Epigenetic MLH1 silencing concurs with mismatch repair deficiency in sporadic, naturally occurring colorectal cancer in rhesus macaques.

BACKGROUND: Naturally occurring colorectal cancers (CRC) in rhesus macaques share many features with their human counterparts and are useful models for cancer immunotherapy; but mechanistic data are lacking regarding the comparative molecular pathogenesis of these cancers. METHODS: We conducted state-of-the-art imaging including CT and PET, clinical assessments, and pathological review of 24 rhesus macaques with naturally occurring CRC. Additionally, we molecularly characterized these tumors utilizing immunohistochemistry (IHC), microsatellite instability assays, DNAseq, transcriptomics, and developed a DNA methylation-specific qPCR assay for MLH1, CACNA1G, CDKN2A, CRABP1, and NEUROG1, human markers for CpG island methylator phenotype (CIMP). We furthermore employed Monte-Carlo simulations to in-silico model alterations in DNA topology in transcription-factor binding site-rich promoter regions upon experimentally demonstrated DNA methylation. RESULTS: Similar cancer histology, progression patterns, and co-morbidities could be observed in rhesus as reported for human CRC patients. IHC identified loss of MLH1 and PMS2 in all cases, with functional microsatellite instability. DNA sequencing revealed the close genetic relatedness to human CRCs, including a similar mutational signature, chromosomal instability, and functionally-relevant mutations affecting KRAS (G12D), TP53 (R175H, R273*), APC, AMER1, ALK, and ARID1A. Interestingly, MLH1 mutations were rarely identified on a somatic or germline level. Transcriptomics not only corroborated the similarities of rhesus and human CRCs, but also demonstrated the significant downregulation of MLH1 but not MSH2, MSH6, or PMS2 in rhesus CRCs. Methylation-specific qPCR suggested CIMP-positivity in 9/16 rhesus CRCs, but all 16/16 exhibited significant MLH1 promoter hypermethylation. DNA hypermethylation was modelled to affect DNA topology, particularly propeller twist and roll profiles. Modelling the DNA topology of a transcription factor binding motif (TFAP2A) in the MLH1 promoter that overlapped with a methylation-specific probe, we observed significant differences in DNA topology upon experimentally shown DNA methylation. This suggests a role of transcription factor binding interference in epigenetic silencing of MLH1 in rhesus CRCs. CONCLUSIONS: These data indicate that epigenetic silencing suppresses MLH1 transcription, induces the loss of MLH1 protein, abrogates mismatch repair, and drives genomic instability in naturally occurring CRC in rhesus macaques. We consider this spontaneous, uninduced CRC in immunocompetent, treatment-naïve rhesus macaques to be a uniquely informative model for human CRC.

An Efficient Edge Computing-Enabled Network for Used Cooking Oil Collection.

In Portugal, more than 98% of domestic cooking oil is disposed of improperly every day. This avoids recycling/reconverting into another energy. Is also may become a potential harmful contaminant of soil and water. Driven by the utility of recycled cooking oil, and leveraging the exponential growth of ubiquitous computing approaches, we propose an IoT smart solution for domestic used cooking oil (UCO) collection bins. We call this approach SWAN, which stands for Smart Waste Accumulation Network. It is deployed and evaluated in Portugal. It consists of a countrywide network of collection bin units, available in public areas. Two metrics are considered to evaluate the system's success: (i) user engagement, and (ii) used cooking oil collection efficiency. The presented system should (i) perform under scenarios of temporary communication network failures, and (ii) be scalable to accommodate an ever-growing number of installed collection units. Thus, we choose a disruptive approach from the traditional cloud computing paradigm. It relies on edge node infrastructure to process, store, and act upon the locally collected data. The communication appears as a delay-tolerant task, i.e., an edge computing solution. We conduct a comparative analysis revealing the benefits of the edge computing enabled collection bin vs. a cloud computing solution. The studied period considers four years of collected data. An exponential increase in the amount of used cooking oil collected is identified, with the developed solution being responsible for surpassing the national collection totals of previous years. During the same period, we also improved the collection process as we were able to more accurately estimate the optimal collection and system's maintenance intervals.

Histo-blood group A is a risk factor for severe COVID-19.

OBJECTIVES: Evaluate the impact of ABO histo-blood group type on COVID-19 severity. BACKGROUND: ABO histo-blood type has been associated with different outcomes in infectious diseases. It has also shown a higher proportion of type A patients with SARS-CoV-2. In this observational study, extracted from an ongoing clinical trial on the efficacy of convalescent plasma transfused in COVID-19 patients, we describe the impact of ABO blood type on the risk of developing severe COVID-19. MATERIALS AND METHODS: Seventy-two consecutive patients (37 type A, 23 type O, 11 type B, 1 type AB) with severe (respiratory failure) COVID-19 were included. Control group was composed of 160 individuals randomly selected from the same populational basis. RESULTS: Blood group A was overrepresented (51.39%) in the patient group in relation to the control group (30%), whereas blood group O was less represented (31.94%) in patient than in control group (48%). Odds ratio (A vs. O) was 2.581 (1.381-4.817), CI 95%; p = 0.004. Also, blood group A patients appeared to have more severe disease, given by the scores of the Sequential Organ Failure Assessment and Simplified Acute Physiologic Score 3 (p = 0.036 and p = 0.058, respectively). CONCLUSION: Histo-blood type A is associated with a higher risk of developing severe COVID-19 in relation to blood type O.

New "Omics" Approaches as Tools to Explore Mechanistic Nanotoxicology.

In the last years, "omics" approaches have been applied to study the toxicity of nanomaterials (NM) with the aim of obtaining insightful information on their biological effects. One of the most developed "omics" field, transcriptomics, expects to find unique profiles of differentially-expressed genes after exposure to NM that, besides providing evidence of their mechanistic mode of action, may also be used as biomarkers for biomonitoring purposes. Moreover, several NM have been associated with epigenetic alterations, i.e., changes in the regulation of gene expression caused by differential DNA methylation, histone tail modification and microRNA expression. Epigenomics research focusing on DNA methylation is increasingly common and the role of microRNAs is being better understood, either promoting or suppressing biological pathways. Moreover, the proteome is a highly dynamic system that changes constantly in response to a stimulus. Therefore, proteomics can identify changes in protein abundance and/or variability that lead to a better understanding of the underlying mechanisms of action of NM while discovering biomarkers. As to genomics, it is still not well developed in nanotoxicology. Nevertheless, the individual susceptibility to NM mediated by constitutive or acquired genomic variants represents an important component in understanding the variations in the biological response to NM exposure and, consequently, a key factor to evaluate possible adverse effects in exposed individuals. By elucidating the molecular changes that are involved NM toxicity, the new "omics" studies are expected to contribute to exclude or reduce the handling of hazardous NM in the workplace and support the implementation of regulation to protect human health.

Genetic diversity and correlation between morphological traits of pequi fruits (Caryocar brasiliense Camb.) with and without thorns at the endocarp.

Morphological characteristics of pequi fruits (Caryocar brasiliense) allows us to obtain information for the conservation, breeding, and detect genetic variability. Thus, the aims of this research were to characterize the genetic diversity of Caryocar brasiliense that produce fruits with and without thorn at the endocarp; determine the important characters in the study of genetic diversity, and to estimate phenotypic and genotypic correlations. 80 fruits with thorns and 90 fruits without thorns were evaluated. Data were used for analysis: Euclidian distance as a measure of dissimilarity and the Tocher method for delimitation of groups; Principal Component Analysis, and genotypic and phenotypic correlations. Genetic dissimilarity of C. brasiliense ranged from 0.066 (B6-D6) to 0.908 (A14-B3). Tocher method allowed dividing the matrices into three groups, the dendrogram into five groups, and the principal components allowed the distribution in 8 groups. We observed 15 significant correlations for characters of fruit with thorns and 31 correlations for characters of fruit without thorns. The weight of the fruit (with thorns) and the pyrene yield (without thorns) are relevant correlations for production. The groupings generated allowed the classification of the matrices into distinct sets. Allowed the identification of potential producers plants that could be used in breeding programs.

Samanea tubulosa Benth. (Fabaceae): Antinociceptive effect on acute pain in mice: K+ATP channel and opioid activity.

Samanea tubulosa Benth. it has been widely used in traditional medicine to treat inflammatory processes. The present study aimed to investigate the antinociceptive effect and mechanism of action of the fractions obtained from the Samanea tubulosa pods in mice. The antinociceptive activity was evaluated in formalin, capsaicin and glutamate tests and the. The possible mechanisms of action involved in the antinociceptive effect of the hexane and ethyl acetate fraction in the opioid system, also the the K + ATP channels and the L-arigine pathways of nitric oxide were evaluated. The chemical characterization analysis revealed in the hexane fraction the presence of triterpenes such as lupenone and lupeol. In the glutamate test, the hexane and ethyl acetate fractions showed antinociceptive activity at the dose of 12.5 and 25 mg kg-1. The antinociception produced by the hexane and ethyl acetate fractions was significantly reversed by naloxone, indicating that the fractions act through the opioid pathway. Antinociceptive response of the ethyl acetate fraction was blocked by glibenclamide, indicating that this fraction acts via the K + ATP channels activation. It is concluded that the fractions under study exert antinociceptive activity possibly related to the opioid route and through K+ ATP channels activation.

Male and female breast cancer: the two faces of the same genetic susceptibility coin.

BACKGROUND: Breast cancer (BC) is the most common cancer in women. In contrast, male BC is about 100 times less common than in women, being considered a rare disease. Male BC may be a distinctive subtype of BC and available data seems to indicate that male BC has a higher dependence on genetic variants than female BC. Nevertheless, the same prognostic and predictive markers are used to determine optimal management strategies for both male and female BC. Several studies have assessed the role of genetic polymorphisms (SNPs) in DNA repair genes in female BC susceptibility. However, data on male BC is scarce. Thus, the current study aimed to assess the role of SNPs in XRCC1, MUTYH and TP53 genes in a male cohort of BC, and, in addition, compare the male data with matched results previously genotyped in female BC patients. METHODS: The male BC cohort was genotyped through Real-Time PCR using TaqMan Assays for several SNPs previously analysed in Portuguese female BC patients. RESULTS: The results obtained indicate significant differences in BC susceptibility between males and females for the XRCC1 rs1799782, MUTYH rs3219489 and TP53 rs1042522 and rs8064946 variants. CONCLUSIONS: In males, XRCC1 and TP53 variants, when in heterozygosity, seem to be related with lower susceptibility for BC, contrasting with higher susceptibility for a MUTYH variant in females. These findings may help to explain the difference in incidence of BC between the two sexes.

Biomarkers of effect as determined in human biomonitoring studies on hexavalent chromium and cadmium in the period 2008-2020.

A number of human biomonitoring (HBM) studies have presented data on exposure to hexavalent chromium [Cr(VI)] and cadmium (Cd), but comparatively few include results on effect biomarkers. The latter are needed to identify associations between exposure and adverse outcomes (AOs) in order to assess public health implications. To support improved derivation of EU regulation and policy making, it is of great importance to identify the most reliable effect biomarkers for these heavy metals that can be used in HBM studies. In the framework of the Human Biomonitoring for Europe (HBM4EU) initiative, our study aim was to identify effect biomarkers linking Cr(VI) and Cd exposure to selected AOs including cancer, immunotoxicity, oxidative stress, and omics/epigenetics. A comprehensive PubMed search identified recent HBM studies, in which effect biomarkers were examined. Validity and applicability of the markers in HBM studies are discussed. The most frequently analysed effect biomarkers regarding Cr(VI) exposure and its association with cancer were those indicating oxidative stress (e.g., 8-hydroxy-2'-deoxyguanosine (8-OHdG), malondialdehyde (MDA), glutathione (GSH)) and DNA or chromosomal damage (comet and micronucleus assays). With respect to Cd and to some extent Cr, ß-2-microglobulin (B2-MG) and N-acetyl-ß-D-glucosaminidase (NAG) are well-established, sensitive, and the most common effect biomarkers to relate Cd or Cr exposure to renal tubular dysfunction. Neutrophil gelatinase-associated lipocalin (NGAL) and kidney injury molecule (KIM)-1 could serve as sensitive biomarkers of acute kidney injury in response to both metals, but need further investigation in HBM studies. Omics-based biomarkers, i.e., changes in the (epi-)genome, transcriptome, proteome, and metabolome associated with Cr and/or Cd exposure, are promising effect biomarkers, but more HBM data are needed to confirm their significance. The combination of established effect markers and omics biomarkers may represent the strongest approach, especially if based on knowledge of mechanistic principles. To this aim, also mechanistic data were collected to provide guidance on the use of more sensitive and specific effect biomarkers. This also led to the identification of knowledge gaps relevant to the direction of future research.

Effect of percutaneous aortic valve position on stress map in ascending aorta: A fluid-structure interaction analysis.

Transcatheter aortic valve implantation (TAVI) is an increasingly widespread procedure. Although this intervention is indicated for high and low surgical risk patients, some issues still remain, such as prosthesis positioning optimization in the aortic annulus. Coaxial positioning of the percutaneous prosthesis influences directly on the aortic wall stress map. The determination of the mechanical stress that acts on the vascular endothelium resulting from blood flow can be considered an important task, since TAVI positioning can lead to unfavorable hemodynamic patterns, resulting in changes in parietal stress, such as those found in post-stenotic dilatation region. This research aims to investigate the influence of the prosthetic valve inclination angle in the mechanical stresses acting in the ascending aortic wall. Aortic compliance and blood flow during cardiac cycle were numerically obtained using fluid structure interaction. The aortic model was developed through segmentation of a computed tomography image of a specific patient submitted to TAVI. When compared to standard position (coaxiality match between the prosthesis and the aortic annulus), the inclination of 4° directed to the left main coronary artery decreased the aortic wall area with high values of wall shear stress and pressure. Coaxial positioning optimization of percutaneous aortic prosthesis may decrease the high mechanical stress area. These changes may be important to reduce the aortic remodeling process, vascular calcification or even the prosthesis half-life. Computational fluid dynamics makes room for personalized medicine, with manufactured prosthesis tailored to each patient.

Chiral Dielectric Metasurfaces for Highly Integrated, Broadband Circularly Polarized Antenna.

We report on the design of a low-profile integrated millimeter-wave antenna for efficient and broadband circularly polarized electromagnetic radiation. The designed antenna comprises a chiral dielectric metasurface built with a 2×2 arrangement of dielectric cylinders with slanted-slots at the center. A broadbeam high-gain with wide axial ratio (AR)<3 dB bandwidth was reached by pairing the electric and magnetic resonances of the dielectric cylinders and the slanted slots when excited by an elliptically polarized driven-patch antenna. This electric-magnetic pairing can be tuned by varying the cylinders diameter and the tilting and rotation angles of the slanted slots. The simulation results indicate impedance-matching bandwidths up to 22.6% (25.3-31.6 GHz) with 3-dB AR bandwidths of 11.6% (26.9-30.2 GHz), which in terms of compactness (0.95λ0×0.95λ0) and performance are superior to previous antenna designs. Since the simulations were performed by assuming materials and geometries easily implementable experimentally, it is hoped that circularly polarized antennas based on chiral metasurfaces can be integrated into 5G and satellite communications.

In-House Three-Dimensional Printing Workflow for Face Shield During COVID-19 Pandemic.

From the beginning of the year 2020, the world was affected by a coronavirus disease (COVID-19) pandemic, caused by SARS-CoV-2, leading to a shortage of personal protective equipment (PPE) at a global level, and thus generating exposure of health professionals to this extremely contagious virus. Within this context, the present work seeks to present an alternative for the production of face shields "face shields," in which it recommends its production "in house" through 3D printing, in principle initiated by Prusa Research, where we download your project of support of facial protectors, proceeding with printing through the 3D printer Gtmax3D Core H5. The authors produced a face shield in ABS, in a total time of 3 hours and 44 minutes. Thus, the model presented proved to be feasible, at a low cost, adding to the list of possibilities to produce inputs necessary to maintain the fight against this epidemic.

ABC Efflux Transporters and the Circuitry of miRNAs: Kinetics of Expression in Cancer Drug Resistance.

Cancer drug resistance (CDR) is a major problem in therapeutic failure. Over 90% of patients with metastatic cancer present CDR. Several mechanisms underlie CDR, including the increased expression of efflux ABC transporters and epigenetic phenomena. Nevertheless, a topic that is not usually addressed is the mechanism underlying the loss of CDR once the challenge to these cells is withdrawn. A KCR cell line (doxorubicin-resistant, expressing ABCB1) was used to induce loss of resistance by withdrawing doxorubicin in culture medium. ABCB1 activity was analysed by fluorescence microscopy and flow cytometry through substrate (DiOC2) retention assays. The expression of 1008 microRNAs was assessed before and after doxorubicin withdrawal. After 16 weeks of doxorubicin withdrawal, a decrease of ABCB1 activity and expression occurred. Moreover, we determined a signature of 23 microRNAs, 13 underexpressed and 10 overexpressed, as a tool to assess loss of resistance. Through pathway enrichment analysis, "Pathways in cancer", "Proteoglycans in cancer" and "ECM-receptor interaction" were identified as relevant in the loss of CDR. Taken together, the data reinforce the assumption that ABCB1 plays a major role in the kinetics of CDR, and their levels of expression are in the dependence of the circuitry of cell miRNAs.

Setting up a collaborative European human biological monitoring study on occupational exposure to hexavalent chromium.

The EU human biomonitoring initiative, HBM4EU, aims to co-ordinate and advance human biomonitoring (HBM) across Europe. Within its remit, the project is gathering new, policy relevant, EU-wide data on occupational exposure to relevant priority chemicals and developing new approaches for occupational biomonitoring. In this manuscript, the hexavalent chromium [Cr(VI)] study design is presented as the first example of this HBM4EU approach. This study involves eight European countries and plans to recruit 400 workers performing Cr(VI) surface treatment e.g. electroplating or stainless steel welding activities. The aim is to collect new data on current occupational exposure to Cr(VI) in Europe and to test new methods for Cr biomonitoring, specifically the analysis of Cr(VI) in exhaled breath condensate (EBC) and Cr in red blood cells (RBC) in addition to traditional urinary total Cr analyses. Furthermore, exposure data will be complemented with early biological effects data, including genetic and epigenetic effects. Personal air samples and wipe samples are collected in parallel to help informing the biomonitoring results. We present standard operational procedures (SOPs) to support the harmonized methodologies for the collection of occupational hygiene and HBM samples in different countries.

Potent Cytotoxic Analogs of Amphidinolides from the Atlantic Octocoral Stragulum bicolor.

Amphidinolides are cytotoxic macrolides produced by symbiotic unicellular microalgae of the genus Amphidinium. Here we describe the identification of four related molecules belonging to this macrolide family isolated from the invertebrate Stragulum bicolor. The new molecules, named amphidinolide PX1-PX3 and stragulin A (1⁻4), show an unprecedented carbon skeleton whose complete stereochemistry has been determined by spectroscopic and computational methods. Differences in the structures of these molecules modulate their biological activity in a panel of tumor cell lines, but the opened derivative stragulin (4) shows a very potent and specific cytotoxic activity (IC50 0.18 µM) against the aggressive human melanoma cell A2058.

An assessment of mosquito collection techniques for xenomonitoring of anopheline-transmitted Lymphatic Filariasis in Ghana.

Monitoring vectors is relevant to ascertain transmission of lymphatic filariasis (LF). This may require the best sampling method that can capture high numbers of specific species to give indication of transmission. Gravid anophelines are good indicators for assessing transmission due to close contact with humans through blood meals. This study compared the efficiency of an Anopheles gravid trap (AGT) with other mosquito collection methods including the box and the Centres for Disease Control and Prevention gravid, light, exit and BioGent-sentinel traps, indoor resting collection (IRC) and pyrethrum spray catches across two endemic regions of Ghana. The AGT showed high trapping efficiency by collecting the highest mean number of anophelines per night in the Western (4.6) and Northern (7.3) regions compared with the outdoor collection methods. Additionally, IRC was similarly efficient in the Northern region (8.9) where vectors exhibit a high degree of endophily. AGT also showed good trapping potential for collecting Anopheles melas which is usually difficult to catch with existing methods. Screening of mosquitoes for infection showed a 0.80-3.01% Wuchereria bancrofti and 2.15-3.27% Plasmodium spp. in Anopheles gambiae. The AGT has shown to be appropriate for surveying Anopheles populations and can be useful for xenomonitoring for both LF and malaria.

Genome of Rhodnius prolixus, an insect vector of Chagas disease, reveals unique adaptations to hematophagy and parasite infection.

Rhodnius prolixus not only has served as a model organism for the study of insect physiology, but also is a major vector of Chagas disease, an illness that affects approximately seven million people worldwide. We sequenced the genome of R. prolixus, generated assembled sequences covering 95% of the genome (∼ 702 Mb), including 15,456 putative protein-coding genes, and completed comprehensive genomic analyses of this obligate blood-feeding insect. Although immune-deficiency (IMD)-mediated immune responses were observed, R. prolixus putatively lacks key components of the IMD pathway, suggesting a reorganization of the canonical immune signaling network. Although both Toll and IMD effectors controlled intestinal microbiota, neither affected Trypanosoma cruzi, the causal agent of Chagas disease, implying the existence of evasion or tolerance mechanisms. R. prolixus has experienced an extensive loss of selenoprotein genes, with its repertoire reduced to only two proteins, one of which is a selenocysteine-based glutathione peroxidase, the first found in insects. The genome contained actively transcribed, horizontally transferred genes from Wolbachia sp., which showed evidence of codon use evolution toward the insect use pattern. Comparative protein analyses revealed many lineage-specific expansions and putative gene absences in R. prolixus, including tandem expansions of genes related to chemoreception, feeding, and digestion that possibly contributed to the evolution of a blood-feeding lifestyle. The genome assembly and these associated analyses provide critical information on the physiology and evolution of this important vector species and should be instrumental for the development of innovative disease control methods.

Antiedematogenic activity of the indole derivative N-salicyloyltryptamine in animal models.

The N-salicyloyltryptamine (NST) is an indole derivative compound analogue to the alkaloid N-benzoyltryptamine. In the present study, the antiedematogenic activity of NST was investigated in animal models. Firstly, the acute toxicity for NST was assessed according to the OECD Guideline no. 423. The potential NST-induced antiedematogenic activity was evaluated by carrageenan-induced paw edema in rats, as well as by dextran-, compound 48/80-, histamine-, serotonin-, capsaicine-, and prostaglandin E2-induced paw edema in mice. The effect of NST on compound 48/80-induced ex vivo mast cell degranulation on mice mesenteric bed was investigated. No death or alteration of behavioral parameters was observed after administration of NST (2000 mg/kg, i.p.) during the observation time of 14 days. The NST (100 and 200 mg/kg, i.p.) inhibited the carrageenan-induced edema from the 1st to the 5th hour (**p<0.01; ***p<0.001). The edematogenic activity induced by dextran, compound 48/80, histamine, serotonin, capsaicin, and prostaglandin E2 was inhibited by NST (100 mg/kg, i.p.) throughout the observation period (**p<0.01; ***p<0.001). The pretreatment with NST (50, 100 or 200 mg/kg, i.p) attenuates the compound 48/80-induced mast cell degranulation (**p<0.01; ***p<0.001). Thus, the inhibition of both mast cell degranulation and release of endogenous mediators are probably involved in the NST-induced antiedematogenic effect.

Probing the Role of the Hinge Segment of Cytochrome P450 Oxidoreductase in the Interaction with Cytochrome P450.

NADPH-cytochrome P450 reductase (CPR) is the unique redox partner of microsomal cytochrome P450s (CYPs). CPR exists in a conformational equilibrium between open and closed conformations throughout its electron transfer (ET) function. Previously, we have shown that electrostatic and flexibility properties of the hinge segment of CPR are critical for ET. Three mutants of human CPR were studied (S243P, I245P and R246A) and combined with representative human drug-metabolizing CYPs (isoforms 1A2, 2A6 and 3A4). To probe the effect of these hinge mutations different experimental approaches were employed: CYP bioactivation capacity of pre-carcinogens, enzyme kinetic analysis, and effect of the ionic strength and cytochrome b5 (CYB5) on CYP activity. The hinge mutations influenced the bioactivation of pre-carcinogens, which seemed CYP isoform and substrate dependent. The deviations of Michaelis-Menten kinetic parameters uncovered tend to confirm this discrepancy, which was confirmed by CYP and hinge mutant specific salt/activity profiles. CPR/CYB5 competition experiments indicated a less important role of affinity in CPR/CYP interaction. Overall, our data suggest that the highly flexible hinge of CPR is responsible for the existence of a conformational aggregate of different open CPR conformers enabling ET-interaction with structural varied redox partners.

Isolation of Chamigrene Sesquiterpenes and Absolute Configuration of Isoobtusadiene from the Brittle Star Ophionereis reticulata.

The chemical study of the Brazilian brittle star Ophionereis reticulata led to the isolation of three chamigrene sesquiterpenes, including the partially characterized isoobtusadiene (1), its unreported acetyl derivative (2), and the known (+)-elatol (3). The complete elucidation of the structures 1 and 2 was accomplished by 1D and 2D NMR spectroscopy. The first assignment of the absolute configuration of the isoobtusadiene skeleton is suggested as 6S,9R,10S on the basis of the NMR analysis of the Mosher's ester derivatives of 1 and the ECD study of the acetyl derivative 2. Chamigrenes are typical constituents of Laurencia red algae. O. reticulata is a predator with a preference for algae. Thus, the origin of these metabolites can be likely ascribed to diet.

Diet enriched with the Amazon fruit açaí (Euterpe oleracea) prevents electrophysiological deficits and oxidative stress induced by methyl-mercury in the rat retina.

BACKGROUND: The protective effect of a diet supplemented by the Amazonian fruit Euterpe oleracea (EO) against methylmercury (MeHg) toxicity in rat retina was studied using electroretinography (ERG) and biochemical evaluation of oxidative stress. METHOD: Wistar rats were submitted to conventional diet or EO-enriched diet for 28 days. After that, each group received saline solution or 5 mg/kg/day of MeHg for 7 days. Full-field single flash, flash and flicker ERGs were evaluated in the following groups: control, EO, MeHg, and EO+MeHg. The amplitudes of the a-wave, b-wave, photopic negative response from rod and/or cone were measured by ERGs as well as the amplitudes and phases of the fundamental component of the sine-wave flicker ERG. Lipid peroxidation was determined by thiobarbituric acid reactive species. RESULTS: All ERG components had decreased amplitudes in the MeHg group when compared with controls. EO-enriched food had no effect on the non-intoxicated animals. The intoxicated animals and those that received the supplemented diet presented significant amplitude reductions of the cone b-wave and of the fundamental flicker component when compared with non-intoxicated control. The protective effect of the diet on scotopic conditions was only observed for bright flashes eliciting a mixed rod and cone response. There was a significant increase of lipid peroxidation in the retina from animals exposed to MeHg and EO-supplemented diet was able to prevent MeHg-induced oxidative stress in retinal tissue. CONCLUSION: These findings open up perspectives for the use of diets supplemented with EO as a protective strategy against visual damage induced by MeHg.