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Dinosaurs and pterosaurs have remarkable diversity and disparity through most of the Mesozoic Era1-3. Soon after their origins, these reptiles diversified into a number of long-lived lineages, evolved unprecedented ecologies (for example, flying, large herbivorous forms) and spread across Pangaea4,5. Recent discoveries of dinosaur and pterosaur precursors6-10 demonstrated that these animals were also speciose and widespread, but those precursors have few if any well-preserved skulls, hands and associated skeletons11,12. Here we present a well-preserved partial skeleton (Upper Triassic, Brazil) of the new lagerpetid Venetoraptor gassenae gen. et sp. nov. that offers a more comprehensive look into the skull and ecology of one of these precursors. Its skull has a sharp, raptorial-like beak, preceding that of dinosaurs by around 80 million years, and a large hand with long, trenchant claws that firmly establishes the loss of obligatory quadrupedalism in these precursor lineages. Combining anatomical information of the new species with other dinosaur and pterosaur precursors shows that morphological disparity of precursors resembles that of Triassic pterosaurs and exceeds that of Triassic dinosaurs. Thus, the 'success' of pterosaurs and dinosaurs was a result of differential survival among a broader pool of ecomorphological variation. Our results show that the morphological diversity of ornithodirans started to flourish among early-diverging lineages and not only after the origins of dinosaurs and pterosaurs.
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Dinossauros , Filogenia , Répteis , Animais , Bico/anatomia & histologia , Dinossauros/anatomia & histologia , Dinossauros/classificação , Répteis/anatomia & histologia , Répteis/classificação , Crânio/anatomia & histologia , Fósseis , EsqueletoRESUMO
The vertebrate retina is generated by retinal progenitor cells (RPCs), which produce >100 cell types. Although some RPCs produce many cell types, other RPCs produce restricted types of daughter cells, such as a cone photoreceptor and a horizontal cell (HC). We used genome-wide assays of chromatin structure to compare the profiles of a restricted cone/HC RPC and those of other RPCs in chicks. These data nominated regions of regulatory activity, which were tested in tissue, leading to the identification of many cis-regulatory modules (CRMs) active in cone/HC RPCs and developing cones. Two transcription factors, Otx2 and Oc1, were found to bind to many of these CRMs, including those near genes important for cone development and function, and their binding sites were required for activity. We also found that Otx2 has a predicted autoregulatory CRM. These results suggest that Otx2, Oc1 and possibly other Onecut proteins have a broad role in coordinating cone development and function. The many newly discovered CRMs for cones are potentially useful reagents for gene therapy of cone diseases.
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Dissecação , Fator 6 Nuclear de Hepatócito/metabolismo , Fatores de Transcrição Otx/metabolismo , Retina/crescimento & desenvolvimento , Células Fotorreceptoras Retinianas Cones/metabolismo , Fatores de Transcrição/metabolismo , Animais , Sítios de Ligação , Galinhas , Cromatina , Regulação da Expressão Gênica no Desenvolvimento , Redes Reguladoras de Genes , Fator 6 Nuclear de Hepatócito/genética , Fatores de Transcrição Otx/genética , Retina/metabolismo , Células-TroncoRESUMO
BACKGROUND: Probiotic bacteria inhibit aggregation, biofilm formation, and dimorphism of Candida spp. However, the effects of a new probiotic, Streptococcus dentisani, on the growth of Candida albicans and Candida glabrata biofilms are unknown. OBJECTIVE: To determine the effect of S. dentisani on the different phases of C. albicans and C. glabrata biofilm development. METHODS: Growth quantification and ultrastructural analyses were performed on biofilms of C. albicans ATCC 90028, C. glabrata ATCC 2001, and clinical isolates of C. albicans from oral candidiasis (CA-C1), caries (CA-CR1), and periodontal pocket (CA-P1) treated with cell suspensions of S. dentisani CECT 7746. Cell viability was determined by quantifying colony-forming units (CFU/mL). The ultrastructural analyses were done with atomic force microscopy. RESULTS: S. dentisani induced a significant reduction (p < 0.05) of CFU/mL of immature and mature biofilm in all strains of C. albicans and C. glabrata. Microscopic analysis revealed that S. dentisani reduced C. albicans density in mixed biofilm. The fungus-bacteria interaction affected cell membrane integrity in yeast. CONCLUSION: For the first time, our data elucidate the antifungal effect of S. dentisani on the development of C. albicans and C. glabrata biofilms, supporting its usefulness as a niche-specific probiotic to prevent and treat oral dysbiosis.
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When electron-rich arylpyrrolinium salts are irradiated with ultraviolet light in the presence of Michael acceptors, the pyrrolinyl and aryl fragments add to the activated and polarized double bond in a regioselective manner, forming two C-C bonds and fragmenting the substrate. In this paper, we present a model for this intriguing reaction, supported by spectroscopy and computational analyses, and provide evidence for rectifying previously misassigned structures. We postulate that the photochemical reaction is inefficient because the reaction between the twisted intramolecular charge-transfer state and the olefin competes with fluorescence from this state upon photon absorption. We also discuss the practical advantages of performing this photochemical reaction in a continuous flow setup. Additionally, we explore several subsequent reactions that allow us to further modify the products of the photochemical step, ultimately leading to the creation of new chemical structures.
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BACKGROUND: Phosphate buffer is often used as a replacement for the physiological bicarbonate buffer in pharmaceutical dissolution testing, although there are some discrepancies in their properties making it complicated to extrapolate dissolution results in phosphate to the in vivo situation. This study aims to characterize these discrepancies regarding solubility and dissolution behavior of ionizable compounds. METHODS: The dissolution of an ibuprofen powder with a known particle size distribution was simulated in silico and verified experimentally in vitro at two different doses and in two different buffers (5 mM pH 6.8 bicarbonate and phosphate). RESULTS: The results showed that there is a solubility vs. dissolution mismatch in the two buffers. This was accurately predicted by the in-house simulations based on the reversible non-equilibrium (RNE) and the Mooney models. CONCLUSIONS: The results can be explained by the existence of a relatively large gap between the initial surface pH of the drug and the bulk pH at saturation in bicarbonate but not in phosphate, which is caused by not all the interfacial reactions reaching equilibrium in bicarbonate prior to bulk saturation. This means that slurry pH measurements, while providing surface pH estimates for buffers like phosphate, are poor indicators of surface pH in the intestinal bicarbonate buffer. In addition, it showcases the importance of accounting for the H2CO3-CO2 interconversion kinetics to achieve good predictions of intestinal drug dissolution.
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Bicarbonatos , Liberação Controlada de Fármacos , Ibuprofeno , Fosfatos , Solubilidade , Soluções Tampão , Bicarbonatos/química , Concentração de Íons de Hidrogênio , Ibuprofeno/química , Fosfatos/química , Tamanho da Partícula , Simulação por Computador , Pós/química , Cinética , Química Farmacêutica/métodosRESUMO
BACKGROUND: There is a lack of information on house dust mite (HDM) sensitization and phenotype distribution in patients with severe asthma (SA) living permanently at high-altitude (HA) in tropical regions, which may be different. OBJECTIVE: The aim of this study was to characterize adults with SA in a tropical high altitude city (2,640 m): Bogotá, Colombia. MATERIAL AND METHODS: This observational cross-sectional study included severe asthmatic outpatients (n = 129) referred to the ASMAIRE program of the Fundación Neumológica Colombiana in Bogotá (2,640 m). Clinical history, spirometry, total IgE, blood eosinophils, and skin prick test (SPT), including HDM allergens, were performed. Phenotype definitions: Allergic/atopic (AA): IgE ≥100 IU/mL and/or at least one positive SPT; eosinophilic (EOS): blood eosinophils ≥300 cells/µL; type 2-high: AA and/or EOS phenotype; type 2-low: non-AA/non-EOS phenotype (IgE <100 IU/mL, negative SPT, and blood eosinophils <300 cells/µL). RESULTS: A total of 129 adults with SA were included, 79.8% female. Phenotype distribution: AA: 61.2%; EOS: 37.2%; type 2-high: 72.1%; type 2-low: 27.9%. Among AA patients, HDM sensitization was present in 87% and 34.9% were non-eosinophilic. There was a significant overlap between the phenotypes. CONCLUSIONS: In contrast to non-tropical high-altitude regions, we found a high frequency of HDM sensitization in patients with AA phenotype living in a tropical high-altitude city. We also found a discrete lower frequency of EOS phenotype with no other significant differences in the phenotypic distribution compared to that described at low altitudes. We propose that tropical location may modify the effect of high altitude on HDM concentrations and allergenicity.
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Asma , Hipersensibilidade , Humanos , Adulto , Animais , Feminino , Masculino , Asma/epidemiologia , Pyroglyphidae , Altitude , Imunoglobulina E , Dermatophagoides pteronyssinus , Alérgenos , Testes Cutâneos , Antígenos de Dermatophagoides , PoeiraRESUMO
PURPOSE: To investigate the impact of anti-VEGF therapy on vascular metrics in eyes with macular edema secondary to central retinal vein occlusion (CRVO) using wider field swept-source OCT angiography (WF SS-OCTA). METHODS: We included 23 eyes with macular edema associated with non-ischemic CRVO from 22 patients treated with anti-VEGF therapy (median number of injections: 5 [2-9]). Changes in vessel density (VD), vessel skeletonized density (VSD), and foveal avascular zone (FAZ) parameters were measured using WF SS-OCTA. Visual acuity (VA) and central subfield thickness (CST) were also measured. RESULTS: Median CST decreased significantly from 369 µm (305-531) to 267 µm (243-300, p < 0.001). VD and VSD parameters in 12 × 12 mm images showed significant reductions. For instance, VSD in the whole retina decreased from a median of 13.37 (11.22-13.74) to 11.29 (9.36-12.97, p = 0.013). Additionally, a significant increase in FAZ circularity was found, suggesting improved microvascular integrity. Significant inverse correlations were found between the number of anti-VEGF injections and all VSD and VD parameters on the 12 × 12 mm images (p < 0.05). Notably, the reductions in VSD and VD on 12 × 12 mm angiograms in the deep capillary plexus (DCP) after each injection significantly correlated with increased logMAR VA (worse VA). CONCLUSION: Anti-VEGF therapy in CRVO patients not only mitigates macular edema but also alters the overall microvascular morphology and functionality as revealed by WF SS-OCTA.
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Inibidores da Angiogênese , Ranibizumab , Oclusão da Veia Retiniana , Tomografia de Coerência Óptica , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Inibidores da Angiogênese/uso terapêutico , Inibidores da Angiogênese/administração & dosagem , Bevacizumab/uso terapêutico , Bevacizumab/administração & dosagem , Angiofluoresceinografia/métodos , Seguimentos , Fundo de Olho , Injeções Intravítreas , Edema Macular/tratamento farmacológico , Edema Macular/diagnóstico , Edema Macular/etiologia , Edema Macular/fisiopatologia , Ranibizumab/administração & dosagem , Receptores de Fatores de Crescimento do Endotélio Vascular/uso terapêutico , Receptores de Fatores de Crescimento do Endotélio Vascular/antagonistas & inibidores , Receptores de Fatores de Crescimento do Endotélio Vascular/administração & dosagem , Oclusão da Veia Retiniana/tratamento farmacológico , Oclusão da Veia Retiniana/diagnóstico , Oclusão da Veia Retiniana/fisiopatologia , Vasos Retinianos/diagnóstico por imagem , Vasos Retinianos/patologia , Estudos Retrospectivos , Tomografia de Coerência Óptica/métodos , Resultado do Tratamento , Fator A de Crescimento do Endotélio Vascular/antagonistas & inibidores , Acuidade VisualRESUMO
Zika virus (ZIKV) infections have been associated with severe clinical outcomes, which may include neurological manifestations, especially in newborns with intrauterine infection. However, licensed vaccines and specific antiviral agents are not yet available. Therefore, a safe and low-cost therapy is required, especially for pregnant women. In this regard, metformin, an FDA-approved drug used to treat gestational diabetes, has previously exhibited an anti-ZIKA effect in vitro in HUVEC cells by activating AMPK. In this study, we evaluated metformin treatment during ZIKV infection in vitro in a JEG3-permissive trophoblast cell line. Our results demonstrate that metformin affects viral replication and protein synthesis and reverses cytoskeletal changes promoted by ZIKV infection. In addition, it reduces lipid droplet formation, which is associated with lipogenic activation of infection. Taken together, our results indicate that metformin has potential as an antiviral agent against ZIKV infection in vitro in trophoblast cells.
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Metformina , Infecção por Zika virus , Zika virus , Recém-Nascido , Gravidez , Feminino , Humanos , Infecção por Zika virus/tratamento farmacológico , Linhagem Celular Tumoral , Trofoblastos , Antivirais/farmacologia , Metformina/farmacologiaRESUMO
BACKGROUND: Alpha-1 antitrypsin deficiency (AATD) is an underrecognized genetic disorder associated mainly with pulmonary emphysema and Chronic Obstructive Pulmonary Disease (COPD). All individuals with COPD regardless of age or ethnicity should be tested for AATD, but in Colombia its prevalence in unknown. MAIN OBJECTIVE: To determine the prevalence of the genetic mutations, present in AATD in adult patients with COPD in Colombia, using a genotyping test on cells from the oral mucosa. METHODS: This was a multicentre, observational, cross-sectional study which included adult patients attending seven COPD care centres in Colombia. Demographic data, medical history, including history of exposure to smoking and biomass smoke, most recent spirometry, pharmacological and non-pharmacological treatment received, serum AAT levels, and mutations detected by the genotyping test were recorded for all the recruited patients. For the comparison of variables between the groups with and without mutation, we used the X2 test for the qualitative variables and the Student's t-test or Mann-Whitney U test according to their distribution. MAIN FINDINGS: We collected a sample of 1,107 patients, the median age was 73.8 years (87.6-79.9). Mutations were documented in 144 patients (13.01%), the majority had the M/S mutation (78.50%), followed by M/Z (9.72%). One patient had a ZZ mutation and two patients had null alleles. In total, 23 patients had mutations associated with serum AAT deficiency (levels below 60 mg/dl). CONCLUSIONS: Genetic mutations were documented in 13.01% of patients with COPD in Colombia and 2.07% were AATD-related, showing that there is a significant number of underdiagnosed patients.
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Doença Pulmonar Obstrutiva Crônica , Deficiência de alfa 1-Antitripsina , Idoso , Humanos , alfa 1-Antitripsina/genética , Deficiência de alfa 1-Antitripsina/complicações , Deficiência de alfa 1-Antitripsina/epidemiologia , Deficiência de alfa 1-Antitripsina/genética , Colômbia/epidemiologia , Estudos Transversais , Mutação , Prevalência , Doença Pulmonar Obstrutiva Crônica/epidemiologia , Doença Pulmonar Obstrutiva Crônica/genética , Doença Pulmonar Obstrutiva Crônica/diagnóstico , Idoso de 80 Anos ou maisRESUMO
BACKGROUND: Pulmonary hypertension (PH) is associated with decreased exercise tolerance in chronic obstructive pulmonary disease (COPD) patients, but in the altitude the response to exercise in those patients is unknown. Our objective was to compare exercise capacity, gas exchange and ventilatory alterations between COPD patients with PH (COPD-PH) and without PH (COPD-nonPH) residents at high altitude (2640 m). METHODS: One hundred thirty-two COPD-nonPH, 82 COPD-PH, and 47 controls were included. Dyspnea by Borg scale, oxygen consumption (VO2), work rate (WR), ventilatory equivalents (VE/VCO2), dead space to tidal volume ratio (VD/VT), alveolar-arterial oxygen tension gradient (AaPO2), and arterial-end-tidal carbon dioxide pressure gradient (Pa-ETCO2) were measurement during a cardiopulmonary exercise test. For comparison of variables between groups, Kruskal-Wallis or one-way ANOVA tests were used, and stepwise regression analysis to test the association between PH and exercise capacity. RESULTS: All COPD patients had a lower exercise capacity and higher PaCO2, A-aPO2 and VD/VT than controls. The VO2 % predicted (61.3 ± 20.6 vs 75.3 ± 17.9; p < 0.001) and WR % predicted (65.3 ± 17.9 vs 75.3 ± 17.9; p < 0.001) were lower in COPD-PH than in COPD-nonPH. At peak exercise, dyspnea was higher in COPD-PH (p = 0.011). During exercise, in COPD-PH, the PaO2 was lower (p < 0.001), and AaPO2 (p < 0.001), Pa-ETCO2 (p = 0.033), VE/VCO2 (p = 0.019), and VD/VT (p = 0.007) were higher than in COPD-nonPH. In the multivariate analysis, PH was significantly associated with lower peak VO2 and WR (p < 0.001). CONCLUSION: In COPD patients residing at high altitude, the presence of PH was an independent factor related to the exercise capacity. Also, in COPD-PH patients there were more dyspnea and alterations in gas exchange during the exercise than in those without PH.
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Hipertensão Pulmonar , Doença Pulmonar Obstrutiva Crônica , Altitude , Dispneia/etiologia , Teste de Esforço , Tolerância ao Exercício/fisiologia , Humanos , Hipertensão Pulmonar/complicações , Doença Pulmonar Obstrutiva Crônica/complicações , Troca Gasosa Pulmonar/fisiologiaRESUMO
Loperamide is a µ-opioid agonist with poor gastrointestinal absorption, mainly because of its modest aqueous solubility and being a P-glycoprotein (Pgp) efflux substrate. Nevertheless, studies associated with therapeutic effects strongly suggest that loperamide holds potential pharmacological advantages over traditional µ-opioid agonists commonly used for analgesia. Thus, in this Communication, we assessed in MDCK-hMDR1 cell lines the effects over loperamide uptake and efflux ratio, when loaded into Eudragit RS (ERS) nanocarriers coated with poloxamer 188 (P188). ERS was chosen for enhancing loperamide aqueous dispersibility and P188 as a potential negative Pgp modulator. In uptake assays, it was observed that Pgp limited the accumulation of loperamide into cells and that preincubation with P188, but not coincubation, led to increasing loperamide uptake at a similar extent of Pgp pharmacological inhibition. On the other hand, the efflux ratio displayed no alterations when Pgp was pharmacologically inhibited, whereas ERS/P188 nanocarriers effectively enhanced loperamide uptake and absorptive transepithelial transport. The latter suggests that loperamide transport across cells is significantly influenced by the presence of the unstirred water layer (UWL), which could hinder the visualization of Pgp-efflux effects during transport assays. Thus, results in this work highlight that formulating loperamide into this nanocarrier enhances its uptake and transport permeability.
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Antidiarreicos/administração & dosagem , Portadores de Fármacos/química , Loperamida/administração & dosagem , Subfamília B de Transportador de Cassetes de Ligação de ATP/genética , Subfamília B de Transportador de Cassetes de Ligação de ATP/metabolismo , Resinas Acrílicas/química , Administração Oral , Animais , Antidiarreicos/farmacocinética , Disponibilidade Biológica , Cães , Humanos , Absorção Intestinal , Mucosa Intestinal/metabolismo , Loperamida/farmacocinética , Células Madin Darby de Rim Canino , Metacrilatos/química , Nanopartículas/química , Permeabilidade , Poloxâmero/química , Proteínas Recombinantes/genética , Proteínas Recombinantes/metabolismo , SolubilidadeRESUMO
The development of vaccines is a crucial response against the COVID-19 pandemic and innovative nanovaccines could increase the potential to address this remarkable challenge. In the present study a B cell epitope (S461-493) from the spike protein of SARS-CoV-2 was selected and its immunogenicity validated in sheep. This synthetic peptide was coupled to gold nanoparticles (AuNP) functionalized with SH-PEG-NH2 via glutaraldehyde-mediated coupling to obtain the AuNP-S461-493 candidate, which showed in s.c.-immunized mice a superior immunogenicity (IgG responses) when compared to soluble S461-493; and led to increased expression of relevant cytokines in splenocyte cultures. Interestingly, the response triggered by AuNP-S461-493 was similar in magnitude to that induced using a conventional strong adjuvant (Freund's adjuvant). This study provides a platform for the development of AuNP-based nanovaccines targeting specific SARS-CoV-2 epitopes.
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Vacinas contra COVID-19 , Epitopos de Linfócito B , Ouro , Imunogenicidade da Vacina , Nanopartículas Metálicas , Peptídeos , Glicoproteína da Espícula de Coronavírus , Animais , Vacinas contra COVID-19/síntese química , Vacinas contra COVID-19/química , Vacinas contra COVID-19/imunologia , Vacinas contra COVID-19/farmacologia , Epitopos de Linfócito B/química , Epitopos de Linfócito B/imunologia , Epitopos de Linfócito B/farmacologia , Ouro/química , Ouro/farmacologia , Células HEK293 , Humanos , Nanopartículas Metálicas/química , Nanopartículas Metálicas/uso terapêutico , Camundongos , Camundongos Endogâmicos BALB C , Peptídeos/síntese química , Peptídeos/química , Peptídeos/imunologia , Peptídeos/farmacologia , Ovinos , Glicoproteína da Espícula de Coronavírus/química , Glicoproteína da Espícula de Coronavírus/imunologia , Glicoproteína da Espícula de Coronavírus/farmacologiaRESUMO
BACKGROUND: Total knee arthroplasty (TKA) is one of the most common procedures in orthopedic surgery and not always matches with patient's expectations of pain relief and function improvement. The aim of this study was to assess risk factors for developing moderate to severe acute postoperative pain (APOP) after TKA using the PAIN OUT questionnaire. METHODS: Prospective, multicentre, international cohort study within the PAIN OUT project. Patients' outcomes were measured with 11-point numerical rating scales (0 = null, 10 = worst possible). Patient and analgesic/anesthetic treatment were assessed. Odds ratio for moderate-severe pain was calculated for each variable and if they were statistically significant in the univariate logistic model, variables were fitted into a multivariate logistic regression model. The effect size was assessed by Cohen's d coefficient. RESULTS: In total, 968 patients were evaluated. The multivariate model identified chronic preoperative pain (P < .001), general anesthesia (P = .020), and receiving chronic opioids before (P = .020) or after the surgery (P < .001) as factors associated with moderate-severe APOP. No protective factors were observed. CONCLUSIONS: Our model identified several risk factors for APOP. From our results, preoperative chronic pain, general anesthesia and the use of opioid analgesics could be predictors for higher APOP. These findings may help establish new strategies for the treatment of pain in TKR. More studies should be carried out to identify acute pain predictors and to develop better strategies of pain management for risk patients.
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Artroplastia do Joelho , Analgésicos Opioides , Estudos de Coortes , Humanos , Dor Pós-Operatória , Estudos Prospectivos , Sistema de Registros , Fatores de RiscoRESUMO
Virus-like particles (VLPs) are protein-based, nanoscale, self-assembling, cage architectures, which have relevant applications in biomedicine. They can be used for the development of vaccines, imaging approaches, drug and gene therapy delivery systems, and in vitro diagnostic methods. Today, three relevant viruses are targeted using VLP-based recombinant vaccines. VLP-based drug delivery, nanoreactors for therapy, and imaging systems are approaches under development with promising outcomes. Several VLP-based vaccines are under clinical evaluation. Herein, an updated view on the VLP-based biomedical applications is provided; advanced methods for the production, functionalization, and drug loading of VLPs are described, and perspectives for the field are identified.
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Tecnologia Biomédica/métodos , Sistemas de Liberação de Medicamentos/métodos , Terapia Genética/métodos , Imagem Molecular/métodos , Vacinas de Partículas Semelhantes a Vírus/genética , DNA Viral/genética , Composição de Medicamentos/métodos , Engenharia Genética , Vetores Genéticos/genética , RNA Viral/genéticaRESUMO
PURPOSE: MDCK cells are commonly used to assess drug permeability, but the existence of various strains merits a comparative functional study. Since metformin absorption is largely mediated by transporters and paracellular diffusion, we used it to functionally compare MDCK-wt and MDCK-II. METHODS: Uptake, bidirectional transport and efflux experiments were performed using different buffers, pH, and a panel of transporter inhibitors. Relative contributions to total transport in both strains were estimated. RESULTS: Metformin uptake into MDCK-wt was linear but saturable in MDCK-II. Uptake into MDCK-wt or -II was promoted at pH 5.4 or 8.4, respectively. Quinidine and cimetidine similarly inhibited uptake in both strains. Lopinavir (PMAT specific) at pH 5.4 or pyrimethamine (MATE specific) at pH 8.4 differentially inhibited MDCK-wt or -II, respectively. Transport at pH 7.4 was absorptive regardless of strains, but secretory (MDCK-II) or absorptive (MDCK-wt) at pH 5.4. Efflux was largely basolateral in both strains. While paracellular permeability was similar between strains, total transport was dominated by transporters in MDCK-II or paracellular diffusion in MDCK-wt. CONCLUSIONS: Metformin transport revealed functional differences between MDCK strains. Apical uptake was governed by MATE in MDCK-II or PMAT in MDCK-wt, such that metformin transport was either secretory or absorptive, respectively.
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Metformina/metabolismo , Animais , Biofilmes , Transporte Biológico/efeitos dos fármacos , Adesão Celular , Células Cultivadas , Cimetidina/metabolismo , Difusão , Cães , Humanos , Concentração de Íons de Hidrogênio , Lopinavir/metabolismo , Células Madin Darby de Rim Canino , Pirimetamina/metabolismo , Quinidina/metabolismoRESUMO
Whereas ornithischian dinosaurs are well known from Jurassic and Cretaceous deposits, deciphering the origin and early evolution of the group remains one of the hardest challenges for palaeontologists. So far, there are no unequivocal records of ornithischians from Triassic beds. Here, we present an alternative evolutionary hypothesis that suggests consideration of traditional 'silesaurids' as a group of low-diversity clades representing a stem group leading to core ornithischians (i.e. unambiguous ornithischians, such as Heterodontosaurus tucki). This is particularly interesting because it fills most of the ghost lineages that emerge from the Triassic. Following the present hypothesis, the lineage that encompasses the Jurassic ornithischians evolved from 'silesaurids' during the Middle to early Late Triassic, while typical 'silesaurids' shared the land ecosystems with their relatives until the Late Triassic, when the group completely vanished. Therefore, Ornithischia changes from an obscure to a well-documented clade in the Triassic and is represented by records from Gondwana and Laurasia. Furthermore, according to the present hypothesis, Ornithischia was the first group of dinosaurs to adopt an omnivorous/herbivorous diet. However, this behaviour was achieved as a secondary step instead of an ancestral condition for ornithischians, as the earliest member of the clade is a faunivorous taxon. This pattern was subsequently followed by sauropodomorph dinosaurs. Indeed, the present scenario favours the independent acquisition of an herbivorous diet for ornithischians and sauropodomorphs during the Triassic, whereas the previous hypotheses suggested the independent acquisition for sauropodomorphs, ornithischians, and 'silesaurids'.
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Dinossauros , Animais , Evolução Biológica , Dieta , Dinossauros/anatomia & histologia , Ecossistema , Fósseis , FilogeniaRESUMO
The main studies on the corrosion of metals induced by microorganisms are directed only to the surface of the metal, without considering the presence of welds between these surfaces. For this reason, we evaluated the difference of microbial community grown in carbon steel coupons, and two different types of welds, E7018 and Tungsten electrodes, exposed under simulated microcosm. After 30 days, they were recovered, the biofilms scraped and the microbial communities analyzed by 16S rRNA gene sequencing. The results showed that there was a differentiated distribution among the three samples collected. Proteobacteria phylum composed most of the species described in all samples. At the class level, Gammaproteobacteria was the most detected, followed by Alphaproteobacteria and Flavobacteriia. The most prevalent order was Alteromonadales, which was present in Weld2, followed by Rhodobacteriales, which was more prevalent in Fe1020 and Weld1. The orders Cytophagales, Sphingomonadales, and Burkholderiales were described in higher number in Fe1020, whereas Oceanospirillales, Thiotrichales, Flavobacteriales, Rhodospirillales, and Kordiimonadales were higher in samples Weld1 and Weld2. The analyses between the three evaluated conditions show the presences of bacterial groups preferred by different types of metal, suggesting that approaches in the control of biocorrosion should take into account the chemical composition of the metal.
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Microbiota/genética , Água do Mar/química , Aço/química , Soldagem , Bactérias/classificação , Bactérias/genética , Bactérias/isolamento & purificação , Bactérias/metabolismo , Biodiversidade , Biofilmes/crescimento & desenvolvimento , Carbono/química , Corrosão , RNA Ribossômico 16S/genética , Tungstênio/químicaRESUMO
PURPOSE: Arterial blood gases (ABG) are influenced by the altitude above sea level, age and sex. Most studies have been conducted at sea level and in small populations ascending to or residents at very high altitudes. Our objective was to evaluate the ventilation and ABG by age and sex in an Andean population resident at high altitude (2640 m). METHODS: Analytical cross-sectional study was done in healthy volunteers. ABG and minute ventilation (VE) were measured. T test and ANOVA for differences by sex and age, and Pearson test for correlations between age, VE and ABG were performed. RESULTS: We included 374 adults, 55% women from 18 to 83 years and hemoglobin of 15.7 ± 1.6 g/dl. There was a significant decrease in PaO2 and SaO2 and an increase in P(A - a)O2 with age (p < 0.001). Unlike men, with age women had a significant increase in PaCO2 and a higher decrease in PaO2. The correlations between age, the decrease in PaO2 and the increase in PaCO2 were greater in women than in men. The VE adjusted to body surface area decreased with age, but this correlation was significantly higher in women. CONCLUSIONS: In this study, with a considerable number of healthy adults living at high altitude (2640 m), we established the physiological impact of altitude, aging and gender in ABG. The PaO2 and PaCO2 were significantly lower and the hemoglobin values slightly higher than described at sea level. In addition to PaO2 decline with age, there was an age-related increase in PaCO2 in women, associated with a greater reduction of VE.
Assuntos
Artérias/metabolismo , Artérias/fisiologia , Oxigênio/sangue , Descanso/fisiologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Altitude , Gasometria/métodos , Estudos Transversais , Feminino , Hemoglobinas/metabolismo , Humanos , Pulmão/metabolismo , Pulmão/fisiologia , Masculino , Pessoa de Meia-Idade , Respiração , Adulto JovemRESUMO
In order to evaluate the corrosive action of microorganisms on 316L metal exposed directly to a marine environment, a system was designed to immerse coupons in seawater. After periods of 30, 60 and 90 days, the coupons were recovered, the corrosion rates evaluated and the biofilm samples on their surface were analyzed by 16S rRNA gene sequencing. The results of the corrosion rate showed an acceleration over the entire experimental period. Alpha diversity measurements showed higher rates after 60 days of the experiment, while abundance measurements showed higher rates after 90 days of exposure to the marine environment. The beta-diversity results showed a clear separation between the three conditions and proximity in the indices between replicates of the same experimental condition. The results of 16S rRNA gene sequencing showed that after 30 days of exposure to seawater, there was massive representativeness of the pioneer bacteria, Gamma and Alphaproteobacteria, with emphasis on the genera Alcanivorax, Oceanospirillum and Shewanella. At the 60-day analysis, the Gammaproteobacteria class remained dominant, followed by Alphaproteobacteria and Flavobacteria, and the main representatives were Flexibacter and Pseudoalteromonas. In the last analysis, after 90 days, a change in the described bacterial community profile was observed. The Gammaproteobacteria class was still the largest in diversity and OTUs. The most predominant genera in number of OTUs were Alteromonas, Bacteriovorax and, Nautella. Our results describe a change in the microbial community over coupons directly exposed to the marine environment, suggesting a redirection to the formation of a mature biofilm. The conditions created by the biofilm structure suggest said condition favor biocorrosion on the analyzed coupons.
Assuntos
Bactérias/genética , Corrosão , Microbiota/genética , Análise de Sequência de DNA/métodos , Aço Inoxidável/análise , Organismos Aquáticos/genética , DNA Bacteriano/análise , DNA Bacteriano/genética , RNA Ribossômico 16S/genética , Água do Mar/microbiologiaRESUMO
Discoveries in Carnian-aged rocks are establishing a rich and diverse dinosaurian fauna at the so-called 'dawn of the age of dinosaurs' in the Late Triassic of Western Gondwana. Accordingly, Brazilian strata from the Candelária Sequence have contributed extensively to this trend. Here, we present a new dinosaurian specimen (CAPPA/UFSM 0200) from this geological unit. The material was collected at a fossiliferous site that had no previous record of dinosaurs. Our specimen comprises a single ilium, which we describe in detail. Its anatomy is consistent with Carnian sauropodomorph dinosaurs, but differs from coeval specimens by several features, although we do not discard the possibility of these features being the result of intraspecific variation. In part of our phylogenetic investigation, CAPPA/UFSM 0200 was recovered within Saturnaliinae, a group comprised of Carnian sauropodomorphs from South America. However, based on examination of better-sampled coeval taxa, a character (a strong rugosity in the ilium) supporting this less inclusive position might be related to intraspecific variation and so, should be carefully considered. This study increases the distribution of dinosaur remains in fossiliferous units from southern Brazil and adds to the discussion regarding intraspecific variation and its implications in the phylogeny of early dinosaurs.