106 results on '"Dias GM"'
Search Results
2. P14 Large neck anterior communicating artery aneurysm treated with WEB: an unusual approach
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Almeida Silva, JM, primary, Rezende, AL, additional, Rodrigues, PM, additional, Dias, GM, additional, and Hazzan, MA, additional
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- 2022
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3. MODELING LONG QT SYNDROME IN IPS-DERIVED CARDIOMYOCYTES FROM A PATIENT HARBORING THE KCNQ1- I588T MUTATION
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Barbosa, RAQ, primary, Silva-dos-Santos, D, additional, Pires-Ferreira, R, additional, Araujo, DS, additional, Farjun, B, additional, Dias, GM, additional, Coutinho, J, additional, Vaz, IM, additional, Borgonovo, T, additional, Cruz-Filho, FES, additional, Campos-de-Carvalho, AC, additional, Kasai-Brunswick, TH, additional, and Carvalho, AB, additional
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- 2021
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4. IS IT POSSIBLE TO MODEL JERVELL AND LANGE-NIELSEN SYNDROME (JLNS) USING PATIENT-SPECIFIC INDUCED PLURIPOTENT STEM CELLS (IPSC)?
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Fraga, JO, primary, Silva dos Santos, D, additional, Ferreira, RP, additional, Coutinho, KCS, additional, Leitão, IC, additional, Asensi, KD, additional, Gubert, F, additional, De Figueiredo, AF, additional, Dias, GM, additional, Cruz, FESF, additional, Sternick, EB, additional, de Carvalho, AC Campos, additional, Carvalho, AB, additional, and Kasai-Brunswick, TH, additional
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- 2021
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5. Spatial and temporal diversity of non-native biofouling species associated with marinas in two Angolan bays
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Pestana, LB, primary, Dias, GM, additional, and Marques, AC, additional
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- 2020
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6. Spontaneous resolution of an isolated cervical anterior spinal artery aneurysm after subarachnoid hemorrhage
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de Oliveira Mf, Dias Gm, Rotta Jm, Rotta Ma, Rezende Al, and Pahl Fh
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medicine.medical_specialty ,Subarachnoid hemorrhage ,treatment ,business.industry ,Anterior spinal artery ,Case Report ,medicine.disease ,intracranial aneurysm ,nervous system diseases ,Surgery ,Text mining ,Aneurysm ,medicine.artery ,Diagnosis ,cardiovascular system ,medicine ,cardiovascular diseases ,Neurology (clinical) ,business - Abstract
Background: Isolated cervical anterior spinal artery aneurysms are extremely rare. Subarachnoid hemorrhage (SAH) secondary to such lesions have been described only in six cases to the best of our knowledge. Case Description: We describe an unusual clinical picture of SAH due to rupture of anterior spinal artery aneurysm in a patient with previous normal angiogram. Due to the location of the aneurysm and clinical status of the patient, conservative management was proposed, and she was discharged to further follow-up. Monthly routine angiograms revealed resolution of the aneurysm 90 days after bleeding, which was highly suggestive of vascular dissection. Conclusion: We highlight the need to consider these aneurysms in the differential diagnosis of SAH, especially when occurring in the posterior fossa and when angiography findings are inconclusive.
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- 2014
7. Microgeographical differentiation between morphotypes of Trididemnum orbiculatum (Tunicata: Ascidiacea) in southeastern Brazil
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Dias, GM, primary, Abreu, AG, additional, Silva, FOM, additional, and Solferini, VN, additional
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- 2009
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8. Effects of competition on sexual and clonal reproduction of a tunicate: the importance of competitor identity
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Dias, GM, primary, Delboni, CGM, additional, and Duarte, LFL, additional
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- 2008
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9. Bacteriological Profile of Bile in Patients Undergoing Laparoscopic Cholecystectomy
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Cruz, Cat, primary, Mendelssonh, P, additional, Pedrosa, A, additional, Reys, LG, additional, Puttini, SMB, additional, and Dias, GM, additional
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- 2004
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10. The path to fertility: Current approaches to mare endometritis and endometrosis.
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Ferreira-Dias GM, Alpoim-Moreira J, Szóstek-Mioduchowska A, Rebordão MR, and Skarzynski DJ
- Abstract
The path to fertility in the mare requires an understanding of the hormonal influences, the immune response, genetics, and epigenetic mechanisms involved not only in physiological reproductive processes, but also such pathologies as endometritis and endometrosis. Endometritis may lead to endometrosis establishment. In the presence of endometritis, neutrophils arrive at the mare endometrium, and form neutrophil extracellular traps. While NETosis plays pivotal roles, prolonged inflammation can lead to chronic endometritis, endometrosis, and fertility issues. Matrix metalloproteinases and epigenetic changes influence the course of endometrosis. Inhibitors of specific enzymes involved in NETosis and epigenetic inhibitors have shown potential in reducing pro-fibrotic effects. Collagen type III (COL3) has emerged as a putative biomarker, correlating with endometrosis and useful in fertility assessment. Thus, COL3 may offer a non-invasive diagnostic tool, as a complement to histopathological methods. Epigenetic modifications and miRNA expressions offer new avenues for therapeutic strategies, emphasizing the importance of understanding the cellular mechanisms at play in mare endometrial fibrosis., Competing Interests: >Conflicts of interest: The authors have no conflict of interest to declare., (Copyright © The Author(s).)
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- 2024
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11. Exploring the diversity and functional profile of microbial communities of Brazilian soils with high salinity and oil contamination.
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Mariano DCO, Dias GM, Castro MR, Tschoeke DA, de Oliveira FJS, Sérvulo EFC, and Neves BC
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Environmental pollution associated with the petroleum industry is a major problem worldwide. Microbial degradation is extremely important whether in the extractive process or in bioremediation of contaminants. Assessing the local microbiota and its potential for degradation is crucial for implementing effective bioremediation strategies. Herein, contaminated soil samples of onshore oil fields from a semiarid region in the Northeast of Brazil were investigated using metagenomics and metataxonomics. These soils exhibited hydrocarbon contamination and high salinity indices, while a control sample was collected from an uncontaminated area. The shotgun analysis revealed the predominance of Actinomycetota and Pseudomonadota, while 16S rRNA gene amplicon analysis of the samples showed Actinomycetota, Bacillota, and Pseudomonadota as the most abundant. The Archaea domain phylotypes were assigned to Thermoproteota and Methanobacteriota. Functional analysis and metabolic profile of the soil microbiomes exhibited a broader metabolic repertoire in the uncontaminated soil, while degradation pathways and surfactant biosynthesis presented higher values in the contaminated soils, where degradation pathways of xenobiotic and aromatic compounds were also present. Biosurfactant synthetic pathways were abundant, with predominance of lipopeptides. The present work uncovers several microbial drivers of oil degradation and mechanisms of adaptation to high salinity, which are pivotal traits for sustainable soil recovery strategies., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 The Authors.)
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- 2024
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12. DNA damage and repair in patients undergoing myocardial perfusion single-photon emission computed tomography.
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De Lorenzo A, Dos Santos Fernandes MC, Romeiro F, Arpini AP, and Dias GM
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- Humans, Female, Male, Middle Aged, Aged, Technetium Tc 99m Sestamibi, Myocardial Perfusion Imaging methods, BRCA1 Protein genetics, Comet Assay, DNA Damage, Tomography, Emission-Computed, Single-Photon methods, DNA Repair genetics
- Abstract
As patient exposure to ionizing radiation from medical imaging and its risks are continuing issues, this study aimed to evaluate DNA damage and repair markers after myocardial perfusion single-photon emission computed tomography (MPS). Thirty-two patients undergoing Tc-99m sestamibi MPS were studied. Peripheral blood was collected before radiotracer injection at rest and 60-90 min after injection. The comet assay (single-cell gel electrophoresis) was performed with peripheral blood cells to detect DNA strand breaks. Three descriptors were evaluated: the percentage of DNA in the comet tail, tail length, and tail moment (the product of DNA tail percentage and tail length). Quantitative PCR (qPCR) was performed to evaluate the expression of five genes related to signaling pathways in response to DNA damage and repair (ATM, ATR, BRCA1, CDKN1A, and XPC). Mann-Whitney's test was employed for statistical analysis; p < 0.05 was considered significant. Mean Tc-99m sestamibi dose was 15.1 mCi. After radiotracer injection, comparing post-exposure to pre-exposure samples of each of the 32 patients, no statistically significant differences of the DNA percentage in the tail, tail length or tail moment were found. qPCR revealed increased expression of BRCA1 and XPC, without any significant difference regarding the other genes. No significant increase in DNA strand breaks was detected after a single radiotracer injection for MPS. There was activation of only two repair genes, which may indicate that, in the current patient sample, the effects of ionizing radiation on the DNA were not large enough to trigger intense repair responses, suggesting the absence of significant DNA damage., (© 2024. The Author(s).)
- Published
- 2024
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13. Does the incorporation of shell waste from aquaculture in the construction of marine facilities affect the structure of the marine sessile community?
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Queiroz TDC, Yokoyama LQ, and Dias GM
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- Animals, Ecosystem, Aquatic Organisms, Animal Shells, Bivalvia physiology, Ostreidae physiology, Aquaculture, Biodiversity
- Abstract
The growth of the human population causes significant harm to ecosystems, directly affecting the biological diversity of coastal areas by replacing natural habitats with artificial structures such as breakwaters, ports, and marinas. The hard substrate from those marine facilities lacks the topographic complexity of natural habitats. Because of that, artificial habitats usually do not support a diverse community to the same extent as rocky shores in the surroundings. To address this issue and bring a strategic solution to the improper disposal of shell waste from aquaculture farms, we evaluated how increasing the environmental heterogeneity of walls by incorporating mussel and oyster shells on artificial concrete affected the diversity of sessile organisms from the subtidal zone. Adding shells to concrete positively affected ascidians' richness. Substrates with added shells supported more species than flat substrates in total. They promoted species that did not occur on flat substrates that simulated the traditional walls of marinas and harbors. However, it did not affect the number of bryozoans and the average species richness. Consequently, incorporating shells resulted in communities with completely distinct structures from those on flat substrates. Adding shells affected the community structure, reducing the dominance by the exotic bryozoan Schizoporella errata, and promoting the occurrence of other groups, such as ascidians. Using shell residues from aquaculture on marina walls adds substrate for colonization. Still, it is also likely to provide refuges for fragile and vulnerable organisms, like crevices and pits in natural habitats. Because of that, the increment in diversity was mostly group-specific and restricted to ascidians. This research reinforces the importance of creating complex artificial coastal structures, inspired by the blue economy, for a more heterogeneous coverage of sessile communities and reduced presence and dominance of exotic species. Thus, the strategy tested here, besides the effects on the sessile community, also supports efforts to reduce inappropriate waste disposal in the environment., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)
- Published
- 2024
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14. Methicillin-resistant Staphylococcus aureus and coagulase-negative Staphylococcus produce antimicrobial substances against members of the skin microbiota in children with atopic dermatitis.
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Guimarães LC, Garcia GD, Cavalcante FS, Dias GM, de Farias FM, Saintive S, Abad ED, Ferreira DC, and Dos Santos KRN
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- Humans, Child, Bacteriocins genetics, Anti-Bacterial Agents pharmacology, Child, Preschool, Microbial Sensitivity Tests, Dermatitis, Atopic microbiology, Methicillin-Resistant Staphylococcus aureus genetics, Skin microbiology, Coagulase genetics, Coagulase metabolism, Microbiota, Staphylococcus genetics
- Abstract
Coagulase-negative Staphylococcus (CoNS) species inhibiting Staphylococcus aureus has been described in the skin of atopic dermatitis (AD) patients. This study evaluated whether Staphylococcus spp. from the skin and nares of AD and non-AD children produced antimicrobial substances (AMS). AMS production was screened by an overlay method and tested against NaOH, proteases and 30 indicator strains. Clonality was assessed by pulsed-field gel electrophoresis. Proteinaceous AMS-producers were investigated for autoimmunity by the overlay method and presence of bacteriocin genes by polymerase chain reaction. Two AMS-producers had their genome screened for AMS genes. A methicillin-resistant S. aureus (MRSA) produced proteinaceous AMS that inhibited 51.7% of the staphylococcal indicator strains, and it was active against 60% of the colonies selected from the AD child where it was isolated. On the other hand, 57 (8.8%) CoNS from the nares and skin of AD and non-AD children, most of them S. epidermidis (45.6%), reduced the growth of S. aureus and other CoNS species. Bacteriocin-related genes were detected in the genomes of AMS-producers. AMS production by CoNS inhibited S. aureus and other skin microbiota species from children with AD. Furthermore, an MRSA colonizing a child with AD produced AMS, reinforcing its contribution to dysbiosis and disease severity., (© The Author(s) 2024. Published by Oxford University Press on behalf of FEMS.)
- Published
- 2024
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15. The impact of habitat complexity on the structure of marine sessile communities and larvae supply.
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Marchetti OC, Titotto S, and Dias GM
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- Animals, Larva, Ecosystem, Biomass, Bryozoa, Urochordata
- Abstract
Coastal infrastructure replaces complex and heterogeneous natural habitats with flat, two-dimensional concrete walls, reducing refuges against predation, which modifies the composition and identity of the dominant species in sessile communities. This modification in the community structure can also change the reproductive propagules available in plankton, affecting the recruitment dynamics in communities from natural habitats nearby. Here, we tested the combined effects of the habitat type (simple vs. complex with holes) and predation on the diversity, larval production, and structure of sessile communities from a recreational marina. Complex substrates showed a larger biomass and a greater abundance of solitary organisms, mainly ascidians and bivalves, that benefited from refuges. Barnacles and calcified encrusting bryozoans dominated simple, flat substrates. The difference in dominance affected the pool of larvae produced by the communities. After eight months, communities growing on flat substrates produced more barnacle larvae than those from complex substrates, where larvae of ascidians were more abundant. However, this difference disappeared after 18 months of community development. The difference in the pool of larvae between simple and complex substrates did not affect the structure of the community on flat substrates nearby, which was determined by the predation regime. In the studied region, communities in artificial environments are under intense predation control, suppressing eventual recruitment differences in communities developing in flat substrates. Large interventions that modify habitat topography, creating refuges in the subtidal zone, can change the dynamic of the sessile communities in artificial habitats and, consequently, the larval supply in the vicinities. However, differences in larval supply will only translate in distinct sessile communities when the scale of intervention encompasses large areas, and other processes do not buffer the differences in recruitment., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Ltd. All rights reserved.)
- Published
- 2024
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16. CAN TEMPORARY ARTERY CATHETERIZATION EXTEND LIMITS OF ISCHEMIA TIME FOR MACROREPLANTATION?
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Iamaguchi RB, Dias GM, Iwase FDC, Rezende MR, and Mattar R
- Abstract
We observe delayed referrals to appropriate Microsurgery Unit and definitive treatment of traumatic limb amputations. Cases with wrist proximal amputations have a deadline for surgical replantation as these configure life-threatening injuries., Objective: To analyze patients with traumatic proximal wrist upper limb amputations with prolonged ischemic time who underwent temporary artery catheterization to assess stump viability and results., Methods: A case-series study including all patients with a proximal wrist upper limb amputation and a cold ischemic time equal to or above six hours from 2017 to 2021., Results: In total, two surgeons operated eight patients who had experienced forearm amputation injuries. Median ischemia time totaled eight hours. All patients required additional surgeries, most commonly split-thickness skin graft or fixation revision (three patients). This study obtained five successful macroreimplantations. The mean cold ischemia time was longer in the group with successful macroreimplantations (7.4 hours) than of the unsuccessful group (9 hours)., Conclusion: Macroreplantations require immediate referral to microsurgery and, although temporary artery catheterization helps surgical decision making, the technique seems to fail to influence outcomes. Level of Evidence IV, Retrospective Case Series. , Competing Interests: All authors declare no potential conflict of interest related to this article.
- Published
- 2023
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17. MRI changes and clinical characteristics in temporomandibular joints with displacement of the articular disk without reduction - a cross-sectional observational study.
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Dias GM, Grossmann E, Carvalho ACP, Devito KL, Dos Santos MF, and Ferreira LA
- Abstract
Objectives: This study examined changes in magnetic resonance imaging (MRI) of temporomandibular joints (TMJ) with anterior displacement disk without reduction (DDwoR) and its correlation to clinical symptoms., Methods: 190 individuals with DDwoR were evaluated according to Diagnostic Criteria for Temporomandibular Disorders (DC/TMD) and MRI. Pain's chronicity/intensity and limited mouth opening (locking) were correlated with: TMJ degeneration (MRI T1), effusion (T2), disc's shape and position (proton density)., Results: In 103 TMJ with DDwoR, hemiconvex shape (41.6%), sclerosis (45.6%) and mild effusion (47.6%) were the most prevalent findings. There was not association ( p > .05) between: different DDwoR positions with pain's intensity/chronicity; effusion with locking. Disk deformation was associated with degeneration ( p = .034) and pain's intensity ( p = .006). Locking was associated with degeneration ( p = .05)., Conclusions: Condylar osteodegeneration is often related to DDwoR. Locking by DDwoR is associated with severe levels of chronic pain and articular disk deformation.
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- 2023
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18. Characterization of Peptaibols Produced by a Marine Strain of the Fungus Trichoderma endophyticum via Mass Spectrometry, Genome Mining and Phylogeny-Based Prediction.
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Castro GS, Sousa TF, da Silva GF, Pedroso RCN, Menezes KS, Soares MA, Dias GM, Santos AO, Yamagishi MEB, Faria JV, Januário AH, and Koolen HHF
- Abstract
Trichoderma is recognized as a prolific producer of nonribosomal peptides (NRPs) known as peptaibols, which have remarkable biological properties, such as antimicrobial and anticancer activities, as well as the ability to promote systemic resistance in plants against pathogens. In this study, the sequencing of 11-, 14- and 15-res peptaibols produced by a marine strain of Trichoderma isolated from the ascidian Botrylloides giganteus was performed via liquid chromatography coupled to high-resolution tandem mass spectrometry (LC-MS/MS). Identification, based on multilocus phylogeny, revealed that our isolate belongs to the species T. endophyticum , which has never been reported in marine environments. Through genome sequencing and genome mining, 53 biosynthetic gene clusters (BGCs) were identified as being related to bioactive natural products, including two NRP-synthetases: one responsible for the biosynthesis of 11- and 14-res peptaibols, and another for the biosynthesis of 15-res. Substrate prediction, based on phylogeny of the adenylation domains in combination with molecular networking, permitted extensive annotation of the mass spectra related to two new series of 15-res peptaibols, which are referred to herein as "endophytins". The analyses of synteny revealed that the origin of the 15-module peptaibol synthetase is related to 18, 19 and 20-module peptaibol synthetases, and suggests that the loss of modules may be a mechanism used by Trichoderma species for peptaibol diversification. This study demonstrates the importance of combining genome mining techniques, mass spectrometry analysis and molecular networks for the discovery of new natural products.
- Published
- 2023
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19. Seeding artificial habitats with native benthic species can prevent the occurrence of exotic organisms.
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Ohayashi NS, Rodrigues ID, Marchetti OC, and Dias GM
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- Animals, Ecosystem, Atlantic Ocean, Introduced Species, Bryozoa, Urochordata, Porifera
- Abstract
Seeding native species on pillars and platforms of marinas and harbors has been suggested to reduce space availability and prevent the colonization of exotic nuisance species, which are usually associated with coastal urbanization. The efficacy of seeding, however, has been tested mainly on the intertidal zone. To test how seeding native species in the subtidal zone affects the subsequent colonization and spread of exotic species and the community diversity, we deployed 10 PVC plates seeded with adults of the native sponge Mycale angulosa, 10 with the native ascidian Symplegma rubra, both covering about 6% of the available substrate, and 10 plates free of any intervention in a recreational marina from the Southwestern Atlantic Ocean. We then assessed the diversity and structure of the sessile community across treatments after eight months. Seeding the substrate with S. rubra resulted in no difference to unseeded communities, which were dominated by the exotic bryozoan Schizoporella errata (>66% of the substrate) and supported on average 16.9 ± 1.3 and 14.2 ± 2.0 morphospecies, respectively. However, seeding the substrate with M. angulosa resulted in a distinct community dominated by the seeded sponge (>97% of the substrate) and supporting only 3.2 ± 0.5 morphospecies. Besides, all 13 registered exotic species were reported from communities seeded with S. rubra, 11 from the unseeded communities, but only three were observed in those seeded with M. angulosa. While the consequences of the low diversity of the community seeded with M. angulosa must be addressed since poor communities are usually associated with low biotic resistance to invasion, seeding resulted in a high dominance of the native sponge, reducing the monopolization of resources by exotic species. These results suggest that seeding the substrate with native species should be implemented along with other interventions for managing artificial habitats in the coastal zone., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier Ltd. All rights reserved.)
- Published
- 2022
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20. Genome sequence of Pseudomonas aeruginosa PA1-Petro-A role model of environmental adaptation and a potential biotechnological tool.
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de Oliveira HL, Dias GM, and Neves BC
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Pseudomonas aeruginosa is a ubiquitous microorganism, capable of colonizing a wide range of habitats due to its metabolic versatility and wide adaptability to different conditions. Industrial and environmental research involving petroleum microbiology play a pivotal role in controlling many technical, operational, and environmental issues. P. aeruginosa PA1-Petro strain was isolated from oil production water in Northeastern Brazil. Herein we report the genomic sequencing and annotation of PA1-Petro, and a comparative genomics study against two widely used reference P. aeruginosa strains (PAO1 and PA14). PA1-Petro has a genome of 6,893,650 bp, the largest among the three analyzed in this study, with a 65.87% GC content. The analyzes resulted in a wide repertoire of 544 unique genes in PA1-Petro, and the highest copy numbers of common genes among the three strains (PA1-Petro, PAO1 and PA14). Unique sequences are hypothetical proteins, prophage sequences, mobile genetic elements, transcriptional regulators, metal resistance genes to copper, tellurium and arsenic, type IE CRISPR-Cas, Type VI Secretion System (T6SS)-associated proteins, and a toxin-antitoxin system. Taken together, these results provide intriguing insights on adaptive evolution within PA1-Petro genome, adding unprecedented information to the species' plasticity and ubiquitous characteristics., Competing Interests: The authors declare no conflict of interest., (© 2022 The Author(s).)
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- 2022
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21. Evaluation of DNA damage induced by ionizing radiation from myocardial perfusion imaging: a pilot study.
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Arpini AP, De Lorenzo A, Moritz A, Pereira JP, and Dias GM
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- Aged, DNA Damage, Female, Humans, Male, Middle Aged, Perfusion, Pilot Projects, Radiation, Ionizing, Myocardial Perfusion Imaging methods, Technetium Tc 99m Sestamibi
- Abstract
Background: As patient exposure to ionizing radiation raises concern about malignancy risks, this study evaluated the effect of ionizing radiation on patients undergoing myocardial perfusion imaging (MPI) using the comet assay, a method for detection of DNA damage., Methods: Patients without cancer, acute or autoimmune diseases, recent surgery or trauma, were studied. Gated single-photon myocardial perfusion imaging was performed with Tc-99m sestamibi. Peripheral blood was collected before radiotracer injection at rest and 60-90 min after injection. Single-cell gel electrophoresis (comet assay) was performed with blood lymphocytes to detect strand breaks, which determine a "comet tail" of variable size, visually scored by 3 observers in a fluorescence microscope after staining (0: no damage, no tail; 1: small damage; 2: large damage; 3: full damage). A damage index was calculated as a weighted average of the cell scores., Results: Among the 29 individuals included in the analysis, age was 65.3 ± 9.9 years and 18 (62.1%) were male. The injected radiotracer dose was 880.6 ± 229.4 MBq. Most cells (approximately 70%) remained without DNA fragmentation (class 0) after tracer injection. There were nonsignificant increases of classes 1 and 2 of damage. Class 3 was the least frequent both before and after radiotracer injection, but displayed a significant, 44% increase after injection., Conclusion: While lymphocytes mostly remained in class 0, an increase in class 3 DNA damage was detected. This may suggest that, despite a probable lack of biologically relevant DNA damage, there is still a need for tracer dose reductions in MPI., (© 2022. The Author(s).)
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- 2022
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22. Radiofluorination of a highly potent ATM inhibitor as a potential PET imaging agent.
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Fraser CR, Ajenjo J, Veal M, Dias GM, Chan C, O'Neill E, Destro G, Lau D, Pacelli A, Gouverneur V, Hueting R, and Cornelissen B
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Purpose: Ataxia telangiectasia mutated (ATM) is a key mediator of the DNA damage response, and several ATM inhibitors (ATMi) are currently undergoing early phase clinical trials for the treatment of cancer. A radiolabelled ATMi to determine drug pharmacokinetics could assist patient selection in a move towards more personalised medicine. The aim of this study was to synthesise and investigate the first
18 F-labelled ATM inhibitor [18 F]1 for non-invasive imaging of ATM protein and ATMi pharmacokinetics., Methods: Radiofluorination of a confirmed selective ATM inhibitor (1) was achieved through substitution of a nitro-precursor with [18 F]fluoride. Uptake of [18 F]1 was assessed in vitro in H1299 lung cancer cells stably transfected with shRNA to reduce expression of ATM. Blocking studies using several non-radioactive ATM inhibitors assessed binding specificity to ATM. In vivo biodistribution studies were performed in wild-type and ATM-knockout C57BL/6 mice using PET/CT and ex vivo analysis. Uptake of [18 F]1 in H1299 tumour xenografts was assessed in BALB/c nu/nu mice., Results: Nitro-precursor 2 was synthesised with an overall yield of 12%. Radiofluorination of 2 achieved radiochemically pure [18 F]1 in 80 ± 13 min with a radiochemical yield of 20 ± 13% (decay-corrected) and molar activities up to 79.5 GBq/μmol (n = 11). In vitro, cell-associated activity of [18 F]1 increased over 1 h, and retention of [18 F]1 dropped to 50% over 2 h. [18 F]1 uptake did not correlate with ATM expression, but could be reduced significantly with an excess of known ATM inhibitors, demonstrating specific binding of [18 F]1 to ATM. In vivo, fast hepatobiliary clearance was observed with tumour uptake ranging 0.13-0.90%ID/g after 1 h., Conclusion: Here, we report the first radiofluorination of an ATM inhibitor and its in vitro and in vivo biological evaluations, revealing the benefits but also some limitations of18 F-labelled ATM inhibitors., (© 2022. The Author(s).)- Published
- 2022
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23. Ozone Impact on Emission of Biogenic Volatile Organic Compounds in Three Tropical Tree Species From the Atlantic Forest Remnants in Southeast Brazil.
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Moura BB, Bolsoni VP, de Paula MD, Dias GM, and de Souza SR
- Abstract
Plants emit a broad number of Biogenic Volatile Organic Compounds (BVOCs) that can impact urban ozone (O
3 ) production. Conversely, the O3 is a phytotoxic pollutant that causes unknown alterations in BVOC emissions from native plants. In this sense, here, we characterized the constitutive and O3 -induced BVOCs for two (2dO3 ) and four (4dO3 ) days of exposure (O3 dose 80 ppb) and evaluated the O3 response by histochemical techniques to detect programmed cell death (PCD) and hydrogen peroxide (H2 O2 ) in three Brazilian native species. Croton floribundus Spreng, Astronium graveolens Jacq, and Piptadenia gonoacantha (Mart.) JF Macbr, from different groups of ecological succession (acquisitive and conservative), different carbon-saving defense strategies, and specific BVOC emissions. The three species emitted a very diverse BVOC composition: monoterpenes (MON), sesquiterpenes (SEQ), green leaf volatiles (GLV), and other compounds (OTC). C. floribundus is more acquisitive than A. graveolens . Their most representative BVOCs were methyl salicylate-MeSA (OTC), (Z) 3-hexenal, and (E)-2-hexenal (GLV), γ-elemene and (-)-β-bourbonene (SEQ) β-phellandrene and D-limonene (MON), while in A. graveolens were nonanal and decanal (OTC), and α-pinene (MON). Piptadenia gonoachanta is more conservative, and the BVOC blend was limited to MeSA (OTC), (E)-2-hexenal (GLV), and β-Phellandrene (MON). The O3 affected BVOCs and histochemical traits of the three species in different ways. Croton floribundus was the most O3 tolerant species and considered as an SEQ emitter. It efficiently reacted to O3 stress after 2dO3, verified by a high alteration of BVOC emission, the emergence of the compounds such as α-Ionone and trans-ß-Ionone, and the absence of H2 O2 detection. On the contrary, A. graveolens , a MON-emitter, was affected by 2dO3 and 4dO3 , showing increasing emissions of α-pinene and β-myrcene, (MON), γ-muurolene and β-cadinene (SEQ) and H2 O2 accumulation. Piptadenia gonoachanta was the most sensitive and did not respond to BVOCs emission, but PCD and H2 O2 were highly evidenced. Our results indicate that the BVOC blend emission, combined with histochemical observations, is a powerful tool to confirm the species' tolerance to O3 . Furthermore, our findings suggest that BVOC emission is a trade-off associated with different resource strategies of species indicated by the changes in the quality and quantity of BVOC emission for each species., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Moura, Bolsoni, de Paula, Dias and Souza.)- Published
- 2022
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24. Predator control of marine communities increases with temperature across 115 degrees of latitude.
- Author
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Ashton GV, Freestone AL, Duffy JE, Torchin ME, Sewall BJ, Tracy B, Albano M, Altieri AH, Altvater L, Bastida-Zavala R, Bortolus A, Brante A, Bravo V, Brown N, Buschmann AH, Buskey E, Barrera RC, Cheng B, Collin R, Coutinho R, De Gracia L, Dias GM, DiBacco C, Flores AAV, Haddad MA, Hoffman Z, Erquiaga BI, Janiak D, Campeán AJ, Keith I, Leclerc JC, Lecompte-Pérez OP, Longo GO, Matthews-Cascon H, McKenzie CH, Miller J, Munizaga M, Naval-Xavier LPD, Navarrete SA, Otálora C, Palomino-Alvarez LA, Palomo MG, Patrick C, Pegau C, Pereda SV, Rocha RM, Rumbold C, Sánchez C, Sanjuan-Muñoz A, Schlöder C, Schwindt E, Seemann J, Shanks A, Simoes N, Skinner L, Suárez-Mozo NY, Thiel M, Valdivia N, Velez-Zuazo X, Vieira EA, Vildoso B, Wehrtmann IS, Whalen M, Wilbur L, and Ruiz GM
- Subjects
- Animals, Global Warming, Oceans and Seas, Aquatic Organisms, Biomass, Fishes, Hot Temperature, Invertebrates, Predatory Behavior
- Abstract
Early naturalists suggested that predation intensity increases toward the tropics, affecting fundamental ecological and evolutionary processes by latitude, but empirical support is still limited. Several studies have measured consumption rates across latitude at large scales, with variable results. Moreover, how predation affects prey community composition at such geographic scales remains unknown. Using standardized experiments that spanned 115° of latitude, at 36 nearshore sites along both coasts of the Americas, we found that marine predators have both higher consumption rates and consistently stronger impacts on biomass and species composition of marine invertebrate communities in warmer tropical waters, likely owing to fish predators. Our results provide robust support for a temperature-dependent gradient in interaction strength and have potential implications for how marine ecosystems will respond to ocean warming.
- Published
- 2022
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25. Identification of a novel pathogenic variant in FBN1 associated with Marfan Syndrome.
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Pereira JP, Ferreira JR, Botelho APA, Melo MM, and Dias GM
- Abstract
Aortic diseases arising in Marfan Syndrome (MFS), such as in aneurysms and dissections of the thoracic aorta, are related to genetic alterations in the FBN1 gene. Databases, such as Universal Mutations-FBN1, ClinVar and The Human Gene Mutation, contain more than a thousand FBN1 mutations associated with MFS. The FBN1 gene, which encodes fibrillin-1, is responsible for the integral production of different protein domains. Possible genetic changes may lead to a weakening of blood vessels, leading to the development of aortopathies. In this study, we present the association of a novel FBN1 variant with MFS. The proband is a man who presented ascending aortic aneurysm and dissection (TAAD) at 42-yr-old, which was surgically treated. Clinical investigations were performed in all family members enrolled in the study. Marfan signs were observed in the proband, daughters and granddaughter. Direct sequencing of the FBN1 gene in the proband identified a novel truncation variant p.(Glu2019Ter) and a cascade screening were done. The variant was classified as pathogenic and causal for MFS according to the American College of Medical Genetics and Genomics (ACMG) criteria and revised Ghent nosology for MFS diagnosis, respectively. Proband's daughter and granddaughter harbor the variant, however without aortic alteration. This work reports for the first time a patient with the FBN1-p.(Glu2019Ter) variant and its association with MFS/TAAD., (Cold Spring Harbor Laboratory Press.)
- Published
- 2022
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26. Genome-wide analysis reveals a rhamnolipid-dependent modulation of flagellar genes in Pseudomonas aeruginosa PAO1.
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Castro MR, Dias GM, Salles TS, Cabral NM, Mariano DCO, Oliveira HL, Abdelhay ESFW, Binato R, and Neves BC
- Subjects
- Bacterial Proteins genetics, Bacterial Proteins metabolism, Glycolipids genetics, Glycolipids metabolism, Pseudomonas aeruginosa genetics, Pseudomonas aeruginosa metabolism
- Abstract
Pseudomonas aeruginosa is an opportunistic pathogen and an important model organism for the study of bacterial group behaviors, including cell motility and biofilm formation. Rhamnolipids play a pivotal role in biofilm formation and motility phenotypes in P. aeruginosa, possibly acting as wetting agents and mediating chemotactic stimuli. However, no biochemical mechanism or gene regulatory network has been investigated in regard to rhamnolipids' modulation of those group behaviors. Using DNA microarrays, we investigated the transcriptomic profiles in the stationary phase of growth of wild-type P. aeruginosa PAO1 and a rhlA-mutant strain, unable to produce rhamnolipids. A total of 134 genes were differentially expressed, comprising different functional categories, indicating a significant physiological difference between the rhamnolipid-producing and -non-producing strains. Interestingly, several flagellar genes are repressed in the mutant strain, which directly relates to the inability of the rhlA-minus strain to develop a swarming-motility phenotype. Supplementation with exogenous rhamnolipids has partially restored flagellar gene expression in the mutant strain. Our results show significant evidence that rhamnolipids, the major biosynthetic products of rhlABC pathway, seem to modulate gene expression in P. aeruginosa., (© 2021. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)
- Published
- 2022
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27. Enduring regardless the conditions: Plasticity in modular growth as a strategy to cope with hydrodynamic variation by the invasive sun-coral (Tubastraea spp.).
- Author
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Tanasovici RM, Dias GM, Kitahara MV, and Vieira EA
- Subjects
- Animals, Atlantic Ocean, Coral Reefs, Ecosystem, Hydrodynamics, Anthozoa, Bryozoa
- Abstract
The susceptibility of a community to invasions is not the only factor influencing the success of the introduction of non-indigenous species (NIS). Because the conditions of the invaded environment tend to be unpredictable, plastic responses should increase the success of NIS in a new environment. Sun-corals are invaders in the Atlantic Ocean that present a range of strategies and plastic responses to deal with stress and distinct environmental conditions. We experimentally tested the plastic responses of sun-corals when exposed to different predation pressures and hydrodynamics in a recreational marina where sun-corals abundance varies spatially along with the environmental conditions. We separated young sun-coral colonies in two experiments: one controlling the presence of predators and the other manipulating water motion. While predation had no effect, revealing that even small young colonies are somehow protected against predators, corals increased colony area under reduced water motion but grew more polyps under greater water motion. These results highlight that plasticity in modular growth may be important for sun-corals to successfully invade distinct regions despite the hydrodynamic conditions. Increasing the colony area implicate in monopolization of space in calmer waters whilst growing more polyps allows it to have more mouths for feeding in turbulent food-poor waters. This response is particularly interesting as it is similar to the response of another NIS in the same site-the bryozoan Schizoporella errata. Phenotypic plasticity of reproductive strategies, including asexual propagation as observed here, appears to be relevant for modular NIS by facilitating the success on the invasion process in variable habitats., (Copyright © 2022 Elsevier Ltd. All rights reserved.)
- Published
- 2022
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28. Nanotechnology for a Sustainable Future: Addressing Global Challenges with the International Network4Sustainable Nanotechnology.
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Pokrajac L, Abbas A, Chrzanowski W, Dias GM, Eggleton BJ, Maguire S, Maine E, Malloy T, Nathwani J, Nazar L, Sips A, Sone J, van den Berg A, Weiss PS, and Mitra S
- Subjects
- Nanotechnology, Sustainable Development, United Nations
- Abstract
Nanotechnology has important roles to play in international efforts in sustainability. We discuss how current and future capabilities in nanotechnology align with and support the United Nations' Sustainable Development Goals. We argue that, as a field, we can accelerate the progress toward these goals both directly through technological solutions and through our special interdisciplinary skills in communication and tackling difficult challenges. We discuss the roles of targeting solutions, technology translation, the circular economy, and a number of examples from national efforts around the world in reaching these goals. We have formed a network of leading nanocenters to address these challenges globally and seek to recruit others to join us.
- Published
- 2021
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29. MYH7 p.Glu903Gln Is a Pathogenic Variant Associated With Hypertrophic Cardiomyopathy.
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Dias GM, Lamounier Júnior A, Seifert M, Barájas-Martinez H, Barr D, Sternick EB, Medina-Acosta E, Campos de Carvalho AC, and Cruz Filho FES
- Subjects
- Adolescent, Adult, Amino Acid Substitution, Female, Humans, Male, Middle Aged, Cardiac Myosins genetics, Cardiomyopathy, Hypertrophic genetics, Mutation, Missense, Myosin Heavy Chains genetics
- Published
- 2021
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30. Toward a Healthy and Environmentally Sustainable Campus Food Environment: A Scoping Review of Postsecondary Food Interventions.
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Lee KM, Dias GM, Boluk K, Scott S, Chang YS, Williams TE, and Kirkpatrick SI
- Subjects
- Environment, Food Supply, Humans, Food, Refuse Disposal
- Abstract
Interventions are urgently needed to transform the food system and shift population eating patterns toward those consistent with human health and environmental sustainability. Postsecondary campuses offer a naturalistic setting to trial interventions to improve the health of students and provide insight into interventions that could be scaled up in other settings. However, the current state of the evidence on interventions to support healthy and environmentally sustainable eating within postsecondary settings is not well understood. A scoping review of food- and nutrition-related interventions implemented and evaluated on postsecondary campuses was conducted to determine the extent to which they integrate considerations related to human health and/or environmental sustainability, as well as to synthesize the nature and effectiveness of interventions and to identify knowledge gaps in the literature. MEDLINE (via PubMed), CINAHL, Scopus, and ERIC were searched to identify articles describing naturalistic campus food interventions published in English from January 2015 to December 2019. Data were extracted from 38 peer-reviewed articles, representing 37 unique interventions, and synthesized according to policy domains within the World Cancer Research Foundation's NOURISHING framework. Most interventions were focused on supporting human health, whereas considerations related to environmental sustainability were minimal. Interventions to support human health primarily sought to increase nutrition knowledge or to make complementary shifts in food environments, such as through nutrition labeling at point of purchase. Interventions to support environmental sustainability often focused on reducing food waste and few emphasized consumption patterns with lower environmental impacts. The implementation of integrated approaches considering the complexity and interconnectivity of human and planetary health is needed. Such approaches must go beyond the individual to alter the structural determinants that shape our food system and eating patterns., (© The Author(s) 2021. Published by Oxford University Press on behalf of the American Society for Nutrition.)
- Published
- 2021
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31. Optimization of (-)-cubebin biotransformation to (-)-hinokinin by the marine fungus Absidia coerulea 3A9.
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de Souza JM, Santos MFC, Pedroso RCN, Pimenta LP, Siqueira KA, Soares MA, Dias GM, Pietro RCLR, Ramos HP, Silva MLA, Pauletti PM, Veneziani RCS, Ambrósio SR, Braun GH, and Januário AH
- Subjects
- 4-Butyrolactone chemical synthesis, Aquatic Organisms metabolism, Biotransformation, Seawater chemistry, 4-Butyrolactone analogs & derivatives, Absidia, Benzodioxoles chemical synthesis, Lignans chemical synthesis, Lignans chemistry, Lignans metabolism
- Abstract
The genus Absidia is widely used in the biotransformation of different classes of natural products. This study evaluates the ability of the Absidia coerulea 3A9 marine derived strain isolated from the ascidian Distaplia stilyfera to perform biotransformations by conducting assays with (-)-cubebin, as substrate. The experiment was optimized using the experimental design proposed by Plackett-Burman for seven factors and eight experiments, to establish the biotransformation conditions that would allow maximum production of biotransformed dibenzylbutyrolactone (-)-hinokinin. An analytical method based on Reverse-Phase-High Performance Liquid Chromatography (RP-HPLC) was developed to quantify the fungal biotransformation product. The factor that influenced the (-)-hinokinin peak area the most positively was the percentage of seawater (%seawater) given that its %relative standard deviation (%RSD) showed a 32.92% deviation from the real value., (© 2021. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)
- Published
- 2021
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32. Colonization history meets further niche processes: how the identity of founders modulates the way predation structure fouling communities.
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Vieira EA, Flores AAV, and Dias GM
- Subjects
- Animals, Ecosystem, Predatory Behavior
- Abstract
Community assembly relies on deterministic niche-based processes (e.g., biotic interactions), and stochastic sources of unpredictable variation (e.g., colonization history), that combined will influence late-stage community structure. When community founders present distinct functional traits and a colonization-competition trade-off is not operating, initial colonization can result in late-stage assemblages of variable diversity and composed by different species sets, depending if early colonizers facilitate or inhibit subsequent colonization and survival. By experimentally manipulating the functional identity of founders and predators access during the development of fouling communities, we tested how founder traits constrain colonization history, species interactions and thereby regulate community diversity. We used as founders functionally different fouling organisms (colonial and solitary ascidians, and arborescent and flat-encrusting bryozoans) to build experimental communities that were exposed or protected against predation using a caging approach. Ascidians and bryozoans are pioneer colonizers in benthic communities and also good competitors, but the soft-body of ascidians makes them more susceptible to predators than mineralized bryozoans. When ascidians were founders, their dominance (but not richness) was reduced by predation, resulting in no effects of predators on overall diversity. Conversely, when bryozoans were founders, both space limitation and predator effects resulted in species-poor communities, with reduced number and cover of ascidian species and high overall dominance at the end of the experiment. We, thus, highlight that current species interactions and colonization contingencies related to founder identity should not be viewed as isolated drivers of community organization, but rather as strongly interacting processes underlying species distribution patterns and diversity., (© 2021. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)
- Published
- 2021
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33. Evaluation of antileishmanial activity of harzialactone a isolated from the marine-derived fungus Paecilomyces sp.
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Braun GH, Ramos HP, Candido ACBB, Pedroso RCN, Siqueira KA, Soares MA, Dias GM, Magalhães LG, Ambrósio SR, Januário AH, and Pietro RCLR
- Subjects
- Animals, Aquatic Organisms, Drug Evaluation, Preclinical methods, Lactones chemistry, Lactones isolation & purification, Leishmaniasis, Cutaneous drug therapy, Macrophages, Peritoneal parasitology, Mice, Inbred BALB C, Molecular Structure, Paecilomyces isolation & purification, Mice, Antiprotozoal Agents pharmacology, Lactones pharmacology, Leishmania mexicana drug effects, Paecilomyces chemistry
- Abstract
Fractionation of extracts from the culture broth of the marine-derived fungus, Paecilomyces sp. 7A22, resulted in the isolation of the harzialactone A ( HA ), a known compound previously isolated from fungi of marine environments. The chemical structure of HA was determined by spectroscopic analyses. Upon evaluation of HA on antileishmanial assays against Leishmania amazonensis , HA exhibited significant activity against promastigotes forms with IC
50 of 5.25 µg mL-1 and moderate activity against intracellular amastigotes with IC50 of 18.18 µg mL-1 . This is the first report on the antileishmanial activity of HA , and the effects of HA presented in this work suggest that this class of compounds are suitable for future biological in vitro and in vivo studies for the search of natural products with activity against Leishmania spp. Furthermore, the present results corroborate marine-derived fungi as a promising source of natural products with antiparasitic activity.- Published
- 2021
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34. Development and testing of the Sustainable Nutrition Environment Measures Survey for retail stores in Ontario.
- Author
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Mollaei S, Dias GM, and Minaker LM
- Subjects
- Ontario, Reproducibility of Results, Surveys and Questionnaires, Commerce, Food Supply
- Abstract
Objective: To develop and test a tool to assess the price and availability of low-carbon footprint and nutritionally balanced dietary patterns in retail food environments in Ontario, Canada., Design: Availability and price of selected food from discount and regular grocery stores (n 23) in urban/rural areas of northern/southern Ontario were assessed with the Sustainable Nutrition Environment Measures Survey in 2017., Setting: Ontario, Canada., Results: Inter-rater reliability was high for price (intra-class correlation coefficients = 0·819) and for availability (Cohen's κ = 0·993). The tool showed 78 % of the selected food items were available in all stores. Overall, price differences were small between urban and rural locations, and northern and southern Ontario. The greatest price difference was between discount and regular stores., Conclusions: The tool showed excellent inter-rater agreement. Researchers and public health dietitians can use this tool for research, practice and policy to link consumer-level health outcomes to the retail environment.
- Published
- 2021
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35. Artificial habitats induce plasticity in colonies of the marine bryozoan Schizoporella errata.
- Author
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Dias GM, Dutra FS, and Duarte RC
- Subjects
- Animals, Aquatic Organisms, Bryozoa genetics, Bryozoa growth & development, Bryozoa physiology, Bryozoa anatomy & histology, Ecosystem
- Abstract
Modular organization provides flexibility for colonial animals to deal with variable and unpredictable environmental conditions since each module has specific tasks within the colony, such as feeding, defending or reproducing. Depending on the selecting pressures, sessile organisms may phenotypically adjust the morphology of each module or modify their density, increasing individual fitness. Here we used the marine bryozoan Schizoporella errata (Cheilostomata, Schizoporellidae) to test how the divergent conditions between two artificial habitats, the location inside a marina (IM) and the external wall of the breakwater (BW), affect colony size and the density of the distinct modules. The density of avicularia and ovicells, modules related to defense and reproduction, respectively, did not differ between habitats. However, colonies growing in the turbulent waters of BW were, in general, larger and had higher density of feeding autozooids than those at IM. Reciprocal transplants of bryozoan clones indicated that trait variation is genotype-dependent but varies according to the environmental conditions at the assigned location. The occurrence of larger colonies with more zooids in BW is probably linked to the easier feeding opportunity offered by the small diffusive boundary layer around the colony at this location. Since in colonial polymorphic organisms each module (zooid) performs a specific function, the phenotypic response is not uniform across colonies, affecting only those modules that are susceptible to variations in the main selective pressures. Understanding the importance of colony-level plasticity is relevant to predict how modularity will contribute to organisms to deal with human-induced environmental changes in coastal habitats., (© 2020 Wiley Periodicals, Inc.)
- Published
- 2021
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36. [ 18 F]AZD2461, an Insight on Difference in PARP Binding Profiles for DNA Damage Response PET Imaging.
- Author
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Guibbal F, Hopkins SL, Pacelli A, Isenegger PG, Mosley M, Torres JB, Dias GM, Mahaut D, Hueting R, Gouverneur V, and Cornelissen B
- Subjects
- Animals, Boron chemistry, Cell Line, Tumor, Copper chemistry, Esters chemistry, Mice, Inbred BALB C, Mice, Nude, Phthalazines chemical synthesis, Phthalazines pharmacology, Piperazines chemistry, Piperazines pharmacology, Piperidines chemical synthesis, Piperidines pharmacology, Poly(ADP-ribose) Polymerase Inhibitors chemistry, Poly(ADP-ribose) Polymerase Inhibitors pharmacology, Protein Binding drug effects, Tissue Distribution, Xenograft Model Antitumor Assays, DNA Damage, Fluorine Radioisotopes chemistry, Phthalazines chemistry, Piperidines chemistry, Poly(ADP-ribose) Polymerases metabolism, Positron-Emission Tomography
- Abstract
Background: Poly (ADP-ribose) polymerase (PARP) inhibitors are extensively studied and used as anti-cancer drugs, as single agents or in combination with other therapies. Most radiotracers developed to date have been chosen on the basis of strong PARP1-3 affinity. Herein, we propose to study AZD2461, a PARP inhibitor with lower affinity towards PARP3, and to investigate its potential for PARP targeting in vivo., Methods: Using the Cu-mediated
18 F-fluorodeboronation of a carefully designed radiolabelling precursor, we accessed the18 F-labelled isotopologue of the PARP inhibitor AZD2461. Cell uptake of [18 F]AZD2461 in vitro was assessed in a range of pancreatic cell lines (PSN-1, PANC-1, CFPAC-1 and AsPC-1) to assess PARP expression and in vivo in xenograft-bearing mice. Blocking experiments were performed with both olaparib and AZD2461., Results: [18 F]AZD2461 was efficiently radiolabelled via both manual and automated procedures (9 % ± 3 % and 3 % ± 1 % activity yields non-decay corrected). [18 F]AZD2461 was taken up in vivo in PARP1-expressing tumours, and the highest uptake was observed for PSN-1 cells (7.34 ± 1.16 %ID/g). In vitro blocking experiments showed a lesser ability of olaparib to reduce [18 F]AZD2461 binding, indicating a difference in selectivity between olaparib and AZD2461., Conclusion: Taken together, we show the importance of screening the PARP selectivity profile of radiolabelled PARP inhibitors for use as PET imaging agents.- Published
- 2020
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37. Early Detection in a Mouse Model of Pancreatic Cancer by Imaging DNA Damage Response Signaling.
- Author
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Knight JC, Torres JB, Goldin R, Mosley M, Dias GM, Bravo LC, Kersemans V, Allen PD, Mukherjee S, Smart S, and Cornelissen B
- Subjects
- Animals, Disease Models, Animal, Male, Mice, Neoplasm Grading, Pancreatic Neoplasms pathology, DNA Damage, Early Detection of Cancer, Pancreatic Neoplasms diagnostic imaging, Pancreatic Neoplasms genetics, Signal Transduction, Single Photon Emission Computed Tomography Computed Tomography
- Abstract
Despite its widespread use in oncology, the PET radiotracer
18 F-FDG is ineffective for improving early detection of pancreatic ductal adenocarcinoma (PDAC). An alternative strategy for early detection of pancreatic cancer involves visualization of high-grade pancreatic intraepithelial neoplasias (PanIN-3s), generally regarded as the noninvasive precursors of PDAC. The DNA damage response is known to be hyperactivated in late-stage PanINs. Therefore, we investigated whether the SPECT imaging agent111 In-anti-γH2AX-TAT allows visualization of the DNA damage repair marker γH2AX in PanIN-3s in an engineered mouse model of PDAC, to facilitate early detection of PDAC. Methods: Genetically engineered KPC (KRasLSL.G12D/+ ; p53LSL.R172H/+ ; PdxCre) mice were imaged with18 F-FDG and111 In-anti-γH2AX-TAT. The presence of PanIN/PDAC as visualized by histologic examination was compared with autoradiography and immunofluorescence. Separately, the survival of KPC mice imaged with111 In-anti-γH2AX-TAT was evaluated. Results: In KPC mouse pancreata, γH2AX expression was increased in high-grade PanINs but not in PDAC, corroborating earlier results obtained from human pancreas sections. Uptake of111 In-anti-γH2AX-TAT, but not111 In-IgG-TAT or18 F-FDG, within the pancreas correlated positively with the age of KPC mice, which correlated with the number of high-grade PanINs.111 In-anti-γH2AX-TAT localizes preferentially in high-grade PanIN lesions but not in established PDAC. Younger, non-tumor-bearing KPC mice that show uptake of111 In-anti-γH2AX-TAT in the pancreas survive for a significantly shorter time than mice with physiologic111 In-anti-γH2AX-TAT uptake. Conclusion:111 In-anti-γH2AX-TAT imaging allows noninvasive detection of DNA damage repair signaling upregulation in preinvasive PanIN lesions and is a promising new tool to aid in the early detection and staging of pancreatic cancer., (© 2020 by the Society of Nuclear Medicine and Molecular Imaging.)- Published
- 2020
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38. Neutrophils, monocytes and other immune components in the equine endometrium: Friends or foes?
- Author
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Skarzynski DJ, Szóstek-Mioduchowska AZ, Rebordão MR, Jalali BM, Piotrowska-Tomala KK, Leciejewska N, Łazarczyk M, and Ferreira-Dias GM
- Subjects
- Animals, Endometrium immunology, Epigenesis, Genetic, Female, Horses genetics, Horses immunology, Monocytes immunology, Neutrophils immunology, Endometrium physiology, Horses physiology, Monocytes physiology, Neutrophils physiology
- Abstract
The innate and adaptive immune mechanisms are key components of regulation of reproductive physiological function and uterine disorders in equine uterus. The predominant immunological response in equine endometrium, characterized by an innate immune response, occurs under estrogens influence, in the follicular phase. Although, the increase in immune-related genes in equine endometrium during estrus has been suggested to play a role in uterine clearance after mating, immune cells and their product, i.e. cytokines play also mandatory role in the luteal development and maintenance, regression of equine corpus luteum, as well as in early pregnancy. Innate immune response is nonspecific and acts as the first line of defense against pathogens, foreign stimuli that include constituents of seminal fluid and local infections (endometritis). It has been recently established that a phagocytosis-independent mechanism to restrain bacteria, by means of neutrophil extracellular traps (NETs) formation, is involved in pathogenesis of in mare endometrial fibrosis (endometrosis). Moreover, persistent macrophages and mast cell activation could also have pro-fibrotic roles by secreting great amounts of pro-fibrotic factors and lead to fibrosis. This review will highlight the involvement of immune key components of the innate and adaptive immune system and their products in equine uterus and their contribution to reproductive physiological function and uterine disorders., Competing Interests: Declaration of competing interest The authors declare that there are no conflicts of interest., (Copyright © 2020. Published by Elsevier Inc.)
- Published
- 2020
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39. Bioactive Aliphatic Sulfates from Marine Invertebrates.
- Author
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Kellner Filho LC, Picão BW, Silva MLA, Cunha WR, Pauletti PM, Dias GM, Copp BR, Bertanha CS, and Januario AH
- Subjects
- Animals, Antifungal Agents chemistry, Antifungal Agents pharmacology, Echinodermata chemistry, Humans, Larva chemistry, Urochordata chemistry, Aquatic Organisms chemistry, Biological Products chemistry, Biological Products pharmacology, Invertebrates chemistry, Sulfates chemistry, Sulfates pharmacology
- Abstract
The occurrence of sulfated steroids and phenolics in marine organisms is quite widespread, being typically reported from Echinoderms. In contrast, alkane and alkene aliphatic sulfates are considerably rarer with examples being reported from a diverse array of organisms including echinoderms, sponges and ascidians. While no ecological roles for these metabolites have been proposed, they do exhibit a diverse array of biological activities including thrombin inhibition; the ability to induce metamorphosis in larvae; antiproliferative, antibacterial and antifungal properties; and metalloproteinase inhibition. Of particular interest and an avenue for future development is the finding of antifouling properties with low or nontoxic effects to the environment. This review focuses on alkyl sulfates and related sulfamates, their structures and biological activities. Spectroscopic and spectrometric techniques that can be used to recognize the presence of sulfate groups are also discussed, data for which will enhance the ability of researchers to recognize this class of chemically- and biologically-interesting marine natural products.
- Published
- 2019
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40. Exotic species dominate marinas between the two most populated regions in the southwestern Atlantic Ocean.
- Author
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Oricchio FT, Marques AC, Hajdu E, Pitombo FB, Azevedo F, Passos FD, Vieira LM, Stampar SN, Rocha RM, and Dias GM
- Subjects
- Animals, Aquatic Organisms classification, Atlantic Ocean, Biota, Brazil, Bryozoa classification, Bryozoa growth & development, Ecosystem, Human Activities, Humans, Introduced Species, Polychaeta classification, Polychaeta growth & development, Population Dynamics, Urochordata classification, Urochordata growth & development, Aquatic Organisms growth & development
- Abstract
Human occupation of coastal areas promotes the establishment of non-native species but information on bioinvasions is usually biased toward the Northern Hemisphere. We assessed non-native species' importance in sessile communities at six marinas along the most urbanized area of the Southwestern Atlantic coastline. We found 67 species, of which 19 are exotic. The most frequent species was the exotic polychaete Branchiomma luctuosum, while the most abundant was the exotic bryozoan Schizoporella errata that monopolized the substrata in three marinas. Along with S. errata, the exotic polychaete Hydroides elegans and ascidian Styela plicata dominated space in the three remaining marinas, while native species were in general rare. We show that communities associated with artificial substrata along this Brazilian urbanized area are dominated by exotic species and that using abundance data along with species identity can improve our understanding of the importance of exotic species for the dynamics of biological communities., (Copyright © 2019 Elsevier Ltd. All rights reserved.)
- Published
- 2019
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41. Comparative genomics of Paraburkholderia kururiensis and its potential in bioremediation, biofertilization, and biocontrol of plant pathogens.
- Author
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Dias GM, de Sousa Pires A, Grilo VS, Castro MR, de Figueiredo Vilela L, and Neves BC
- Subjects
- Animals, Brazil, Burkholderiaceae isolation & purification, Genome, Bacterial, Korea, Metabolic Networks and Pathways genetics, Plant Diseases prevention & control, Plants microbiology, Sequence Analysis, DNA, Virulence Factors genetics, Biodegradation, Environmental, Burkholderiaceae genetics, Genomics, Pest Control, Biological
- Abstract
Burkholderia harbors versatile Gram-negative species and is β-Proteobacteria. Recently, it was proposed to split the genus in two main branches: one of animal and plant pathogens and another, Paraburkholderia, harboring environmental and plant-beneficial species. Currently, Paraburkholderia comprises more than 70 species with ability to occupy very diverse environmental niches. Herein, we sequenced and analyzed the genome of Paraburkholderia kururiensis type strain KP23
T , and compared to P. kururiensis M130, isolated in Brazil, and P. kururiensis susbp. thiooxydans, from Korea. This study focused on the gene content of the three genomes with special emphasis on their potential of plant-association, biocontrol, and bioremediation. The comparative analyses revealed several genes related to plant benefits, including biosynthesis of IAA, ACC deaminase, multiple efflux pumps, dioxygenases, and degradation of aromatic compounds. Importantly, a range of genes for protein secretion systems (type III, IV, V, and VI) were characterized, potentially involved in P. kururiensis well documented ability to establish endophytic association with plants. These findings shed light onto bacteria-plant interaction mechanisms at molecular level, adding novel information that supports their potential application in bioremediation, biofertilization, and biocontrol of plant pathogens. P. kururiensis emerges as a promising model to investigate adaptation mechanisms in different ecological niches., (© 2019 The Authors. MicrobiologyOpen published by John Wiley & Sons Ltd.)- Published
- 2019
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42. A Carbon-Fiber Sheet Resistor for MR-, CT-, SPECT-, and PET-Compatible Temperature Maintenance in Small Animals.
- Author
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Kersemans V, Gilchrist S, Wallington S, Allen PD, Gomes AL, Dias GM, Cornelissen B, Kinchesh P, and Smart SC
- Subjects
- Animals, Female, Mice, Mice, Inbred CBA, Models, Animal, Multimodal Imaging methods, Positron-Emission Tomography methods, Tomography, Emission-Computed, Single-Photon methods, Body Temperature physiology, Carbon Fiber, Heating instrumentation, Image Processing, Computer-Assisted methods, Magnetic Resonance Imaging methods, Tomography, X-Ray Computed methods
- Abstract
A magnetic resonance (MR)-, computed tomography (CT)-, single-photon emission computed tomography (SPECT)-, and positron emission tomography (PET)-compatible carbon-fiber sheet resistor for temperature maintenance in small animals where space limitations prevent the use of circulating fluids was developed. A 250 Ω carbon-fiber sheet resistor was mounted to the underside of an imaging cradle. Alternating current, operating at 99 kHz, and with a power of 1-2 W, was applied to the resistor providing a cradle base temperature of ∼37°C. Temperature control was implemented with a proportional-integral-derivative controller, and temperature maintenance was demonstrated in 4 mice positioned in both MR and PET/SPECT/CT scanners. MR and CT compatibility were also shown, and multimodal MR-CT-PET-SPECT imaging of the mouse abdomen was performed in vivo. Core temperature was maintained at 35.5°C ± 0.2°C. No line-shape, frequency, or image distortions attributable to the current flow through the heater were observed on MR. Upon CT imaging, no heater-related artifacts were observed when carbon-fiber was used. Multimodal imaging was performed and images could be easily coregistered, displayed, analyzed, and presented. Carbon fiber sheet resistors powered with high-frequency alternating current allow homeothermic maintenance that is compatible with multimodal imaging. The heater is small, and it is easy to produce and integrate into multimodal imaging cradles., Competing Interests: Conflict of Interest: The authors have no conflict of interest to declare.
- Published
- 2019
- Full Text
- View/download PDF
43. Colonial ascidians strongly preyed upon, yet dominate the substrate in a subtropical fouling community.
- Author
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Hiebert LS, Vieira EA, Dias GM, Tiozzo S, and Brown FD
- Subjects
- Animals, Brazil, Population Dynamics, Species Specificity, Biofouling, Food Chain, Urochordata physiology
- Abstract
Higher diversity and dominance at lower latitudes has been suggested for colonial species. We verified this pattern in species richness of ascidians, finding that higher colonial-to-solitary species ratios occur in the tropics and subtropics. At the latitudinal region with the highest ratio, in southeastern Brazil, we confirmed that colonial species dominate space on artificial plates in two independent studies of five fouling communities. We manipulated settlement plates to measure effects of predation and competition on growth and survivorship of colonial versus solitary ascidians. Eight species were subjected to a predation treatment, i.e. caged versus exposed to predators, and a competition treatment, i.e. leaving versus removing competitors, to assess main and interactive effects. Predation had a greater effect on growth and survivorship of colonial compared to solitary species, whereas competition did not show consistent patterns. We hypothesize that colonial ascidians dominate at this subtropical site despite being highly preyed upon because they regrow when partially consumed and can adjust in shape and space to grow into refuges. We contend that these means of avoiding mortality from predation can have large influences on diversification patterns of colonial species at low latitudes, where predation intensity is greater.
- Published
- 2019
- Full Text
- View/download PDF
44. Dual-isotope imaging allows in vivo immunohistochemistry using radiolabelled antibodies in tumours.
- Author
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Knight JC, Mosley MJ, Kersemans V, Dias GM, Allen PD, Smart S, and Cornelissen B
- Subjects
- Animals, Cell Line, Tumor, Humans, Immunoconjugates pharmacokinetics, Immunohistochemistry, Isotope Labeling, Mice, Receptor, ErbB-2 metabolism, Tissue Distribution, Immunoconjugates chemistry, Indium Radioisotopes, Positron-Emission Tomography methods, Radioisotopes, Tomography, Emission-Computed, Single-Photon methods, Zirconium
- Abstract
While radiolabelled antibodies have found great utility as PET and SPECT imaging agents in oncological investigations, a notable shortcoming of these agents is their propensity to accumulate non-specifically within tumour tissue. The degree of this non-specific contribution to overall tumour uptake is highly variable and can ultimately lead to false conclusions. Therefore, in an effort to obtain a reliable measure of inter-individual differences in non-specific tumour uptake of radiolabelled antibodies, we demonstrate that the use of dual-isotope imaging overcomes this issue, enables true quantification of epitope expression levels, and allows non-invasive in vivo immunohistochemistry. The approach involves co-administration of (i) an antigen-targeting antibody labelled with zirconium-89 (
89 Zr), and (ii) an isotype-matched non-specific control IgG antibody labelled with indium-111 (111 In). As an example, the anti-HER2 antibody trastuzumab was radiolabelled with89 Zr, and co-administered intravenously together with its111 In-labelled non-specific counterpart to mice bearing human breast cancer xenografts with differing HER2 expression levels (MDA-MB-468 [HER2-negative], MDA-MB-231 [low-HER2], MDA-MB-231/H2N [medium-HER2], and SKBR3 [high-HER2]). Simultaneous PET/SPECT imaging using a MILabs Vector4 small animal scanner revealed stark differences in the intratumoural distribution of [89 Zr]Zr-trastuzumab and [111 In]In-IgG, highlighting regions of HER2-mediated uptake and non-specific uptake, respectively. Normalisation of the tumour uptake values and tumour-to-blood ratios obtained with [89 Zr]Zr-trastuzumab against those obtained with [111 In]In-IgG yielded values which were most strongly correlated (R = 0.94; P = 0.02) with HER2 expression levels for each breast cancer type determined by Western blot and in vitro saturation binding assays, but not non-normalised uptake values. Normalised intratumoural distribution of [89 Zr]Zr-trastuzumab correlated well with intratumoural heterogeneity HER2 expression., (Copyright © 2019 The Authors. Published by Elsevier Inc. All rights reserved.)- Published
- 2019
- Full Text
- View/download PDF
45. How Echocardiographic Deformation Indices Can Distinguish Different Types of Left Ventricular Hypertrophy.
- Author
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Pena JLB, Santos WC, Araújo SA, Dias GM, and Sternick EB
- Subjects
- Adult, Athletes, Data Accuracy, Glycogen Storage Disease Type IIb diagnostic imaging, Humans, Male, Echocardiography methods, Hypertrophy, Left Ventricular diagnostic imaging
- Published
- 2018
- Full Text
- View/download PDF
46. When too much isn't enough: Does current food production meet global nutritional needs?
- Author
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Kc KB, Dias GM, Veeramani A, Swanton CJ, Fraser D, Steinke D, Lee E, Wittman H, Farber JM, Dunfield K, McCann K, Anand M, Campbell M, Rooney N, Raine NE, Acker RV, Hanner R, Pascoal S, Sharif S, Benton TG, and Fraser EDG
- Subjects
- Agriculture methods, Conservation of Natural Resources, Greenhouse Gases adverse effects, Humans, Sustainable Development, Agriculture statistics & numerical data, Crops, Agricultural supply & distribution, Feeding Behavior physiology, Food Supply statistics & numerical data, Nutritional Requirements physiology, Population Growth
- Abstract
Sustainably feeding the next generation is often described as one of the most pressing "grand challenges" facing the 21st century. Generally, scholars propose addressing this problem by increasing agricultural production, investing in technology to boost yields, changing diets, or reducing food waste. In this paper, we explore whether global food production is nutritionally balanced by comparing the diet that nutritionists recommend versus global agricultural production statistics. Results show that the global agricultural system currently overproduces grains, fats, and sugars while production of fruits and vegetables and protein is not sufficient to meet the nutritional needs of the current population. Correcting this imbalance could reduce the amount of arable land used by agriculture by 51 million ha globally but would increase total land used for agriculture by 407 million ha and increase greenhouse gas emissions. For a growing population, our calculations suggest that the only way to eat a nutritionally balanced diet, save land and reduce greenhouse gas emissions is to consume and produce more fruits and vegetables as well as transition to diets higher in plant-based protein. Such a move will help protect habitats and help meet the Sustainable Development Goals., Competing Interests: The authors have declared that no competing interests exist.
- Published
- 2018
- Full Text
- View/download PDF
47. Research proposal: inflammation and oxidative stress in coronary artery bypass surgery graft: comparison between diabetic and non-diabetic patients.
- Author
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Romano E Silva AC, Dias GM, de Carvalho JJ, De Lorenzo A, and Kasal DAB
- Subjects
- Adolescent, Adult, Coronary Artery Disease physiopathology, Cross-Sectional Studies, Diabetes Complications, Diabetes Mellitus, Humans, Male, Research Design, Coronary Artery Bypass, Coronary Artery Disease immunology, Inflammation, Oxidative Stress
- Abstract
Background: Diabetes mellitus patients (DM) have more severe progression of atherosclerotic disease than non-diabetic (NDM) individuals. In situ inflammation and oxidative stress are key points in the pathophysiology of atherosclerosis, a concept largely based on animal model research. There are few studies comparing inflammation and oxidative stress parameters in medium-sized arteries between DM and NDM patients. A fragment of the internal mammary artery used in coronary artery bypass grafting (CABG) will be employed for this purpose OBJECTIVE: To assess the expression of inflammatory markers tumor necrosis factor-α, transforming growth factor-β1, nuclear factor kappa B, the enzymes superoxide dismutase, and catalase in the vascular wall of the arterial graft used in CABG, comparing DM and NDM patients RESULTS: The present study will add information to the vascular degenerative processes occurring in diabetic patients.
- Published
- 2018
- Full Text
- View/download PDF
48. Generation of patient-specific induced pluripotent stem cell lines from one patient with Jervell and Lange-Nielsen syndrome, one with type 1 long QT syndrome and two healthy relatives.
- Author
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Kasai-Brunswick TH, Silva Dos Santos D, Ferreira RP, Araujo DS, Dias GM, Coutinho JLA, Cruz FESF, Sternick EB, Gubert F, Oliveira JCG, Vaz IM, Borgonovo T, Brofman PRS, Moura-Neto RS, Silva R, Campos-de-Carvalho AC, and Carvalho AB
- Subjects
- Cell Differentiation, Humans, Jervell-Lange Nielsen Syndrome pathology, Kruppel-Like Factor 4, Induced Pluripotent Stem Cells metabolism, Jervell-Lange Nielsen Syndrome genetics, Long QT Syndrome complications
- Abstract
Four human iPSC cell lines (one Jervell and Lange-Nielsen Syndrome, one Long QT Syndrome-type 1 and two healthy controls) were generated from peripheral blood obtained from donors belonging to the same family. CytoTune™-iPS 2.0 Sendai Reprogramming Kit (containing OCT3/4, KLF4, SOX2 and cMYC as reprogramming factors) was used to generate all cell lines. The four iPSCs have normal karyotype, express pluripotency markers as determined by RT-PCR and flow cytometry and differentiated spontaneously in vitro into cells of the three germ layers, confirming their pluripotent capacity., (Copyright © 2018 The Authors. Published by Elsevier B.V. All rights reserved.)
- Published
- 2018
- Full Text
- View/download PDF
49. Two bifunctional desferrioxamine chelators for bioorthogonal labeling of biovectors with zirconium-89.
- Author
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Gao F, Ieritano C, Chen KT, Dias GM, Rousseau J, Bénard F, and Seimbille Y
- Abstract
We report two bifunctional chelators, DFO-Cys and DFO-CBT, to label biovectors with zirconium-89 according to the 2-cyanobenzothiazole/1,2-aminothiol cycloaddition. Their features are high labeling yields, rapid and efficient bioconjugation, metabolically stable luciferin-based end products, and applicability to orthogonal two-step labeling of sensitive biomolecules.
- Published
- 2018
- Full Text
- View/download PDF
50. 89 Zr for antibody labeling and in vivo studies - A comparison between liquid and solid target production.
- Author
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Dias GM, Ramogida CF, Rousseau J, Zacchia NA, Hoehr C, Schaffer P, Lin KS, and Bénard F
- Subjects
- Animals, Deferoxamine pharmacokinetics, Female, Mice, Positron Emission Tomography Computed Tomography, Tissue Distribution, Trastuzumab pharmacokinetics, Deferoxamine chemistry, Isotope Labeling methods, Radioisotopes chemistry, Trastuzumab chemistry, Zirconium chemistry
- Abstract
Introduction: Zirconium-89 (
89 Zr, t1/2 =78.4h) liquid target (LT) production offers an approach to introduce this positron-emitting isotope to cyclotron centres without the need for a separate solid target (ST) production set up. We compared the production, purification, and antibody radiolabeling yields of89 Zr-(LT) and89 Zr-(ST), and assessed the feasibility of89 Zr-(LT) for preclinical PET/CT., Methods:89 Zr-(ST) production was performed with an89 Y foil on a TR 19 cyclotron at 13.8MeV. For LT production; an aqueous solution of yttrium nitrate (Y(NO3 )3 ·6H2 O) was irradiated on a TR 13 cyclotron at 12MeV.89 Zr was purified from the ST or LT material with hydroxamate resin, and used to radiolabel p-SCN-Bn-Deferoxamine (DFO)-conjugated Trastuzumab. MicroPET-CT imaging was performed at 1, 3 and 5days post-injection of89 Zr-DFO-Trastuzumab from ST or LT with biodistribution analysis on day 5., Results: Irradiation of the ST yielded 2.88±1.07GBq/μA with a beam current of 14.0±3.8μA and irradiation time of 137±48min at end of bombardment while LT yielded 0.27±0.05GBq/μA with a beam current of 9.9±2.2μA and irradiation time of 221±29min. Radiolabeling of DFO-Trastuzumab with89 Zr-(ST) or89 Zr-(LT) was successful with purity>97% and specific activity>0.12MBq/μg (of antibody). MicroPET-CT imaging and biodistribution profiles showed similar uptake of89 Zr-(ST)-DFO-Trastuzumab and89 Zr-(LT)-DFO-Trastuzumab in tumor and all organs of interest., Conclusion:89 Zr-(LT) was effectively used to prepare antibody bioconjugates with specific activities suitable for small animal imaging. PET imaging and biodistribution revealed similar behaviours between bioconjugates labeled with89 Zr produced from the two target systems., Advances in Knowledge and Implications for Patient Care: These results have important implications for the production of PET isotopes such as89 Zr to cyclotron facilities with only LT capabilities - such as most clinical centres - expanding the availability of89 Zr-immunoPET., (Copyright © 2017. Published by Elsevier Inc.)- Published
- 2018
- Full Text
- View/download PDF
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