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1.
Biol Bull ; 237(1): 26-35, 2019 08.
Artigo em Inglês | MEDLINE | ID: mdl-31441701

RESUMO

In this quantitative proteomics study we determined the variety and relative abundance of toxins present in enriched preparations of two nematocyst types isolated from the primary tentacles of the adult medusa stage of the hydrozoan Olindias sambaquiensis. The two nematocyst types were microbasic mastigophores and microbasic euryteles, and these were recovered from the macerated tentacle tissues by using a differential centrifugation approach. Soluble protein extracts from these nematocysts were tagged with tandem mass tag isobaric labels and putative toxins identified using tandem mass spectrometry coupled with a stringent bioinformatics annotation pipeline. Astonishingly, the venom composition of the two capsule types was nearly identical, and there was also little difference in the comparative abundance of toxins between the two nematocyst preparations. This homogeneity suggested that the same toxin complement was present regardless of the penetrative ability of the nematocyst type. Predicted toxin protein families that constituted the venom closely matched those of the toxic proteome of O. sambaquiensis published four years previously, suggesting that venom composition in this species changes little over time. Retaining an array of different nematocyst types to deliver a single venom, rather than sustaining the high metabolic cost necessary to maintain a dynamically evolving venom, may be more advantageous, given the vastly different interspecific interactions that adult medusa encounter in coastal zones.

2.
Integr Comp Biol ; 2019 Jul 27.
Artigo em Inglês | MEDLINE | ID: mdl-31353399

RESUMO

For many years methodological constraints limited insights on the molecular biology of non-model organisms. However, the development of various sequencing platforms has led to an explosion of transcriptomic and genomic data on non-model systems. As a consequence the molecular drivers of organismal phenotypes are becoming clearer and the chemicals that animals use to detect and respond to their environments are increasingly being revealed-this latter area inspired our symposium theme. The papers in this volume broadly address this theme by their more specific focus in one of the following general areas: 1) sensory biology and the molecular basis of perception, 2) chemicals deployed to deal with the biotic and abiotic environment, and 3) chemical interactions along the parasite-mutualist continuum. Here we outline and synthesize the content of these papers-an exercise which demonstrates that sophisticated gene repertoires enable early diverging metazoans to encode many of the signaling, sensory, defensive, and offensive capacities typically associated with animals that have complex nervous systems. We then consider opportunities and associated challenges that may delay progress in comparative functional biochemistry, a reinvigorated field that can be expected to rapidly expand with new 'omics data. Future knowledge of chemical adaptations should afford new perspectives on the comparative evolution of chemical mediators.

3.
Int. braz. j. urol ; 45(3): 435-448, May-June 2019. tab, graf
Artigo em Inglês | LILACS-Express | ID: biblio-1012324

RESUMO

ABSTRACT Objectives: Prostate cancer is the most common and fatal cancer amongst Brazilian males. The quality of prostate cancer care in Brazil was systematically reviewed and compared to United Kingdom (UK) National Institute for Health and Care Excellence (NICE) guidelines, which are considered an international benchmark in care, to deter- mine any treatment gaps in Brazilian practice. Materials and Methods: A systematic review of Brazilian and UK literature was under- taken. Additionally, quality of life scores was measured using a FACT-P questionnaire of 36 prostate cancer patients attending the Farmácia Universitária da Universidade de São Paulo (FARMUSP). These scores were compared against NICE care measures for patient safety, clinical efficacy and quality of life indicators determined by either quantitative or qualitative methods. Key findings: The quality of prostate cancer care in Brazil was considered good when compared to NICE guidelines. However, FACT-P data strongly indicated a poor under- standing of treatment received by Brazilian patients and that their mental health needs were not being met. Conclusions: NICE quality statements that address the holistic needs of patients should be implemented into Brazilian outpatient care plans. Addressing the non-medical concerns of patients may improve quality of life and can be easily rolled-out through existing Brazilian pharmacy services at no financial cost to the Brazilian Unified Health System (SUS).

4.
Integr Comp Biol ; 2019 Jun 21.
Artigo em Inglês | MEDLINE | ID: mdl-31225595

RESUMO

Venomous animals can deploy toxins for both predation and defense. These dual functions of toxins might be expected to promote the evolution of new venoms and alteration of their composition. Cnidarians are the most ancient venomous animals but our present understanding of their venom diversity is compromised by poor taxon sampling. New proteomic data were therefore generated to characterize toxins in venoms of a staurozoan, a hydrozoan and an anthozoan. We then used a novel clustering approach to compare venom diversity in cnidarians to other venomous animals. Comparison of the presence or absence of 32 toxin protein families indicated venom composition did not vary widely amongst the 11 cnidarian species studied. Unsupervised clustering of toxin peptide sequences suggested that toxin composition of cnidarian venoms is just as complex as that in many venomous bilaterians, including marine snakes. The adaptive significance of maintaining a complex and relatively invariant venom remains unclear. Future study of cnidarian venom diversity, venom variation with nematocyst types and in different body regions are required to better understand venom evolution.

5.
Appl Microbiol Biotechnol ; 103(13): 5161-5166, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31104099

RESUMO

L-asparaginase is an enzyme produced by microorganisms, plants, and animals, which is used clinically for the treatment for acute lymphoblastic leukemia (ALL) and, in the food industry, to control acrylamide formation in baked foods. The purpose of this review was to evaluate the available literature regarding microbial sources of L-asparaginase, culture media used to achieve maximum enzyme expression in microbial fermentations, and assay methods employed to assess L-asparaginase activity. Studies were gathered by searching PubMed, and Web of Science databases before January 22, 2018, with no time restrictions. The articles were evaluated according to the source of L-asparaginase being studied, the nitrogen source in the culture medium, the type of sample, and the method employed to evaluate L-asparaginase activity. Bacterial L-asparaginase appeared to be the most commonly studied source of the enzyme and, most often, the enzyme activity was assayed from crude protein extracts using the Nessler method, which is an indirect measurement of asparaginase activity that determines the concentration of ammonia generated after the action of the enzyme on the substrate, L-asparagine. However, ammonia is also generated throughout microbial fermentations and this endogenous ammonia will also reduce the Nessler reagent if crude microbial extracts are used to determine total L-asparaginase activity. We suggest that current estimates of L-asparaginase activity reported in the literature may be overestimated when Nessler reagent is used, since we were unable to find a single study that made reference to the possible inference of fermentation derived ammonia.

6.
Integr Comp Biol ; 2019 May 23.
Artigo em Inglês | MEDLINE | ID: mdl-31120488

RESUMO

Environmental stress from UV radiation, elevated temperatures or metal toxicity can lead to Reactive Oxygen Species in cells, leading to oxidative DNA damage, premature aging, neurodegenerative diseases and cancer. The transcription factor Nrf2 (Nuclear factor [erythroid-derived 2]-like 2), activates many cytoprotective proteins within the nucleus to maintain homeostasis during oxidative stress. In vertebrates, Nrf2 levels are regulated by the Kelch-family protein Keap1 in the absence of stress according to a canonical redox control pathway. Little, however, is known about the redox control pathway used in early diverging metazoans. Our study examines the presence of known oxidative stress regulatory elements within non-bilaterian metazoans including free living and parasitic cnidarians, ctenophores, placozoans and sponges. Cnidarians, with their pivotal position as the sister phylum to bilaterians, play an important role in understanding the evolutionary history of response to oxidative stress. Through comparative genomic and transcriptomic analysis our results show that Nrf homologs evolved early in metazoans, while Keap1 appeared later in the last common ancestor of cnidarians and bilaterians. However, key Nrf-Keap1 interacting domains are not conserved within the cnidarian lineage, suggesting this important pathway evolved with the radiation of bilaterians. Several known downstream Nrf targets are present in cnidarians suggesting that cnidarian Nrf plays an important role in oxidative stress response even in the absence of Keap1. Comparative analyses of key oxidative stress sensing and response proteins in early diverging metazoans thus provide important insights into the molecular basis of how these lineages interact with their environment and suggest a shared evolutionary history of regulatory pathways. Exploration of these pathways may prove important for the study of cancer therapeutics and broader research in oxidative stress, senescence and the functional responses of early diverging metazoans to environmental change.

7.
Int Braz J Urol ; 45(3): 435-448, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31038864

RESUMO

OBJECTIVES: Prostate cancer is the most common and fatal cancer amongst Brazilian males. The quality of prostate cancer care in Brazil was systematically reviewed and compared to United Kingdom (UK) National Institute for Health and Care Excellence (NICE) guidelines, which are considered an international benchmark in care, to determine any treatment gaps in Brazilian practice. MATERIALS AND METHODS: A systematic review of Brazilian and UK literature was undertaken. Additionally, quality of life scores was measured using a FACT-P questionnaire of 36 prostate cancer patients attending the Farmácia Universitária da Universidade de São Paulo (FARMUSP). These scores were compared against NICE care measures for patient safety, clinical effi cacy and quality of life indicators determined by either quantitative or qualitative methods. Key fi ndings: The quality of prostate cancer care in Brazil was considered good when compared to NICE guidelines. However, FACT-P data strongly indicated a poor understanding of treatment received by Brazilian patients and that their mental health needs were not being met. CONCLUSIONS: NICE quality statements that address the holistic needs of patients should be implemented into Brazilian outpatient care plans. Addressing the non-medical concerns of patients may improve quality of life and can be easily rolled-out through existing Brazilian pharmacy services at no fi nancial cost to the Brazilian Unifi ed Health System (SUS).


Assuntos
Assistência Ambulatorial/normas , Assistência Farmacêutica/normas , Neoplasias da Próstata/tratamento farmacológico , Garantia da Qualidade dos Cuidados de Saúde/métodos , Qualidade de Vida , Brasil , Lista de Checagem/normas , Humanos , Masculino , Padrões de Referência , Inquéritos e Questionários/normas , Reino Unido
8.
Food Technol Biotechnol ; 56(2): 270-277, 2018 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-30228802

RESUMO

Three metagenomic libraries were constructed using surface sediment samples from the northern Adriatic Sea. Two of the samples were taken from a highly polluted and an unpolluted site respectively. The third sample from a polluted site had been enriched using crude oil. The results of the metagenome analyses were incorporated in the REDPET relational database (http://redpet.bioinfo.pbf.hr/REDPET), which was generated using the previously developed MEGGASENSE platform. The database includes taxonomic data to allow the assessment of the biodiversity of metagenomic libraries and a general functional analysis of genes using hidden Markov model (HMM) profiles based on the KEGG database. A set of 22 specialised HMM profiles was developed to detect putative genes for hydrocarbon-degrading enzymes. Use of these profiles showed that the metagenomic library generated after selection on crude oil had enriched genes for aerobic n-alkane degradation. The use of this system for bioprospecting was exemplified using potential alkB and almA genes from this library.

9.
Biochimie ; 154: 35-44, 2018 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-30071261

RESUMO

Mycosporine-like amino acids (MAAs) are UVR-absorbing metabolites typically produced by cyanobacteria and marine algae, but their properties are not limited to direct sun screening protection. Herein, we examine the antioxidant activities of porphyra-334 and shinorine and demonstrate that these MAAs are prospective activators of the cytoprotective Keap1-Nrf2 pathway. The ability of porphyra-334 and shinorine to bind with Keap1 was determined using fluorescence polarization (FP) and thermal shift assays to detect Keap1 receptor antagonism. Concomitantly, the ability of porphyra-334 and shinorine to dissociate Nrf2 from Keap1 was confirmed also by measurement of increased mRNA expression of Nrf2 targeted genes encoding oxidative stress defense proteins in primary skin fibroblasts prior and post UVR exposure. Surprisingly, enhanced transcriptional regulation was only promoted by MAAs in cells after exposure to UVR-induced oxidative stress. Furthermore, the in-vitro antioxidant activities of porphyra-334 and shinorine determined by the DPPH free-radical quenching assay were low in comparison to ascorbic acid. However, their antioxidant capacity determined by the ORAC assay to quench free radicals via hydrogen atom transfer is substantial. Hence, the dual nature of MAAs to provide antioxidant protection may offer a prospective chemotherapeutic strategy to prevent or retard the progression of multiple degenerative disorders of ageing.


Assuntos
Antioxidantes , Cicloexanonas , Cicloexilaminas , Fibroblastos/metabolismo , Regulação da Expressão Gênica/efeitos dos fármacos , Glicina/análogos & derivados , Proteína 1 Associada a ECH Semelhante a Kelch , Fator 2 Relacionado a NF-E2 , Antioxidantes/química , Antioxidantes/farmacologia , Cicloexanonas/química , Cicloexanonas/farmacologia , Cicloexilaminas/química , Cicloexilaminas/farmacologia , Fibroblastos/citologia , Glicina/química , Glicina/farmacologia , Humanos , Proteína 1 Associada a ECH Semelhante a Kelch/antagonistas & inibidores , Proteína 1 Associada a ECH Semelhante a Kelch/química , Proteína 1 Associada a ECH Semelhante a Kelch/metabolismo , Fator 2 Relacionado a NF-E2/antagonistas & inibidores , Fator 2 Relacionado a NF-E2/química , Fator 2 Relacionado a NF-E2/metabolismo
10.
J Mol Microbiol Biotechnol ; 28(5): 225-235, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30783060

RESUMO

Three different polyhydroxyalkanoate (PHA) synthase genes (Ralstonia eutropha H16, Aeromonas sp. TSM81 or Aeromonas hydrophila ATCC7966 phaC) were introduced into the chromosome of two Pseudomonas strains: a native medium-chain-length 3-polyhydroxyalkanoate (PHAMCL) producer (Pseudomonas sp. LFM046) and a UV-induced mutant strain unable to produce PHA (Pseudomonas sp. LFM461). We reported for the first time the insertion of a chromosomal copy of phaC using the transposon system mini-Tn7. Stable antibiotic marker-free and plasmid-free recombinants were obtained. Subsequently, P(3HB-co-3HAMCL) was produced by these recombinants using glucose as the sole carbon source, without the need for co-substrates and under antibiotic-free conditions. A recombinant harboring A. hydrophila phaC produced a terpolyester composed of 84.2 mol% of 3-hydroxybutyrate, 6.3 mol% of 3-hydroxyhexanoate, and 9.5 mol% of 3-hydroxydecanoate from only glucose. Hence, we were successful in increasing the industrial potential of Pseudomonas sp. LFM461 strain by producing PHA copolymers containing 3HB and 3HAMCL using an unrelated carbon source, for the first time in a plasmid- and antibiotic-free bioprocess.


Assuntos
Plasmídeos/genética , Poli-Hidroxialcanoatos/biossíntese , Poli-Hidroxialcanoatos/genética , Pseudomonas/genética , Pseudomonas/metabolismo , Ácido 3-Hidroxibutírico/metabolismo , Aciltransferases/genética , Aeromonas/genética , Aeromonas hydrophila/genética , Antibacterianos , Proteínas de Bactérias/genética , Proteínas de Bactérias/metabolismo , Caproatos/metabolismo , Cromossomos Bacterianos , Meios de Cultura/química , Cupriavidus necator/genética , Ácidos Decanoicos/metabolismo , Glucose/metabolismo , Mutação , Pseudomonas/enzimologia , Transformação Bacteriana
11.
Food Technol Biotechnol ; 55(2): 251-257, 2017 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-28867956

RESUMO

The MEGGASENSE platform constructs relational databases of DNA or protein sequences. The default functional analysis uses 14 106 hidden Markov model (HMM) profiles based on sequences in the KEGG database. The Solr search engine allows sophisticated queries and a BLAST search function is also incorporated. These standard capabilities were used to generate the SCATT database from the predicted proteome of Streptomyces cattleya. The implementation of a specialised metagenome database (AMYLOMICS) for bioprospecting of carbohydrate-modifying enzymes is described. In addition to standard assembly of reads, a novel 'functional' assembly was developed, in which screening of reads with the HMM profiles occurs before the assembly. The AMYLOMICS database incorporates additional HMM profiles for carbohydrate-modifying enzymes and it is illustrated how the combination of HMM and BLAST analyses helps identify interesting genes. A variety of different proteome and metagenome databases have been generated by MEGGASENSE.

12.
Toxicon ; 137: 19-26, 2017 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-28711466

RESUMO

Cnidarians are probably the oldest group of animals to be venomous, yet our current picture of cnidarian venom evolution is highly imbalanced due to limited taxon sampling. High-throughput tandem mass spectrometry was used to determine venom composition of the scyphozoan Chrysaora lactea and two cubozoans Tamoya haplonema and Chiropsalmus quadrumanus. Protein recruitment patterns were then compared against 5 other cnidarian venom proteomes taken from the literature. A total of 28 putative toxin protein families were identified, many for the first time in Cnidaria. Character mapping analysis revealed that 17 toxin protein families with predominantly cytolytic biological activities were likely recruited into the cnidarian venom proteome before the lineage split between Anthozoa and Medusozoa. Thereafter, venoms of Medusozoa and Anthozoa differed during subsequent divergence of cnidarian classes. Recruitment and loss of toxin protein families did not correlate with accepted phylogenetic patterns of Cnidaria. Selective pressures that drive toxin diversification independent of taxonomic positioning have yet to be identified in Cnidaria and now warrant experimental consideration.

13.
Curr Med Chem ; 2017 May 29.
Artigo em Inglês | MEDLINE | ID: mdl-28554325

RESUMO

Excessive human exposure to solar ultraviolet radiation (UVR) continues to be a major public health concern, with skin cancer rates increasing year on year. The major protective measure is the use of synthetic UVR filters formulated into sunscreens, but there is growing concern that these chemicals cause damage to delicate marine ecosystems. One alternative is the use of biocompatible mycosporine-like amino acids (MAA), which occur naturally and are found predominantly in a wide range of marine species. Their role within nature is mainly thought to be photoprotective. This is a consequence of their optical properties but there is increasing evidence that they are also antioxidants at a chemical level, as well by activation of endogenous cell antioxidant defence mechanisms. However, their potential for human photoprotection is largely understudied. This review explores the role of MAA in nature and considers the literature available on the use of MAA within human models for photoprotection.

14.
Sci Rep ; 6: 27740, 2016 06 14.
Artigo em Inglês | MEDLINE | ID: mdl-27297177

RESUMO

In mammals, the master transcription regulator of antioxidant defences is provided by the Nrf2 protein. Phylogenetic analyses of Nrf2 sequences are used here to derive a molecular clock that manifests persuasive evidence that Nrf2 orthologues emerged, and then diverged, at two time points that correlate with well-established geochemical and palaeobiological chronologies during progression of the 'Great Oxygenation Event'. We demonstrate that orthologues of Nrf2 first appeared in fungi around 1.5 Ga during the Paleoproterozoic when photosynthetic oxygen was being absorbed into the oceans. A subsequent significant divergence in Nrf2 is seen during the split between fungi and the Metazoa approximately 1.0-1.2 Ga, at a time when oceanic ventilation released free oxygen to the atmosphere, but with most being absorbed by methane oxidation and oxidative weathering of land surfaces until approximately 800 Ma. Atmospheric oxygen levels thereafter accumulated giving rise to metazoan success known as the Cambrian explosion commencing at ~541 Ma. Atmospheric O2 levels then rose in the mid Paleozoic (359-252 Ma), and Nrf2 diverged once again at the division between mammals and non-mammalian vertebrates during the Permian-Triassic boundary (~252 Ma). Understanding Nrf2 evolution as an effective antioxidant response may have repercussions for improved human health.


Assuntos
Atmosfera/química , Evolução Molecular , Fator 2 Relacionado a NF-E2/genética , Oxigênio/análise , Animais , Sequência de Bases , Códon/genética , Terra (Planeta) , Fungos/metabolismo , Mamíferos/metabolismo , Filogenia
15.
Toxicon ; 119: 1-7, 2016 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-27169682

RESUMO

Jellyfish venoms are of medical and biotechnological importance, with toxins displaying antimicrobial, analgesic and anti-tumor activities. Although proteolytic enzymes have also been described, detailed characterisation of these proteins is scant in Olindias spp. High throughput mass spectrometry profiling of cnidarian venoms has become increasingly popular since the first description of the proteomic profile of putative toxins isolated from nematocysts of the hydrozoan jellyfish Olindias sambaquiensis describing the presence of orthologous enzymes as presented in venoms of advanced species as snakes. Rigorous bioinformatics analyses can aid functional annotation, but biochemical assays are prerequisite to unambiguously assign toxic function to a peptide or protein. Here we present results that experimentally confirm previously predicted proteomic analysis that crude venom extracts from tentacles of O. sambaquiensis are composed of polypeptides with metalloproteinase, serine proteinase and phospholipases A2 activities. Surprisingly, levels of serine proteinase and phospholipase A2 activities were comparable to those observed in venoms of Bothrops snakes which were used as positive controls in this study. Hence, these data offer new opportunities to explore serine proteinase and phospholipase A2 activities in the clinical sequelae following O. sambaquiensis envenomation, with future possible biopharmaceutical applications.


Assuntos
Venenos de Cnidários/química , Animais , Venenos de Cnidários/enzimologia , Metaloproteases/metabolismo , Fosfolipases A2/metabolismo , Proteólise , Serina Proteases/metabolismo
16.
BMC Genomics ; 16: 774, 2015 Oct 13.
Artigo em Inglês | MEDLINE | ID: mdl-26464356

RESUMO

BACKGROUND: Gene duplication followed by adaptive selection is a well-accepted process leading to toxin diversification in venoms. However, emergent genomic, transcriptomic and proteomic evidence now challenges this role to be at best equivocal to other processess . Cnidaria are arguably the most ancient phylum of the extant metazoa that are venomous and such provide a definitive ancestral anchor to examine the evolution of this trait. METHODS: Here we compare predicted toxins from the translated genome of the coral Acropora digitifera to putative toxins revealed by proteomic analysis of soluble proteins discharged from nematocysts, to determine the extent to which gene duplications contribute to venom innovation in this reef-building coral species. A new bioinformatics tool called HHCompare was developed to detect potential gene duplications in the genomic data, which is made freely available ( https://github.com/rgacesa/HHCompare ). RESULTS: A total of 55 potential toxin encoding genes could be predicted from the A. digitifera genome, of which 36 (65 %) had likely arisen by gene duplication as evinced using the HHCompare tool and verified using two standard phylogeny methods. Surprisingly, only 22 % (12/55) of the potential toxin repertoire could be detected following rigorous proteomic analysis, for which only half (6/12) of the toxin proteome could be accounted for as peptides encoded by the gene duplicates. Biological activities of these toxins are dominatedby putative phospholipases and toxic peptidases. CONCLUSIONS: Gene expansions in A. digitifera venom are the most extensive yet described in any venomous animal, and gene duplication plays a significant role leading to toxin diversification in this coral species. Since such low numbers of toxins were detected in the proteome, it is unlikely that the venom is evolving rapidly by prey-driven positive natural selection. Rather we contend that the venom has a defensive role deterring predation or harm from interspecific competition and overgrowth by fouling organisms. Factors influencing translation of toxin encoding genes perhaps warrants more profound experimental consideration.


Assuntos
Antozoários/genética , Evolução Molecular , Duplicação Gênica , Proteoma/genética , Sequência de Aminoácidos , Animais , Antozoários/patogenicidade , Venenos de Cnidários/genética , Venenos de Cnidários/toxicidade , Genoma , Nematocisto/metabolismo , Filogenia , Proteoma/toxicidade , Seleção Genética
17.
Genome Announc ; 3(5)2015 Sep 10.
Artigo em Inglês | MEDLINE | ID: mdl-26358601

RESUMO

The genome sequence of the first Streptomyces species isolated from the Brazilian Caatinga is reported here. Genes related to environmental stress tolerance were prevalent and included many secondary metabolic gene clusters.

18.
Free Radic Biol Med ; 88(Pt B): 373-380, 2015 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-26117326

RESUMO

An essential requirement for the evolution of early eukaryotic life was the development of effective means to protect against metabolic oxidative stress and exposure to environmental toxicants. In present-day mammals, the master transcription factor Nrf2 regulates basal level homeostasis and inducible expression of numerous detoxifying and antioxidant genes. To examine early evolution of the Keap1-Nrf2 pathway, we present bioinformatics analyses of distant homology of mammalian Keap1 and Nrf2 proteins across the Kingdoms of Life. Software written for this analysis is made freely available on-line. Furthermore, utilizing protein modeling and virtual screening methods, we demonstrate potential for Nrf2 activation by competitive inhibition of its binding to Keap1, specifically by UV-protective fungal mycosporines and marine mycosporine-like amino acids (MAAs). We contend that coevolution of Nrf2-activating secondary metabolites by fungi and other extant microbiota may provide prospective compound leads for the design of new therapeutics to target activation of the human Keap1-Nrf2 pathway for treating degenerative diseases of ageing.


Assuntos
Evolução Molecular , Peptídeos e Proteínas de Sinalização Intracelular/química , Peptídeos e Proteínas de Sinalização Intracelular/metabolismo , Fator 2 Relacionado a NF-E2/química , Fator 2 Relacionado a NF-E2/metabolismo , Animais , Biologia Computacional , Bases de Dados Genéticas , Humanos , Modelos Moleculares , Filogenia , Homologia de Sequência de Aminoácidos , Transdução de Sinais/fisiologia , Software
19.
J Pediatr Pharmacol Ther ; 20(2): 90-104, 2015 Mar-Apr.
Artigo em Inglês | MEDLINE | ID: mdl-25964726

RESUMO

OBJECTIVES: Antibiotic-associated diarrhea (AAD) is a well-recognized adverse reaction to oral penicillins. This review analyzed the literature to determine the incidence of AAD following amoxicillin, amoxicillin/clavulanate, and penicillin V oral therapy in pediatric clinical trials. METHODS: An advanced search was conducted in MEDLINE and Embase databases for articles in any language reporting the incidence of AAD following oral penicillin therapy for any indicated infection in children (0-17 years). The search was limited to clinical trials. Articles were excluded if treatment was related to chronic conditions, involved concomitant antimicrobials, or if the dose or number of patients was not specified. RESULTS: Four hundred thirty-five articles relating to clinical trials were identified (307 from Embase; 128 from MEDLINE). Thirty-five articles reporting on 42 studies were included for analysis. The indications included acute otitis media, sinusitis, pharyngitis, and pneumonia. Thirty-three trials reported on amoxicillin/clavulanate, 6 on amoxicillin, and 3 on penicillin V. In total, the 42 trials included 7729 children who were treated with an oral penicillin. On average, 17.2% had AAD. Data were pooled for each penicillin. The AAD incidence was 19.8% for amoxicillin/clavulanate, 8.1% for amoxicillin, and 1.2% for penicillin V. The amoxicillin/clavulanate data were analyzed according to formulation: pooled-average. The incidence of ADD was 24.6% for the 4:1 formulation, 12.8% for the 7:1 formulation, 19.0% for the 8:1 formulation, and 20.2% for the 14:1 formulation. CONCLUSIONS: These results demonstrate substantially increased incidence of AAD following use of amoxicillin/clavulanate, compared to use of amoxicillin and penicillin V, as well as varying AAD rates with diffierent amoxicillin/clavulanate formulations. These findings warrant consideration when prescribing. The underlying mechanisms of AAD in children remain unclear.

20.
Syst Appl Microbiol ; 38(3): 189-97, 2015 May.
Artigo em Inglês | MEDLINE | ID: mdl-25857844

RESUMO

Samples were collected from sea sediments at seven sites in the northern Adriatic Sea that included six sites next to industrial complexes and one from a tourist site (recreational beach). The samples were assayed for alkanes and polycyclic aromatic hydrocarbons. The composition of the hydrocarbon samples suggested that industrial pollution was present in most cases. A sample from one site was also grown aerobically under crude oil enrichment in order to evaluate the response of indigenous bacterial populations to crude oil exposure. Analysis of 16S rRNA gene sequences showed varying microbial biodiversity depending on the level of pollution--ranging from low (200 detected genera) to high (1000+ genera) biodiversity, with lowest biodiversity observed in polluted samples. This indicated that there was considerable biodiversity in all sediment samples but it was severely restricted after exposure to crude oil selection pressure. Phylogenetic analysis of putative alkB genes showed high evolutionary diversity of the enzymes in the samples and suggested great potential for bioremediation and bioprospecting. The first systematic analysis of bacterial communities from sediments of the northern Adriatic Sea is presented, and it will provide a baseline assessment that may serve as a reference point for ecosystem changes and hydrocarbon degrading potential--a potential that could soon gain importance due to plans for oil exploitation in the area.


Assuntos
Bactérias/classificação , Bactérias/isolamento & purificação , Biodiversidade , Sedimentos Geológicos/microbiologia , Água do Mar/química , Poluentes da Água/análise , Aerobiose , Alcanos/análise , Bactérias/genética , Bactérias/crescimento & desenvolvimento , Proteínas de Bactérias/genética , Análise por Conglomerados , DNA Ribossômico/química , DNA Ribossômico/genética , Hidrocarbonetos/análise , Oceanos e Mares , Filogenia , Hidrocarbonetos Policíclicos Aromáticos/análise , RNA Ribossômico 16S/genética , Análise de Sequência de DNA
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