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1.
Int J Behav Nutr Phys Act ; 20(1): 122, 2023 10 10.
Artigo em Inglês | MEDLINE | ID: mdl-37817251

RESUMO

BACKGROUND: The Nutri-Score is a candidate for the harmonized mandatory front-of-pack nutrition label enabling consumers in the European Union to make healthier food choices. Nutri-Score classifies foods (including beverages) from A (high nutritional quality) to E (low nutritional quality) based on the foods' qualifying and disqualifying components. We aimed to evaluate the updated Nutri-Score for foods (2022) and beverages (2023) in a Norwegian setting by exploring its ability to discriminate the nutritional quality of foods within categories. Additionally, we assessed Nutri-Scores' ability to classify foods in accordance with the Norwegian food-based dietary guidelines (FBDGs). METHODS: The updated Nutri-Score was calculated for 1,782 foods in a Norwegian food database. The discriminatory ability of the updated Nutri-Score was considered by exploring the distribution of Nutri-Score within categories of foods using boxplots and frequency tables, and by examining which qualifying and disqualifying components that contributed most to the Nutri-Score class. Accordance with the Norwegian FBDGs was assessed by exploring Nutri-Score for foods specifically mentioned in the guidelines. RESULTS: Overall, the updated Nutri-Score seemed to discriminate the nutritional quality of foods within categories, in a Norwegian setting. The foods' content of salt and the beverages' content of sugar were components contributing the most to Nutri-Scores' discriminatory ability. Furthermore, in most cases the updated Nutri-Score classified foods in accordance with the Norwegian FBDGs. However, there were minor inconsistencies in how Nutri-Score classified certain foods, such as the inabilities to discriminate between full-fat and low-fat/leaner cheeses, cremes and processed meats (sausages), and between whole grain and refined pasta/rice. CONCLUSIONS: We observed an overall acceptable discriminatory performance of the updated Nutri-Score in a Norwegian setting and in most cases the updated Nutri-Score classified foods in accordance with the Norwegian FBDGs. However, minor inconsistencies were observed. Together with the FBDGs, the updated Nutri-Score could be a useful tool in guiding consumers towards healthier food choices in Norway, but consumer evaluations are warranted to fully assess the performance of the updated Nutri-Score in a Norwegian context.


Assuntos
Rotulagem de Alimentos , Preferências Alimentares , Valor Nutritivo , Humanos , Comportamento do Consumidor , Noruega
2.
Naturwissenschaften ; 108(5): 43, 2021 Sep 07.
Artigo em Inglês | MEDLINE | ID: mdl-34491425

RESUMO

Diminishing prospects for environmental preservation under climate change are intensifying efforts to boost capture, storage and sequestration (long-term burial) of carbon. However, as Earth's biological carbon sinks also shrink, remediation has become a key part of the narrative for terrestrial ecosystems. In contrast, blue carbon on polar continental shelves have stronger pathways to sequestration and have increased with climate-forced marine ice losses-becoming the largest known natural negative feedback on climate change. Here we explore the size and complex dynamics of blue carbon gains with spatiotemporal changes in sea ice (60-100 MtCyear-1), ice shelves (4-40 MtCyear-1 = giant iceberg generation) and glacier retreat (< 1 MtCyear-1). Estimates suggest that, amongst these, reduced duration of seasonal sea ice is most important. Decreasing sea ice extent drives longer (not necessarily larger biomass) smaller cell-sized phytoplankton blooms, increasing growth of many primary consumers and benthic carbon storage-where sequestration chances are maximal. However, sea ice losses also create positive feedbacks in shallow waters through increased iceberg movement and scouring of benthos. Unlike loss of sea ice, which enhances existing sinks, ice shelf losses generate brand new carbon sinks both where giant icebergs were, and in their wake. These also generate small positive feedbacks from scouring, minimised by repeat scouring at biodiversity hotspots. Blue carbon change from glacier retreat has been least well quantified, and although emerging fjords are small areas, they have high storage-sequestration conversion efficiencies, whilst blue carbon in polar waters faces many diverse and complex stressors. The identity of these are known (e.g. fishing, warming, ocean acidification, non-indigenous species and plastic pollution) but not their magnitude of impact. In order to mediate multiple stressors, research should focus on wider verification of blue carbon gains, projecting future change, and the broader environmental and economic benefits to safeguard blue carbon ecosystems through law.


Assuntos
Mudança Climática , Camada de Gelo , Regiões Antárticas , Carbono , Ecossistema , Retroalimentação , Concentração de Íons de Hidrogênio , Água do Mar
4.
S Afr J Surg ; 61(1): 27-29, 2023 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-37052285

RESUMO

SUMMARY: Lip reconstruction following excision of cutaneous malignancy should be carefully planned to avoid discarding useful tissue. In this report, we describe two cases in which the usually discarded Burrow's triangles of the cheek advancement flap are used to reconstruct adjacent anatomical structures, thus improving the functional and aesthetic outcome of the reconstruction.


Assuntos
Lábio , Procedimentos de Cirurgia Plástica , Neoplasias Cutâneas , Humanos , Estética , Lábio/cirurgia , Neoplasias Cutâneas/cirurgia , Retalhos Cirúrgicos
5.
Fam Pract ; 29(5): 503-10, 2012 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-22234552

RESUMO

OBJECTIVE: Denmark has a health care system with free and equal access to care irrespective of age and socio-economic status (SES). We conducted a cross-sectional study to investigate a possible association between SES and blood pressure (BP) control of hypertensive patients treated in general practice. METHODS: We enrolled 184 general practices and 5260 hypertensive patients. The general practitioners reported information about BP and diagnosis of diabetes. Information about education, income, antihypertensive drug treatment and other co-morbidity was retrieved from relevant registers from Statistics Denmark. The outcome measure was BP control defined as BP <140/90 mmHg in general and <130/80 mmHg in diabetics. RESULTS: Patients <65 years and with an educational level of 10-12 years had increased odds ratio (OR) of BP control compared to patients with an educational level <10 years. Patients ≥65 years had increased OR of BP control if they were married/cohabiting as compared to being single, whereas education and income had no impact in this age group. Diabetics had significantly reduced odds of BP control irrespective of age, educational or income level. CONCLUSIONS: Despite equal access to care for all patients, SES had significant impact on BP control in this survey. Diabetes and cardiovascular disease also had a substantial influence irrespective of age, educational and income level.


Assuntos
Acessibilidade aos Serviços de Saúde , Hipertensão/tratamento farmacológico , Classe Social , Fatores Etários , Idoso , Estudos Transversais , Dinamarca , Angiopatias Diabéticas/tratamento farmacológico , Escolaridade , Feminino , Medicina Geral , Humanos , Masculino , Pessoa de Meia-Idade , Avaliação de Resultados em Cuidados de Saúde , Sistema de Registros
6.
Fam Pract ; 28(6): 599-607, 2011 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-21596691

RESUMO

BACKGROUND: Most hypertensive patients are managed in primary care in Denmark, but previous studies have shown that only 21-43% of hypertensive patients achieve optimal blood pressure (BP) control. Antihypertensive drug treatment, risk factors and cardiovascular disease (CVD) are some of the important factors to consider when optimizing the individual treatment strategy in hypertensive patients. OBJECTIVE: To examine treatment of BP according to Danish guidelines (BP < 140/90 mmHg generally and <130/80 mmHg for diabetics) in a population from general practice in relation to risk factors, CVD and diagnosis of diabetes. METHODS: A cross-sectional study comprising 184 practices and 5413 hypertensive patients was carried out in Denmark. The general practitioners filled in information on each patient's risk factors, CVD and antihypertensive drug treatment. Patients filled in a questionnaire on risk factors. The outcome measures were optimal BP control according to Danish guidelines and antihypertensive drug treatment. RESULTS: Mean patient age was 65.9 years [95% confidence interval (CI): 65.6-66.1]. Optimal BP control was achieved in 29.1% (95% CI: 27.9-30.3) of the study population. Among 842 diabetics with or without CVD, optimal BP control was achieved in 10.9% (95% CI: 8.8-10.3), while 38.7% (35.5-41.9) of patients with CVD achieved optimal BP control. The majority of all patients were treated with 1 (32.5%, 95% CI: 32.5 (31.3-33.8)) or two antihypertensive drugs (39.0%, 95% CI: 38.2-40.8). In hypertensive diabetics, 17.7% were not treated with an angiotensin-converting enzyme inhibitor or angiotensin-receptor blocker. CONCLUSION: In general practice, the proportion of hypertensive patients achieving optimal BP control is inadequate. The majority of hypertensive patients are treated with only one or two antihypertensive drugs.


Assuntos
Anti-Hipertensivos/uso terapêutico , Doenças Cardiovasculares/complicações , Diabetes Mellitus/fisiopatologia , Hipertensão/tratamento farmacológico , Atenção Primária à Saúde/estatística & dados numéricos , Antagonistas Adrenérgicos beta/uso terapêutico , Idoso , Inibidores da Enzima Conversora de Angiotensina/uso terapêutico , Pressão Sanguínea , Índice de Massa Corporal , Bloqueadores dos Canais de Cálcio/uso terapêutico , Estudos Transversais , Dinamarca , Diuréticos/uso terapêutico , Feminino , Humanos , Hipercolesterolemia/complicações , Hipertensão/complicações , Modelos Logísticos , Masculino , Atividade Motora , Guias de Prática Clínica como Assunto , Fatores de Risco , Fumar , Inquéritos e Questionários
7.
J Fish Biol ; 76(7): 1856-62, 2010 May.
Artigo em Inglês | MEDLINE | ID: mdl-20557637

RESUMO

Diet composition of the expanding southern species European anchovy Engraulis encrasicolus in the western Baltic Sea was investigated. Results revealed an interesting case of bentho-pelagic coupling with potential implications for local fish species through competition for food resources.


Assuntos
Dieta , Comportamento Alimentar , Peixes/fisiologia , Animais , Conteúdo Gastrointestinal
8.
Appl Radiat Isot ; 153: 108830, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31437722

RESUMO

The aim of the European Metrology Research Project MetroBeta is to improve the knowledge of the shapes of beta spectra, both in terms of theoretical calculation and measurement. The precise knowledge of beta spectra is required for the activity standardisation of pure beta emitters. Metallic magnetic calorimeters (MMCs), a type of cryogenic detectors, with the beta emitter embedded in the absorber have proven to be among the best beta spectrometers, in particular for low-energy beta transitions. Within this project, new designs of MMCs optimized for five different beta energy ranges were developed and a new detector module was constructed. The beta spectra of 151Sm, 14C and 99Tc have been measured so far; additional measurements with 36Cl are under preparation. Improved theoretical calculation methods and complementary measurement techniques complete the project.

9.
Nat Commun ; 9(1): 2845, 2018 07 20.
Artigo em Inglês | MEDLINE | ID: mdl-30030424

RESUMO

Amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD) share key features, including accumulation of the RNA-binding protein TDP-43. TDP-43 regulates RNA homeostasis, but it remains unclear whether RNA stability is affected in these disorders. We use Bru-seq and BruChase-seq to assess genome-wide RNA stability in ALS patient-derived cells, demonstrating profound destabilization of ribosomal and mitochondrial transcripts. This pattern is recapitulated by TDP-43 overexpression, suggesting a primary role for TDP-43 in RNA destabilization, and in postmortem samples from ALS and FTD patients. Proteomics and functional studies illustrate corresponding reductions in mitochondrial components and compensatory increases in protein synthesis. Collectively, these observations suggest that TDP-43 deposition leads to targeted RNA instability in ALS and FTD, and may ultimately cause cell death by disrupting energy production and protein synthesis pathways.


Assuntos
Esclerose Lateral Amiotrófica/genética , Proteínas de Ligação a DNA/metabolismo , Demência Frontotemporal/genética , Mutação , Estabilidade de RNA , Idoso , Idoso de 80 Anos ou mais , Proteína C9orf72/genética , Proteínas de Ligação a DNA/genética , Feminino , Fibroblastos/metabolismo , Proteínas de Fluorescência Verde/metabolismo , Humanos , Células-Tronco Pluripotentes Induzidas/citologia , Masculino , Pessoa de Meia-Idade , Mitocôndrias/metabolismo
10.
Curr Biol ; 10(18): 1135-8, 2000 Sep 21.
Artigo em Inglês | MEDLINE | ID: mdl-10996796

RESUMO

The distal portion of mouse chromosome 12 is imprinted. To date, however, Gtl2 is the only imprinted gene identified on chromosome 12. Gtl2 encodes multiple alternatively spliced transcripts with no apparent open reading frame. Using conceptuses with maternal or paternal uniparental disomy for chromosome 12 (UPD12), we found that Gtl2 is expressed from the maternal allele and methylated at the 5' end of the silent paternal allele. A reciprocally imprinted gene, Delta-like (Dlk), with homology to genes involved in the Notch signalling pathway was identified 80kb upstream of Gtl2. Dlk was expressed exclusively from the paternal allele in both the embryo and placenta, but the CpG-island promoter of Dlk was completely unmethylated on both parental alleles. Rather, a paternally methylated region was identified in the last exon of the active Dlk allele. The proximity, reciprocal imprinting and methylation in this domain are reminiscent of the co-ordinately regulated Igf2-H19 imprinted domain on mouse chromosome 7. Like H19 and Igf2, Gtl2 and Dlk were found to be co-expressed in the same tissues throughout development, though not after birth. These results have implications for the regulation, function and evolution of imprinted domains.


Assuntos
Metilação de DNA , Regulação da Expressão Gênica no Desenvolvimento , Impressão Genômica , Proteínas de Homeodomínio/genética , Proteínas de Membrana/genética , Alelos , Animais , Cromossomos , DNA/metabolismo , Embrião de Mamíferos/metabolismo , Proteínas de Homeodomínio/metabolismo , Peptídeos e Proteínas de Sinalização Intracelular , Proteínas de Membrana/metabolismo , Camundongos , RNA Mensageiro/genética , RNA Mensageiro/metabolismo
11.
Zootaxa ; 4269(3): 346-378, 2017 05 23.
Artigo em Inglês | MEDLINE | ID: mdl-28610323

RESUMO

The endemic North American stag beetle tribe Platyceroidini Paulsen & Hawks (Coleoptera: Lucanidae: Lucaninae) is reviewed. All primary types were studied and the existing generic and species concepts are subsequently corrected. Based on study of the male genitalia and external morphology, the previously monotypic genus Platyceropsis Benesh is reduced to subgeneric status under Platyceroides Benesh, new status, and the species Platyceroides laticollis (Casey) and Platyceroides keeni (Casey) new combination are transferred to this subgenus. Praocerus, new subgenus, is created to contain the species Platyceroides latus (Fall), and P. viriditinctus (Benesh). In the nominal subgenus, confusion has resulted from the historic misapplication of the oldest available name, Platyceroides agassii (LeConte), resulting in significant underestimation of the number of extant taxa. Lectotypes are designated for four species-group names (listed in their original combinations): Platycerus latus Fall, Platycerus opacus Fall, Platycerus pacificus Casey, and Platycerus parvicollis Casey. Four new species (Platyceroides barrae, P. infernus, P. pampinatus, and P. umpquus) are described from California and Oregon, United States of America. The following species are valid and are removed from synonymy with P. agassii: P. pacificus (Casey), revised status, and P. californicus (Casey), revised status. The synonym Platycerus parvicollis Casey is transferred from Platyceroides agassii to P. californicus, new synonymy. With the addition of four new species and the correction of the mistaken synonymies the total number of species in the tribe Platyceroidini is now 16.


Assuntos
Besouros , Distribuição Animal , Animais , California , Masculino , Oregon
12.
Cytogenet Genome Res ; 113(1-4): 109-15, 2006.
Artigo em Inglês | MEDLINE | ID: mdl-16575169

RESUMO

Genomic imprinting in mammals results in mono-allelic expression of about 80 genes depending on the parental origin of the alleles. Though the epigenetic mechanisms underlying imprinting are rather clear, little is known about the genetic basis for these epigenetic mechanisms. It is still rather enigmatic which sequence features discriminate imprinted from non-imprinted genes/regions and why and how certain sequence elements are recognized and differentially marked in the germlines. It seems likely that specific DNA elements serve as signatures that guide the necessary epigenetic modification machineries to the imprinted regions. Inter- and intraspecific comparative genomic studies suggest that the unusual occurrence and distribution of various types of repetitive elements within imprinted regions may represent such genomic imprinting signatures. In this review we summarize the various observations made and discuss them in light of experimental data.


Assuntos
Impressão Genômica , RNA não Traduzido/genética , Sequências Repetitivas de Ácido Nucleico , Animais , Feminino , Fertilização , Humanos , Masculino , Mamíferos/genética , Camundongos , MicroRNAs/genética , RNA Nucleolar Pequeno/genética , Retroelementos/genética , Sequências de Repetição em Tandem/genética
13.
Zootaxa ; 4154(5): 595-600, 2016 Aug 24.
Artigo em Inglês | MEDLINE | ID: mdl-27615864

RESUMO

Two new species of South American Glaresidae (Coleoptera: Scarabaeoidea) are described: Glaresis smithi Paulsen, new species from Argentina, and Glaresis mondacai Paulsen, new species from Chile and Peru. The species are compared to their closest congener, Glaresis fritzi Martínez et al., and a key is provided for the known South American species of the genus Glaresis Erichson.


Assuntos
Besouros/classificação , Distribuição Animal , Estruturas Animais/anatomia & histologia , Estruturas Animais/crescimento & desenvolvimento , Animais , Argentina , Tamanho Corporal , Chile , Besouros/anatomia & histologia , Besouros/crescimento & desenvolvimento , Ecossistema , Feminino , Masculino , Tamanho do Órgão , Peru
14.
Aliment Pharmacol Ther ; 44(1): 78-87, 2016 07.
Artigo em Inglês | MEDLINE | ID: mdl-27137875

RESUMO

BACKGROUND: Studies of the increasing use of proton pump inhibitors (PPIs) have mainly focused on prevalent long-term use and associations with gastrointestinal morbidity and comedication. Little is known about non-medical characteristics of first-time users of PPI, and predictors of initiating long-term use of PPIs. AIMS: To describe medical and non-medical characteristics of first-time PPI users during a 10-year period and to analyse predictors of initiation of long-term use (>60 defined daily doses (DDDs) within 6 months) of PPIs. METHODS: A nationwide cohort study of first-time users of PPI. Data were collected from Danish national registers. Individuals redeeming their first prescription for a PPI (omeprazole, lansoprazole, pantoprazole, rabeprazole, esomeprazole) in 2001 and 2011 were identified. Redemption of more than 60 DDDs of PPI within 6 months defined long-term use. Logistic regression models were used to determine the associations between previous diagnoses, comedication and socio-economic characteristics and initiation of long-term use of PPIs in 2011. RESULTS: From 2001 to 2011 incidence of first-time users increased with an incidence rate ratio of 1.53 and mean quantity of PPI redeemed at first prescription increased by 44.6%. In 2011 a total of 37.6% redeemed >60 DDDs within 6 months, and 96% of the long-term users did not have a diagnosis registered which indicated treatment. New onset long-term use was significantly associated with low income and low educational level when adjusting for other predisposing variables. CONCLUSIONS: Proton pump inhibitor treatment is increasingly initiated with larger quantities prescribed for indications that are unidentifiable from the registers. Morbidity and comedication seem to be the strongest predictors of new onset long-term use of PPIs. However, there is also an independent social gradient.


Assuntos
Inibidores da Bomba de Prótons/uso terapêutico , 2-Piridinilmetilsulfinilbenzimidazóis/uso terapêutico , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Estudos de Coortes , Esomeprazol/uso terapêutico , Feminino , Humanos , Lansoprazol/uso terapêutico , Masculino , Pessoa de Meia-Idade , Omeprazol/uso terapêutico , Pantoprazol , Rabeprazol/uso terapêutico , Adulto Jovem
15.
Oncogene ; 20(42): 5964-71, 2001 Sep 20.
Artigo em Inglês | MEDLINE | ID: mdl-11593403

RESUMO

Blockage of transcription has been shown to induce the tumor suppressor p53 in human cells. We here show that RNA synthesis inhibitors blocking the phosphorylation of the carboxyl terminal domain (CTD) of RNA polymerase II, such as DRB and H7, induced rapid nuclear accumulation of p53 proteins that were not phosphorylated at ser15 or acetylated at lys382. In contrast, agents that inhibit the elongation phase of transcription, such as UV light, camptothecin or actinomycin D, induced the accumulation of nuclear p53 proteins that were modified at both of these sites. Furthermore, using a panel of DNA repair-deficient cells we show that persistent DNA lesions in the transcribed strand of active genes are responsible for the induction of the ser15 and lys382 modifications following UV-irradiation. We conclude that inhibition of transcription is sufficient for the accumulation of p53 in the nucleus regardless of whether the ser15 site of p53 is phosphorylated or not. Importantly, blockage of the elongation phase of transcription triggers a distinct signaling pathway leading to p53 modifications on ser15 and lys382. We propose that the elongating RNA polymerase complex may act as a sensor of DNA damage and as an integrator of cellular stress signals.


Assuntos
Lisina/metabolismo , Serina/metabolismo , Transcrição Gênica , Proteína Supressora de Tumor p53/metabolismo , Acetilação , Núcleo Celular/metabolismo , Células Cultivadas , Síndrome de Cockayne/genética , Síndrome de Cockayne/metabolismo , Dano ao DNA , Regulação da Expressão Gênica , Humanos , Inibidores da Síntese de Ácido Nucleico/farmacologia , Fosforilação , Regiões Promotoras Genéticas , RNA Polimerase II/fisiologia , Células Tumorais Cultivadas , Raios Ultravioleta , Xeroderma Pigmentoso/genética , Xeroderma Pigmentoso/metabolismo
16.
Oncogene ; 34(43): 5472-81, 2015 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-25659587

RESUMO

Cellular inhibitor of apoptosis proteins 1 and 2 (c-IAP1/2) have central roles in signal transduction mediated by numerous receptors that participate in inflammatory and immune responses. In certain pathways, such as activation of NF-κB, their degradation is a major regulatory event and is physiologically induced by activation of receptors. In addition, a number of synthetic compounds have been developed that also target the c-IAPs and induce their degradation. However, the extent of a synthetic IAP antagonist's ability to mirror the transcriptional program by a physiological signal remains unclear. Here we take a systems approach to compare the transcriptional programs triggered by activation of CD30, a well-characterized receptor previously shown to induce the degradation of the c-IAPs, to SM-164, a synthetic IAP antagonist that specifically triggers c-IAP degradation. Employing a technique that allows the specific analysis of newly transcribed RNA, we have generated comparative transcriptome profiles for CD30 activation and SM-164 treatment. Analysis of these profiles revealed that the genes regulated by each stimulus were not completely shared, indicating novel functions of IAP antagonists and consequences of c-IAP1/2 degradation. The data identified a role for c-IAP1/2 in the regulation of the ribosome and protein synthesis, which was subsequently confirmed by biological assays. These findings expand our knowledge of the roles of c-IAP1/2 in signaling and provide insight into the mechanism of synthetic IAP antagonists, furthering our understanding of their therapeutic potential.


Assuntos
Proteínas Inibidoras de Apoptose/antagonistas & inibidores , Transdução de Sinais/efeitos dos fármacos , Animais , Compostos Bicíclicos Heterocíclicos com Pontes/farmacologia , Células CHO , Linhagem Celular , Linhagem Celular Tumoral , Cricetulus , Humanos , Proteínas Inibidoras de Apoptose/genética , Antígeno Ki-1/genética , NF-kappa B/genética , Transdução de Sinais/genética , Transcrição Gênica/efeitos dos fármacos , Transcrição Gênica/genética , Transcriptoma/efeitos dos fármacos , Transcriptoma/genética , Triazóis/farmacologia
17.
Protein Sci ; 2(3): 357-65, 1993 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-8453374

RESUMO

Cytochrome P450cam (P450CIA1) catalyzes the hydroxylation of camphor and several substrate analogues such as norcamphor and 1-methyl-norcamphor. Hydroxylation was found experimentally at the 3, 5, and 6 positions of norcamphor, but only at the 5 and 6 positions of 1-methyl-norcamphor. In the catalytic cycle, the hydroxylation of substrate is coupled to the consumption of NADH. For camphor, the degree of coupling is 100%, but for both norcamphor and 1-methyl-norcamphor, the efficiency is dramatically lowered to 12% and 50%, respectively. Based on an examination of the active site of P450cam, it appeared that mutating position 185 might dramatically alter the product specificity and coupling of hydroxylation of norcamphor by P450cam. Analysis of molecular dynamics trajectories of norcamphor bound to the T185F mutant of cytochrome P450cam predicted that hydroxylation at the 3 position should be abolished and that the coupling should be dramatically increased. This mutant was constructed and the product profile and coupling experimentally determined. The coupling was doubled, and hydroxylation at the 3 position was essentially abolished. Both of these results are in agreement with the prediction.


Assuntos
Sistema Enzimático do Citocromo P-450/metabolismo , Oxigenases de Função Mista/metabolismo , Sítios de Ligação , Cânfora 5-Mono-Oxigenase , Simulação por Computador , Sistema Enzimático do Citocromo P-450/química , Sistema Enzimático do Citocromo P-450/genética , Escherichia coli/genética , Hidroxilação , Oxigenases de Função Mista/química , Oxigenases de Função Mista/genética , Modelos Químicos , Mutagênese Sítio-Dirigida , Norbornanos/química , Norbornanos/metabolismo , Engenharia de Proteínas , Especificidade por Substrato
18.
Neoplasia ; 3(4): 331-8, 2001.
Artigo em Inglês | MEDLINE | ID: mdl-11571633

RESUMO

Phenylbutyrate (PB) is a histone deacetylase inhibitor that has been shown to induce differentiation and apoptosis in various cancer cell lines. Although these effects are most likely due to modulation of gene expression, the specific genes and gene products responsible for the effects of PB are not well characterized. In this study, we used cDNA expression arrays and Western blot to assess the effect that PB has on the expression of various cancer and apoptosis-regulatory gene products. We show that PB attenuates the expression of the apoptosis antagonist Bcl-X(L), the double-strand break repair protein DNA-dependent protein kinase, the prostate progression marker caveolin-1, and the pro-angiogenic vascular endothelial growth factor. Furthermore, PB was found to act in synergy with ionizing radiation to induce apoptosis in prostate cancer cells. Taken together, our results point to the possibility that PB may be an effective anti-prostate cancer agent when used in combination with radiation or chemotherapy and for the inhibition of cancer progression.


Assuntos
Caveolinas/metabolismo , Proteínas de Ligação a DNA , Fatores de Crescimento Endotelial/metabolismo , Linfocinas/metabolismo , Fenilbutiratos/farmacologia , Neoplasias da Próstata/metabolismo , Proteínas Serina-Treonina Quinases/metabolismo , Proteínas Proto-Oncogênicas c-bcl-2/metabolismo , Células Tumorais Cultivadas/efeitos dos fármacos , Apoptose/efeitos dos fármacos , Western Blotting , Caveolina 1 , Ciclo Celular/efeitos dos fármacos , Ciclo Celular/efeitos da radiação , Cobalto/farmacologia , Proteína Quinase Ativada por DNA , Regulação para Baixo/fisiologia , Citometria de Fluxo , Perfilação da Expressão Gênica , Humanos , Masculino , Proteínas Nucleares , Análise de Sequência com Séries de Oligonucleotídeos , Neoplasias da Próstata/tratamento farmacológico , Transfecção , Células Tumorais Cultivadas/metabolismo , Células Tumorais Cultivadas/efeitos da radiação , Fator A de Crescimento do Endotélio Vascular , Fatores de Crescimento do Endotélio Vascular , Proteína bcl-X
19.
Gene ; 248(1-2): 89-97, 2000 May 02.
Artigo em Inglês | MEDLINE | ID: mdl-10806354

RESUMO

The ascomycete, Leptosphaeria maculans, causes blackleg disease of oilseed Brassica spp. such as canola (Brassica napus). We have cloned a gene encoding endopolygalacturonase, pg1, and two genes encoding cellulases, cel1 and cel2, in L. maculans. These genes are not clustered in the genome, as they are located on different chromosomes. The deduced amino acid sequences of all three genes predict an N-terminal signal sequence, as is common for secreted fungal enzymes that degrade plant cell walls. The endopolygalacturonase encoded by pg1 shows the highest similarity (54% amino acid identity) to endopolygalacturonase 4 from Botrytis cinerea. Both cel1 and cel2 appear to encode cellobiohydrolase, and neither gene encodes a recognizable cellulose-binding domain or linker region. Transcription of pg1 is induced in cultures containing 1% polygalacturonic acid or pectin, and cel1 is induced in 1% cellulose or carboxymethylcellulose, as shown by Northern analysis. Glucose represses the induction of cel1 caused by cellulose and carboxymethylcellulose, but does affect transcription of pg1. Transcription of cel2 (but not cel1 or pg1) is detectable during infection of B. napus and B. juncea cotyledons and leaves using reverse transcription-PCR.


Assuntos
Ascomicetos/genética , Brassica/microbiologia , Parede Celular/metabolismo , Celulase/genética , Poligalacturonase/genética , Sequência de Aminoácidos , Ascomicetos/enzimologia , Brassica/metabolismo , Celulase/metabolismo , Clonagem Molecular , DNA Complementar/química , DNA Complementar/genética , DNA Complementar/isolamento & purificação , DNA de Plantas/química , DNA de Plantas/genética , Regulação Enzimológica da Expressão Gênica , Regulação Fúngica da Expressão Gênica , Genes de Plantas/genética , Isoenzimas/genética , Isoenzimas/metabolismo , Dados de Sequência Molecular , Doenças das Plantas/microbiologia , Poligalacturonase/metabolismo , Alinhamento de Sequência , Análise de Sequência de DNA , Homologia de Sequência de Aminoácidos , Transcrição Gênica
20.
J Biomol Struct Dyn ; 9(2): 187-203, 1991 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-1741957

RESUMO

The structure and internal motions of the active site residues of camphor-bound cytochrome P450cam have been evaluated on the basis of a 175 psec molecular dynamics simulation. The active site residues generally show very small deviations away from their starting crystal positions. These residues also generally show much smaller fluctuations than for the enzyme as a whole. Phe 87 is dynamically very unusual and is suggested to play a role in substrate movement into and/or out of the active site. The average distance between the heme iron and atoms C5, C6, and C3 of camphor is 5.3, 6.0, and 7.0 A, respectively. This trend is consistent with the experimentally observed stereospecificity of the hydroxylation reaction. On the basis of distance and angle criteria, both 5-exo and 5-endo hydrogen abstraction are predicted to occur during the hydroxylation reaction; although the 5-exo pathway is expected to be 3-fold more likely.


Assuntos
Cânfora/química , Sistema Enzimático do Citocromo P-450/química , Oxigenases de Função Mista/química , Sítios de Ligação , Cânfora/metabolismo , Cânfora 5-Mono-Oxigenase , Simulação por Computador , Sistema Enzimático do Citocromo P-450/metabolismo , Ligação de Hidrogênio , Oxigenases de Função Mista/metabolismo , Conformação Proteica , Especificidade por Substrato , Termodinâmica
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