Catalytic conversion of caffeine into molecules of valuable interest via N-demethylation reaction

This work aims to apply catalytic processes to promote the conversion of caffeine into valuable dimethylxanthines via N-demethylation reaction. Thus, we seek to evaluate the products formed and propose the reactions involved and their mechanisms. Reaction conditions were evaluated including different concentrations of Fenton reagent and ascorbic acid to evaluate caffeine oxidation. Theobromine, paraxanthine, and theophylline formation was proven by HPLC-DAD and mass spectrometry analysis evidencing the N-demethylation reactions, via radicals, with about 1 % yield. These results open the way for new N-demethylation reaction routes to be studied with applications for caffeine and other biomolecules in diverse areas such as biochemistry and medicinal chemistry. Application of the Fenton catalysis as alternative to promote the conversion of caffeine in other xanthines by N-demethylation. In this scenario was verified the capability of ascorbic acid in promoting same reaction, both environmentally friendly processes. This work investigates the possibility of using a well known biocompound as a precursor to obtain value added molecules.This study was financially supported by the Coordenação de Aperfeiçoamento de Pessoal de Nível Superior – Brasil (CAPES) – Finance Code 001 and by CIMO (UIDB/00690/2020) through FEDER under Program PT2020. In addition, the authors acknowledge Central de Análise e Prospecção Química – CAPQ and Laboratório Central de Biologia Molecular (LCBM), Chemistry Department/UFLA for their technical support. Jose L. Diaz De Tuesta acknowledges the financial support through the program of Atracción al Talento of Comunidad de Madrid (Spain) for the individual research grant 2022-T1/AMB-23946.info:eu-repo/semantics/publishedVersio

Kinetic insights on wet peroxide oxidation of caffeine using EDTA-functionalized low-cost catalysts prepared from compost generated in municipal solid waste treatment facilities

Nowadays, sorted organic fraction of municipal solid waste is typically treated by anaerobic digestion processes, resulting therein a solid stream, further processed to obtain compost, whose production is higher than the existing demand as fertilizer. The current work proposes an alternative strategy for the recovering of compost through the production of low-cost catalysts by calcination (1073 K) and sulfuric acid treatments, followed by sequential functionalization with tetraethyl orthosilicate (TEOS) and ethylenediamine tetraacetic acid (EDTA). Activity and stability of the catalysts are assessed in the wet peroxide oxidation of synthetic wastewater effluents contaminated with caffeine, a model micro-pollutant, achieving its complete removal after 6 h at 353– 383 K and catalyst loads of 0.5–2.5 g L−1. The increase of the catalytic activity of the materials upon functionalization with TEOS and EDTA is demonstrated and a kinetic modeling of caffeine degradation and hydrogen peroxide consumption with the best catalyst is assessed by pseudo-first power-law rate equations.This work was financially supported by project ‘‘VALORCOMP - Valorización de compost y otros desechos procedentes de la fracción orgánica de los residuos municipales’’, 0119_VALORCOMP_2_P, through FEDER under Program INTERREG; and CIMO (UIDB/00690/2020) through FEDER under Program PT2020.info:eu-repo/semantics/publishedVersio

Application of catalysts developed from compost derived from municipal solid waste in the removal of caffeine by wet peroxide oxidation

Nowadays, waste management through mechanical biological treatment (MBT) consists on the use of the separated organic fraction of municipal solid waste (MSW) to feed anaerobic digestion processes, resulting therein a solid stream, further processed to compost, which can be used as fertilizer. Currently, the production of compost from MBT is higher than the existing demand, and the expected developments on up-coming directives ruling “End-of-waste” criteria are leading to barriers on the use of waste-derived fertilizers (European Commision, 2013). In this context, the current work proposes an alternative strategy to the valorisation of compost, through the production of low-cost materials to be applied in the catalytic wet peroxide oxidation (CWPO) of synthetic wastewater effluents contaminated with caffeine, used as a model pollutant of emerging concern. Caffeine is the most consumed psychoactive drug worldwide. It is one of the components of painkillers, medication against migraine, fatigue, drowsiness and breathing problems. Its consumption is also associated with an overall lower risk of malignant growth like hepatocellular, endometrial or colorectal cancer (Ganzenko et al., 2015). However, the effect of caffeine and its environmental degradation products on aquatic living species is not properly known. Caffeine, is a world wide consumed psychoactive drug, in a way that becomes a persistent compound and cannot be efficiently removed by municipal wastewater treatment facilities (Ganzenko et al., 2015). As a consequence, caffeine and its metabolites are present in the effluents of wastewater treatment plants (Gracia-Lor et al., 2017).This work was financially supported by project “VALORCOMP - Valorización de compost y otros desechos procedentes de la fracción orgánica de los residuos municipales”, 0119_VALORCOMP_2_P, and project “AIProcMat@N2020 - Advanced Industrial Processes and Materials for a Sustainable Northern Region of Portugal 2020”, reference NORTE-01-0145-FEDER-000006, supported by NORTE 2020, under the Portugal 2020 Partnership Agreement, through FEDER, and Project Associate Laboratory LSRE-LCM - UID/EQU/50020/2019 - funded by national funds through FCT/MCTES (PIDDAC).info:eu-repo/semantics/publishedVersio

Tilapia male urinary pheromone stimulates female reproductive axis

Mozambique tilapia males congregate in leks where they establish dominance hierarchies and attract females to spawn in sandy pits. Dominant males store more urine than subordinates and the pattern of urination and the high sensitivity of females to male urine suggest chemical signalling via the urine. Here we show that pre-ovulated and post-spawn females when exposed to dominant male urine increased significantly, in less than 1 h, the release rate of the maturation-inducing steroid 17,20bdihydroxypregn- 4-en-3-one which is maintained elevated for at least 6 h. This indicates a pheromonal role for male urine in the synchronisation of spawning. Furthermore, we show that the lack of affinity of 17,20bP to sex steroid binding globulin explains, at least partly, its rapid release and lack of detection in the blood. Thus tilapia urine involvement in several communication processes confirms that cichlids have evolved a sophisticated chemical signalling system together with their complex visual, acoustic and behavioural displays

Stanniocalcin 1 effects on the renal gluconeogenesis pathway in rat and fish

The mammalian kidney contributes significantly to glucose homeostasis through gluconeogenesis. Considering that stanniocalcin 1 (STC1) regulates ATP production, is synthesized and acts in different cell types of the nephron, the present study hypothesized that STC1 may be implicated in the regulation of gluconeogenesis in the vertebrate kidney. Human STC1 strongly reduced gluconeogenesis from C-14-glutamine in rat renal medulla (MD) slices but not in renal cortex (CX), nor from C-14-lactic acid. Total PEPCK activity was markedly reduced by hSTC1 in MD but not in CX. Pck2 (mitochondrial PEPCK isoform) was down-regulated by hSTC1 in MD but not in CX. In fish (Dicentrarchus labrax) kidney slices, both STC1-A and -B isoforms decreased gluconeogenesis from C-14-acid lactic, while STC1-A increased gluconeogenesis from C-14-glutamine. Overall, our results demonstrate a role for STC1 in the control of glucose synthesis via renal gluconeogenesis in mammals and suggest that it may have a similar role in teleost fishes. (C) 2015 Elsevier Ireland Ltd. All rights reserved.Conselho Nacional de Desenvolvimento Cientifico e Tecnologico (CNPq) Brazil; Foundation for Science and Technology of Portugal [PTDC/MAR/121279/2010]; bilateral programme CAPES (Brazil)/GRICES (Portugal) CAPES/GRICES [215/08]info:eu-repo/semantics/publishedVersio

Genetic signatures of parental contribution in black and white populations in Brazil

Two hundred and three individuals classified as white were tested for 11 single nucleotide polymorphisms plus two insertion/deletions in their Y-chromosomes. A subset of these individuals (n = 172) was also screened for sequences in the first hypervariable segment of their mitochondrial DNA (mtDNA). In addition, complementary studies were done for 11 of the 13 markers indicated above in 54 of 107 black subjects previously investigated in this southern Brazilian population. The prevalence of Y-chromosome haplogroups among whites was similar to that found in the Azores (Portugal) or Spain, but not to that of other European countries. About half of the European or African mtDNA haplogroups of these individuals were related to their places of origin, but not their Amerindian counterparts. Persons classified in these two categories of skin color and related morphological traits showed distinct genomic ancestries through the country. These findings emphasize the need to consider in Brazil, despite some general trends, a notable heterogeneity in the pattern of admixture dynamics within and between populations/groups

Age at symptom onset and death and disease duration in genetic frontotemporal dementia : an international retrospective cohort study

Background: Frontotemporal dementia is a heterogenous neurodegenerative disorder, with about a third of cases being genetic. Most of this genetic component is accounted for by mutations in GRN, MAPT, and C9orf72. In this study, we aimed to complement previous phenotypic studies by doing an international study of age at symptom onset, age at death, and disease duration in individuals with mutations in GRN, MAPT, and C9orf72. Methods: In this international, retrospective cohort study, we collected data on age at symptom onset, age at death, and disease duration for patients with pathogenic mutations in the GRN and MAPT genes and pathological expansions in the C9orf72 gene through the Frontotemporal Dementia Prevention Initiative and from published papers. We used mixed effects models to explore differences in age at onset, age at death, and disease duration between genetic groups and individual mutations. We also assessed correlations between the age at onset and at death of each individual and the age at onset and at death of their parents and the mean age at onset and at death of their family members. Lastly, we used mixed effects models to investigate the extent to which variability in age at onset and at death could be accounted for by family membership and the specific mutation carried. Findings: Data were available from 3403 individuals from 1492 families: 1433 with C9orf72 expansions (755 families), 1179 with GRN mutations (483 families, 130 different mutations), and 791 with MAPT mutations (254 families, 67 different mutations). Mean age at symptom onset and at death was 49\ub75 years (SD 10\ub70; onset) and 58\ub75 years (11\ub73; death) in the MAPT group, 58\ub72 years (9\ub78; onset) and 65\ub73 years (10\ub79; death) in the C9orf72 group, and 61\ub73 years (8\ub78; onset) and 68\ub78 years (9\ub77; death) in the GRN group. Mean disease duration was 6\ub74 years (SD 4\ub79) in the C9orf72 group, 7\ub71 years (3\ub79) in the GRN group, and 9\ub73 years (6\ub74) in the MAPT group. Individual age at onset and at death was significantly correlated with both parental age at onset and at death and with mean family age at onset and at death in all three groups, with a stronger correlation observed in the MAPT group (r=0\ub745 between individual and parental age at onset, r=0\ub763 between individual and mean family age at onset, r=0\ub758 between individual and parental age at death, and r=0\ub769 between individual and mean family age at death) than in either the C9orf72 group (r=0\ub732 individual and parental age at onset, r=0\ub736 individual and mean family age at onset, r=0\ub738 individual and parental age at death, and r=0\ub740 individual and mean family age at death) or the GRN group (r=0\ub722 individual and parental age at onset, r=0\ub718 individual and mean family age at onset, r=0\ub722 individual and parental age at death, and r=0\ub732 individual and mean family age at death). Modelling showed that the variability in age at onset and at death in the MAPT group was explained partly by the specific mutation (48%, 95% CI 35\u201362, for age at onset; 61%, 47\u201373, for age at death), and even more by family membership (66%, 56\u201375, for age at onset; 74%, 65\u201382, for age at death). In the GRN group, only 2% (0\u201310) of the variability of age at onset and 9% (3\u201321) of that of age of death was explained by the specific mutation, whereas 14% (9\u201322) of the variability of age at onset and 20% (12\u201330) of that of age at death was explained by family membership. In the C9orf72 group, family membership explained 17% (11\u201326) of the variability of age at onset and 19% (12\u201329) of that of age at death. Interpretation: Our study showed that age at symptom onset and at death of people with genetic frontotemporal dementia is influenced by genetic group and, particularly for MAPT mutations, by the specific mutation carried and by family membership. Although estimation of age at onset will be an important factor in future pre-symptomatic therapeutic trials for all three genetic groups, our study suggests that data from other members of the family will be particularly helpful only for individuals with MAPT mutations. Further work in identifying both genetic and environmental factors that modify phenotype in all groups will be important to improve such estimates. Funding: UK Medical Research Council, National Institute for Health Research, and Alzheimer's Society

New insights into the genetic etiology of Alzheimer's disease and related dementias

Characterization of the genetic landscape of Alzheimer's disease (AD) and related dementias (ADD) provides a unique opportunity for a better understanding of the associated pathophysiological processes. We performed a two-stage genome-wide association study totaling 111,326 clinically diagnosed/'proxy' AD cases and 677,663 controls. We found 75 risk loci, of which 42 were new at the time of analysis. Pathway enrichment analyses confirmed the involvement of amyloid/tau pathways and highlighted microglia implication. Gene prioritization in the new loci identified 31 genes that were suggestive of new genetically associated processes, including the tumor necrosis factor alpha pathway through the linear ubiquitin chain assembly complex. We also built a new genetic risk score associated with the risk of future AD/dementia or progression from mild cognitive impairment to AD/dementia. The improvement in prediction led to a 1.6- to 1.9-fold increase in AD risk from the lowest to the highest decile, in addition to effects of age and the APOE ε4 allele

Discitis In Children. Study Of 8 Cases [discite Em Crianças. Estudo De Oito Casos.]

The authors report the study of eight children with discitis diagnosed through clinical, neurological and orthopedic evaluation. The evidence of self limiting inflammation or infection of the intervertebral disk space and of soft tissue were available by image studies. Findings with routine roentgenograms, computed tomography and magnetic resonance imaging are discussed.52453553