of annual average radiation dose and represents 99.27% of total...     

Assessment of synthetic cannabinoid FUB-AMB and its ester hydrolysis metabolite in human liver microsomes and human blood samples using UHPLC–MS/MS

FUB-AMB, an indazole carboxamide synthetic cannabinoid recreational drug, was one of the compounds most frequently reported to governmental agencies worldwide between 2016 and 2019. It has been implicated in intoxications and fatalities, posing a risk to public health. In the current study, FUB-AMB was incubated with human liver microsomes (HLM) to assess its metabolic fate and stability and to determine if its major ester hydrolysis metabolite (M1) was present in 12 authentic forensic human blood samples from driving under the influence of drug cases and postmortem investigations using UHPLC–MS/MS. FUB-AMB was rapidly metabolized in HLM, generating M1 that was stable through a 120-min incubation period, a finding that indicates a potential long detection window in human biological samples. M1 was identified in all blood samples, and no parent drug was detected. The authors propose that M1 is a reliable marker for inclusion in laboratory blood screens for FUB-AMB; this metabolite may be pharmacologically active like its precursor FUB-AMB. M1 frequently appears in samples in which the parent drug is undetectable and can point to the causative agent. The results suggest that it is imperative that synthetic cannabinoid laboratory assay panels include metabolites, especially known or potential pharmacologically active metabolites, particularly for compounds with short half-lives.     

Surface-Modified Carbon Materials for CO2 Electroreduction

The electrochemical reduction of CO₂ to produce sustainable fuels and chemicals has attracted great attention in recent years. It is shown that surface-modified carbons catalyze the CO₂RR. This study reports a strategy to modify the surface of commercially available carbon materials by adding oxygen and nitrogen surface groups without modifying its graphitic structure. Clear differences in CO₂RR activity, selectivity and the turnover frequency between the surface-modified carbons were observed, and these differences were ascribed to the nature of the surface groups chemistry and the point of zero charge (PZC). The results show that nitrogen-containing surface groups are highly selective towards the formation of CO from the electroreduction of CO₂ in comparison with the oxygen-containing surface groups, and the carbon without surface groups. This demonstrates that the selectivity of carbon for CO₂RR can be rationally tuned by simply altering the surface chemistry via surface functionalization.