EDXRF study of Tupi-Guarani archaeological ceramics.

A set of indian Brazilian pottery fragments belonging to Tupi-Guarani tradition has been studied by an archaeometric non-destructive technique. The pottery fragments were accidentally discovered in the Santa Dalmacia farm, sited near Cambé city at the north of Paraná Brazilian state. Each one of these fragments came from different ceramic recipients and their physical characteristics are very similar. The EDXRF measurements were performed employing both an X-ray tube and three radioisotope sources (Fe, Cd and Pu). The compositional data of the ceramics paste and pigments is investigated. For detection of the elements within the ceramic paste, the fragments were irradiated at the center of the lateral section, while several superficial areas with remaining plastic decoration were also chosen and irradiated at the convex and concave sides of each fragment. A paste-subtracted compositional data of the remaining pigments was statically extracted from the XRF analysis of each area. A program based on the graphic polygonal representation method was developed and used to correlate the representative intensity data of each fragment.Um conjunto de fragmentos cerâmicos indígenas brasileiros pertencentes à Tradição Tupi-Guarani foi estudado por uma técnica arqueométrica não destrutiva. Os fragmentos cerâmicos foram descobertos acidentalmente na fazenda Santa Dalmácia, situada próximo da cidade de Cambé, no norte do estado do Paraná. Cada um desses fragmentos veio de diferentes recipientes cerâmicos e suas características físicas são muito similares. As medidas EDXRF foram realizadas empregando tanto um tubo de raios X como três fontes de radioisótopos (55Fe, 109Cd e 238Pu). Os dados de composição da pasta cerâmica e dos pigmentos são investigados. Para detecção dos elementos contidos na pasta cerâmica, os fragmentos foram irradiados no centro da secção lateral, enquanto algumas áreas com decoração plástica remanescente também foram escolhidas e irradiadas nos lados convexo e côncavo de cada fragmento. Foram obtidas as composições dos pigmentos remanescentes em cada área analisada, subtraindo-se do espectro XRF da área considerada o espectro XRF da pasta cerâmica. Um programa baseado no método de representação poligonal gráfica foi desenvolvido e usado para correlacionar a intensidade representativa de cada fragmento

Selection and validation of reference genes by RT-qPCR under photoperiodic induction of flowering in sugarcane ( Saccharum spp.)

Although reference genes have previously been used in the expression analysis of genes involved in sugarcane flowering they had not been experimentally validated for stability and consistency of expression between different samples over a wide range of experimental conditions. Here we report the analysis of candidate reference genes in different tissue types, at different temporal time-points, in both short and long day photoperiodic treatments. The stability of the candidate reference genes in all conditions was evaluated with NormFinder, BestKeeper, and RefFinder algorithms that complement each other for a more robust analysis. As the Normfinder algorithm was more appropriate for our experimental conditions, greater emphasis was placed on Normfinder when choosing the most stable genes. UBQ1 and TUB were shown to be the most stable reference genes to use for normalizing RT-qPCR gene expression data during floral induction, whilst 25SrRNA1 and GAPDH were the least stable. Their use as a reference gene pair was validated by analyzing the expression of two differentially expressed target genes (PIL5 and LHP1). The UBQ1/TUB reference genes combination was able to reveal small significant differences in gene expression of the two target genes that were not detectable when using the least stable reference gene combination. These results can be used to inform the choice of reference genes to use in the study of the sugarcane floral induction pathway. Our work also demonstrates that both PIL5 and LHP1 are significantly up-regulated in the initial stages of photoperiodic induction of flowering in sugarcane

Development of Potential Multi-Target Inhibitors for Human Cholinesterases and Beta-Secretase 1: A Computational Approach

Alzheimer’s disease causes chronic neurodegeneration and is the leading cause of dementia in the world. The causes of this disease are not fully understood but seem to involve two essential cerebral pathways: cholinergic and amyloid. The simultaneous inhibition of AChE, BuChE, and BACE-1, essential enzymes involved in those pathways, is a promising therapeutic approach to treat the symptoms and, hopefully, also halt the disease progression. This study sought to identify triple enzymatic inhibitors based on stereo-electronic requirements deduced from molecular modeling of AChE, BuChE, and BACE-1 active sites. A pharmacophore model was built, displaying four hydrophobic centers, three hydrogen bond acceptors, and one positively charged nitrogen, and used to prioritize molecules found in virtual libraries. Compounds showing adequate overlapping rates with the pharmacophore were subjected to molecular docking against the three enzymes and those with an adequate docking score (n = 12) were evaluated for physicochemical and toxicological parameters and commercial availability. The structure exhibiting the greatest inhibitory potential against all three enzymes was subjected to molecular dynamics simulations (100 ns) to assess the stability of the inhibitor-enzyme systems. The results of this in silico approach indicate ZINC1733 can be a potential multi-target inhibitor of AChE, BuChE, and BACE-1, and future enzymatic assays are planned to validate those results.PPBE and PPGCF/UEFS; Fundação de Amparo à Pesquisa do Estado de Minas Gerais—FAPEMIG, grants APQ-02741-17, APQ-00855-19, APQ-01733-21, and APQ-04559-22Conselho Nacional de Desenvolvimento Científico e Tecnológico—CNPq-Brazil, grants 305117/2017-3, 426261/2018-6Fellowship of 2021 (grant 310108/2020-9

Structural basis of GC-1 selectivity for thyroid hormone receptor isoforms

Background: Thyroid receptors, TRα and TRβ, are involved in important physiological functions such as metabolism, cholesterol level and heart activities. Whereas metabolism increase and cholesterol level lowering could be achieved by TRβ isoform activation, TRα activation affects heart rates. Therefore, β-selective thyromimetics have been developed as promising drug-candidates for treatment of obesity and elevated cholesterol level. GC-1 [3,5-dimethyl-4-(4'-hydroxy-3'-isopropylbenzyl)-phenoxy acetic acid] has ability to lower LDL cholesterol with 600- to 1400-fold more potency and approximately two- to threefold more efficacy than atorvastatin (Lipitor©) in studies in rats, mice and monkeys. Results: To investigate GC-1 specificity, we solved crystal structures and performed molecular dynamics simulations of both isoforms complexed with GC-1. Crystal structures reveal that, in TRα Arg228 is observed in multiple conformations, an effect triggered by the differences in the interactions between GC-1 and Ser277 or the corresponding asparagine (Asn331) of TRβ. The corresponding Arg282 of TRβ is observed in only one single stable conformation, interacting effectively with the ligand. Molecular dynamics support this model: our simulations show that the multiple conformations can be observed for the Arg228 in TRα, in which the ligand interacts either strongly with the ligand or with the Ser277 residue. In contrast, a single stable Arg282 conformation is observed for TRβ, in which it strongly interacts with both GC-1 and the Asn331. Conclusion: Our analysis suggests that the key factors for GC-1 selectivity are the presence of an oxyacetic acid ester oxygen and the absence of the amino group relative to T3. These results shed light into the β-selectivity of GC-1 and may assist the development of new compounds with potential as drug candidates to the treatment of hypercholesterolemia and obesity