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Seven new abietane diterpenoids, comprising medusanthol A–G (1–3, 5, 7–9) and two previously identified analogs (4 and 6), were isolated from the hexane extract of the aerial parts of Medusantha martiusii. The structures of the compounds were elucidated by HRESIMS, 1D/2D NMR spectroscopic data, IR spectroscopy, NMR calculations with DP4+ probability analysis, and ECD calculations. The anti-neuroinflammatory potential of compounds 1–7 was evaluated by determining their ability to inhibit the production of nitric oxide (NO) and the proinflammatory cytokine TNF-α in BV2 microglia stimulated with LPS and IFN-γ. Compounds 1–4 and 7 exhibited decreased NO levels at a concentration of 12.5 µM. Compound 1 demonstrated strong activity with an IC50 of 3.12 µM, and compound 2 had an IC50 of 15.53 µM; both compounds effectively reduced NO levels compared to the positive control quercetin (IC50 11.8 µM). Additionally, both compounds significantly decreased TNF-α levels, indicating their potential as promising anti-neuroinflammatory agents. [ABSTRACT FROM AUTHOR]

Genomic replication is a critical, regulated process that ensures accurate genetic information duplication. In eukaryotic cells, strategies have evolved to prevent conflicts between replication and transcription. Giardia lamblia, a binucleated protozoan, alternates between tetraploid and octaploid genomes during its cell cycle. Using single-molecule techniques like DNA combing and nanopore-based sequencing, we investigated the spatio-temporal organization of DNA replication, replication fork progression and potential head-on replication-transcription collisions in Giardia trophozoites. Our findings indicate that Giardia chromosomes are replicated from only a few active origins, which are widely spaced and exhibit faster replication rates compared to those in other protozoan parasites. Immunofluorescence assays revealed that -20% of trophozoites show asynchronous replication between nuclei. Forksense and gene ontology analyses disclosed that genes in regions with potential head-on collisions are linked to chromatin dynamics, cell cycle regulation and DNA replication/repair pathways, possibly explaining the observed asynchronous replication in part of the population. This study offers the first comprehensive view of replication dynamics in Giardia, which is the pathogen that causes giardiasis, a diarrheal disease impacting millions worldwide. [ABSTRACT FROM AUTHOR]

FeSbO4 powder was prepared using the solid-state reaction method in this work. Afterward, the dense and porous ceramics were obtained by sintering the pressed powder calcined at temperatures of 900 and 1000 °C for 4 h. Rietveld profile analysis of the X-ray powder diffraction data showed that FeSbO4 adopts the trirutile-type structure (space group P42/mnm, with a ≅ 4.63 Å and c ≅ 9.23 Å). SEM images showed that the powder calcined at 900 °C after being sintered at 1200 °C resulted in ceramics of higher crystallinity, larger grains, and consequently, low porosity. The dielectric properties were measured in the frequency range of 10−1 Hz–1 MHz as a function of temperature (25–250 °C). The real (σ′) and imaginary (σ″) parts of the complex conductivity increase with rising annealing temperature for both samples. The real conductivity in the AC region for = 100 kHz was 1.59 × 10 − 6   S · cm − 1 and 7.04 × 10 − 7   S · cm − 1 for the ceramic samples obtained from the powder calcined at 900 (C-900) and 1000 °C (C-1000), respectively. Furthermore, the dielectric constants (k′) measured at room temperature and f = 100   kHz   were 13.77 (C-900) and 6.27 (C-1000), while the activation energies of the grain region were Ea = 0.53 eV and Ea = 0.49 eV, respectively. Similar activation energy (Ea = 0.52 eV and 0.49 eV) was also obtained by the brick-layer model and confirmed by the adjustment of activation energy by DC measurements which indicated an absence of the porosity influence on the parameter. Additionally, loss factor values were obtained to be equal to 3.8 (C-900) and 5.99 (C-1000) for measurements performed at 100 Hz, suggesting a contribution of the conductivity originated from the combination or accommodation of the pores in the grain boundary region. Our results prove that the microstructural factors that play a critical role in the electrical and dielectric properties are the average grain size and the porosity interspersed with the grain boundary region. [ABSTRACT FROM AUTHOR]

The Asteraceae, one of the largest families among angiosperms, is chemically characterised by the production of sesquiterpene lactones (SLs). A total of 1,111 SLs, which were extracted from 658 species, 161 genera, 63 subtribes and 15 tribes of Asteraceae, were represented and registered in two dimensions in the SISTEMATX, an in-house software system, and were associated with their botanical sources. The respective 11 block of descriptors: Constitutional, Functional groups, BCUT, Atom-centred, 2D autocorrelations, Topological, Geometrical, RDF, 3D-MoRSE, GETAWAY and WHIM were used as input data to separate the botanical occurrences through self-organising maps. Maps that were generated with each descriptor divided the Asteraceae tribes, with total index values between 66.7% and 83.6%. The analysis of the results shows evident similarities among the Heliantheae, Helenieae and Eupatorieae tribes as well as between the Anthemideae and Inuleae tribes. Those observations are in agreement with systematic classifications that were proposed by Bremer, which use mainly morphological and molecular data, therefore chemical markers partially corroborate with these classifications. The results demonstrate that the atom-centred and RDF descriptors can be used as a tool for taxonomic classification in low hierarchical levels, such as tribes. Descriptors obtained through fragments or by the two-dimensional representation of the SL structures were sufficient to obtain significant results, and better results were not achieved by using descriptors derived from three-dimensional representations of SLs. Such models based on physico-chemical properties can project new design SLs, similar structures from literature or even unreported structures in two-dimensional chemical space. Therefore, the generated SOMs can predict the most probable tribe where a biologically active molecule can be found according Bremer classification. [ABSTRACT FROM AUTHOR]

Single-celled eukaryote genomes predominantly replicate through multiple origins. Although origin usage during the S-phase has been elucidated in some of these organisms, few studies have comparatively approached this dynamic. Here, we developed a user-friendly website able to calculate the length of the cell cycle phases for any organism. Next, using a formula developed by our group, we showed a comparative analysis among the minimum number of replication origins (MO) required to duplicate an entire chromosome within the S-phase duration in trypanosomatids ( Trypanosoma cruzi , Leishmania major , and Trypanosoma brucei ) and yeasts ( Saccharomyces cerevisiae and Schizosaccharomyces pombe) . Using the data obtained by our analysis, it was possible to predict the MO required in a situation of replication stress. Also, our findings allow establishing a threshold for the number of origins, which serves as a parameter for genome approaches that map origins. Moreover, our data suggest that when compared to yeasts, trypanosomatids use much more origins than the minimum needed. This is the first time a comparative analysis of the minimum number of origins has been successfully applied. These data may provide new insight into the understanding of the replication mechanism and a new methodological framework for studying single-celled eukaryote genomes.

Two new terpenoids, (+)-3-oxo-thermarol and 11-acetoxyeudesman-4alpha-methyl-5alpha-ol along with the (+)- thermarol were isolated from the aerial parts of Salzmmania nitida. The structures and unambiguous 1H and 13C chemical shift assignments were established by spectroscopic means, including homo and heteronuclear techniques.