Crystal structures of five 6-mercaptopurine derivatives

The crystal structures of five 6-mercaptopurine derivatives, viz. 2-[(9-acetyl-9H-purin-6-yl)sulfan-yl]-1-(3-meth-oxy-phen-yl)ethan-1-one (1), C16H14N4O3S, 2-[(9-acetyl-9H-purin-6-yl)sulfan-yl]-1-(4-meth-oxy-phen-yl)ethan-1-one (2), C16H14N4O3S, 2-[(9-acetyl-9H-purin-6-yl)sulfan-yl]-1-(4-chloro-phen-yl)ethan-1-one (3), C15H11ClN4O2S, 2-[(9-acetyl-9H-purin-6-yl)sulfan-yl]-1-(4-bromo-phen-yl)ethan-1-one (4), C15H11BrN4O2S, and 1-(3-meth-oxy-phen-yl)-2-[(9H-purin-6-yl)sulfan-yl]ethan-1-one (5), C14H12N4O2S. Compounds (2), (3) and (4) are isomorphous and accordingly their mol-ecular and supra-molecular structures are similar. An analysis of the dihedral angles between the purine and exocyclic phenyl rings show that the mol-ecules of (1) and (5) are essentially planar but that in the case of the three isomorphous compounds (2), (3) and (4), these rings are twisted by a dihedral angle of approximately 38°. With the exception of (1) all mol-ecules are linked by weak C-H⋯O hydrogen bonds in their crystals. There is π-π stacking in all compounds. A Cambridge Structural Database search revealed the existence of 11 deposited compounds containing the 1-phenyl-2-sulfanyl-ethanone scaffold; of these, only eight have a cyclic ring as substituent, the majority of these being heterocycles.info:eu-repo/semantics/publishedVersio

Fine-tuning of the hydrophobicity of caffeic acid: studies on the antimicrobial activity against Staphylococcus aureus and Escherichia coli

The increased bacterial multidrug resistance caused by inappropriate use and overuse of antimicrobials is a global concern. To circumvent this issue, a quest for the development of new active agents has been widely recognized. Some phytochemical products, produced by plants as part of their chemical defense strategies, are regarded as new stimulii to develop novel antimicrobials that are not as vulnerable as current drugs to bacterial resistance mechanisms. In this study, the antimicrobial activity and mode of action of caffeic acid (CAF) and a series of CAF alkyl esters was assessed against Escherichia coli and Staphylococcus aureus, with the aim of analyzing the influence of the alkyl ester side chain length on the activity. Minimum inhibitory concentration (MIC), minimum bactericidal concentration (MBC), changes in physicochemical surface properties and intracellular potassium leakage were used as physiological indices for the antimicrobial mode of action. CAF alkyl esters were found to be effective antimicrobial agents against both bacteria. Their activity was directly dependent on their lipophilicity, which affected bacterial susceptibility, the physicochemical properties of the bacteria and the integrity of the membranes. E. coli was less susceptible than S. aureus to the action of the compounds. Longer alkyl side chains were more effective against the Gram-positive bacterium, while medium length alkyl side chain compounds were more effective against the Gram-negative bacterium. Caffeic acid derivatives are proposed to act as cell permeabilizers, inducing membrane alterations, causing rupture with potassium leakage, particularly on the Gram positive bacterium, and consequent cell death

Microbiological evaluation of homemade mayonnaise and self-serve acai sold in Araguaína, Tocantins

Abstract Foodborne diseases are common illnesses caused by the consumption of food contaminated with microorganisms, such as viruses, fungi, bacteria, and protozoa. Every year, 600 million people become ill and 420,000 people die as a result of consuming contaminated food. Therefore, food safety is an important issue. In this study, samples of homemade spiced mayonnaise and self-serve acai sold in the city of Araguaína, Tocantins, Brazil were analyzed for microbiological contaminants. Acai was collected from 10 stores, one sample from each store, and tested for mold, yeast, and coliforms, as well as coliform identification and total and thermotolerant coliform counts. Mayonnaise was collected from 20 snack bars, one sample from each. These samples were inoculated on MacConkey and Salmonella Shigella agar plates, and the plates were analyzed for growth. Salmonella spp. were detected in some Mayonnaise samples, and coliforms were detected in all acai samples; 60% of samples had thermotolerant coliforms, and only 40% were within the limits established by ANVISA. The collected samples of mayonnaise and acai were contaminated with molds and yeasts above the established limit of 103 CFU/g. Thus, the analyzed mayonnaise and acai samples were contaminated and unfit for consumption, demonstrating the importance of hygienic-sanitary measures in food handling

The genetic landscape of mitochondrial diseases in the next-generation sequencing era: a Portuguese cohort study

Introduction: Rare disorders that are genetically and clinically heterogeneous, such as mitochondrial diseases (MDs), have a challenging diagnosis. Nuclear genes codify most proteins involved in mitochondrial biogenesis, despite all mitochondria having their own DNA. The development of next-generation sequencing (NGS) technologies has revolutionized the understanding of many genes involved in the pathogenesis of MDs. In this new genetic era, using the NGS approach, we aimed to identify the genetic etiology for a suspected MD in a cohort of 450 Portuguese patients.Methods: We examined 450 patients using a combined NGS strategy, starting with the analysis of a targeted mitochondrial panel of 213 nuclear genes, and then proceeding to analyze the whole mitochondrial DNA.Results and Discussion: In this study, we identified disease-related variants in 134 (30%) analyzed patients, 88 with nuclear DNA (nDNA) and 46 with mitochondrial DNA (mtDNA) variants, most of them being pediatric patients (66%), of which 77% were identified in nDNA and 23% in mtDNA. The molecular analysis of this cohort revealed 72 already described pathogenic and 20 novel, probably pathogenic, variants, as well as 62 variants of unknown significance. For this cohort of patients with suspected MDs, the use of a customized gene panel provided a molecular diagnosis in a timely and cost-effective manner. Patients who cannot be diagnosed after this initial approach will be further selected for whole-exome sequencing.Conclusion: As a national laboratory for the study and research of MDs, we demonstrated the power of NGS to achieve a molecular etiology, expanding the mutational spectrum and proposing accurate genetic counseling in this group of heterogeneous diseases without therapeutic options

LRR-RLK family from two Citrus species: Genome-wide identification and evolutionary aspects

Background: Leucine-rich repeat receptor-like kinases (LRR-RLKs) represent the largest subfamily of plant RLKs. The functions of most LRR-RLKs have remained undiscovered, and a few that have been experimentally characterized have been shown to have important roles in growth and development as well as in defense responses. Although RLK subfamilies have been previously studied in many plants, no comprehensive study has been performed on this gene family in Citrus species, which have high economic importance and are frequent targets for emerging pathogens. In this study, we performed in silico analysis to identify and classify LRR-RLK homologues in the predicted proteomes of Citrus clementina (clementine) and Citrus sinensis (sweet orange). In addition, we used large-scale phylogenetic approaches to elucidate the evolutionary relationships of the LRR-RLKs and further narrowed the analysis to the LRR-XII group, which contains several previously described cell surface immune receptors. Results: We built integrative protein signature databases for Citrus clementina and Citrus sinensis using all predicted protein sequences obtained from whole genomes. A total of 300 and 297 proteins were identified as LRR-RLKs in C. clementina and C. sinensis, respectively. Maximum-likelihood phylogenetic trees were estimated using Arabidopsis LRR-RLK as a template and they allowed us to classify Citrus LRR- 34 RLKs into 16 groups. The LRR-XII group showed a remarkable expansion, containing approximately 150 paralogs encoded in each Citrus genome. Phylogenetic analysis also demonstrated the existence of two distinct LRR-XII clades, each one constituted mainly by RD and non-RD kinases. We identified 68 orthologous pairs from the C. clementina and C. sinensis LRR-XII genes. In addition, among the paralogs, we identified a subset of 78 and 62 clustered genes probably derived from tandem duplication events in the genomes of C. clementina and C. sinensis, respectively. Conclusions: This work provided the first comprehensive evolutionary analysis of the LRR-RLKs in Citrus. A large expansion of LRR-XII in Citrus genomes suggests that it might play a key role in adaptive responses in host-pathogen co-evolution, related to the perennial life cycle and domestication of the citrus crop species

MAMMALS IN PORTUGAL : A data set of terrestrial, volant, and marine mammal occurrences in P ortugal

Mammals are threatened worldwide, with 26% of all species being includedin the IUCN threatened categories. This overall pattern is primarily associatedwith habitat loss or degradation, and human persecution for terrestrial mam-mals, and pollution, open net fishing, climate change, and prey depletion formarine mammals. Mammals play a key role in maintaining ecosystems func-tionality and resilience, and therefore information on their distribution is cru-cial to delineate and support conservation actions. MAMMALS INPORTUGAL is a publicly available data set compiling unpublishedgeoreferenced occurrence records of 92 terrestrial, volant, and marine mam-mals in mainland Portugal and archipelagos of the Azores and Madeira thatincludes 105,026 data entries between 1873 and 2021 (72% of the data occur-ring in 2000 and 2021). The methods used to collect the data were: live obser-vations/captures (43%), sign surveys (35%), camera trapping (16%),bioacoustics surveys (4%) and radiotracking, and inquiries that represent lessthan 1% of the records. The data set includes 13 types of records: (1) burrowsjsoil moundsjtunnel, (2) capture, (3) colony, (4) dead animaljhairjskullsjjaws, (5) genetic confirmation, (6) inquiries, (7) observation of live animal (8),observation in shelters, (9) photo trappingjvideo, (10) predators dietjpelletsjpine cones/nuts, (11) scatjtrackjditch, (12) telemetry and (13) vocalizationjecholocation. The spatial uncertainty of most records ranges between 0 and100 m (76%). Rodentia (n=31,573) has the highest number of records followedby Chiroptera (n=18,857), Carnivora (n=18,594), Lagomorpha (n=17,496),Cetartiodactyla (n=11,568) and Eulipotyphla (n=7008). The data setincludes records of species classified by the IUCN as threatened(e.g.,Oryctolagus cuniculus[n=12,159],Monachus monachus[n=1,512],andLynx pardinus[n=197]). We believe that this data set may stimulate thepublication of other European countries data sets that would certainly contrib-ute to ecology and conservation-related research, and therefore assisting onthe development of more accurate and tailored conservation managementstrategies for each species. There are no copyright restrictions; please cite thisdata paper when the data are used in publications.info:eu-repo/semantics/publishedVersio

Multicenter validation of PIM3 and PIM2 in Brazilian pediatric intensive care units

ObjectiveTo validate the PIM3 score in Brazilian PICUs and compare its performance with the PIM2.MethodsObservational, retrospective, multicenter study, including patients younger than 16 years old admitted consecutively from October 2013 to September 2019. We assessed the Standardized Mortality Ratio (SMR), the discrimination capability (using the area under the receiver operating characteristic curve – AUROC), and the calibration. To assess the calibration, we used the calibration belt, which is a curve that represents the correlation of predicted and observed values and their 95% Confidence Interval (CI) through all the risk ranges. We also analyzed the performance of both scores in three periods: 2013–2015, 2015–2017, and 2017–2019.Results41,541 patients from 22 PICUs were included. Most patients aged less than 24 months (58.4%) and were admitted for medical conditions (88.6%) (respiratory conditions = 53.8%). Invasive mechanical ventilation was used in 5.8%. The median PICU length of stay was three days (IQR, 2–5), and the observed mortality was 1.8% (763 deaths). The predicted mortality by PIM3 was 1.8% (SMR 1.00; 95% CI 0.94–1.08) and by PIM2 was 2.1% (SMR 0.90; 95% CI 0.83–0.96). Both scores had good discrimination (PIM3 AUROC = 0.88 and PIM2 AUROC = 0.89). In calibration analysis, both scores overestimated mortality in the 0%–3% risk range, PIM3 tended to underestimate mortality in medium-risk patients (9%–46% risk range), and PIM2 also overestimated mortality in high-risk patients (70%–100% mortality risk).ConclusionsBoth scores had a good discrimination ability but poor calibration in different ranges, which deteriorated over time in the population studied