69 results on '"Moura RR"'
Search Results
2. A genetic variant of NLRP1 gene is associated with asbestos body burden in patients with malignant pleural mesothelioma.
- Author
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Crovella, S., Moura, RR., Cappellani, S., Celsi, F., Trevisan, E., Schneider, M., Brollo, A., Nicastro, EM., Vita, F., Finotto, L., Zabucchi, G., and Borelli, V.
- Subjects
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TOXICOLOGY of asbestos , *PATHOGENIC microorganisms , *MICROBIAL virulence , *MOLECULAR genetics , *MESOTHELIOMA - Abstract
The presence of asbestos bodies (ABs) in lung parenchyma is considered a histopathologic hallmark of past exposure to asbestos fibers, of which there was a population of longer fibers. The mechanisms underlying AB formation are complex, involving inflammatory responses and iron (Fe) metabolism. Thus, the responsiveness to AB formation is variable, with some individuals appearing to be poor AB formers. The aim of this study was to disclose the possible role of genetic variants of genes encoding inflammasome and iron metabolism proteins in the ability to form ABs in a population of 81 individuals from North East Italy, who died after having developed malignant pleural mesothelioma (MPM). This study included 86 genetic variants distributed in 10 genes involved in Fe metabolism and 7 genetic variants in two genes encoding for inflammasome molecules. Genotypes/haplotypes were compared according to the number of lung ABs. Data showed that the NLRPl rs12150220 missense variant (H155L) was significantly correlated with numbers of ABs in MPM patients. Specifically, a low number of ABs was detected in individuals carrying the NLRPl rs12150220 A/T genotype. Our findings suggest that the NLRP1 inflammasome might contribute in the development of lung ABs. It is postulated that the NLRPl missense variant may be considered as one of the possible host genetic factors contributing to individual variability in coating efficiency, which needs to be taken when assessing occupational exposure to asbestos. [ABSTRACT FROM AUTHOR]
- Published
- 2018
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- View/download PDF
3. Pronuclear Embryo Yield in Canindé and Saanen Goats for DNA Microinjection
- Author
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Moura, RR, primary, Lopes-Junior, ES, additional, Teixeira, DIA, additional, Serova, IA, additional, Andreeva, LE, additional, Melo, LM, additional, and Freitas, VJF, additional
- Published
- 2009
- Full Text
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4. Pronuclear Embryo Yield in Canindé and Saanen Goats for DNA Microinjection.
- Author
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Moura, RR, Lopes-Junior, ES, Teixeira, DIA, Serova, IA, Andreeva, LE, Melo, LM, and Freitas, VJF
- Subjects
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GOAT breeds , *EMBRYOLOGY , *DNA , *MICROINJECTIONS , *PROGESTATIONAL hormones , *LUTEINIZING hormone releasing hormone , *RECOMBINANT proteins - Abstract
Contents [ABSTRACT FROM AUTHOR]
- Published
- 2010
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5. A genetic variant of NLRP1 gene is associated with asbestos body burden in patients with malignant pleural mesothelioma
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Francesca Vita, Giuliano Zabucchi, Elisa Trevisan, Sergio Crovella, E.M. Nicastro, L. Finotto, Manuela Schneider, Violetta Borelli, Alessandro Brollo, S. Cappellani, Fulvio Celsi, Ronald Moura, Crovella, Sergio, Moura, Rr, Cappellani, Stefania, Celsi, Fulvio, Trevisan, Elisa, Manuele, Schneider, Alessandro, Brollo, Nicastro, Enza Maria., Vita, Francesca, Luigi, Finotto, Giuliani, Zabucchi, and Borelli, Violetta
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Male ,Mesothelioma ,0301 basic medicine ,asbestos bodie ,Lung Neoplasms ,Health, Toxicology and Mutagenesis ,Population ,NLR Proteins ,Biology ,Toxicology ,medicine.disease_cause ,Asbestos ,03 medical and health sciences ,0302 clinical medicine ,inflammasome ,Occupational Exposure ,Genotype ,medicine ,Humans ,Missense mutation ,education ,Lung ,Gene ,Adaptor Proteins, Signal Transducing ,Aged ,Aged, 80 and over ,education.field_of_study ,asbestos bodies ,Mesothelioma, Malignant ,Haplotype ,Genetic Variation ,Inflammasome ,Middle Aged ,medicine.disease ,mesothelioma ,NLRP1 gene ,030104 developmental biology ,Italy ,030220 oncology & carcinogenesis ,Immunology ,Body Burden ,Female ,Apoptosis Regulatory Proteins ,medicine.drug - Abstract
The presence of asbestos bodies (ABs) in lung parenchyma is considered a histopathologic hallmark of past exposure to asbestos fibers, of which there was a population of longer fibers. The mechanisms underlying AB formation are complex, involving inflammatory responses and iron (Fe) metabolism. Thus, the responsiveness to AB formation is variable, with some individuals appearing to be poor AB formers. The aim of this study was to disclose the possible role of genetic variants of genes encoding inflammasome and iron metabolism proteins in the ability to form ABs in a population of 81 individuals from North East Italy, who died after having developed malignant pleural mesothelioma (MPM). This study included 86 genetic variants distributed in 10 genes involved in Fe metabolism and 7 genetic variants in two genes encoding for inflammasome molecules. Genotypes/haplotypes were compared according to the number of lung ABs. Data showed that the NLRP1 rs12150220 missense variant (H155L) was significantly correlated with numbers of ABs in MPM patients. Specifically, a low number of ABs was detected in individuals carrying the NLRP1 rs12150220 A/T genotype. Our findings suggest that the NLRP1 inflammasome might contribute in the development of lung ABs. It is postulated that the NLRP1 missense variant may be considered as one of the possible host genetic factors contributing to individual variability in coating efficiency, which needs to be taken when assessing occupational exposure to asbestos.
- Published
- 2018
6. DEFB1 polymorphisms are involved in susceptibility to human papillomavirus infection in Brazilian gynaecological patients
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Ronald Moura, Luisa Zupin, Antonio Carlos de Freitas, Antonio Victor Campos Coelho, Sergio Crovella, Ludovica Segat, Bárbara Simas Chagas, Segat, Ludovica, Zupin, Luisa, Moura, Rr, Coelho, Av, Chagas, B, Freitas, Ac, and Crovella, Sergio
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Microbiology (medical) ,Adult ,beta-Defensins ,lcsh:Arctic medicine. Tropical medicine ,Adolescent ,lcsh:RC955-962 ,Population ,lcsh:QR1-502 ,Single-nucleotide polymorphism ,Biology ,Polymorphism, Single Nucleotide ,Reproductive Tract Infections ,lcsh:Microbiology ,Young Adult ,antimicrobial peptides ,genetic polymorphisms ,medicine ,SNP ,Humans ,Genetic Predisposition to Disease ,education ,human papillomavirus ,Aged ,Genetics ,education.field_of_study ,Innate immune system ,cervical lesion ,Haplotype ,Papillomavirus Infections ,Case-control study ,HPV infection ,DEFB1 ,DEFB1, antimicrobial peptides, human papillomavirus, genetic polymorphisms, cervical lesion ,Articles ,Middle Aged ,medicine.disease ,Beta defensin ,Haplotypes ,Case-Control Studies ,Immunology ,Female ,Brazil - Abstract
The human beta defensin 1 (hBD-1) antimicrobial peptide is a member of the innate immune system known to act in the first line of defence against microorganisms, including viruses such as human papillomavirus (HPV). In this study, five functional polymorphisms (namely g-52G>A, g-44C>G and g-20G>A in the 5’UTR and c.*5G>A and c.*87A>G in the 3’UTR) in the DEFB1 gene encoding for hBD-1 were analysed to investigate the possible involvement of these genetic variants in susceptibility to HPV infection and in the development of HPV-associated lesions in a population of Brazilian women. The DEFB1 g-52G>A and c.*5G>A single-nucleotide polymorphisms (SNPs) and the GCAAA haplotype showed associations with HPV-negative status; in particular, the c.*5G>A SNP was significantly associated after multiple test corrections. These findings suggest a possible role for the constitutively expressed beta defensin-1 peptide as a natural defence against HPV in the genital tract mucosa.
- Published
- 2014
7. Keratin variants in Pyoderma Gangrenosum: pathogenetic insights from a Whole Exome Sequencing-based bioinformatic analysis.
- Author
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Moltrasio C, Moura RR, Brandão L, Tricarico PM, Suleman M, Maronese CA, Crovella S, and Marzano AV
- Abstract
Pyoderma gangrenosum (PG) is an inflammatory skin disorder belonging to the group of neutrophilic dermatoses. Clinically, it is typified by cutaneous ulcers with distinctive erythemato-violaceous borders and may occur alone or in association with other inflammatory, autoinflammatory or neoplastic conditions. Although its pathophysiology remains incompletely understood, mounting evidence points towards a predisposing genetic background as well as a dysregulation of both the innate and adaptive immune responses, with follicular or epidermal structures as putative initial targets. To investigate genetic factors associated with PG susceptibility and severity (arbitrarily defined as unilesional and multilesional), whole exome sequencing was performed on eleven unrelated PG patients. Eight carried at least one variant in keratin encoding genes, including, KRT18, KRT20, KRT23, KRT32, and KRT33B. Strikingly, a recurrent variant (rs77999286) in the KRT18 gene was identified in 5/6 patients with multilesional and in 1/5 of those with unilesional PG. AlphaFold modelling and mutation analysis showed the destabilizing effect of the KRT18 rs77999286 variant on protein structure. Furthermore, immunohistochemistry revealed undetectable KRT18 staining in lesional as compared with healthy control skin. Overall, these findings suggest keratin variants may have a role in PG pathogenesis and indicate the KRT18 rs77999286 variant as a potential genetic factor linked to multilesional disease., (Copyright © 2025 The Authors. Published by Elsevier Inc. All rights reserved.)
- Published
- 2025
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8. Influences of sociality and maternal size on reproductive strategies: trade-offs between offspring size and quantity in five Anelosimus species (Araneae, Theridiidae).
- Author
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Xavier GM, Moura RR, Vasconcellos-Neto J, and Gonzaga MO
- Subjects
- Humans, Animals, Female, Social Behavior, Body Size, Reproduction, Spiders
- Abstract
Individuals can experience accentuated disputes for resources when living with many conspecifics, even in situations in which cooperative behaviors assure benefits associated with an increase in the frequency of food acquisition and in diet breadth. Thus, intraspecific competition may exert a significant selective pressure on social animals. Theoretical models suggest that females of social species could improve their fitness by producing relatively large offspring, since body size can provide competitive advantages during foraging activities. As female reserves are limited, the production of large offspring would occur at the expense of their number. Using five Anelosimus (Araneae, Theridiidae) species, we assessed whether the social ones produce fewer and larger eggs than the subsocials. In addition, we tested the effect of female size on the adoption of each particular reproductive strategy. Small females could hypothetically invest in producing large offspring since they cannot produce as many offspring as large females. Our results suggested that, indeed, sociality influences reproductive strategies. Females of social species produced fewer and larger offspring than females of subsocial species. Subsociality, in turn, would benefit the production of many small spiderlings, possibly because a large number of siblings is important to maintain and expand new webs and to subdue prey during their initial instars. Our results also indicated that large females produce more eggs without necessarily reduce their sizes. We discussed how the costs and benefits of group living may influence reproductive strategies., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)
- Published
- 2024
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9. Beyond classical theories: An integrative mathematical model of mating dynamics and parental care.
- Author
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Araujo G and Moura RR
- Subjects
- Male, Female, Animals, Sex Ratio, Sexual Behavior, Animal, Biological Evolution, Models, Biological, Reproduction
- Abstract
Classical theories, such as Bateman's principle and Trivers' parental investment theory, attempted to explain the coevolution of sexual selection and parental care through simple verbal arguments. Since then, quantitative models have demonstrated that it is rarely that simple because many non-intuitive structures and non-linear relationships are actually at play. In this study, we propose a new standard for models of mating dynamics and parental care, emphasizing the clarity and use of mathematical and probabilistic arguments, the meaning of consistency conditions, and the key role of spatial densities and the law of mass action. We used adaptive dynamics to calculate the evolutionary trajectory of the total care duration. Our results clearly show how the outcomes of parental care evolution can be diverse, depending on the quantitative balance between a set of dynamical forces arising from relevant differences and conditions in the male and female populations. The intensity of sexual selection, synergy of care, care quality, and relative mortality rates during mating interactions and caring activities act as forces driving evolutionary transitions between uniparental and biparental care. Sexual selection reduces the care duration of the selected sex, uniparental care evolves in the sex that offers the higher care quality, higher mortality during mating interactions of one sex leads to more care by that sex, and higher mortality during caring activities of one sex favours the evolution of uniparental care in the other sex. Both synergy and higher overall mortality during mating interactions can stabilize biparental care when sexual selection reduces the care duration of the selected sex. We discuss how the interaction between these forces influences the evolution of care patterns, and how sex ratios can vary and be interpreted in these contexts. We also propose new directions for future developments of our integrative model, creating new comparable analyses that share the same underlying assumptions and dynamical frameworks., (© 2023 European Society for Evolutionary Biology.)
- Published
- 2023
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10. Different molecular pathways are disrupted in Pyoderma gangrenosum patients and are associated with the severity of the disease.
- Author
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Moura RR, Brandão L, Moltrasio C, Agrelli A, Tricarico PM, Maronese CA, Crovella S, and Marzano AV
- Subjects
- Humans, Pyoderma Gangrenosum genetics, Pyoderma Gangrenosum pathology
- Abstract
Pyoderma gangrenosum (PG) is a rare inflammatory skin disease classified within the spectrum of neutrophilic dermatoses. The pathophysiology of PG is yet incompletely understood but a prominent role of genetics facilitating immune dysregulation has been proposed. This study investigated the potential contribution of disrupted molecular pathways in determining the susceptibility and clinical severity of PG. Variant Enrichment Analysis, a bioinformatic pipeline applicable for Whole Exome Sequencing data was performed in unrelated PG patients. Eleven patients were enrolled, including 5 with unilesional and 6 with multilesional PG. Fourteen pathways were exclusively enriched in the "multilesional" group, mainly related to immune system (i.e., type I interferon signaling pathway), cell metabolism and structural functions. In the "unilesional" group, nine pathways were found to be exclusively enriched, mostly related to cell signaling and cell metabolism. Genetically altered pathways involved in immune system biology and wound repair appear to be nodal pathogenic drivers in PG pathogenesis., (© 2023. The Author(s).)
- Published
- 2023
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11. Clinical and Molecular Characterization of Hidradenitis Suppurativa: A Practical Framework for Novel Therapeutic Targets.
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Moltrasio C, Tricarico PM, Moura RR, Brandão L, Crovella S, and Marzano AV
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- Humans, Skin pathology, Genetic Association Studies, Epidermis pathology, Biomarkers, Hidradenitis Suppurativa drug therapy, Hidradenitis Suppurativa genetics
- Abstract
Background: The pathophysiological picture underlying hidradenitis suppurativa (HS) and its syndromic forms is still patchy, thus presenting a great challenge for dermatologists and researchers since just by better understanding the pathogenesis of disease we could identify novel therapeutic targets., Methods: We propose a practical framework to improve subcategorization of HS patients and support the genotype-phenotype correlation, useful for endotype-directed therapies development., Results: This framework includes (i) clinical work-up that involves the collection of demographic, lifestyle, and clinical data as well as the collection of different biological samples; (ii) genetic-molecular work-up, based on multi-omics analysis in combination with bioinformatics pipelines to unravel the complex etiology of HS and its syndromic forms; (iii) functional studies, - represented by skin fibroblast cell cultures, reconstructed epidermal models (both 2D and 3D) and organoids -, of candidate biomarkers and genetic findings necessary to validate novel potential molecular mechanisms possibly involved and druggable in HS; (iv) genotype-phenotype correlation and clinical translation in tailored targeted therapies., Conclusion: Omic findings should be merged and integrated with clinical data; moreover, the skin-omic profiles from each HS patient should be matched and integrated with the ones already reported in public repositories, supporting the efforts of the researchers and clinicians to discover novel biomarkers and molecular pathways with the ultimate goal of providing faster development of novel patient-tailored therapeutic approaches., (© 2023 The Author(s). Published by S. Karger AG, Basel.)
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- 2023
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12. A rare loss-of-function genetic mutation suggest a role of dermcidin deficiency in hidradenitis suppurativa pathogenesis.
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Tricarico PM, Gratton R, Dos Santos-Silva CA, de Moura RR, Ura B, Sommella E, Campiglia P, Del Vecchio C, Moltrasio C, Berti I, D'Adamo AP, Elsherbini AMA, Staudenmaier L, Chersi K, Boniotto M, Krismer B, Schittek B, and Crovella S
- Subjects
- Child, Humans, Mutation, Peptides genetics, Peptides metabolism, Skin metabolism, Male, Female, Anti-Infective Agents metabolism, Dermcidins, Hidradenitis Suppurativa genetics, Hidradenitis Suppurativa metabolism
- Abstract
Hidradenitis suppurativa (HS) is a chronic inflammatory skin disease with a multifactorial aetiology that involves a strict interplay between genetic factors, immune dysregulation and lifestyle. Familial forms represent around 40% of total HS cases and show an autosomal dominant mode of inheritance of the disease. In this study, we conducted a whole-exome sequence analysis on an Italian family of 4 members encompassing a vertical transmission of HS. Focusing on rare damaging variants, we identified a rare insertion of one nucleotide (c.225dupA:p.A76Sfs*21) in the DCD gene encoding for the antimicrobial peptide dermcidin (DCD) that was shared by the proband, his affected father and his 11-years old daughter. Since several transcriptome studies have shown a significantly decreased expression of DCD in HS skin, we hypothesised that the identified frameshift insertion was a loss-of-function mutation that might be associated with HS susceptibility in this family. We thus confirmed by mass spectrometry that DCD levels were diminished in the affected members and showed that the antimicrobial activity of a synthetic DCD peptide resulting from the frameshift mutation was impaired. In order to define the consequences related to a decrease in DCD activity, skin microbiome analyses of different body sites were performed by comparing DCD mutant and wild type samples, and results highlighted significant differences between the groins of mutated and wild type groups. Starting from genetic analysis conducted on an HS family, our findings showed, confirming previous transcriptome results, the potential role of the antimicrobial DCD peptide as an actor playing a crucial part in the etio-pathogenesis of HS and in the maintenance of the skin's physiological microbiome composition; so, we can hypothesise that DCD could be used as a novel target for personalised therapeutic approach., 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 Tricarico, Gratton, Santos-Silva, Moura, Ura, Sommella, Campiglia, Del Vecchio, Moltrasio, Berti, D’Adamo, Elsherbini, Staudenmaier, Chersi, Boniotto, Krismer, Schittek and Crovella.)
- Published
- 2022
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13. Peptides for Coating TiO 2 Implants: An In Silico Approach.
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Agrelli A, Vasconcelos NF, Silva RCSD, Mendes-Marques CL, Arruda IRS, Oliveira PSS, Santos LRL, Andrade AN, Moura RR, Bernardo-Menezes LC, Silva NPD, and Machado G
- Subjects
- Peptides, Integrins, Coated Materials, Biocompatible chemistry, Titanium pharmacology, Titanium chemistry
- Abstract
Titanium is usually used in the manufacturing of metal implants due to its biocompatibility and high resistance to corrosion. A structural and functional connection between the living bone and the surface of the implant, a process called osseointegration, is mandatory for avoiding prolonged healing, infections, and tissue loss. Therefore, osseointegration is crucial for the success of the implantation procedure. Osseointegration is a process mediated by bone-matrix progenitor cells' proteins, named integrins. In this study, we used an in silico approach to assemble and test peptides that can be strategically used in sensitizing TiO
2 implants in order to improve osseointegration. To do so, we downloaded PDB structures of integrins α5β1, αvβ3, and αIIbβ3; their biological ligands; and low-cost proteins from the Protein Data Bank, and then we performed a primary (integrin-protein) docking analysis. Furthermore, we modeled complex peptides with the potential to bind to the TiO2 surface on the implant, as well as integrins in the bone-matrix progenitor cells. Then we performed a secondary (integrin-peptide) docking analysis. The ten most promising integrin-peptide docking results were further verified by molecular dynamics (MD) simulations. We recognized 82 peptides with great potential to bind the integrins, and therefore to be used in coating TiO2 implants. Among them, peptides 1 (GHTHYHAVRTQTTGR), 3 (RKLPDATGR), and 8 (GHTHYHAVRTQTLKA) showed the highest binding stability during the MD simulations. This bioinformatics approach saves time and more effectively directs in vitro studies., Competing Interests: The authors declare no conflict of interest.- Published
- 2022
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14. Variant Enrichment Analysis to Explore Pathways Disruption in a Necropsy Series of Asbestos-Exposed Shipyard Workers.
- Author
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Crovella S, Moura RR, Brandão L, Vita F, Schneider M, Zanconati F, Finotto L, Zacchi P, Zabucchi G, and Borelli V
- Subjects
- Humans, Autopsy, Asbestos toxicity, Mesothelioma chemically induced, Mesothelioma genetics, Mesothelioma, Malignant, Lung Neoplasms chemically induced, Lung Neoplasms genetics, Occupational Exposure adverse effects
- Abstract
The variant enrichment analysis (VEA), a recently developed bioinformatic workflow, has been shown to be a valuable tool for whole-exome sequencing data analysis, allowing finding differences between the number of genetic variants in a given pathway compared to a reference dataset. In a previous study, using VEA, we identified different pathway signatures associated with the development of pulmonary toxicities in mesothelioma patients treated with radical hemithoracic radiation therapy. Here, we used VEA to discover novel pathways altered in individuals exposed to asbestos who developed or not asbestos-related diseases (lung cancer or mesothelioma). A population-based autopsy study was designed in which asbestos exposure was evaluated and quantitated by investigating objective signs of exposure. We selected patients with similar exposure to asbestos. Formalin-fixed paraffin-embedded (FFPE) tissues were used as a source of DNA and whole-exome sequencing analysis was performed, running VEA to identify potentially disrupted pathways in individuals who developed thoracic cancers induced by asbestos exposure. By using VEA analysis, we confirmed the involvement of pathways considered as the main culprits for asbestos-induced carcinogenesis: oxidative stress and chromosome instability. Furthermore, we identified protective genetic assets preserving genome stability and susceptibility assets predisposing to a worst outcome.
- Published
- 2022
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15. Association of hoarding case identification and animal protection programs to socioeconomic indicators in a major metropolitan area of Brazil.
- Author
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de Moura RR, de Castro WAC, Farinhas JH, da Cunha GR, Pegoraro MMO, Kmetiuk LB, Dos Santos AP, and Biondo AW
- Abstract
The present study assessed the identification of animal and object hoarding disorder cases by contact and mapping and the presence of animal protection programs in association with seven social-economic indicators of the metropolitan area of the ninth-biggest metropolitan area of Brazil. City Secretaries of Health and Environment provided demographic information and responded to a questionnaire. Overall, a very high level of hoarding case identification per municipality was associated with a higher Human Development Index, population, density, and income and related to distance from Curitiba, the capital of Parana State. Low and very low levels of hoarding case identification were related to greater area, higher Social Vulnerability Index (SVI), inequality, illiteracy, and rural areas. Very high identification level of animal protection programs was also associated with higher HDI, density and population, urban area, and high income, and geographical area. Similarly, low and very low levels of animal protection programs identification were major explained by low income, illiteracy, and distance related to higher population, urbanization, and higher HDI. In summary, better identification of hoarding cases and animal protection programs have shown an association with better socioeconomic indicators and higher population, density, and urban area. Whether municipalities with better human socioeconomic indicators may stimulate society's demands for identification of cases of individuals with hoarding disorder and animal programs should be further established. Regardless, animal health and welfare have been associated with improving human quality of life in a major Brazilian metropolitan area., 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 de Moura, de Castro, Farinhas, da Cunha, Pegoraro, Kmetiuk, dos Santos and Biondo.)
- Published
- 2022
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16. Know your enemy: The dragonfly Erythrodiplax fusca (Libellulidae) uses eavesdropping to obtain information about potential rivals.
- Author
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Pinto NS, De Marco P, and Moura RR
- Subjects
- Aggression, Animals, Behavior, Animal, Cues, Female, Male, Territoriality, Water, Odonata
- Abstract
Animals can eavesdrop on other competitors during territorial defense disputes to better choose rivals weaker than themselves and increase the chances of monopolizing resources. In dragonflies, males often compete for access to water bodies, which attract sexually receptive females to mate and lay eggs. During the breeding season, satellite males can observe fights between territory owners and intruders and, therefore, obtain information about potential rivals through visual cues. Consequently, weaker competitors may face more intense competition than stronger ones when defending a territory. In this study, we conducted field experiments with the dragonfly Erythrodiplax fusca to investigate whether eavesdropping on territorial disputes, using visual cues, affects the intensity of competition that territory owners face. We recorded the number of intruders that engage in disputes against males that recently occupied territories in two groups: the "eavesdropping" group (i.e., individuals with access to rivals' prior information) and the control group (i.e., competitors with no access to prior information). The number of intruders was greater in the eavesdropping group compared to the control group. This effect depended on the interaction between the size of the territory owners and the presence of eavesdropping. The number of intruders decreased with increase in the size of the owners in the presence of eavesdropping, but this relationship did not occur in the control group. We discuss the implications of our findings for the male decision-making process to initiate agonistic disputes and how investigating eavesdropping behavior can improve current models of conflict resolution in animals., (Copyright © 2022 Elsevier B.V. All rights reserved.)
- Published
- 2022
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17. An overview of Zika virus genotypes and their infectivity.
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Bernardo-Menezes LC, Agrelli A, Oliveira ASLE, Moura RR, Crovella S, and Brandão LAC
- Subjects
- Genotype, Humans, RNA metabolism, Flavivirus genetics, Zika Virus genetics, Zika Virus Infection epidemiology
- Abstract
Zika virus (ZIKV) is an enveloped, single-stranded RNA arbovirus belonging to the genus Flavivirus. It was first isolated from a sentinel monkey in Uganda in 1947. More recently, ZIKV has undergone rapid geographic expansion and has been responsible for outbreaks in Southeast Asia, the Pacific Islands, and America. In this review, we have highlighted the influence of viral genetic variants on ZIKV pathogenesis. Two major ZIKV genotypes (African and Asian) have been identified. The Asian genotype is subdivided into Southwest Asia, Pacific Island, and American strains, and is responsible for most outbreaks. Non-synonymous mutations in ZIKV proteins C, prM, E, NS1, NS2A, NS2B, NS3, and NS4B were found to have a higher prevalence and association with virulent strains of the Asian genotype. Consequently, the Asian genotype appears to have acquired higher cellular permissiveness, tissue persistence, and viral tropism in human neural cells. Therefore, mutations in specific coding regions of the Asian genotype may enhance ZIKV infectivity. Considering that mutations in the genomes of emerging viruses may lead to new virulent variants in humans, there is a potential for the re-emergence of new ZIKV cases in the future.
- Published
- 2022
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18. Individual specialization and generalization in predator-prey dynamics: The determinant role of predation efficiency and prey reproductive rates.
- Author
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Araujo G and Moura RR
- Subjects
- Animals, Population Dynamics, Predatory Behavior, Reproduction
- Abstract
Individual specialization and generalization refer to the breadth of prey types consumed by predators among all available prey. The ecological factors mechanistically determining individual differences and the coexistence of foraging strategies remain to be clarified. Formal quantitative models can elucidate the complex nonlinear mechanisms underlying predator-prey interactions. In this study, we built a dynamical model with multiple prey, with different nutritional values and reproductive rates, which are consumed by specialist and generalist predators. We then analyzed the viability of individual foraging strategies in all possible scenarios. Relative prey fertility and relative efficiency of predation, rather than prey nutritional value, determined the success of specialists and generalists. Less reproducing prey and the specialists relying on them face the highest danger of extinction, while generalists cannot thrive where specialists are sufficiently efficient in relation to the number of available prey. Our study provides new perspectives for empirical studies on individual specialization., 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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19. Variant Enrichment Analysis to Explore Pathways Functionality in Complex Autoinflammatory Skin Disorders through Whole Exome Sequencing Analysis.
- Author
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Brandão LAC, Moura RR, Marzano AV, Moltrasio C, Tricarico PM, and Crovella S
- Subjects
- Cell Movement genetics, Endothelial Cells pathology, Homeostasis genetics, Humans, Inflammation pathology, Neutrophils pathology, Signal Transduction genetics, Skin Diseases pathology, Exome Sequencing methods, Inflammation genetics, Skin pathology, Skin Diseases genetics
- Abstract
The challenge of unravelling the molecular basis of multifactorial disorders nowadays cannot rely just on association studies searching for potential causative variants shared by groups of patients and not present in healthy individuals; indeed, association studies have as a main limitation the lack of information on the interactions between the disease-causing variants. Thus, new genomic analysis tools focusing on disrupted pathways rather than associated gene variants are required to better understand the complexity of a disease. Therefore, we developed the Variant Enrichment Analysis (VEA) workflow, a tool applicable for whole exome sequencing data, able to find differences between the numbers of genetic variants in a given pathway in comparison with a reference dataset. In this study, we applied VEA to discover novel pathways altered in patients with complex autoinflammatory skin disorders, namely PASH ( n = 9), 3 of whom are overlapping with SAPHO) and PAPASH ( n = 3). With this approach we have been able to identify pathways related to neutrophil and endothelial cells homeostasis/activations, as disrupted in our patients. We hypothesized that unregulated neutrophil transendothelial migration could elicit increased neutrophil infiltration and tissue damage. Based on our findings, VEA, in our experimental dataset, allowed us to predict novel pathways impaired in subjects with autoinflammatory skin disorders.
- Published
- 2022
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20. One Health Index (OHI) applied to Curitiba, the ninth-largest metropolitan area of Brazil, with concomitant assessment of animal, environmental, and human health indicators.
- Author
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de Moura RR, Chiba de Castro WA, Farinhas JH, Pettan-Brewer C, Kmetiuk LB, Dos Santos AP, and Biondo AW
- Abstract
One Health has been defined as a comprehensive approach to human, animal, and environmental health, but unsuccessful in providing a specific index for city, state, or country assessment. Accordingly, the present study aimed to calculate the One Health Index (OHI) in 29 cities of the Curitiba metropolitan area, the ninth largest in Brazil. Animal and Environmental health indicators were obtained from the city secretary of environment. The social vulnerability index (SVI) was used as the overall human health indicator. The indicators were parameterized following a binary logic Principal component analysis (PCA) was applied in association with city population, per capita income, and distance from the capital Curitiba. Permutational multivariate analysis of variance (PERMANOVA) was applied using the three first coefficients of the principal components obtained from Principal Component Analysis Plot (PCA) and exploring a pairwise comparison between the scenario ranges. A value of p less than 0.05 was considered significant. Overall, a higher OHI was associated with a higher city population and income, and shorter distance from the capital, and tendency of low-income cities to present lower OHI compared to higher-income cities. In conclusion, the OHI proposed herein portrays a holistic representation of a city's overall health. Moreover, animal issues should be considered part of local to global sustainability, considering OHI to calculate sustainability indexes., 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., (© 2022 The Authors.)
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- 2022
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21. Biological Pathways Associated With the Development of Pulmonary Toxicities in Mesothelioma Patients Treated With Radical Hemithoracic Radiation Therapy: A Preliminary Study.
- Author
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Crovella S, Revelant A, Muraro E, Moura RR, Brandão L, Trovò M, Steffan A, Zacchi P, Zabucchi G, Minatel E, and Borelli V
- Abstract
Radical hemithoracic radiotherapy (RHR), after lung-sparing surgery, has recently become a concrete therapeutic option for malignant pleural mesothelioma (MPM), an asbestos-related, highly aggressive tumor with increasing incidence and poor prognosis. Although the toxicity associated to this treatment has been reduced, it is still not negligible and must be considered when treating patients. Genetic factors appear to play a role determining radiotherapy toxicity. The aim of this study is the identification of biological pathways, retrieved through whole exome sequencing (WES), possibly associated to the development of lung adverse effects in MPM patients treated with RHR. The study included individuals with MPM, treated with lung-sparing surgery and chemotherapy, followed by RHR with curative intent, and followed up prospectively for development of pulmonary toxicity. Due to the strong impact of grade 3 pulmonary toxicities on the quality of life, compared with less serious adverse events, for genetic analyses, patients were divided into a none or tolerable pulmonary toxicity (NoSTox) group (grade ≤2) and a severe pulmonary toxicity (STox) group (grade = 3). Variant enrichment analysis allowed us to identify different pathway signatures characterizing NoSTox and Stox patients, allowing to formulate hypotheses on the protection from side effects derived from radiotherapy as well as factors predisposing to a worst response to the treatment. Our findings, being aware of the small number of patients analyzed, could be considered a starting point for the definition of a panel of pathways, possibly helpful in the management of MPM patients., 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 © 2021 Crovella, Revelant, Muraro, Moura, Brandão, Trovò, Steffan, Zacchi, Zabucchi, Minatel and Borelli.)
- Published
- 2021
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22. The effect of agricultural intensification and water-locking on the world's largest coastal lagoonal system.
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Bueno C, Alves FL, Pinheiro LM, Perez L, Agostini VO, Fernandes EHL, Möller OO, Weschenfelder J, Pinho GLL, Wallner-Kersanach M, Moura RR, Durán JM, Etchevers I, Costa LDF, Werlang CC, Bortolin E, Machado E, Figueira RCL, Ferreira PAL, Andrade C, Fornaro L, and García-Rodríguez F
- Subjects
- Environmental Monitoring, Eutrophication, Geologic Sediments, Humans, Plastics, Water, Metals, Heavy analysis, Trace Elements analysis, Water Pollutants, Chemical analysis
- Abstract
The palaeolimnological conditions of Mirim Lagoon, a large coastal shallow lagoon under the influence of historical human impacts related to the development of the primary sector of the economy were reconstructed. The first significant human impact consisted of locking the estuarine system to induce the transition from brackish to freshwater conditions. During this transition, the sedimentation rate consistently increased from pre-disturbance values of 0.25 cm yr
-1 to >1 cm yr-1 . A concomitant increase in nitrogen and carbon values was recorded indicating a related eutrophication process. The highest nutrient levels were achieved during the 1990s after the incorporation of cutting-edge technologies for agricultural production such as high-yielding varieties of rice resistant to climate variability and pests, and the use of inorganic fertilisers, pesticides and water supply controlled by irrigation. After 2011, the soybean production boosted and the area cultivated with this oilseed equalled the area of rice paddies, i.e., 2 × 105 ha. A sharp decrease in δ13 C from -19 to -24‰ and in δ15 N from 6 to 2‰ were observed in the sedimentary record, indicating a major shift in the composition of the organic matter after the agricultural intensification. Trace elements Cr, Cu, Ni and Zn showed a high positive correlation with Al and Fe, and enrichment factors near 1, indicating a natural and terrigenous source of these elements and also unpolluted conditions. However, the increase of As after 1990 and the positive correlation with Pb was associated with agricultural practices. All elemental ratios (K/Al, Ti/Al and V/Cr) showed constant pre-disturbance trends and a turning point ca. the 1990s. Microplastics were detected from the beginning of the 1990s and increased towards recent sediments, thus corroborating an anthropogenically impacted scenario. Therefore, the development of the primary sector of the economy exerted clear impacts on the environmental quality of the system., 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 © 2021 Elsevier B.V. All rights reserved.)- Published
- 2021
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23. Influence of web traits, height, and daily periods of exposition on prey captured by orb-weaver spiders.
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Xavier GM, Quero A, Moura RR, Vieira C, Meira FA, and Gonzaga MO
- Subjects
- Animals, Humans, Phenotype, Silk, Predatory Behavior, Spiders
- Abstract
Orb-webs show diversity in several traits, including silk types, architecture, physical properties, locale, and period of exposition. The investigation of how they determine the identity of intercepted prey is important to functional ecology and to the evaluation of trophic niche partitioning within communities. However, the influence of several of these variables on the composition of intercepted insects remains to be determined. In this study, we evaluated the effects of web architectural traits, height, and daily periods of exposition on the interception of different insects in terms of sizes, masses, and taxa. We conducted observations of prey intercepted by the orb webs of 16 sympatric spider species and artificial webs. We found that all orb webs mainly intercepted small and light insects, sharing the most abundant insect families found in the study area. However, spiders that show nocturnal activity, more radii in their webs, large and high webs captured heavier insects. Other orb-web traits, such as the density of capture threads did not influence the kind of intercepted insects. We discuss why some variables affected prey interceptions in terms of mass. Finally, we discuss the implications of these influential variables to functional ecology, niche differentiation, and how behavioral assessments can complete this investigation in future studies., (Copyright © 2021 Elsevier B.V. All rights reserved.)
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- 2021
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24. CIITA gene polymorphism (rs3087456) in systemic lupus erythematosus and rheumatoid arthritis: A population-based cohort study.
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Lima SC, Gomes da Silva IIF, Nascimento DQ, de Moura RR, Mesquita MDS, Asano NMJ, Fernandes GV, Valente LM, Rushansky E, Mariano MHQA, Xavier RM, Chies JAB, Crovella S, and Sandrin-Garcia P
- Subjects
- Case-Control Studies, Cohort Studies, Genetic Predisposition to Disease, Genotype, Humans, Polymorphism, Single Nucleotide, Arthritis, Rheumatoid genetics, Lupus Erythematosus, Systemic genetics, Nuclear Proteins genetics, Trans-Activators genetics
- Abstract
Systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA) are influenced by genetic variants in immune system HLA genes. The Class II Major Histocompatibility Complex Transactivator (CIITA) is an important co-activator of the HLA transcriptional complex; the single nucleotide variant (SNV) rs3087456 localized in the gene promoter region (-168 A/G) has been reported as able to modify its transcription level. In our study, we assessed CIITA rs3087456 SNV in 1,044 Brazilians from two Brazilian regions (Northeast and South) to verify the association with susceptibility and clinical manifestations of (SLE) and (RA) using TaqMan SNP Genotyping Assays System. We observed a protection for a recessive model (GG x AA+AG) for RA susceptibility and increased risk for erosion development in AG genotype patients. No significant association was observed for SLE susceptibility; however, we observed significant increased risk for Class IV and V nephritis development in G allele and GG genotype patients. In conclusion, we showed the contribution of CIITA rs3087456 to SLE or RA clinical features and RA susceptibility in the studied populations., (© 2021 John Wiley & Sons Ltd.)
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- 2021
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25. In silico analysis of molecular interactions between HIV-1 glycoprotein gp120 and TNF receptors.
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Alves NMP, de Moura RR, Bernardo LC, Agrelli A, de Oliveira ASLE, da Silva NP, Crovella S, and Brandão LAC
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- Apoptosis physiology, Humans, Inflammation metabolism, Inflammation virology, Molecular Docking Simulation methods, Signal Transduction physiology, Virus Internalization, Glycoproteins metabolism, HIV Envelope Protein gp120 metabolism, HIV-1 pathogenicity, Receptors, Tumor Necrosis Factor metabolism
- Abstract
Proinflammatory microenvironmental is crucial for the Human Immunodeficiency Virus Type 1 (HIV-1) pathogenesis. The viral glycoprotein 120 (gp120) must interact with the CD4+ T cell chemokine receptor (CCR5) and a co-receptor C-X-C chemokine receptor type 4 (CXCR4) to let the virus entry into the host cells. However, the interaction of the viral particle with other cell surface receptors is mandatory for its attachment and subsequently entry. Tumor Necrosis Factor receptor type I (TNFR1), type II (TNFR2) and Fas are a superfamily of transmembrane proteins involved in canonical inflammatory pathway and cell death by apoptosis as responses against viral pathogens. In our study, we performed an in silico evaluation of the molecular interactions between viral protein gp120 and TNF receptors (TNFR1, TNFR2 and Fas). Protein structures were retrieved from Protein Databank (PDB), and Molecular Docking and dynamics were performed using ClusPro 2.0 server and GROMACS software, respectively. We observed that gp120 is able to bind TNFR1, TNFR2 and Fas receptors, although only the TNFR2-gp120 complex demonstrated to produce a stable and durable binding. Our findings suggest that gp120 may act as an agonist to TNF-α and also function as an attachment factor in HIV-1 entry process. These molecular interaction by gp120 may be the key to HIV-1 immunopathogenesis. In conclusion, gp120 may stimulate pro-inflammatory and apoptotic signaling transduction pathways mediated by TNFR2 and may act as an attachment factor retaining HIV-1 viral particles on the host cell surface., (Copyright © 2021 Elsevier B.V. All rights reserved.)
- Published
- 2021
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26. Araneophagy as an alternative foraging tactic to kleptoparasitism in two Argyrodinae (Araneae: Theridiidae) species.
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Meira FA, Moura RR, and Gonzaga MO
- Subjects
- Animals, Female, Male, Predatory Behavior, Spiders
- Abstract
Kleptoparasitism is assumed to be the main foraging strategy in some animal groups, such as the spiders of the subfamily Argyrodinae (Theridiidae). However, some species may also feed on silk threads, egg sacs, or even their hosts. The conditions determining these alternative foraging tactics remain unknown for most species. We performed field observations, stable isotope analysis and laboratory experiments to investigate kleptoparasitism and araneophagy of Argyrodes elevatus and Faiditus caudatus in webs of Manogea porracea (Araneidae). We evaluated the following hypotheses: (1) both species exhibit higher trophic positions than their hosts and closest to an araneophagic sympatric species; (2) host web selection is influenced by the presence of alternative resources (adult male and female, and egg sacs); and (3) they preferentially consume egg sacs instead of stored prey items. Both argyrodines showed higher trophic positions than their female hosts and closest to an araneophagic spider species. The invaders were found mainly on host webs with one adult and egg sacs and with egg sacs only. Finally, A. elevatus preferred to feed on prey captured by the host spider instead of egg sacs. We discussed the factors that can potentially determine the choices between foraging exclusively as kleptoparasites and consuming the hosts., (Copyright © 2021 Elsevier B.V. All rights reserved.)
- Published
- 2021
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27. Immunoinformatic approach to assess SARS-CoV-2 protein S epitopes recognised by the most frequent MHC-I alleles in the Brazilian population.
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Moura RR, Agrelli A, Santos-Silva CA, Silva N, Assunção BR, Brandão L, Benko-Iseppon AM, and Crovella S
- Subjects
- Brazil, Gene Frequency, HLA Antigens genetics, Histocompatibility Antigens Class I genetics, Host-Pathogen Interactions, Humans, Molecular Docking Simulation, Molecular Dynamics Simulation, Protein Binding, Protein Conformation, SARS-CoV-2 pathogenicity, Epitope Mapping, Epitopes, HLA Antigens immunology, Histocompatibility Antigens Class I immunology, SARS-CoV-2 immunology, Spike Glycoprotein, Coronavirus immunology
- Abstract
Aims: Brazil is nowadays one of the epicentres of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic and new therapies are needed to face it. In the context of specific immune response against the virus, a correlation between Major Histocompatibility Complex Class I (MHC-I) and the severity of the disease in patients with COVID-19 has been suggested. Aiming at better understanding the biology of the infection and the immune response against the virus in the Brazilian population, we analysed SARS-CoV-2 protein S peptides in order to identify epitopes able to elicit an immune response mediated by the most frequent MHC-I alleles using in silico methods., Methods: Our analyses consisted in searching for the most frequent Human Leukocyte Antigen (HLA)-A, HLA-B and HLA-C alleles in the Brazilian population, excluding the genetic isolates; then, we performed: molecular modelling for unsolved structures, MHC-I binding affinity and antigenicity prediction, peptide docking and molecular dynamics of the best fitted MHC-I/protein S complexes., Results: We identified 24 immunogenic epitopes in the SARS-CoV-2 protein S that could interact with 17 different MHC-I alleles (namely, HLA-A*01:01; HLA-A*02:01; HLA-A*11:01; HLA-A*24:02; HLA-A*68:01; HLA-A*23:01; HLA-A*26:01; HLA-A*30:02; HLA-A*31:01; HLA-B*07:02; HLA-B*51:01; HLA-B*35:01; HLA-B*44:02; HLA-B*35:03; HLA-C*05:01; HLA-C*07:01 and HLA-C*15:02) in the Brazilian population., Conclusions: Being aware of the intrinsic limitations of in silico analysis (mainly the differences between the real and the Protein Data Bank (PDB) structure; and accuracy of the methods for simulate proteasome cleavage), we identified 24 epitopes able to interact with 17 MHC-I more frequent alleles in the Brazilian population that could be useful for the development of strategic methods for vaccines against SARS-CoV-2., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2021. No commercial re-use. See rights and permissions. Published by BMJ.)
- Published
- 2021
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28. ADA2 deficiency (DADA2) associated with Evans syndrome and a severe ADA2 genotype.
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Ferriani MPL, Valera ET, de Sousa GR, Sandrin-Garcia P, de Moura RR, Hershfield MS, and de Carvalho LM
- Subjects
- Agammaglobulinemia complications, Agammaglobulinemia drug therapy, Anemia, Hemolytic, Autoimmune complications, Anemia, Hemolytic, Autoimmune drug therapy, Antirheumatic Agents therapeutic use, Child, Etanercept therapeutic use, Female, Glucocorticoids therapeutic use, Humans, Immunoglobulins, Intravenous therapeutic use, Immunologic Factors therapeutic use, Mutation, Missense, Pedigree, Sequence Deletion, Severe Combined Immunodeficiency complications, Severe Combined Immunodeficiency drug therapy, Thrombocytopenia complications, Thrombocytopenia drug therapy, Adenosine Deaminase genetics, Agammaglobulinemia genetics, Anemia, Hemolytic, Autoimmune genetics, Intercellular Signaling Peptides and Proteins genetics, Severe Combined Immunodeficiency genetics, Thrombocytopenia genetics
- Published
- 2021
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29. A novel trophobiotic interaction between a Neotropical stink bug and an ant species: Insights into potential benefits to the host plant.
- Author
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Moura RR and Carvalho RL
- Subjects
- Animals, Brazil, Herbivory, Plants, Symbiosis, Ants, Heteroptera
- Abstract
Trophobiotic interactions occur when phytophagous insects provide a sugary liquid, the honeydew, for ants and obtain defence against predators or parasitoids. The plants may indirectly benefit from an increased ant foraging activity by reducing the herbivorous abundance. These three trophic interactions have been previously studied for several species, but mainly involving plants with extrafloral nectaries, which is a plant structure that also produce attractive substances for ants. Previous studies have reported an ant preference for honeydew over extrafloral nectary content. Therefore, trophobiosis can be an important mediator of ant-plant interactions. In this study, we describe a trophobiotic interaction between Edessa contermina stink bugs and Camponotus blandus ants on the Byrsonima verbascifolia plants occurring in a conservation area of Brazilian savanna. Stink bugs excreted a sugary liquid which was consumed by the ants, and C. blandus ants were observed consuming potential parasitoids. Stink bugs were more abundant in plants containing high food supply and shelter availability. The occurrence of ants depended of the number of inflorescences and trunk circumference of B. verbascifolia. Ant abundance, however, was positively correlated with stink bug abundance and the number of inflorescences. Herbivory was not explained by neither plant architecture nor ant abundance. This high ant activity may benefit plants from a protection against herbivory, but we did not detect this effect during the study period. Hence, the interaction among ants and plants was apparently commensal. We concluded that plant traits were important in ant attraction, but stink bugs foraging also increased ant activity on the plant, but mainly on inflorescences. Therefore, the plant may benefit from an increased defence of inflorescences rather than leaves., (Copyright © 2020 Elsevier B.V. All rights reserved.)
- Published
- 2021
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30. Reanalysis of Gene Expression Profiles of CD4+ T Cells Treated with HIV-1 Latency Reversal Agents.
- Author
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Campos Coelho AV, Moura RR, and Crovella S
- Abstract
The human immunodeficiency virus (HIV-1) causes a progressive depletion of CD4+ T cells, hampering immune function. Current experimental strategies to fight the virus focus on the reactivation of latent HIV-1 in the viral reservoir to make the virus detectable by the immune system, by searching for latency reversal agents (LRAs). We hypothesize that if common molecular pathways elicited by the presence of LRAs are known, perhaps new, more efficient, "shock-and-kill" strategies can be found. Thus, the objective of the present study is to re-evaluate RNA-Seq assays to find differentially expressed genes (DEGs) during latency reversal via transcriptome analysis. We selected six studies (45 samples altogether: 16 negative controls and 29 LRA-treated CD4+ T cells) and 11 LRA strategies through a systematic search in Gene Expression Omnibus (GEO) and PubMed databases. The raw reads were trimmed, counted, and normalized. Next, we detected consistent DEGs in these independent experiments. AZD5582, romidepsin, and suberanilohydroxamic acid (SAHA) were the LRAs that modulated most genes. We detected 948 DEGs shared by those three LRAs. Gene ontology analysis and cross-referencing with other sources of the literature showed enrichment of cell activation, differentiation and signaling, especially mitogen-activated protein kinase ( MAPK ) and Rho-GTPases pathways.
- Published
- 2020
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31. Increased risk of dizziness in human immunodeficiency virus-infected patients taking zidovudine and efavirenz combination: a Brazilian cohort study.
- Author
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Valeriano JJLS, Carvalho-Silva WHV, Coelho AVC, Moura RR, Arraes LC, Brandão LAC, Crovella S, and Guimarães RL
- Subjects
- Adult, Brazil, Depression chemically induced, Drug Therapy, Combination adverse effects, Female, Humans, Male, Middle Aged, Retrospective Studies, Sleep Initiation and Maintenance Disorders chemically induced, Survival Analysis, Time Factors, Alkynes adverse effects, Anti-HIV Agents adverse effects, Benzoxazines adverse effects, Cyclopropanes adverse effects, Dizziness chemically induced, HIV Infections drug therapy, Reverse Transcriptase Inhibitors adverse effects, Zidovudine adverse effects
- Abstract
Objectives: Neuropsychiatric adverse effects (NPAE) related to efavirenz, mainly dizziness, is detrimental to human immunodeficiency virus (HIV) treatment. Our study aims at evaluating if zidovudine use potentiates the risk of dizziness related to efavirenz when used together and whether there are significant differences in over time distribution of this NPAE and others relatively frequents regarding efavirenz regimen without zidovudine., Methods: Human immunodeficiency virus-infected patients under efavirenz-containing different therapy were enrolled. A retrospective analysis of official medical records was accomplished to collect clinical data regarding NPAE occurrence and severity. Univariate statistic and statistical model based on survival analyses were performed., Key Findings: One hundred sixty-two patients were included, of these seventy-seven (47.5%) had NPAE reported, such as dizziness (more frequent), depression and insomnia. Univariate statistical analysis demonstrated that the combined use of efavirenz with zidovudine increased the NPAE risk (OR: 2.5; P-value: 0.008), mainly dizziness risk (OR: 3.5; P-value: 0.009) and survival analysis showed that such combination is associated with dizziness occurrence faster (HR: 2.9; P-value: 0.02)., Conclusions: The results may contribute to clarify the dizziness occurrence dynamics in therapy with efavirenz and zidovudine by identifying susceptibilities and assisting in the choice of combined antiretroviral therapy., (© 2020 Royal Pharmaceutical Society.)
- Published
- 2020
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32. Towards simplicity and accuracy: Assessing traditional and new estimators of orb-web capture thread length.
- Author
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Xavier GM, Moura RR, and Gonzaga MO
- Subjects
- Animals, Silk, Predatory Behavior physiology, Spiders physiology
- Abstract
Before using estimators, it is essential to consider their efficiency in order to avoid bias in results. Due to the architectural and structural complexity of spider webs, some important variables involved in prey capture are usually estimated based on a few measurements obtained from photographs. One of these variables is the capture thread length (CTL), which can provide valuable information on foraging behaviours and the energetic investment in prey capture. However, many of the webs found in the field are damaged, and there is no automatic method to measure the CTL. Therefore, the determination of a simple and accurate estimator of this variable is important to several studies involving spider foraging strategies. In this study, we assessed the accuracy of traditional and new CTL estimators and their vulnerability to web shape and asymmetry. Our results validated the accuracy of the previous estimators. However, we also presented a simple new estimator that can be even more accurate, irrespective of whether the webs exhibit circular shapes or asymmetry in thread investment between superior and inferior web parts. Moreover, we presented an accurate CTL estimator for non-circular orb webs, for which the traditional ones are not applicable., (Copyright © 2020 Elsevier B.V. All rights reserved.)
- Published
- 2020
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33. Distribution of pesticides in agricultural and urban soils of Brazil: a critical review.
- Author
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Fernandes CLF, Volcão LM, Ramires PF, Moura RR, and Da Silva Júnior FMR
- Subjects
- Brazil, Environmental Monitoring, Soil, Agriculture, Hydrocarbons, Chlorinated, Pesticide Residues analysis, Pesticides analysis, Soil Pollutants analysis
- Abstract
The extensive use of pesticides leads to soil contamination and is harmful to environmental health. Brazil is considered the world's largest consumer of pesticides; however, there is no published review of the distribution and concentration of pesticides in the Brazilian soils. Thus, the objective of this study was to analyze the occurrence of pesticide residues in Brazilian soils through a systematic review of the data obtained from the official records of government agencies and scientific literature. Further, this review aims to estimate the risk quotient using the data extracted from these studies and compare it with the values from current legislation. The studies on pesticides were selected and screened, out of which 21 scientific articles were included in this review. The studies highlighted that 55 pesticides were detected in the soils in Brazil. Of these, 58% belonged to the chemical class of organochlorines and their concentration ranged from 0.0002-1243.68 mg kg-1. DDT (0.00002-1243.68 mg kg-1), HCH (0.00007-962.00 mg kg-1) and diuron (0.0031-4.16 mg kg-1) contributed to highest pesticide concentrations in soil. Residential soils had higher pesticide concentrations and greater risk factors than the agricultural soils. Moreover, 20% of the studies detected mixtures containing more than 10 types of pesticides. This study concluded that the specific scenarios evaluated by the reviewed studies do not reflect the current pesticide use and contamination in Brazil and there is a need for more information related to pesticide contamination in soils.
- Published
- 2020
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34. Mutational landscape of Zika virus strains worldwide and its structural impact on proteins.
- Author
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Agrelli A, de Moura RR, Crovella S, and Brandão LAC
- Subjects
- Amino Acid Sequence genetics, Mutation, Protein Conformation, Zika Virus pathogenicity, Genome, Viral genetics, Viral Proteins genetics, Zika Virus genetics
- Abstract
Zika virus (ZIKV) has spread globally and has been linked to the onset of microcephaly and other brain abnormalities. The ZIKV genome consists of an ~10.7 kb positive-stranded RNA molecule that encodes three structural (C, prM and E) and seven nonstructural (5'-NS1-NS2A-NS2B-NS3- NS4A/2K-NS4B-NS5-3') proteins. In this work, we looked for genetic variants in 485 ZIKV complete genomes from GenBank (NCBI) and performed a computational systematic approach using MAESTROweb server to assess the impact of nonsynonymous mutations in ZIKV proteins (C, M, E, NS1, NS2A, NS2B-NS3 protease, NS3 helicase and NS5). Then, we merged the data and correlated it with the phenotypic reports of ZIKV circulating strains. The sensitivity profile of the proteins showed 96 mutational hotspots. We found 22 relevant mutations in proteins C (I80T), NS2A (I34M/T/V, I45V, I80T/V, L113F, A117V, I118V, L128P, V143A, T151A, M199I/V, R207K and L208I) and NS3 helicase (D436G, Y498H, R525K, Q528R and R583K) of the circulating strains. Our analysis exploited the impact of nonsynonymous mutations on ZIKV proteins, their structural and functional insights. The results presented here could advance our current understanding on ZIKV proteins functions and pathogenesis., (Copyright © 2019 Elsevier B.V. All rights reserved.)
- Published
- 2019
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35. ZIKA virus entry mechanisms in human cells.
- Author
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Agrelli A, de Moura RR, Crovella S, and Brandão LAC
- Subjects
- Antiviral Agents pharmacology, Antiviral Agents therapeutic use, Clathrin chemistry, Clathrin metabolism, Endocytosis, Humans, Lectins, C-Type chemistry, Lectins, C-Type metabolism, Membrane Lipids chemistry, Membrane Lipids metabolism, Protein Binding, Receptors, Virus chemistry, Receptors, Virus metabolism, Structure-Activity Relationship, Viral Proteins chemistry, Viral Proteins metabolism, Virus Attachment, Virus Replication, Zika Virus drug effects, Zika Virus Infection drug therapy, Zika Virus Infection metabolism, Host-Pathogen Interactions, Virus Internalization drug effects, Zika Virus physiology, Zika Virus Infection virology
- Abstract
Zika virus (ZIKV) is an enveloped, mosquito-borne Flavivirus, which infects cells through clathrin-mediated endocytosis and fusion employing acidic endosomes. Cell entry is mostly mediated by the viral glycoprotein E, although incomplete particle maturation enables viral protein prM and anionic lipids present in the viral membrane to mediate this process. Incomplete proteolytic maturation results in a set of highly heterogeneous particles. These heterogeneous and dynamic infectious particles offer a variety of possible receptor interaction sites on their surfaces, thus contributing to the wide range of cells susceptible to ZIKV as well as to variation in tissue tropism. This review addresses recent advances in the understanding of ZIKV entry process into cells and put together fundamental questions about viral replication, maturation and host-cell interactions., (Copyright © 2019 Elsevier B.V. All rights reserved.)
- Published
- 2019
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36. Synthesis and antioxidant activity of new lipophilic dihydropyridines.
- Author
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da Costa Cabrera D, Santa-Helena E, Leal HP, de Moura RR, Nery LEM, Gonçalves CAN, Russowsky D, and Montes D'Oca MG
- Subjects
- Antioxidants chemical synthesis, Antioxidants chemistry, Dihydropyridines chemical synthesis, Dihydropyridines chemistry, Dose-Response Relationship, Drug, Hydrophobic and Hydrophilic Interactions, Molecular Structure, Structure-Activity Relationship, Antioxidants pharmacology, Benzothiazoles antagonists & inhibitors, Biphenyl Compounds antagonists & inhibitors, Dihydropyridines pharmacology, Picrates antagonists & inhibitors, Sulfonic Acids antagonists & inhibitors
- Abstract
Dihydropyridines (DHPs) obtained from Hantzsch multicomponent reactions are an important pharmaceutical class of compounds marketed as antihypertensive (e.g., nifedipine, nitrendipine, and amlodipine) drugs. This study synthesized new symmetrical and unsymmetrical long-chain fatty DHPs using multicomponent reactions under metal-free conditions with sulfamic acid as a catalyst. The DHPs were tested for antioxidant activity using three different methods. The insertion of a long chain into the DHP core contributed to antioxidant potential, and compounds derived from nitro aldehydes have better antioxidant potential than the antihypertensive drug nifedipine. In addition, fatty analogs to nifedipine derived from palmitic and oleic chains showed similar antioxidant activity to the common standards butylated hydroxytoluene and vitamin E. These results showed that our new synthesized products may find novel applications as antioxidant additives or for tools for use in drug discovery., (Copyright © 2018 Elsevier Inc. All rights reserved.)
- Published
- 2019
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37. Pleural mesothelioma and lung cancer: the role of asbestos exposure and genetic variants in selected iron metabolism and inflammation genes.
- Author
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Celsi F, Crovella S, Moura RR, Schneider M, Vita F, Finotto L, Zabucchi G, Zacchi P, and Borelli V
- Subjects
- Aged, Aged, 80 and over, Female, Humans, Italy, Lung Neoplasms chemically induced, Male, Mesothelioma chemically induced, Mesothelioma, Malignant, Pleural Neoplasms chemically induced, Prevalence, Retrospective Studies, Risk Factors, Asbestos toxicity, Inflammasomes genetics, Iron metabolism, Lung Neoplasms epidemiology, Mesothelioma epidemiology, Pleural Neoplasms epidemiology
- Abstract
Two of the major cancerous diseases associated with asbestos exposure are malignant pleural mesothelioma (MPM) and lung cancer (LC). In addition to asbestos exposure, genetic factors have been suggested to be associated with asbestos-related carcinogenesis and lung genotoxicity. While genetic factors involved in the susceptibility to MPM were reported, to date the influence of individual genetic variations on asbestos-related lung cancer risk is still poorly understood. Since inflammation and disruption of iron (Fe) homeostasis are hallmarks of asbestos exposure affecting the pulmonary tissue, this study aimed at investigating the association between Fe-metabolism and inflammasome gene variants and susceptibility to develop LC or MPM, by comparing an asbestos-exposed population affected by LC with an "asbestos-resistant exposed population". A retrospective approach similar to our previous autopsy-based pilot study was employed in a novel cohort of autoptic samples, thus giving us the possibility to corroborate previous findings obtained on MPM by repeating the analysis in a novel cohort of autoptic samples. The protective role of HEPH coding SNP was further confirmed. In addition, the two non-coding SNPs, either in FTH1 or in TF , emerged to exert a similar protective role in a new cohort of LC exposed individuals from the same geographic area of MPM subjects. No association was found between NLRP1 and NLRP3 polymorphisms with susceptibility to develop MPM and LC. Further research into a specific MPM and LC "genetic signature" may be needed to broaden our knowledge of the genetic landscape attributed to result in MPM and LC.
- Published
- 2019
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38. Antiretroviral therapy immunologic non-response in a Brazilian population: association study using pharmaco- and immunogenetic markers.
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Coelho AVC, Moura RR, Guimarães RL, Brandão LAC, and Crovella S
- Subjects
- Adolescent, Adult, Antiretroviral Therapy, Highly Active, Brazil, CD4 Lymphocyte Count, Female, Gene Frequency, Genetic Association Studies, Genetic Markers, Humans, Immunogenetic Phenomena drug effects, Immunogenetic Phenomena genetics, Male, Middle Aged, Multivariate Analysis, Retrospective Studies, Statistics, Nonparametric, Viral Load, Young Adult, Anti-Retroviral Agents pharmacology, HIV Infections drug therapy, HIV Infections immunology, Immune System drug effects, Polymorphism, Single Nucleotide immunology
- Abstract
Background: Antiretroviral therapy (ART) saved millions from HIV-1 infection and AIDS, but some patients do not experience adequate CD4+ T cells gain despite achieving viral suppression. The genetic component of this condition is not yet completely elucidated., Objective: To identify predictive genetic markers of immune response to ART., Methods: Case-control study. Out of 176 HIV-infected patients recruited in the city of Recife, Northeast Brazil, 67 patients with no immunologic response were the cases and the remaining 109 patients who responded were the controls. A set of 94 selected single nucleotide polymorphisms (SNPs) involved in antiretroviral drugs pharmacodynamic pathways and immune system homeostasis were genotyped, while the remaining 48 were ancestry informative markers (AIMs) for controlling for eventual hidden population structure., Results: Male patients were overrepresented in non-responder group (p=0.01). Non-responders also started with lower absolute CD4+ T cell counts (p<0.001). We found five SNPs significantly associated with the outcome, being three more frequent in non-responders than responders: rs2243250 (IL4) A allele (p=0.04), rs1128503 (ABCB1) A allele (p=0.03) and rs707265 (CYP2B6) A allele (p=0.02), whereas the other two were less frequent in non-responders: rs2069762 (IL2) C allele (p=0.004) and rs4646437 (CYP3A4) A allele (p=0.04)., Conclusion: Some significant univariate associations remained independently associated at multivariate survival analysis modeling, such as pre-treatment CD4+ T cells counts, IL2 and ABCB1 genotypes, and use of protease inhibitors, yielding a predictive model for the probability for immune response. More studies are needed to unravel the genetic basis of ART immunological non-response., (Copyright © 2018 Sociedade Brasileira de Infectologia. Published by Elsevier España, S.L.U. All rights reserved.)
- Published
- 2018
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39. The complications associated with Resuscitative Endovascular Balloon Occlusion of the Aorta (REBOA).
- Author
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Ribeiro Junior MAF, Feng CYD, Nguyen ATM, Rodrigues VC, Bechara GEK, de-Moura RR, and Brenner M
- Subjects
- Aorta injuries, Balloon Occlusion methods, Hemorrhage etiology, Hemorrhage prevention & control, Hemorrhage surgery, Humans, Injury Severity Score, Myocardial Reperfusion Injury etiology, Resuscitation methods, Aorta pathology, Balloon Occlusion adverse effects, Resuscitation adverse effects
- Abstract
Non-compressible torso hemorrhage (NCTH) remains a significant cause of morbidity and mortality in the field of trauma and emergency medicine. In recent times, there has been a resurgence in the adoption of Resuscitative Endovascular Balloon Occlusion of the Aorta (REBOA) for patients who present with NCTH. Like all medical procedures, there are benefits and risks associated with the REBOA technique. However, in the case of REBOA, these complications are not unanimously agreed upon with varying viewpoints and studies. This article aims to review the current knowledge surrounding the complications of the REBOA technique at each step of its application., Competing Interests: Ethics approval was not required for this review.Dr. Megan Brenner is a Clinical Advisory Board Member––Prytime Medical Inc. All other authors declare that they have no competing interests.Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
- Published
- 2018
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40. Resuscitative endovascular balloon occlusion of the aorta (REBOA): an updated review.
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Ribeiro Júnior MAF, Brenner M, Nguyen ATM, Feng CYD, DE-Moura RR, Rodrigues VC, and Prado RL
- Subjects
- Endovascular Procedures, Humans, Aorta, Balloon Occlusion, Hemorrhage therapy, Resuscitation methods
- Abstract
In a current scenario where trauma injury and its consequences account for 9% of the worlds causes of death, the management of non-compressible torso hemorrhage can be problematic. With the improvement of medicine, the approach of these patients must be accurate and immediate so that the consequences may be minimal. Therefore, aiming the ideal method, studies have led to the development of Resuscitative Endovascular Balloon Occlusion of the Aorta (REBOA). This procedure has been used at select trauma centers as a resuscitative adjunct for trauma patients with non-compressible torso hemorrhage. Although the use of this technique is increasing, its effectiveness is still not clear. This article aims, through a detailed review, to inform an updated view about this procedure, its technique, variations, benefits, limitations and future.
- Published
- 2018
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41. MMAB, a novel candidate gene to be screened in the molecular diagnosis of Mevalonate Kinase Deficiency.
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Mezzavilla M, Moura RR, Celsi F, Tricarico PM, and Crovella S
- Subjects
- Alkyl and Aryl Transferases genetics, Gene Frequency, Genotype, Humans, Mevalonate Kinase Deficiency genetics, Mutation, Phenotype, Alleles, Genetic Association Studies, Mevalonate Kinase Deficiency diagnosis, Molecular Diagnostic Techniques
- Abstract
Mevalonate kinase deficiency (MKD) is an autosomal recessive inflammatory disease. Mutations in MVK gene are associated with MKD with modest genotype-phenotype correlation. In spite of recent guidelines indicating specific MVK mutations for the more severe form or the milder one, little is known about MVK variability within and between populations. The aim of this work is to provide supplementary information about MVK variability useful in the molecular diagnosis of MKD, as well as to unravel the presence of novel genes potentially involved as involved in the clinical heterogeneity of MKD phenotype. We used a population-based approach, coupled with Combined Annotation-Dependent Depletion (CADD) score, to analyze the level of genetic variability for common and putatively deleterious MVK variants. We also performed Exome screening with the Illumina Human Exome Bead Chip on 21 MKD patients to double-check our in silico findings. Haplotype block detection in different populations revealed the existence of two blocks in MVK; interestingly, the first haploblock comprises the promoter region shared with MMAB gene. Analyses of MMAB and MVK genetic variants in 21 MKD patients strengthen our observations showing a novel scenario in which the same mutations commonly associated with MKD are found coupled with different combination of MMAB rs7134594 SNP was already described as associated with HDL cholesterol level and present in the haploblock promoter region. The rs7134594 SNP is reported as an eQTL for MVK and MMAB. Hypothesizing the presence of genetic variants modulating the complex phenotypic spectrum of MKD, we suggest that future directions in screening for MKD pathogenic variants should focus both MMAB and MVK genes.
- Published
- 2018
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42. Synergic effect of oral contraceptives, GSTP1 polymorphisms, and high-risk HPV infection in development of cervical lesions.
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Chagas BS, Gurgel APAD, Paiva Júnior SSL, Lima RCP, Cordeiro MN, Moura RR, Coelho AVC, Nascimento KCG, Silva Neto JC, Crovella S, and Freitas AC
- Subjects
- Adolescent, Adult, Aged, Aged, 80 and over, Female, Humans, Middle Aged, Squamous Intraepithelial Lesions of the Cervix epidemiology, Contraceptives, Oral adverse effects, Glutathione S-Transferase pi genetics, Papillomavirus Infections epidemiology, Polymorphism, Single Nucleotide, Squamous Intraepithelial Lesions of the Cervix genetics
- Abstract
Human papillomavirus (HPV) infection is considered a risk factor for cervical cancer. Even if the high-risk HPV (HR-HPV) infection is necessary, environmental co-factors and genetic susceptibility also play an important role in cervical cancer development. In this study, a possible association of rs1695 GSTP1 polymorphisms, HR-HPV infection, and oral contraceptive use with cancer lesion development in women was investigated. The study population comprised 441 Brazilian women from the Northeast region including 98 HPV-infected women with high-grade squamous intraepithelial lesions, 77 HPV-infected women with low-grade squamous intraepithelial lesions, and 266 HPV-negative women with no lesion, used as a control. Our data did not show a significant association between the GSTP1 polymorphism A/G (rs1695) and any HPV-related cervical abnormalities. However, considering the use of oral contraceptives, the GSTP1 rs1695 polymorphism was associated with higher susceptibility to the development of cervical lesions in HR-HPV-infected women. Our study suggests a synergic effect of oral contraceptive use, GSTP1 polymorphisms, and HR-HPV infection in the development of cervical lesions. Together, these risk factors may induce neoplastic transformation of the cervical squamous epithelium, setting conditions for secondary genetic events leading to cervical cancer.
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- 2017
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43. Temporal variation in size-assortative mating and male mate choice in a spider with amphisexual care.
- Author
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Moura RR and Gonzaga MO
- Subjects
- Animals, Body Size, Competitive Behavior physiology, Female, Fertility physiology, Male, Population Density, Sex Ratio, Spiders anatomy & histology, Time Factors, Mating Preference, Animal physiology, Spiders physiology
- Abstract
Males should be more selective when they have a high investment in reproduction, especially in species with biparental or paternal care. In this context, male mate choice can promote size-assortative mating (SAM) when (1) large males win intrasexual disputes, (2) large females are more fecund, and (3) males prefer larger females to smaller ones. In the spider Manogea porracea, males exhibit high reproductive investment by building their webs above those of females and exhibiting extended care of offspring in the absence of females. Under these circumstances, we expect the occurrence of SAM and male preference for large females. Herein, we performed observations and experiments in the field to evaluate the hypotheses that (1) M. porracea mates assortatively by size and (2) SAM is influenced by male mate choice. Furthermore, we measured variables that could affect mating patterns, the sex ratios, and densities of both sexes. Pairing in M. porracea was positively size-assortative in 2012, but not in 2013. Large males won most disputes for mates and preferred larger females, which produced more eggs. The inconsistency in detection of SAM was due to population dynamics, namely variations in sex ratio and population density across the breeding season. Furthermore, we found that the significance of male mate choice on sexual selection of body size in M. porracea strongly depends on the competition intensity for mating opportunities. The traditional sexual selection hypothesis of SAM needs to be reviewed and must include measures of competition intensity.
- Published
- 2017
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44. CUL5 and APOBEC3G Polymorphisms are Partially Implicated in HIV-1 Infection and Antiretroviral Therapy in a Brazilian Population.
- Author
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da Silva RC, Coelho AVC, de Moura RR, Arraes LC, Brandão LAC, Guimarães RL, and Crovella S
- Subjects
- Adult, Brazil, CD4 Lymphocyte Count, Female, HIV Infections pathology, HIV Infections virology, Humans, Male, Middle Aged, Polymorphism, Single Nucleotide, Retrospective Studies, Treatment Outcome, Viral Load, Young Adult, APOBEC-3G Deaminase genetics, Anti-Retroviral Agents therapeutic use, Cullin Proteins genetics, Genetic Predisposition to Disease, HIV Infections drug therapy, HIV Infections genetics
- Abstract
Background: Host restriction factors are cellular proteins able to diminish or block viral replication in a cell-specific way., Objective and Method: We evaluated the distribution of single nucleotide polymorphisms (SNPs) in APOBEC3G (rs3736685, rs2294367) and CUL5 (rs7117111, rs7103534, rs11212495) genes, among 264 HIV-1 infected (HIV-1+) and 259 unexposed- uninfected individuals from Northeast Brazil, looking for a possible association with susceptibility to HIV-1 infection, viral load during treatment, CD4+ T cell count and therapeutic success of the antiretroviral treatment., Results: The rs11212495 CUL5 G allele and the CUL5 rs7103534-rs7117111 CG haplotype were more frequent among unexposed-uninfected than in HIV-1+ individuals, suggesting an association with a lower HIV-1 infection susceptibility. The APOBEC3G rs2294367 G/C genotype correlated with delayed viral load suppression. Our results showed a great heterogeneity in relation to the literature findings, possibly due to ethnic differences among the studied populations, sample size used in the studies and, also, to the type of controls, i.e. in our study used unexposed-uninfected rather than exposed-uninfected individuals (rare and considered gold standard for susceptibility studies)., Conclusion: Our findings report genetic variants possibly associated with susceptibility to HIV-1 infection (CUL5 rs11212495, rs7103534, rs7117111) and partial viral load control (APOBEC3G rs2294367). Replica studies performed on higher number of subjects are envisaged to confirm our results., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.)
- Published
- 2017
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45. HLA-C Single Nucleotide Polymorphism Associated with Increased Viral Load Level in HIV-1 Infected Individuals from Northeast Brazil.
- Author
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Celerino da Silva R, Moura RR, Victor Campos Coelho A, Arraes LC, Brandão LAC, Crovella S, and Lima Guimarães R
- Subjects
- Adolescent, Adult, Brazil, CD4 Lymphocyte Count, Female, HIV-1 isolation & purification, Humans, Male, Middle Aged, Young Adult, DNA-Binding Proteins genetics, HIV Infections genetics, HIV Infections virology, HLA-C Antigens genetics, Histocompatibility Antigens Class I genetics, Polymorphism, Single Nucleotide, Viral Load
- Abstract
Background: Genetic variations in Human leukocyte antigen C (HLA-C), Zinc ribbon domain containing 1 (ZNRD1) and its antisense RNA (ZNRD1-AS1) genes are known to influence the HIV-1 replication and disease progression., Objective and Method: We evaluated the distribution of HLA-C (rs10484554, rs9264942) and ZNRD1 (rs8321) and ZNRD1-AS1 (rs3869068), single nucleotide polymorphisms (SNPs) in 266 HIV-1-infected and 223 unexposed-uninfected individuals from Northeast Brazil and their relation to HIV-1 infection, CD4 T cells count and viral load pre-treatment., Results: HLA-C SNPs were in Linkage Disequilibrium (D'=0.84), constituting four possible haplotypes. Our results showed that HLA-C, ZNRD1 and ZNRD1-AS1 SNPs as well as HLA-C haplotypes frequencies were not significantly different between HIV-1-infected and unexposed-uninfected individuals. In addition, we analyzed HLA-C and ZNRD-1 and ZNRD1-AS1 SNPs considering CD4+ T cell counts and viral load before the antiretroviral treatment. Individuals carrying HLA-C rs9264942 TT genotype showed a significant increased level of HIV-1 viral load pre-treatment, in comparison with individuals carrying the CC genotype (p-value = 0.0092). Finally, we stratified our findings according to CCR5Δ32 allele presence along with the studied SNPs: no statistically significant influence over viral load pre-treatment has been found., Conclusion: The association between HLA-C rs9264942 SNP and viral load prior treatment in an admixed population from North East Brazil was in agreement with findings from previous studies obtained on different ethnic groups; however more studies should be conducted in order to clarify how HLA-C impair the HIV-1 replication., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.)
- Published
- 2017
- Full Text
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46. Dendritic Cell-Based Immunotherapies to Fight HIV: How Far from a Success Story? A Systematic Review and Meta-Analysis.
- Author
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Coelho AV, de Moura RR, Kamada AJ, da Silva RC, Guimarães RL, Brandão LA, de Alencar LC, and Crovella S
- Subjects
- Clinical Trials as Topic, HIV Infections immunology, HIV Infections prevention & control, Humans, AIDS Vaccines therapeutic use, Dendritic Cells immunology, HIV Infections drug therapy, Immunotherapy methods
- Abstract
The scientific community still faces the challenge of developing strategies to cure HIV-1. One of these pursued strategies is the development of immunotherapeutic vaccines based on dendritic cells (DCs), pulsed with the virus, that aim to boost HIV-1 specific immune response. We aimed to review DCs-based therapeutic vaccines reports and critically assess evidence to gain insights for the improvement of these strategies. We performed a systematic review, followed by meta-analysis and meta-regression, of clinical trial reports. Twelve studies were selected for meta-analysis. The experimental vaccines had low efficiency, with an overall success rate around 38% (95% confidence interval = 26.7%-51.3%). Protocols differed according to antigen choice, DC culture method, and doses, although multivariate analysis did not show an influence of any of them on overall success rate. The DC-based vaccines elicited at least some immunogenicity, that was sometimes associated with plasmatic viral load transient control. The protocols included both naïve and antiretroviral therapy (ART)-experienced individuals, and used different criteria for assessing vaccine efficacy. Although the vaccines did not work as expected, they are proof of concept that immune responses can be boosted against HIV-1. Protocol standardization and use of auxiliary approaches, such as latent HIV-1 reservoir activation and patient genomics are paramount for fine-tuning future HIV-1 cure strategies., Competing Interests: The authors declare no conflict of interest.
- Published
- 2016
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47. Effects of different desensitizing treatments on root dentin permeability.
- Author
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Rosa RR, Calazans FK, Nogueira RD, Lancellotti AC, Gonçalves LS, and Geraldo-Martins VR
- Subjects
- Animals, Cattle, Dentin radiation effects, Dentin Permeability radiation effects, Laser Therapy methods, Lasers, Semiconductor therapeutic use, Microscopy, Electron, Scanning, Random Allocation, Reproducibility of Results, Surface Properties drug effects, Surface Properties radiation effects, Time Factors, Tooth Root radiation effects, Dentifrices chemistry, Dentin drug effects, Dentin Desensitizing Agents chemistry, Dentin Permeability drug effects, Dentin Sensitivity drug therapy, Tooth Root drug effects
- Abstract
The objective of this study was to evaluate the effects of diode laser and a desensitizing dentifrice on dentin permeability. Fifty-two root dentin fragments were obtained (5 × 5mm) and treated with 24% EDTA gel. The samples were divided into 4 groups (n = 13): G1, control (no treatment); G2, diode laser (λ = 908 nm, 1.5 W, continuous mode, 20s); G3, application of abrasive dentifrice for 1 minute (Elmex Sensitive Professional (International Gaba); and G4, application of abrasive dentifrice for 1 minute followed by irradiation with diode laser. Ten samples per group were immersed in 2% methylene blue solution for 4h. The specimens were washed, longitudinally sectioned, observed under optical microscopy, photographed and assessed based on the degree of dye leakage. The remaining samples were observed under scanning electron microscopy (SEM). The leakage data were subjected to ANOVA test, followed by Tukey's t-test (α = 5%). Groups 2, 3 and 4 showed less dye penetration than the control group (p < 0.05), but were similar among each other. SEM images showed that dentinal tubules were open in G1, and fused and occluded in G2. Group 3 showed dentinal tubules that were occluded by the metal ions from the toothpaste. G4 presented similar characteristics to G3, and the presence of fused dentin. The diode laser and the dentifrice were effective in reducing dentinal permeability, and the combination of the two treatments did not show better results than either one used alone.
- Published
- 2016
- Full Text
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48. Frequency of the CCR5-delta32 allele in Brazilian populations: A systematic literature review and meta-analysis.
- Author
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Silva-Carvalho WH, de Moura RR, Coelho AV, Crovella S, and Guimarães RL
- Subjects
- Brazil, Genetic Association Studies, Humans, Risk Factors, Gene Frequency, Receptors, CCR5 genetics, White People genetics
- Abstract
The CCR5 is a chemokine receptor widely expressed by several immune cells that are engaged in inflammatory responses. Some populations have individuals exhibiting a 32bp deletion in the CCR5 gene (CCR5-delta32) that produces a truncated non-functional protein not expressed on the cell surface. This polymorphism, known to be associated with susceptibility to infectious and inflammatory diseases, such as osteomyelitis, pre-eclampsia, systemic lupus erythematous, juvenile idiopathic arthritis, rheumatoid arthritis and HIV/AIDS, is more commonly found in European populations with average frequency of 10%. However, it is also possible to observe a significant frequency in other world populations, such as the Brazilian one. We performed a systematic review and meta-analysis of CCR5-delta32 genetic association studies in Brazilian populations throughout the country to estimate the frequency of this polymorphism. We also compared CCR5-delta32 frequencies across Brazilian regions. The systematic literature reviewed studies involving delta32 allele in Brazilian populations published from 1995 to 2015. Among the reviewed literature, 25 studies including 30 Brazilian populations distributed between the North, Northeast, South and Southeast regions were included in our meta-analysis. We observed an overall allelic frequency of 4% (95%-CI, 0.03-0.05), that was considered moderate and, notably, higher than some European populations, such as Cyprus (2.8%), Italy (3%) and Greece (2.4%). Regarding the regional frequency comparisons between North-Northeast (N-NE) and South-Southeast (S-SE) regions, we observed an allelic frequency of 3% (95%-CI, 0.02-0.04) and 4% (95%-CI, 0.03-0.05), respectively. The populations from S-SE regions had a slightly higher CCR5-delta32 frequency than N-NE regions (OR=1.41, p=0.002). Although there are several studies about the CCR5-delta32 polymorphism and its effect on the immune response of some infectious diseases, this report is the first meta-analysis study that provides a descriptive study of the distribution of CCR5-delta32 allele in Brazilian population., (Copyright © 2016 Elsevier B.V. All rights reserved.)
- Published
- 2016
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49. HLA-G genetic variants and hepatocellular carcinoma: a meta-analysis.
- Author
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Coelho AV, Moura RR, Crovella S, and Celsi F
- Subjects
- 3' Untranslated Regions, Adult, Carcinoma, Hepatocellular immunology, Carcinoma, Hepatocellular pathology, Case-Control Studies, Gene Expression, Gene Frequency, Genotype, HLA-G Antigens immunology, Humans, Liver immunology, Liver pathology, Liver Neoplasms immunology, Liver Neoplasms pathology, Male, Middle Aged, Carcinoma, Hepatocellular genetics, HLA-G Antigens genetics, INDEL Mutation, Liver Neoplasms genetics, Polymorphism, Genetic
- Abstract
Human leukocyte antigen (HLA)-G is a key tolerogenic molecule mainly expressed in the placenta and is crucial for implantation of the embryo and immunological tolerance of the fetus during pregnancy. However, under pathological conditions, such as cancer or viral infections, HLA-G can be expressed in other tissues. The gene coding for HLA-G (HLA-G, chromosome 6p21.3) presents numerous polymorphisms, some of them influencing its expression. One of the most studied, is the 14 bp ins/del (rs371194629) situated at the 3'-UTR of the gene. The insertion is thought to stabilize HLA-G mRNA. Different studies have analyzed the role of rs371194629 in hepatic injury, with either hepatotropic virus infection (i.e., HBV or HCV) or hepatocellular carcinoma (also induced by viral infection). Results from these studies are heterogeneous, differing with ethnicity and population age, and the role of rs371194629 is unclear. For these reasons, we decided to perform a meta-analysis of these results, concluding that the 14-bp ins/del polymorphism does not significantly contribute to hepatic injury., Competing Interests: The authors declare no conflict of interest.
- Published
- 2016
- Full Text
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50. Detecting multiple DNA human profile from a mosquito blood meal.
- Author
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Rabêlo KC, Albuquerque CM, Tavares VB, Santos SM, Souza CA, Oliveira TC, Moura RR, Brandão LA, and Crovella S
- Subjects
- Aedes physiology, Animals, Bites and Stings blood, Blood Cells chemistry, Crime, DNA genetics, Female, Genetic Testing methods, Healthy Volunteers, Humans, Male, Microsatellite Repeats, Aedes chemistry, DNA isolation & purification, DNA Fingerprinting methods, Forensic Genetics methods
- Abstract
Criminal traces commonly found at crime scenes may present mixtures from two or more individuals. The scene of the crime is important for the collection of various types of traces in order to find the perpetrator of the crime. Thus, we propose that hematophagous mosquitoes found at crime scenes can be used to perform genetic testing of human blood and aid in suspect investigation. The aim of the study was to obtain a single Aedes aegypti mosquito profile from a human DNA mixture containing genetic materials of four individuals. We also determined the effect of blood acquisition time by setting time intervals of 24, 48, and 72 h after the blood meal. STR loci and amelogenin were analyzed, and the results showed that human DNA profiles could be obtained from hematophagous mosquitos at 24 h following the blood meal. It is possible that hematophagous mosquitoes can be used as biological remains at the scene of the crime, and can be used to detect human DNA profiles of up to four individuals., Competing Interests: The authors declare no conflict of interest.
- Published
- 2016
- Full Text
- View/download PDF
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