Discovering cellular programs of intrinsic and extrinsic drivers of metabolic traits using LipocyteProfiler.

A primary obstacle in translating genetic associations with disease into therapeutic strategies is elucidating the cellular programs affected by genetic risk variants and effector genes. Here, we introduce LipocyteProfiler, a cardiometabolic-disease-oriented high-content image-based profiling tool that enables evaluation of thousands of morphological and cellular profiles that can be systematically linked to genes and genetic variants relevant to cardiometabolic disease. We show that LipocyteProfiler allows surveillance of diverse cellular programs by generating rich context- and process-specific cellular profiles across hepatocyte and adipocyte cell-state transitions. We use LipocyteProfiler to identify known and novel cellular mechanisms altered by polygenic risk of metabolic disease, including insulin resistance, fat distribution, and the polygenic contribution to lipodystrophy. LipocyteProfiler paves the way for large-scale forward and reverse deep phenotypic profiling in lipocytes and provides a framework for the unbiased identification of causal relationships between genetic variants and cellular programs relevant to human disease.

Neuraminidase is a host-directed approach to regulate neutrophil responses in sepsis and COVID-19.

BACKGROUND AND PURPOSE: Neutrophil overstimulation plays a crucial role in tissue damage during severe infections. Because pathogen-derived neuraminidase (NEU) stimulates neutrophils, we investigated whether host NEU can be targeted to regulate the neutrophil dysregulation observed in severe infections. EXPERIMENTAL APPROACH: The effects of NEU inhibitors on lipopolysaccharide (LPS)-stimulated neutrophils from healthy donors or COVID-19 patients were determined by evaluating the shedding of surface sialic acids, cell activation, and reactive oxygen species (ROS) production. Re-analysis of single-cell RNA sequencing of respiratory tract samples from COVID-19 patients also was carried out. The effects of oseltamivir on sepsis and betacoronavirus-induced acute lung injury were evaluated in murine models. KEY RESULTS: Oseltamivir and zanamivir constrained host NEU activity, surface sialic acid release, cell activation, and ROS production by LPS-activated human neutrophils. Mechanistically, LPS increased the interaction of NEU1 with matrix metalloproteinase 9 (MMP-9). Inhibition of MMP-9 prevented LPS-induced NEU activity and neutrophil response. In vivo, treatment with oseltamivir fine-tuned neutrophil migration and improved infection control as well as host survival in peritonitis and pneumonia sepsis. NEU1 also is highly expressed in neutrophils from COVID-19 patients, and treatment of whole-blood samples from these patients with either oseltamivir or zanamivir reduced neutrophil overactivation. Oseltamivir treatment of intranasally infected mice with the mouse hepatitis coronavirus 3 (MHV-3) decreased lung neutrophil infiltration, viral load, and tissue damage. CONCLUSION AND IMPLICATIONS: These findings suggest that interplay of NEU1-MMP-9 induces neutrophil overactivation. In vivo, NEU may serve as a host-directed target to dampen neutrophil dysfunction during severe infections.

Anti-Mayaro virus activity of a hydroethanolic extract from Fridericia chica (Bonpl.) L. G. Lohmann leaves.

ETHNOPHARMACOLOGICAL RELEVANCE: Mayaro fever is a neglected tropical disease. The region of the most significant circulation of the Mayaro virus (MAYV) is the Amazon rainforest, situated in remote areas that are difficult to access and where medicine is scarce. Thus, the regional population uses plants as an alternative for the treatment of various diseases. Fridericia chica is an endemic plant of tropical regions used in traditional medicine to treat fever, malaise, inflammation, and infectious diseases such as hepatitis B. However, its antiviral activity is poorly understood. AIM OF THE STUDY: This study aimed to investigate the anti-MAYV activity of the hydroethanolic extract of the leaves of Fridericia chica (HEFc) in mammalian cells and its possible mechanism of action. MATERIALS AND METHODS: The antiviral activity of HEFc was studied using Vero cell lines against MAYV. The cytotoxicity and antiviral activity of the extract were evaluated by the 3-(4, 5- dimethyl-2-thiazolyl)-2, 5-diphenyl-2H-tetrazolium bromide (MTT) assay. The overall antiviral activity was confirmed by the plaque forming units (PFU) method. Then, the effects of HEFc on MAYV multiplication kinetics, virus adsorption, penetration, and post-penetration, and its virucidal activity were determined in Vero cells using standard experimental procedures. RESULTS: HEFc exerted a effect against viral infection in Vero cells at a non-cytotoxic concentration, and no virion was detected in the supernatant in a dose-dependent and selective manner. HEFc inhibited MAYV in the early and late stages of the viral multiplication cycle. The extract showed significant virucidal activity at low concentrations and did not affect adsorption or viral internalization stages. In addition, HEFc reduced virions at all post-infection times investigated. CONCLUSIONS: HEFc has good antiviral activity against MAYV, acting directly on the viral particles. This plant extract possesses an excellent and promising potential for developing effective herbal antiviral drugs.

Molecular Dynamics Analysis of Fast-Spreading Severe Acute Respiratory Syndrome Coronavirus 2 Variants and Their Effects on the Interaction with Human Angiotensin-Converting Enzyme 2.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is evolving with mutations in the spike protein, especially in the receptor-binding domain (RBD). The failure of public health measures in some countries to contain the spread of the disease has given rise to novel viral variants with increased transmissibility. However, key questions about how quickly the variants can spread remain unclear. Herein, we performed a structural investigation using molecular dynamics simulations and determined dissociation constant (K D) values using surface plasmon resonance assays of three fast-spreading SARS-CoV-2 variants, alpha, beta, and gamma, as well as genetic factors in host cells that may be related to the viral infection. Our results suggest that the SARS-CoV-2 variants facilitate their entry into the host cell by moderately increased binding affinities to the human ACE2 receptor, different torsions in hACE2 mediated by RBD variants, and an increased spike exposure time to proteolytic enzymes. We also found that other host cell aspects, such as gene and isoform expression of key genes for the infection (ACE2, FURIN, and TMPRSS2), may have few contributions to the SARS-CoV-2 variant infectivity. In summary, we concluded that a combination of viral and host cell factors allows SARS-CoV-2 variants to increase their abilities to spread faster than the wild type.

Unusual natural polycyclic aromatic hydrocarbons in sediment cores of an Amazon estuary.

Polycyclic aromatic hydrocarbons (PAHs) most likely derived from natural sources were observed in two sediment cores covering the last 100 years in an Amazon estuarine region. A considerable change in the PAHs main source was observed in the 1960s. Before the 1960s, the sources of PAHs seem to be related to biogenic and/or early-diagenetic processes. Concentrations of perylene were higher before the 1960s and suggest that its primary source to the sediments in the Amazon region is linked to a short-term diagenetic transformation of their biogenic precursors. The natural formation of alkylated PAHs in sediments was linked to the methylation of the parental aromatic hydrocarbons due to sediment maturation processes and the dehydrogenation of sterols in the sediments. The relatively rapid reaction occurring in recent sediments of the Amazon region suggests the importance of the microbial community in the transformation of biogenic precursors to alkylated-PAHs in the sediments.

Dealing with complex contamination scenarios: using a multi-geochemical approach to assess environmental quality and identify pollution sources in a semi-arid estuary from Brazil.

The Jundiaí-Potengi Estuary (EJP) is located on the semi-arid coast of northeastern Brazil and is influenced by multiple sources of contamination. The sediment quality of EJP was assessed by using a multi-geochemical approach during the dry and wet seasons. Sediments were analyzed for concentrations of nutrients, metals, polycyclic aromatic hydrocarbons (PAHs), pesticides, hormones (natural and synthetic), and sterols. The results were integrated by multivariate methods. The sediment was altered by the presence of contaminants from anthropogenic and natural sources. The middle and lower estuarine areas were considered more degraded in both seasons. In these regions, metals, hormones, sterols, and PAHs were found, indicating that these regions are severely affected by industrial, sanitary and aquaculture effluents, combustion of fossil fuels, and oil spills. The upstream region was contaminated by pesticides. The contamination pattern along the EJP shows the prevalence of local sources which continuously release the chemicals into the estuary. Worse conditions occurred during the rainy season, when the runoff from urban and rural areas is more intense and carries a greater load of contaminants to the EJP.

Tracking the historical urban and rural sources of fecal pollution in a South American tropical semi-arid region using sterols and endocrine-disrupting chemicals.

Sterols and endocrine-disrupting chemicals were analyzed in two dated sediment cores collected in the Jaguaribe river to determine the recent decades' influence of urbanization and agropastoral activities on the inputs of fecal pollution in a semi-arid region of Brazil. Stigmasterol and sitosterol were the most abundant of the 6 sterols examined in both cores, indicating an important contribution of organic matter from mangrove forests to the study region. Coprostanol presented a continuous increase in concentrations from the 1930s to the 2000s in one core, however, showing higher concentrations (>100 ng g-1) in the upper layers of both cores. The sterols diagnostic ratios indicated fecal pollution through both cores, especially from the 1940s to 1970s. The coprostanol levels followed the variations in population growth in the state of Ceará. Estriol and estrone were the most abundant estrogenic hormones found in both cores. These compounds are probably related to the intense livestock activities in the Ceará state, especially after the 1970s. The baseline levels of fecal sterols and estrogen hormones found in this study possibly represent a previous unimpacted scenario and may be used for future evaluations of fecal pollution from urbanization and livestock activities.

Neuraminidase inhibitors rewire neutrophil function in vivo in murine sepsis and ex vivo in COVID-19.

Neutrophil overstimulation plays a crucial role in tissue damage during severe infections. Neuraminidase (NEU)-mediated cleavage of surface sialic acid has been demonstrated to regulate leukocyte responses. Here, we report that antiviral NEU inhibitors constrain host NEU activity, surface sialic acid release, ROS production, and NETs released by microbial-activated human neutrophils. In vivo, treatment with Oseltamivir results in infection control and host survival in peritonitis and pneumonia models of sepsis. Single-cell RNA sequencing re-analysis of publicly data sets of respiratory tract samples from critical COVID-19 patients revealed an overexpression of NEU1 in infiltrated neutrophils. Moreover, Oseltamivir or Zanamivir treatment of whole blood cells from severe COVID-19 patients reduces host NEU-mediated shedding of cell surface sialic acid and neutrophil overactivation. These findings suggest that neuraminidase inhibitors can serve as host-directed interventions to dampen neutrophil dysfunction in severe infections.

Reboot: a straightforward approach to identify genes and splicing isoforms associated with cancer patient prognosis.

Nowadays, the massive amount of data generated by modern sequencing technologies provides an unprecedented opportunity to find genes associated with cancer patient prognosis, connecting basic and translational research. However, treating high dimensionality of gene expression data and integrating it with clinical variables are major challenges to perform these analyses. Here, we present Reboot, an integrative approach to find and validate genes and transcripts (splicing isoforms) associated with cancer patient prognosis from high dimensional expression datasets. Reboot innovates by using a multivariate strategy with penalized Cox regression (LASSO method) combined with a bootstrap approach, in addition to statistical tests and plots to support the findings. Applying Reboot on data from 154 glioblastoma patients, we identified a three-gene signature (IKBIP, OSMR, PODNL1) whose increased derived risk score was significantly associated with worse patients' prognosis. Similarly, Reboot was able to find a seven-splicing isoforms signature related to worse overall survival in 177 pancreatic adenocarcinoma patients with elevated risk scores after uni- and multivariate analyses. In summary, Reboot is an efficient, intuitive and straightforward way of finding genes or splicing isoforms signatures relevant to patient prognosis, which can democratize this kind of analysis and shed light on still under-investigated cancer-related genes and splicing isoforms.

Inferring the heritability of large-scale functional networks with a multivariate ACE modeling approach.

Recent evidence suggests that the human functional connectome is stable at different timescales and is unique. These characteristics posit the functional connectome not only as an individual marker but also as a powerful discriminatory measure characterized by high intersubject variability. Among distinct sources of intersubject variability, the long-term sources include functional patterns that emerge from genetic factors. Here, we sought to investigate the contribution of additive genetic factors to the variability of functional networks by determining the heritability of the connectivity strength in a multivariate fashion. First, we reproduced and extended the connectome fingerprinting analysis to the identification of twin pairs. Then, we estimated the heritability of functional networks by a multivariate ACE modeling approach with bootstrapping. Twin pairs were identified above chance level using connectome fingerprinting, with monozygotic twin identification accuracy equal to 57.2% on average for whole-brain connectome. Additionally, we found that a visual (0.37), the medial frontal (0.31), and the motor (0.30) functional networks were the most influenced by additive genetic factors. Our findings suggest that genetic factors not only partially determine intersubject variability of the functional connectome, such that twins can be identified using connectome fingerprinting, but also differentially influence connectivity strength in large-scale functional networks.

Body image and obesity in children from public primary schools in Acapulco, Mexico: A cross-sectional study.

Background: Childhood obesity is a global problem, causing social and psychological damage, as well as physical health risks. This study estimated the occurrence of body image dissatisfaction in primary schoolchildren aged 9-13 years and investigated its association with obesity and other factors. Methods: A cross-sectional study was conducted, for which 533 students attending three public primary schools in Acapulco were recruited. Students completed a facilitated self-administered questionnaire about their age, sex, socioeconomic level, body image satisfaction, and perception of their parents' body image. We registered anthropometry of the students and calculated body mass index (BMI). We examined the associations of BMI category and other factors with body image dissatisfaction, calculating the cluster-adjusted odds ratio and 95% confidence intervals. Results: From the total number of participants, 75% (181/243) of girls and 73% (170/232) of boys were dissatisfied with their body image and wanted a slimmer body. About half were overweight or obese: 45% (121/271) of girls and 52% (135/262) of boys. Overweight or obese children were much more likely to be dissatisfied with their body image (cluster adjusted: 6.73; 95% CI: 5.42-8.36). No other factors were significantly associated with body image dissatisfaction. One-third of the girls (32%, 86/271) and 17% (45/261) of the boys reported an underweight desired body image. Conclusions: The high level of obesity is a cause for concern and an even higher level of body image dissatisfaction as well. The high dissatisfaction among children suggests that boys, as well as girls in Mexico, may now be subjected to intense social pressure about desirable body image.

Introducción: La obesidad infantil es un problema global que causa daños sociales, psicológicos y en la salud física. Se estimó la ocurrencia de insatisfacción con la imagen corporal en escolares de 9 a 13 años, y su asociación con la obesidad y otros factores. Métodos: Se realizó un estudio transversal en 533 estudiantes de tres escuelas primarias públicas en Acapulco, México. Se aplicó un cuestionario autoadministrado sobre edad, sexo, nivel socioeconómico, satisfacción con la imagen corporal y percepción de la imagen corporal de los padres. Se midieron el peso y la talla, y se calculó el índice de masa corporal (IMC). Se examinaron las asociaciones entre el IMC y otros factores con la insatisfacción con la imagen corporal, y se calculó la razón de momios ajustada por conglomerado y sus intervalos de confianza del 95% (IC 95%). Resultados: El 75% (181/243) de niñas y el 73% (170/232) de niños estaban insatisfechos con su imagen corporal; casi todos deseaban un cuerpo más delgado. El 45% (121/271) de las niñas y el 52% (135/262) de los niños presentaba sobrepeso u obesidad, lo que se asoció con la insatisfacción con su imagen corporal (ajustado por clúster: 6.73; IC 95%: 5.42-8.36). Ningún otro factor se asoció significativamente con la insatisfacción con la imagen corporal. El 32% (86/271) de las niñas y el 17% (45/261) de los niños reportaron una imagen corporal deseada con bajo peso. Conclusiones: El alto nivel de obesidad y el mayor nivel de insatisfacción con la imagen corporal son motivo de preocupación. La insatisfacción sugiere que los niños y las niñas en México pueden verse sometidos a una fuerte presión social sobre la imagen corporal deseable.

Body image and obesity in children from public primary schools in Acapulco, Mexico: A cross-sectional study / Imagen corporal y obesidad en escolares de primarias públicas en Acapulco, México: un estudio transversal

Abstract Background: Childhood obesity is a global problem, causing social and psychological damage, as well as physical health risks. This study estimated the occurrence of body image dissatisfaction in primary schoolchildren aged 9-13 years and investigated its association with obesity and other factors. Methods: A cross-sectional study was conducted, for which 533 students attending three public primary schools in Acapulco were recruited. Students completed a facilitated self-administered questionnaire about their age, sex, socioeconomic level, body image satisfaction, and perception of their parents’ body image. We registered anthropometry of the students and calculated body mass index (BMI). We examined the associations of BMI category and other factors with body image dissatisfaction, calculating the cluster-adjusted odds ratio and 95% confidence intervals. Results: From the total number of participants, 75% (181/243) of girls and 73% (170/232) of boys were dissatisfied with their body image and wanted a slimmer body. About half were overweight or obese: 45% (121/271) of girls and 52% (135/262) of boys. Overweight or obese children were much more likely to be dissatisfied with their body image (cluster adjusted: 6.73; 95% CI: 5.42-8.36). No other factors were significantly associated with body image dissatisfaction. One-third of the girls (32%, 86/271) and 17% (45/261) of the boys reported an underweight desired body image. Conclusions: The high level of obesity is a cause for concern and an even higher level of body image dissatisfaction as well. The high dissatisfaction among children suggests that boys, as well as girls in Mexico, may now be subjected to intense social pressure about desirable body image.

Resumen Introducción: La obesidad infantil es un problema global que causa daños sociales, psicológicos y en la salud física. Se estimó la ocurrencia de insatisfacción con la imagen corporal en escolares de 9 a 13 años, y su asociación con la obesidad y otros factores. Métodos: Se realizó un estudio transversal en 533 estudiantes de tres escuelas primarias públicas en Acapulco, México. Se aplicó un cuestionario autoadministrado sobre edad, sexo, nivel socioeconómico, satisfacción con la imagen corporal y percepción de la imagen corporal de los padres. Se midieron el peso y la talla, y se calculó el índice de masa corporal (IMC). Se examinaron las asociaciones entre el IMC y otros factores con la insatisfacción con la imagen corporal, y se calculó la razón de momios ajustada por conglomerado y sus intervalos de confianza del 95% (IC 95%). Resultados: El 75% (181/243) de niñas y el 73% (170/232) de niños estaban insatisfechos con su imagen corporal; casi todos deseaban un cuerpo más delgado. El 45% (121/271) de las niñas y el 52% (135/262) de los niños presentaba sobrepeso u obesidad, lo que se asoció con la insatisfacción con su imagen corporal (ajustado por clúster: 6.73; IC 95%: 5.42-8.36). Ningún otro factor se asoció significativamente con la insatisfacción con la imagen corporal. El 32% (86/271) de las niñas y el 17% (45/261) de los niños reportaron una imagen corporal deseada con bajo peso. Conclusiones: El alto nivel de obesidad y el mayor nivel de insatisfacción con la imagen corporal son motivo de preocupación. La insatisfacción sugiere que los niños y las niñas en México pueden verse sometidos a una fuerte presión social sobre la imagen corporal deseable.

Organic contaminants and trace metals in the western South Atlantic upper continental margin: Anthropogenic influence on mud depocenters.

Trace metals, dichloro-diphenyl-trichloroethane (DDTs), polychlorinated biphenyls (PCBs), and polycyclic aromatic hydrocarbons (PAHs) were quantified in surface sediments from mud depocenters located in the western South Atlantic upper continental margin. There was no anthropogenic trace metal pollution observed, and the higher As values were attributed to high CaCO3 content in the area. The results indicate PCB sources associated with long-range atmospheric transport in addition to past DDT use for agriculture and pest control. PAHs were mainly originated from biomass and fossil fuel combustion, and their distribution is in alignment with the riverine runoff influence in southern region, which is transported towards the northern regions by coastal currents. Higher concentrations of 2-3 ring PAHs and DDTs in shallow and northern stations indicate a coastal influence. This work presents baseline information on the extent of anthropogenic influence in mud depocenters located in the western South Atlantic upper continental margin, showing these locations as potential source to sink of anthropogenic contaminants.

Identification of a Potential Zika Virus Inhibitor Targeting NS5 Methyltransferase Using Virtual Screening and Molecular Dynamics Simulations.

The NS5 methyltransferase (MTase) has been reported as an attractive molecular target for antivirals discovery against the Zika virus (ZIKV). Here, we report structure-based virtual screening of 42 390 structures from the Development Therapeutics Program (DTP) AIDS Antiviral Screen Database. Among the docked compounds, ZINC1652386 stood out due to its high affinity for MTase in comparison to the cocrystallized ligand MS2042, which interacts with the Asp146 residue in the MTase binding site by hydrogen bonding. Subsequent molecular dynamics simulations predicted that this compound forms a stable complex with MTase within 50 ns. Thus, ZINC1652386 may represent a promising ZIKV methyltransferase inhibitor.

Identification of Zika Virus NS2B-NS3 Protease Inhibitors by Structure-Based Virtual Screening and Drug Repurposing Approaches.

The NS2B-NS3 protease has been identified as an attractive target for drug development against Zika virus (ZIKV) and combined drug repurposing and structure-based virtual screening has improved the development of antiviral drugs. In this study, we performed a structure-based virtual screening of 1861 Food and Administration (FDA) approved drugs available in DrugBank by the selection and docking validation of crystal structure of ZIKV NS2B-NS3 protease (PDB ID 5H4I ) using Glide and DOCK 6 software. The antihistaminic chlorcyclizine (Grid score -24.8 kcal/mol) exhibited the most promising interaction with NS2B-NS3 protease in comparison to crystallography ligand (Grid score -15.6 kcal/mol) by interaction to Tyr161 by hydrophobic interactions in the binding site of NS2B-NS3 which is recognized as an important amino acid in substrate molecular recognition. Cytotoxicity and global antiviral activity assay in Vero cells by MTT method showed that chlorcyclizine reduced the ZIKV induced cytopathic effect (EC50 of 69.0 ± 7.3 µM and SI = 1.9), and explicit molecular dynamics simulations implemented on a NAMD program indicated great stability of chlorcyclizine in protease binding site, suggesting the repurposing of chlorcyclizine as a promising finding in anti-ZIKV drug development.

Influence of sediment parameters on the distribution and fate of PAHs in an estuarine tropical region located in the Brazilian semi-arid (Jaguaribe River, Ceará coast).

18 polycyclic aromatic hydrocarbons (PAHs) were evaluated in the Jaguaribe River to explore the influence of grain size, organic carbon, humic and fulvic acids and black carbon on their adsorption onto sediment. The ∑PAHs concentrations variated from 0.6 to 3752.0 ng g-1 with highest concentrations in the estuarine zone. The PAHs predominant source along the river was from mixed sources, mainly related to biomass combustion, small oil spills related to recreational nautical activities and runoff from cities. Organic and inorganic parameters presented influence on PAHs distribution along the river, with humic acid as a determinant factor. These research findings are of importance to an assessment of the fate and transport of PAHs in estuarine systems.

Characterization of Cu2O/TiO2NTs nanomaterials using EDXRF, XRD and DRS for photocatalytic applications.

TiO2 nanotube arrays (TiO2NTs) were decorated with Cu2O nanoparticles by pulse electrochemical deposition. The Cu2O nanoparticles were uniformly distributed onto TiO2NTs surface and with diameter varying between 50 and 200 nm. The effects of the independent variables on the photocatalytic response were simultaneously assessed by a multivariate statistical design. Energy-Dispersive X-Ray Fluorescence, X-Ray Diffraction, FEG-SEM and Diffuse Reflectance Spectroscopy were employed to Cu2O/TiO2NTs characterization. The Cu2O films obtained on TiO2NTs surface were crystalline. DRS analysis confirmed that the modification of TiO2NTs with Cu2O nanoparticles improved the quantum efficiency of the material. The Cu2O/TiO2NTs photoelectrode shows an intense absorption peak in the visible region decreasing the band gap energy from 3.20eV for TiO2NTs to 2.96 eV for Cu2O/TiO2NTs.

Emerging and traditional organic markers: Baseline study showing the influence of untraditional anthropogenic activities on coastal zones with multiple activities (Ceará coast, Northeast Brazil).

Molecular markers are useful tools to characterize natural and anthropogenic impacts on coastal zones. Distribution of n-alkanes showed that the Pacoti River was predominantly influenced by terrigenous input. Distribution of polycyclic aromatic hydrocarbon (PAH) indices showed a mix of natural sources, especially pyrogenic influences. Sterol and hormone levels showed sewage discharge. Integrated geographic assessment showed that pyrogenic process and sewage discharge are predominant along the river because of natural and different anthropogenic activities. The upstream region is influenced by rural activities such as livestock and discharge from the sewage treatment plant, whereas the estuarine region is influenced by urban and industrial activities, predominantly the discharge of treated or untreated sewage, vehicle traffic, and manufacture of red ceramics. On the other hand, on the river mouth, there is the predominance of aquaculture activities. Traditional anthropogenic markers are not sufficient for producing a comprehensive assessment of anthropogenic impacts in areas with multiple activities.

Influence of anthropogenic activities and risk assessment on protected mangrove forest using traditional and emerging molecular markers (Ceará coast, northeastern Brazil).

Anthropogenic molecular markers were used to assess chemicals inputs and ecological risks associated from multiple sources to sediments in one of the largest tropical mangrove forests of South America, with a particular focus on lesser studied compounds resulting from rural activities. Total concentrations ranged from 23.4 to 228.2 ng g-1 for polycyclic aromatic hydrocarbons (∑PAHs), 750.4 to 5912.5 ng g-1 for aliphatic hydrocarbons (∑AHs), 32.4 to 696.6 ng g-1 for pesticides (∑pesticides), 23.1 to 2109.7 ng g-1 for coprostanol and sterols (∑sterols), 139.3 to 580.2 ng g-1 for naturals hormones (∑natural hormones) and 334.1 to 823.4 ng g-1 for synthetics hormones (∑synthetic hormones). The PAHs and AHs used as traditional anthropogenic markers showed a mixture between natural and anthropogenic sources, related mainly to inputs from higher plants, phytoplankton and both, biomass and petroleum combustion. Rural activities linked to agricultural pest control are the predominant source of pesticides, although minor inputs from pesticides used in urban public health campaigns and household activities were also detected. Synthetic hormones levels are two to three orders of magnitude greater than natural hormones levels and no correlations were observed between the main sewage markers and synthetic hormone concentrations, rural activities such as animal husbandry, which use drugs in management, may be the predominant anthropogenic sources of these compounds in the region. Traditional markers failed to detect ecological risks in rural areas, where synthetic substances (e.g. pesticides and hormones) are widely used and introduced in the environment.

Synthesis and Evaluation of the in vitro Antimicrobial Activity of Triazoles, Morpholines and Thiosemicarbazones.

BACKGROUND: Microbial infections is a global public health problem. The aim of this work was to synthesize and evaluate the antimicrobial activity of novel triazoles, morpholines and thiosemicarbazones. METHODS: Compounds were synthesized using 2,4-Dihydroxyacetophenone and 4-hydroxybenzaldehyde as starting materials. The antimicrobial activity of these compounds against bacteria and yeast was evaluated by the broth microdilution method. RESULTS: The proposed route for synthesis gave high to moderate yields, moreover these compounds were successfully characterized by 1H NMR, 13C NMR and LC-MS. Antimicrobial testing indicated that the thiosemicarbazone and morphine derivatives had the best antimicrobial activity against the microorganisms tested with minimum inhibitory concentrations (MIC) between 0.29 and 5.30 µM. Thiosemicarbazone derivative (12) was able to inhibit the growth of C. tropicalis, with minimum fungicidal concentration (MFC) of 0.55 µM. In addition, this compound was active against E. coli, S. aureus and S. epidermidis, with MIC values ranging from 0.29 to 1.11 µM. Moreover, the morpholine derivative (15) had an MIC value of 0.83 µM against C. albicans and E. coli. CONCLUSION: We have efficiently synthesized a series of eleven novel triazoles, thiosemicarbazones and morpholine derivatives using 2,4-Dihydroxyacetophenone and 4-hydroxybenzaldehyde as starting materials. Thiosemicarbazone derivative (12) showed promising antifungal and antibacterial activity and these findings suggest that this compound can be used as scaffolds to design new antimicrobial drugs.