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1.
Sensors (Basel) ; 23(2)2023 Jan 10.
Artigo em Inglês | MEDLINE | ID: mdl-36679572

RESUMO

Actually, the quality of water is one of the most important indicators of the human environmental impact, the control of which is crucial to avoiding irreversible damage in the future. Nowadays, in parallel to the growth of the chemical industry, new chemical compounds have been developed, such as dyes and medicines. The increasing use of these products has led to the appearance of recalcitrant pollutants in industrial wastewater, and even in the drinking water circuit of our populations. The current work presents a photoreactor prototype that allows the performance of experiments for the decomposition of coloured pollutants using photocatalysis at the laboratory scale. The design of this device included the study of the photometric technique for light emission and the development of a software that allows monitoring the dye degradation process. Open-source hardware platforms, such as Arduino, were used for the monitoring system, which have the advantages of being low-cost platforms. A software application that manages the communication of the reactor with the computer and graphically displays the data read by the sensor was also developed. The results obtained demonstrated that this device can accelerate the photodegradation reaction in addition to monitoring the changes throughout the process.


Assuntos
Poluentes Ambientais , Poluentes Químicos da Água , Humanos , Águas Residuárias , Poluentes Químicos da Água/química
2.
Appetite ; 153: 104728, 2020 10 01.
Artigo em Inglês | MEDLINE | ID: mdl-32387198

RESUMO

The perception that food affects our health has increased over the past fifty years in industrialised Western countries. The notion of "healthy food" has become ubiquitous in medical, political, and media discourse as well as in the discourses of the lay population. This study seeks to understand the social representations of "healthy food" of Brazilian, Spanish and French dietitians and young laywomen. A qualitative and comparative methodology based on 131 individual semi-structured interviews was set up. According to the analysis of the discourses, the notion of "healthy food" is ambivalent and polysemic. Scientific-nutritional rationality is not the only way to think about "healthy food". Two main ways of categorising "healthy foods" are observed in the three countries. They are based on eating analysis criteria that referred to diverse value systems and different scientific, symbolic and moral rationalities: on the one hand, a physiological, nutritional and functional conception, and on the other, an "eco-ideological" conception that took into account production, culture and distribution methods. Though dietitians have a greater technical knowledge of nutrients and metabolic processes than laywomen, professionals and young laywomen, mainly within the same nationality, shared similar discourses concerning the notion of "healthy food", revealing patterns that differentiate each nationality. Taking together, the results reveal that although medical-nutritional discourses are disseminated internationally, discourses on "healthy food" are constructed taking into account social, cultural, symbolic and moral dimensions. These discourses are linked to a historical and sociocultural context.


Assuntos
Alimentos Especializados , Nutricionistas , Brasil , Humanos , Princípios Morais , Inquéritos e Questionários
3.
J Biol Chem ; 293(49): 18903-18913, 2018 12 07.
Artigo em Inglês | MEDLINE | ID: mdl-30315107

RESUMO

The dihydroorotase (DHOase) domain of the multifunctional protein carbamoyl-phosphate synthetase 2, aspartate transcarbamoylase, and dihydroorotase (CAD) catalyzes the third step in the de novo biosynthesis of pyrimidine nucleotides in animals. The crystal structure of the DHOase domain of human CAD (huDHOase) revealed that, despite evolutionary divergence, its active site components are highly conserved with those in bacterial DHOases, encoded as monofunctional enzymes. An important element for catalysis, conserved from Escherichia coli to humans, is a flexible loop that closes as a lid over the active site. Here, we combined mutagenic, structural, biochemical, and molecular dynamics analyses to characterize the function of the flexible loop in the activity of CAD's DHOase domain. A huDHOase chimera bearing the E. coli DHOase flexible loop was inactive, suggesting the presence of distinctive elements in the flexible loop of huDHOase that cannot be replaced by the bacterial sequence. We pinpointed Phe-1563, a residue absolutely conserved at the tip of the flexible loop in CAD's DHOase domain, as a critical element for the conformational equilibrium between the two catalytic states of the protein. Substitutions of Phe-1563 with Ala, Leu, or Thr prevented the closure of the flexible loop and inactivated the protein, whereas substitution with Tyr enhanced the interactions of the loop in the closed position and reduced fluctuations and the reaction rate. Our results confirm the importance of the flexible loop in CAD's DHOase domain and explain the key role of Phe-1563 in configuring the active site and in promoting substrate strain and catalysis.


Assuntos
Aspartato Carbamoiltransferase/química , Carbamoil Fosfato Sintase (Glutamina-Hidrolizante)/química , Di-Hidro-Orotase/química , Aspartato Carbamoiltransferase/genética , Carbamoil Fosfato Sintase (Glutamina-Hidrolizante)/genética , Catálise , Domínio Catalítico , Di-Hidro-Orotase/genética , Humanos , Simulação de Dinâmica Molecular , Mutagênese , Mutação , Fenilalanina/química , Conformação Proteica , Domínios Proteicos
4.
Molecules ; 23(9)2018 Sep 06.
Artigo em Inglês | MEDLINE | ID: mdl-30200657

RESUMO

Alkyl esters are high added value products useful in a wide range of industrial sectors. A methodology based on a simple sol-gel approach (biosilicification) is herein proposed to encapsulate enzymes in order to design highly active and stable biocatalysts. Their performance was assessed through the optimization of valeric acid esterification evaluating the effect of different parameters (biocatalyst load, presence of water, reaction temperature and stirring rate) in different alcoholic media, and comparing two different methodologies: conventional heating and microwave irradiation. Ethyl valerate yields were in the 80⁻85% range under optimum conditions (15 min, 12% m/v biocatalyst, molar ratio 1:2 of valeric acid to alcohol). Comparatively, the biocatalysts were slightly deactivated under microwave irradiation due to enzyme denaturalisation. Biocatalyst reuse was attempted to prove that good reusability of these sol-gel immobilised enzymes could be achieved under conventional heating.


Assuntos
Enzimas Imobilizadas/química , Enzimas/química , Lipase/química , Esterificação , Ácidos Pentanoicos/química , Transição de Fase
5.
Beilstein J Org Chem ; 13: 1439-1445, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28781710

RESUMO

Vanillin is one of the most commonly used natural products, which can also be produced from lignin-derived feedstocks. The chemical synthesis of vanillin is well-established in large-scale production from petrochemical-based starting materials. To overcome this problem, lignin-derived monomers (such as eugenol, isoeugenol, ferulic acid etc.) have been effectively used in the past few years. However, selective and efficient production of vanillin from these feedstocks still remains an issue to replace the existing process. In this work, new transition metal-based catalysts were proposed to investigate their efficiency in vanillin production. Reduced graphene oxide supported Fe and Co catalysts showed high conversion of isoeugenol under mild reaction conditions using H2O2 as oxidizing agent. Fe catalysts were more selective as compared to Co catalysts, providing a 63% vanillin selectivity at 61% conversion in 2 h. The mechanochemical process was demonstrated as an effective approach to prepare supported metal catalysts that exhibited high activity for the production of vanillin from isoeugenol.

6.
BMC Plant Biol ; 14: 248, 2014 Sep 17.
Artigo em Inglês | MEDLINE | ID: mdl-25227589

RESUMO

BACKGROUND: The production of antimicrobial peptides is a common defense strategy of living cells against a wide range of pathogens. Plant snakin peptides inhibit bacterial and fungal growth at extremely low concentrations. However, little is known of their molecular and ecological characteristics, including origin, evolutionary equivalence, specific functions and activity against beneficial microbes. The aim of this study was to identify and characterize snakin-1 from alfalfa (MsSN1). RESULTS: Phylogenetic analysis showed complete congruence between snakin-1 and plant trees. The antimicrobial activity of MsSN1 against bacterial and fungal pathogens of alfalfa was demonstrated in vitro and in vivo. Transgenic alfalfa overexpressing MsSN1 showed increased antimicrobial activity against virulent fungal strains. However, MsSN1 did not affect nitrogen-fixing bacterial strains only when these had an alfalfa origin. CONCLUSIONS: The results reported here suggest that snakin peptides have important and ancestral roles in land plant innate immunity. Our data indicate a coevolutionary process, in which alfalfa exerts a selection pressure for resistance to MsSN1 on rhizobial bacteria. The increased antimicrobial activity against virulent fungal strains without altering the nitrogen-fixing symbiosis observed in MsSN1-overexpressing alfalfa transgenic plants opens the way to the production of effective legume transgenic cultivars for biotic stress resistance.


Assuntos
Peptídeos Catiônicos Antimicrobianos/metabolismo , Medicago sativa/imunologia , Rhizobium/fisiologia , Simbiose , Peptídeos Catiônicos Antimicrobianos/genética , Evolução Biológica , Expressão Gênica , Medicago sativa/microbiologia , Medicago sativa/fisiologia , Imunidade Vegetal , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Plantas Geneticamente Modificadas
7.
J Am Acad Dermatol ; 71(3): 507-15, 2014 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-24894454

RESUMO

BACKGROUND: The prognostic benefit of health care service provision and delivery policies for patients with malignant melanoma (MM) is not yet clear. OBJECTIVE: To analyze the role of health care provision determinants in the initial prognosis of MM. METHODS: A multicenter cross-sectional study was conducted at 14 public hospitals and recruited 3550 patients with MM between 2000 and 2009. The study variables were analyzed using univariate and multivariate models to identify their role in the variations observed. RESULTS: In a 10-year period, the number of patients with MM increased by 78.54%, with primary in situ MM (Tis) or MMs with a Breslow thickness <1 mm (T1) representing 51.72% of the total number of MMs in 2000, increasing to 62.23% by the end of the study period (P = .005). Among the variables that explained the variation in MM frequency the year of diagnosis after 2004 (univariate odds ratio [OR], 1.43 [P < .001]; multivariate OR, 1.36 [P = .005]) and diagnosis in centers with specific fast-track referral systems (univariate OR, 1.24 [P = .01]; multivariate OR, 1.59 [P = .025]) were shown to explain the increasing frequency of Tis-T1 MM. LIMITATIONS: The primary potential limitation of this study is its retrospective nature. CONCLUSION: Health care provision policies and interventions aimed at improving accessibility to specialized care appear to explain the increasing frequency of Tis-T1 MM.


Assuntos
Acessibilidade aos Serviços de Saúde , Melanoma/epidemiologia , Neoplasias Cutâneas/epidemiologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Carcinoma in Situ/epidemiologia , Carcinoma in Situ/patologia , Criança , Pré-Escolar , Estudos Transversais , Feminino , Humanos , Lactente , Masculino , Melanoma/patologia , Pessoa de Meia-Idade , Prevenção Primária , Prognóstico , Estudos Retrospectivos , Neoplasias Cutâneas/patologia , Espanha/epidemiologia , Adulto Jovem
8.
Theriogenology ; 225: 98-106, 2024 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-38801791

RESUMO

Goat bucks are seasonal breeders that show variation in sperm quality, endogenous melatonin (MLT), and presumably in the expression of MLT receptors on the sperm throughout the year, which may modify sperm freezability. The aim of this study was to determine whether sperm freezability is associated with (i) endogenous melatonin levels in seminal plasma and (ii) the expression of sperm plasma membrane melatonin receptors (MT1, MT2). To evaluate this, spermatozoa from seven Saanen goat bucks were cryopreserved throughout the year in Mexico using a standard freezing protocol. Seminal plasma MLT concentrations were determined by ELISA and the expression and localization of MT1 and MT2 were detected by immunocytochemistry and confirmed by western blotting. The recovery rate of progressive motility after thawing was higher in spring than autumn and winter; in contrast, the F pattern (CTC assay) was higher in winter than in the other seasons. A proportional increase in the AR pattern (CTC assay) was smaller in winter than in the other seasons and the proportion of sperm showing high plasma membrane fluidity was higher in spring than in summer and autumn. The seminal plasma MLT concentrations showed no significant interseasonal differences. The MT1 receptor was immunolocalised at the apical region of the sperm head, while MT2 was mainly localised in the neck. The relative expression of MLT receptors showed significant differences between summer and winter for all bands, except at 75 kDa of MT2. In conclusion, there was an association between the relative expression of MT1 and MT2 receptors throughout the year and sperm freezability in goat bucks in México. Post-thaw sperm quality is enhanced in semen samples collected during breeding season.


Assuntos
Criopreservação , Cabras , Melatonina , Estações do Ano , Preservação do Sêmen , Sêmen , Espermatozoides , Animais , Masculino , Melatonina/metabolismo , Melatonina/sangue , Cabras/fisiologia , Cabras/metabolismo , Sêmen/química , Sêmen/metabolismo , Espermatozoides/metabolismo , Espermatozoides/fisiologia , Preservação do Sêmen/veterinária , Criopreservação/veterinária , Receptor MT1 de Melatonina/metabolismo , Receptor MT1 de Melatonina/genética , Receptor MT2 de Melatonina/metabolismo , Receptor MT2 de Melatonina/genética , Análise do Sêmen/veterinária , Receptores de Melatonina/metabolismo
9.
Artigo em Inglês | MEDLINE | ID: mdl-24316846

RESUMO

Aspartate transcarbamoylase (ATCase) catalyzes the synthesis of N-carbamoyl-L-aspartate from carbamoyl phosphate and aspartate in the second step of the de novo biosynthesis of pyrimidines. In prokaryotes, the first three activities of the pathway, namely carbamoyl phosphate synthetase (CPSase), ATCase and dihydroorotase (DHOase), are encoded as distinct proteins that function independently or in noncovalent association. In animals, CPSase, ATCase and DHOase are part of a 243 kDa multifunctional polypeptide named CAD. Up-regulation of CAD is essential for normal and tumour cell proliferation. Although the structures of numerous prokaryotic ATCases have been determined, there is no structural information about any eukaryotic ATCase. In fact, the only detailed structural information about CAD is that it self-assembles into hexamers and trimers through interactions of the ATCase domains. Here, the expression, purification and crystallization of the ATCase domain of human CAD is reported. The recombinant protein, which was expressed in bacteria and purified with good yield, formed homotrimers in solution. Crystallization experiments both in the absence and in the presence of the inhibitor PALA yielded small crystals that diffracted X-rays to 2.1 Å resolution using synchrotron radiation. The crystals appeared to belong to the hexagonal space group P6(3)22, and Matthews coefficient calculation indicated the presence of one ATCase subunit per asymmetric unit, with a solvent content of 48%. However, analysis of the intensity statistics suggests a special case of the P21 lattice with pseudo-symmetry and possibly twinning.


Assuntos
Aspartato Carbamoiltransferase/química , Ácido Aspártico/análogos & derivados , Carbamoil Fosfato Sintase (Glutamina-Hidrolizante)/química , Di-Hidro-Orotase/química , Inibidores Enzimáticos/química , Ácido Fosfonoacéticos/análogos & derivados , Aspartato Carbamoiltransferase/genética , Aspartato Carbamoiltransferase/metabolismo , Ácido Aspártico/química , Ácido Aspártico/metabolismo , Carbamoil Fosfato Sintase (Glutamina-Hidrolizante)/genética , Carbamoil Fosfato Sintase (Glutamina-Hidrolizante)/metabolismo , Cristalização , Cristalografia por Raios X , Di-Hidro-Orotase/genética , Di-Hidro-Orotase/metabolismo , Inibidores Enzimáticos/metabolismo , Escherichia coli/genética , Escherichia coli/metabolismo , Expressão Gênica , Modelos Moleculares , Ácido Fosfonoacéticos/química , Ácido Fosfonoacéticos/metabolismo , Multimerização Proteica , Estrutura Terciária de Proteína , Proteínas Recombinantes/química , Proteínas Recombinantes/genética , Proteínas Recombinantes/metabolismo , Síncrotrons
10.
Front Public Health ; 11: 1243539, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37829098

RESUMO

The Human Papillomavirus (HPV) is the most common sexually transmitted infection and nearly every person who is sexually active will get HPV at some point in their lifetime without having the HPV vaccine. Healthcare Providers (HCPs) and Community Health Workers (CHWs) play an essential role in promoting the HPV vaccine and providing education about HPV in communities. Three focus groups with CHWs (n = 17) and HCPs (n = 7) were conducted and led by trained facilitators. In addition to participating in the focus group, CHWs and HCPs completed a brief questionnaire. Focus groups were voice recorded and transcribed for qualitative analysis. Independent coders conducted content analysis to identify the salient themes of the focus groups. Several important findings emerged from this study highlighting the barriers to HPV knowledge, gaps in the self-perceived role of HPV cancer prevention, and opportunities to action. Financial, knowledge, patriarchy, behaviors, attitudes, and fears were identified as the perceived patient-related barriers to promoting HPV cancer prevention. Both CHWs and HCPs explained that their female patients are often discouraged by their husbands from seeking out sexual health-related healthcare. Finding suggest the need for community tailored education on HPV and "best practice" trainings for HPV prevention that is applicable to both CHWs and HCPs.


Assuntos
Neoplasias , Infecções por Papillomavirus , Vacinas contra Papillomavirus , Humanos , Feminino , Papillomavirus Humano , Infecções por Papillomavirus/prevenção & controle , Agentes Comunitários de Saúde , Conhecimentos, Atitudes e Prática em Saúde
11.
Foods ; 12(20)2023 Oct 11.
Artigo em Inglês | MEDLINE | ID: mdl-37893634

RESUMO

Ethanolic extracts of bay leaves were obtained using the Soxhlet method (extraction yield of 22.3 ± 1.2%) and further analyzed through different methods, thus determining the chemical composition with gas chromatography, phenolic content with the Folin-Ciocalteu technique (11.8 ± 0.4% wt.) and antioxidant power with the radical 2,2'-Azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) method (75.06%). Furthermore, its effect on the growth of two bacteria, Escherichia coli and Bacillus cereus, and on two yeasts, Candida glabrata and Saccharomyces cerevisiae, was determined, showing a minimum inhibitory concentration of 0.65 mg/mL on the growth of B. cereus. Finally, edible films were prepared using different polymers (carboxymethyl cellulose, gum Arabic, polyvinyl pyrrolidone, and polyvinyl alcohol) containing 0, 5, 10, or 15% wt. of bay leaf extract as troubleshooting for perishable fruits, specifically for cultivated strawberry. The prepared composites presented reduced water vapor permeabilities (up to 4.3 × 10-7 g·Pa-1·m-1·h-1), high specific transparencies (≈30%/mm), as well as the effective blocking of ultraviolet radiation (>99.9%). In vivo tests showed that the most suitable treatment for strawberry protection was the impregnation with a composite comprising polyvinyl alcohol and a 15% wt. bay leaf extract, resulting in a noteworthy reduction in mass loss (22% after 6 days). It can be asserted that food packaging with the designed composites would be an effective alternative for the reduction in postharvest losses.

12.
Zoonoses Public Health ; 70(8): 674-683, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-37747079

RESUMO

In late October 2021, one of the veterinarians and the occupational physician of a bovine and swine abattoir from Entre Ríos Province, Argentina were alerted about workers with atypical pneumonia symptoms, raising suspicious of a possible Q fever outbreak. An outbreak epidemiological investigation was carried out. Analysis was based on the description of the study population, according to gender, age, symptoms, and position within the abattoir, as well as on outbreak epidemic curve and its probable origin. Cases of Q fever in the workers were confirmed by serology. Measurements of the association between the evaluated variables and the risk of exposure were investigated and calculated as attack rates. The outbreak occurred between October and November 2021, symptomatically affecting 11 workers, out of a total exposed population of 49 individuals. The index case was a 33-year-old male who started with symptoms on 27 October 2021, and the outbreak extended for at least 17 days. Workers in the clean zone of the slaughter floor had a 4.68 times higher risk of contracting Q fever than people located in other areas. Importantly, two pregnant cows were slaughtered a few days before the outbreak began, which could have been the origin of the outbreak. The present study demonstrates the urgent need to consider Q fever when diagnosing abortive diseases of ruminants in Argentina, as well as in zoonotic disease epidemiological surveillance to inform all actors of the health system.


Assuntos
Doenças dos Bovinos , Doenças Profissionais , Febre Q , Doenças dos Suínos , Masculino , Feminino , Animais , Bovinos , Suínos , Febre Q/epidemiologia , Febre Q/veterinária , Matadouros , Argentina/epidemiologia , Doenças Profissionais/epidemiologia , Doenças Profissionais/veterinária , Surtos de Doenças/veterinária , Doenças dos Bovinos/epidemiologia , Doenças dos Suínos/epidemiologia
13.
Sci Rep ; 13(1): 16443, 2023 09 30.
Artigo em Inglês | MEDLINE | ID: mdl-37777587

RESUMO

Neuroblastoma, the most common type of pediatric extracranial solid tumor, causes 10% of childhood cancer deaths. Despite intensive multimodal treatment, the outcomes of high-risk neuroblastoma remain poor. We urgently need to develop new therapies with safe long-term toxicity profiles for rapid testing in clinical trials. Drug repurposing is a promising approach to meet these needs. Here, we investigated disulfiram, a safe and successful chronic alcoholism treatment with known anticancer and epigenetic effects. Disulfiram efficiently induced cell cycle arrest and decreased the viability of six human neuroblastoma cell lines at half-maximal inhibitory concentrations up to 20 times lower than its peak clinical plasma level in patients treated for chronic alcoholism. Disulfiram shifted neuroblastoma transcriptome, decreasing MYCN levels and activating neuronal differentiation. Consistently, disulfiram significantly reduced the protein level of lysine acetyltransferase 2A (KAT2A), drastically reducing acetylation of its target residues on histone H3. To investigate disulfiram's anticancer effects in an in vivo model of high-risk neuroblastoma, we developed a disulfiram-loaded emulsion to deliver the highly liposoluble drug. Treatment with the emulsion significantly delayed neuroblastoma progression in mice. These results identify KAT2A as a novel target of disulfiram, which directly impacts neuroblastoma epigenetics and is a promising candidate for repurposing to treat pediatric neuroblastoma.


Assuntos
Dissulfiram , Neuroblastoma , Animais , Criança , Humanos , Camundongos , Dissuasores de Álcool/farmacologia , Dissuasores de Álcool/uso terapêutico , Linhagem Celular Tumoral , Dissulfiram/farmacologia , Dissulfiram/uso terapêutico , Regulação para Baixo , Reposicionamento de Medicamentos , Emulsões/uso terapêutico , Histona Acetiltransferases/efeitos dos fármacos , Neuroblastoma/tratamento farmacológico , Neuroblastoma/genética
14.
Sci Rep ; 13(1): 9064, 2023 06 04.
Artigo em Inglês | MEDLINE | ID: mdl-37271755

RESUMO

Prognostic scales may help to optimize the use of hospital resources, which may be of prime interest in the context of a fast spreading pandemics. Nonetheless, such tools are underdeveloped in the context of COVID-19. In the present article we asked whether accurate prognostic scales could be developed to optimize the use of hospital resources. We retrospectively studied 467 files of hospitalized patients after COVID-19. The odds ratios for 16 different biomarkers were calculated, those that were significantly associated were screened by a Pearson's correlation, and such index was used to establish the mathematical function for each marker. The scales to predict the need for hospitalization, intensive-care requirement and mortality had enhanced sensitivities (0.91 CI 0.87-0.94; 0.96 CI 0.94-0.98; 0.96 CI 0.94-0.98; all with p < 0.0001) and specificities (0.74 CI 0.62-0.83; 0.92 CI 0.87-0.96 and 0.91 CI 0.86-0.94; all with p < 0.0001). Interestingly, when a different population was assayed, these parameters did not change considerably. These results show a novel approach to establish the mathematical function of a marker in the development of highly sensitive prognostic tools, which in this case, may aid in the optimization of hospital resources. An online version of the three algorithms can be found at: http://benepachuca.no-ip.org/covid/index.php.


Assuntos
COVID-19 , Humanos , COVID-19/diagnóstico , SARS-CoV-2 , Estudos Retrospectivos , Unidades de Terapia Intensiva , Hospitalização , Cuidados Críticos , Biomarcadores , Probabilidade
15.
Nat Cell Biol ; 7(9): 901-8, 2005 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-16113676

RESUMO

Growth of normal cells is anchorage dependent because signalling through multiple pathways including Erk, phosphatidylinositol-3-OH kinase (PI(3)K) and Rac requires integrin-mediated cell adhesion. Components of these pathways localize to low-density, cholesterol-rich domains in the plasma membrane named 'lipid rafts' or 'cholesterol-enriched membrane microdomains' (CEMM). We previously reported that integrin-mediated adhesion regulates CEMM transport such that cell detachment from the extracellular matrix triggers CEMM internalization and clearance from the plasma membrane. We now report that this internalization is mediated by dynamin-2 and caveolin-1. Internalization requires phosphorylation of caveolin-1 on Tyr 14. A shift in localization of phospho-caveolin-1 from focal adhesions to caveolae induces CEMM internalization upon cell detachment, which mediates inhibition of Erk, PI(3)K and Rac. These data define a novel molecular mechanism for growth and tumour suppression by caveolin-1.


Assuntos
Caveolinas/metabolismo , Endocitose/fisiologia , Integrinas/metabolismo , Microdomínios da Membrana/metabolismo , Animais , Cavéolas/metabolismo , Caveolina 1 , Adesão Celular/fisiologia , Proliferação de Células , Dinamina II/metabolismo , Matriz Extracelular/metabolismo , MAP Quinases Reguladas por Sinal Extracelular/metabolismo , Adesões Focais/metabolismo , Microdomínios da Membrana/ultraestrutura , Camundongos , Camundongos Knockout , Microscopia Eletrônica de Transmissão , Células NIH 3T3 , Invasividade Neoplásica/fisiopatologia , Neoplasias/metabolismo , Fosfatidilinositol 3-Quinases/metabolismo , Fosforilação , Proteínas rac de Ligação ao GTP/metabolismo
16.
J Cell Biol ; 177(4): 683-94, 2007 May 21.
Artigo em Inglês | MEDLINE | ID: mdl-17517963

RESUMO

Development, angiogenesis, wound healing, and metastasis all involve the movement of cells in response to changes in the extracellular environment. To determine whether caveolin-1 plays a role in cell migration, we have used fibroblasts from knockout mice. Caveolin-1-deficient cells lose normal cell polarity, exhibit impaired wound healing, and have decreased Rho and increased Rac and Cdc42 GTPase activities. Directional persistency of migration is lost, and the cells show an impaired response to external directional stimuli. Both Src inactivation and p190RhoGAP knockdown restore the wild-type phenotype to caveolin-1-deficient cells, suggesting that caveolin-1 stimulates normal Rho GTP loading through inactivation of the Src-p190RhoGAP pathway. These findings highlight the importance of caveolin-1 in the establishment of cell polarity during directional migration through coordination of the signaling of Src kinase and Rho GTPases.


Assuntos
Caveolina 1/fisiologia , Movimento Celular/fisiologia , Polaridade Celular/fisiologia , Proteínas rho de Ligação ao GTP/fisiologia , Quinases da Família src/fisiologia , Animais , Caveolina 1/deficiência , Caveolina 1/genética , Linhagem Celular , Células Cultivadas , Fibroblastos/citologia , Fibroblastos/enzimologia , Fibroblastos/fisiologia , Humanos , Camundongos , Camundongos Knockout , Células NIH 3T3 , Transdução de Sinais/fisiologia
17.
Acta Crystallogr Sect F Struct Biol Cryst Commun ; 68(Pt 11): 1341-5, 2012 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-23143245

RESUMO

CAD is a 243 kDa eukaryotic multifunctional polypeptide that catalyzes the first three reactions of de novo pyrimidine biosynthesis: glutamine-dependent carbamyl phosphate synthetase, aspartate transcarbamylase and dihydroorotase (DHO). In prokaryotes, these activities are associated with monofunctional proteins, for which crystal structures are available. However, there is no detailed structural information on the full-length CAD protein or any of its functional domains apart from that it associates to form a homohexamer of ∼1.5 MDa. Here, the expression, purification and crystallization of the DHO domain of human CAD are reported. The DHO domain forms homodimers in solution. Crystallization experiments yielded small crystals that were suitable for X-ray diffraction studies. A diffraction data set was collected to 1.75 Šresolution using synchrotron radiation at the SLS, Villigen, Switzerland. The crystals belonged to the orthorhombic space group C222(1), with unit-cell parameters a=82.1, b=159.3, c=61.5 Å. The Matthews coefficient calculation suggested the presence of one protein molecule per asymmetric unit, with a solvent content of 48%.


Assuntos
Aspartato Carbamoiltransferase/química , Carbamoil Fosfato Sintase (Glutamina-Hidrolizante)/química , Di-Hidro-Orotase/química , Aspartato Carbamoiltransferase/biossíntese , Aspartato Carbamoiltransferase/isolamento & purificação , Carbamoil Fosfato Sintase (Glutamina-Hidrolizante)/biossíntese , Carbamoil Fosfato Sintase (Glutamina-Hidrolizante)/isolamento & purificação , Domínio Catalítico , Cromatografia de Afinidade , Cromatografia em Gel , Cristalização , Cristalografia por Raios X , Di-Hidro-Orotase/biossíntese , Di-Hidro-Orotase/isolamento & purificação , Escherichia coli , Humanos , Luz , Estrutura Quaternária de Proteína , Espalhamento de Radiação
18.
BMC Public Health ; 12: 209, 2012 Mar 19.
Artigo em Inglês | MEDLINE | ID: mdl-22429693

RESUMO

BACKGROUND: The promotion of health and the interventions in community health continue to be one of the pending subjects of our health system. The most prevalent health problems (cardiovascular diseases, cancer, diabetes...) are for the most part related to life habits. We propose a holistic and integral approach as the best option for tackling behavior and its determinants. The research team has elaborated the necessary educational material to realize group teaching, which we call "Health Workshops". The goal of the present study is to evaluate the effectiveness of these Health Workshops in the following terms: Health Related Quality of Life (HRQOL), incorporate and maintain a balanced diet, do physical activity regularly, maintain risk factors such as tension, weight, cholesterol within normal limits and diminish cardiovascular risk. METHODS/DESIGN: Controlled and random clinical testing, comparing a group of persons who have participated in the Health Workshops with a control group of similar characteristics who have not participated in the Health Workshops.Field of study: the research is being done in Health Centers of the city of Barcelona, Spain. POPULATION STUDIED: The group is composed of 108 persons that are actually doing the Health Workshops, and 108 that are not and form the control group. They are assigned at random to one group or the other. DATA ANALYSIS: With Student's t-distribution test to compare the differences between numerical variables or their non parametric equivalent if the variable does not comply with the criteria of normality. (Kolmogorov-Smirnof test). Chi-square test to compare the differences between categorical variables and the Logistic Regression Model to analyze different meaningful variables by dichotomous analysis related to the intervention. DISCUSSION: The Health Workshop proposed in the present study constitutes an innovative approach in health promotion, placing the emphasis on the person's self responsibility for his/her own health.The rhythm of a weekly session during 8 weeks with recommended activities to put into practice, as well as the support of the group is an opportunity to incorporate healthy habits and make a commitment to self-care. The sheets handed out are a Health Manual that can always be consulted after the workshop ends. TRIAL REGISTRATION: Clinical Trials.gov Identifier: NCT01440738.


Assuntos
Dieta/normas , Processos Grupais , Conhecimentos, Atitudes e Prática em Saúde , Promoção da Saúde , Educação de Pacientes como Assunto/normas , Qualidade de Vida , Autocuidado/psicologia , Adolescente , Adulto , Idoso , Algoritmos , Pressão Sanguínea , Peso Corporal , Protocolos Clínicos , Dieta/economia , Feminino , Saúde Holística , Humanos , Masculino , Pessoa de Meia-Idade , Equipe de Assistência ao Paciente , Educação de Pacientes como Assunto/métodos , Avaliação de Programas e Projetos de Saúde , Psicometria , Controle de Qualidade , Fatores de Risco , Inquéritos e Questionários
19.
Inquiry ; 59: 469580221098754, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35502985

RESUMO

The Youth and Young Adults Cancer Knowledge Attitudes and Practices (C-KAP) exploratory study in 2 rural underserved areas in a border community. C-KAP is an interdisciplinary research pilot project led by university scholars in psychology and social work in partnership with community partners. The exploratory cross-sectional mix-method study recruited 141 (n=141) youth and young adults (ages 18-39). This study was informed on empirical research and a bilingual online questionnaire was field-tested, and data was collected via QuestionPro Software. Quantitative analysis was conducted using SPSS version 27. Descriptive statistics and frequency analysis were used for demographics and basic statistics. Chi square tests and Fisher's exact tests between variables were ran to find statistically significant associations. For the qualitative data, independent coders conducted recurrent content analysis to identify themes. Salient themes include knowledge about cancer types; access to health care; prevention; and the perceived impact of COVID-19 pandemic. Findings highlight a lack of knowledge and orientation on cancer in youth and young adults suggesting the need for community tailored education and screening interventions. Other findings reflect gender differences in knowledge and practices, which indicates that a gender-specific lens is needed when delivering education.


Assuntos
COVID-19 , Neoplasias , Adolescente , Adulto , Estudos Transversais , Conhecimentos, Atitudes e Prática em Saúde , Humanos , Pandemias , Projetos Piloto , População Rural , Inquéritos e Questionários , Texas , Adulto Jovem
20.
Eur J Pediatr Surg ; 32(6): 504-511, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-35073590

RESUMO

INTRODUCTION: To investigate the current experience of the ARM-Net Consortium in the management of epididymo-orchitis (EO) in patients with anorectal malformations (ARMs), and to identify specific risk factors and the need for urological care involvement. MATERIALS AND METHODS: We retrospectively collected data of EO in patients with ARM between 2015 and 2019. Data on urological aspects, ARM type, surgical approach, associated anomalies, diagnosis, and treatment of EO were collected and analyzed. RESULTS: Twenty-nine patients were reported by 12 centers. Twenty-six patients with EO (90%) had ARM with a rectourinary fistula. Median age at first EO was 2 years (range: 15 days-27 years). Twenty patients (69%) experienced multiple EO, and 60% of recurrences were ipsilateral. Associated urological anomalies included vesicoureteral reflux (48%), urethral anomalies (41%), neurogenic bladder (41%), and ectopic vas (10%). A positive urine culture during EO was present in 69%. EO was treated with antibiotics (90%), limiting surgical exploration to 14%. Prevention of recurrences included surgery (bulking agents 15%, vasectomy 15%, and orchiectomy 5%) and antibiotic prophylaxis (20%). CONCLUSION: Urologists may encounter patients with EO in ARM patients, frequently with positive urine culture. An appropriate urologic work-up for most ARM patients is necessary to identify and treat underlying risk factors. A practical scheme for the work-up is suggested for a close collaboration between pediatric surgeons and urologists.


Assuntos
Malformações Anorretais , Epididimite , Orquite , Criança , Masculino , Humanos , Recém-Nascido , Orquite/complicações , Orquite/diagnóstico , Malformações Anorretais/complicações , Malformações Anorretais/cirurgia , Estudos Retrospectivos , Epididimite/complicações , Epididimite/diagnóstico , Recidiva
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