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1.
Scand J Med Sci Sports ; 27(4): 418-429, 2017 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-26926496

RESUMO

The main aim of the Swedish physical activity and fitness cohort study (SPAF-1958) was to describe physical fitness, physical activity, health, and lifestyle across part of the lifespan, and to assess the influences on these factors from the environment, personal factors, and genetics. There is inevitable dropout from longitudinal studies, and it may be systematic. The aim of this first paper of the second follow-up of SPAF-1958 was to provide a dropout analysis to consider to what extent the participants, at 52 years of age, remain a representative sample of the original adolescent study population. Additional aims were to provide an overview of the study protocol and the ongoing study population. Ongoing study participants in SPAF born in 1958 were, at the second follow-up at the age of 52, still representative of the study cohort in terms of sex, adolescent geographical area, upper secondary school program, adolescent body composition, muscular strength, and muscular endurance. However, a higher physical activity and, among women, a higher aerobic capacity in adolescence decreased the risk for dropout. It is important when interpreting results from longitudinal studies to adjust for the systematic dropout that could bias the conclusions drawn from the results.


Assuntos
Exercício Físico , Pacientes Desistentes do Tratamento , Aptidão Física , Adolescente , Adulto , Atitude , Estatura , Índice de Massa Corporal , Peso Corporal , Estudos de Coortes , Escolaridade , Teste de Esforço , Feminino , Seguimentos , Força da Mão , Nível de Saúde , Humanos , Estilo de Vida , Modelos Logísticos , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Força Muscular , Educação Física e Treinamento , Fumar/epidemiologia , Suécia/epidemiologia , Adulto Jovem
2.
Heredity (Edinb) ; 117(4): 279-89, 2016 10.
Artigo em Inglês | MEDLINE | ID: mdl-27328654

RESUMO

The Scandinavian wolf population descends from only five individuals, is isolated, highly inbred and exhibits inbreeding depression. To meet international conservation goals, suggestions include managing subdivided wolf populations over Fennoscandia as a metapopulation; a genetically effective population size of Ne⩾500, in line with the widely accepted long-term genetic viability target, might be attainable with gene flow among subpopulations of Scandinavia, Finland and Russian parts of Fennoscandia. Analytical means for modeling Ne of subdivided populations under such non-idealized situations have been missing, but we recently developed new mathematical methods for exploring inbreeding dynamics and effective population size of complex metapopulations. We apply this theory to the Fennoscandian wolves using empirical estimates of demographic parameters. We suggest that the long-term conservation genetic target for metapopulations should imply that inbreeding rates in the total system and in the separate subpopulations should not exceed Δf=0.001. This implies a meta-Ne of NeMeta⩾500 and a realized effective size of each subpopulation of NeRx⩾500. With current local effective population sizes and one migrant per generation, as recommended by management guidelines, the meta-Ne that can be reached is ~250. Unidirectional gene flow from Finland to Scandinavia reduces meta-Ne to ~130. Our results indicate that both local subpopulation effective sizes and migration among subpopulations must increase substantially from current levels to meet the conservation target. Alternatively, immigration from a large (Ne⩾500) population in northwestern Russia could support the Fennoscandian metapopulation, but immigration must be substantial (5-10 effective immigrants per generation) and migration among Fennoscandian subpopulations must nevertheless increase.


Assuntos
Conservação dos Recursos Naturais/métodos , Genética Populacional/métodos , Densidade Demográfica , Lobos/genética , Animais , Fluxo Gênico , Depressão por Endogamia , Modelos Genéticos , Dinâmica Populacional , Países Escandinavos e Nórdicos
3.
Lupus ; 25(6): 602-16, 2016 May.
Artigo em Inglês | MEDLINE | ID: mdl-26768748

RESUMO

OBJECTIVES: To study the effects of a one-year physical activity programme on aerobic capacity, physical activity and health-related quality of life (HRQL) in patients with systemic lupus erythematosus (SLE) by a randomized control design. METHODS: Thirty-five women with low or moderate disease activity and organ damage were randomized to intervention (I) or control (C) group. The intervention during months 0-3 consisted of education, supervised aerobic exercise at high intensity and individual coaching, as well as self-managed physical activity at low-to-moderate intensity. During months 4-12, the physical activity was self-managed and the coaching was successively reduced over time. Outcome measures included: maximal oxygen uptake (VO2 max) from a bicycle ergometer test, self-reported physical activity and HRQL (SF-36). RESULTS: VO2 at sub-max. and max. increased, independent of group, during the one-year study period (main effect of time p < 0.0001). VO2 max. increased between baseline and month 3 (p < 0.0001), between months 3 and 6 (p = 0.01) and the increase was sustained at month 12 (ns). Frequency of physical activity at high intensity also increased, independent of group, during the study period. It was increased at months 3, 6 and 12 compared to baseline (p = 0.02, p < 0.001, p = 0.03). Improvement in mental health between baseline and month 6 (p = 0.002) was seen for the I-group, not the C-group (p = 0.03). Disease activity and organ damage did not change. CONCLUSIONS: Physical activity and aerobic capacity increased after supervised exercise and coaching, and the improvement was sustained during the one-year programme. However, no interactions between the group differences were seen, which suggests that repeated measurements could motivate to increased physical activity and thereby to increased aerobic capacity. As sub-max. VO2 increased over time, training-induced changes in VO2 on-kinetics could be another explanation. Little influence on HRQL was seen after the programme. The study indicates that physical activity at high intensity over one year is tolerated by patients with mild to moderate SLE.


Assuntos
Terapia por Exercício/métodos , Lúpus Eritematoso Sistêmico/terapia , Consumo de Oxigênio/fisiologia , Qualidade de Vida , Adulto , Exercício Físico/fisiologia , Teste de Esforço , Tolerância ao Exercício , Feminino , Humanos , Lúpus Eritematoso Sistêmico/fisiopatologia , Pessoa de Meia-Idade , Índice de Gravidade de Doença , Método Simples-Cego , Fatores de Tempo , Resultado do Tratamento
4.
Mol Ecol ; 23(4): 875-89, 2014 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-24382313

RESUMO

Maintaining effective immune response is an essential factor in the survival of small populations. One of the most important immune gene regions is the highly polymorphic major histocompatibility complex (MHC). We investigated how a population bottleneck and recovery have influenced the diversity and selection in three MHC class II loci, DLA-DRB1, DLA-DQA1 and DLA-DQB1, in the Finnish wolf population. We studied the larger Russian Karelian wolf population for comparison and used 17 microsatellite markers as reference loci. The Finnish and Karelian wolf populations did not differ substantially in their MHC diversities (GST″ = 0.047, P = 0.377), but differed in neutral microsatellite diversities (GST″ = 0.148, P = 0.008). MHC allele frequency distributions in the Finnish population were more even than expected under neutrality, implying balancing selection. In addition, an excess of nonsynonymous compared to synonymous polymorphisms indicated historical balancing selection. We also studied association between helminth (Trichinella spp. and Echinococcus canadensis) prevalence and MHC diversity at allele and SNP level. MHC-heterozygous wolves were less often infected by Trichinella spp. and carriers of specific MHC alleles, SNP haplotypes and SNP alleles had less helminth infections. The associated SNP haplotypes and alleles were shared by different MHC alleles, which emphasizes the necessity of single-nucleotide-level association studies also in MHC. Here, we show that strong balancing selection has had similar effect on MHC diversities in the Finnish and Russian Karelian wolf populations despite significant genetic differentiation at neutral markers and small population size in the Finnish population.


Assuntos
Genética Populacional , Complexo Principal de Histocompatibilidade/genética , Seleção Genética , Lobos/genética , Alelos , Animais , Finlândia , Haplótipos , Helmintos/isolamento & purificação , Heterozigoto , Repetições de Microssatélites , Dados de Sequência Molecular , Polimorfismo Genético , Densidade Demográfica , Lobos/parasitologia
5.
Mol Ecol ; 21(21): 5178-93, 2012 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-22978518

RESUMO

The grey wolves (Canis lupus) of Finland have had a varied history, with a period of rapid population expansion after the mid-1990s followed by a decline with a current census size of about 140 wolves. Here, we investigate the impact of unstable population size and connectivity on genetic diversity and structure in a long-term genetic study of 298 Finnish wolves born in 1995-2009 and genotyped for 17 microsatellite loci. During the initial recovery and prior to population expansion, genetic diversity was high (1995-1997: LD-N(e)  = 67.2; H(o)  = 0.749; H(e)  = 0.709) despite a small census size and low number of breeders (N(c)  < 100; N(b)  < 10) likely reflecting the status of the Russian source population. Surprisingly, observed heterozygosity decreased significantly during the study period (t = -2.643, P = 0.021) despite population expansion, likely a result of an increase in inbreeding (F(IS)  = 0.108 in 2007-2009) owing to a low degree of connectivity with adjacent Russian wolf population (m = 0.016-0.090; F(ST)  = 0.086, P < 0.001) and population crash after 2006. However, population growth had a temporary positive impact on N(e) and number of family lines. This study shows that even strong population growth alone might not be adequate to retain genetic diversity, especially when accompanied with low amount of subsequent gene flow and population decline.


Assuntos
Variação Genética , Genética Populacional , Lobos/genética , Animais , Feminino , Finlândia , Fluxo Gênico , Genótipo , Heterozigoto , Endogamia , Desequilíbrio de Ligação , Masculino , Repetições de Microssatélites , Densidade Demográfica , Crescimento Demográfico , Análise de Sequência de DNA
6.
Scand J Med Sci Sports ; 22(3): 399-409, 2012 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-22612362

RESUMO

There is a pronounced gender difference in the accumulation of plasma ammonia after sprint exercise. Ammonia is a key intermediate in amino acid metabolism, which implies that gender-related differences in plasma and muscle amino acid concentrations after sprint exercise exist. To study this, three bouts of 30-s sprint exercise were performed by healthy females (n=8) and males (n=6). Blood leucine and muscle leucine were collected over the exercise period. Basal arterial plasma and skeletal muscle leucine were 40% higher in males than females (P<0.010 and P<0.020). Plasma, but not muscle, leucine decreased by sprint exercise and more so in males than females (g × t: P=0.025). Increase in ammonia was higher in males than females in both plasma and muscle (g × t: P<0.001 and P=0.003). An opposite pattern was shown for plasma glutamine, where an increase was found in females (P<0.001), but not in males. In conclusion, the lower plasma ammonia after sprint exercise in females seems to be explained by a lower accumulation of ammonia in skeletal muscle and by a buffering of ammonia in the form of glutamine in females. The greater reduction in plasma leucine in males seems to be related to their greater increase in muscle ammonia after sprint exercise.


Assuntos
Ciclismo/fisiologia , Leucina/sangue , Adulto , Análise de Variância , Biópsia , Regulação para Baixo , Feminino , Humanos , Masculino , Músculo Esquelético/fisiologia , Fatores Sexuais , Inquéritos e Questionários
7.
Histochem Cell Biol ; 131(2): 181-9, 2009 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-18825402

RESUMO

There are two oestrogen receptors (ERs), ERalpha and ERbeta. ERbeta protein is expressed in human skeletal muscle in the nuclei of both myofibres and endothelial cells, whether ERalpha protein is present in this tissue is unknown. We studied the expression of ERalpha protein in human skeletal muscle biopsies taken from vastus lateralis from four men, four women, two children and two postmenopausal women. Immunohistochemistry was used to determine the proportions of nuclei that were positively stained for ERalpha, the proportion of ERalpha-positive nuclei located in the muscle fibres and in capillaries and to test for possible co-expression of ERalpha and ERbeta. Both ERs were expressed in all subjects. Of all nuclei, 63% stained for ERalpha with no sex difference. ERalpha was localised both in myofibres and in endothelial cells of the capillaries, 25% of the ERalpha-positive nuclei were located in the capillaries. ERalpha and ERbeta were generally expressed in the same nuclei. The present study shows for the first time the expression of ERalpha protein in human skeletal muscle independently of age and sex. These results might improve understanding of the physiological role of oestrogen in human skeletal muscle and raise new questions about activation of ERs in skeletal muscle.


Assuntos
Receptor alfa de Estrogênio/análise , Receptor beta de Estrogênio/análise , Músculo Esquelético/química , Adulto , Fatores Etários , Núcleo Celular/química , Endotélio Vascular/química , Endotélio Vascular/ultraestrutura , Feminino , Humanos , Imuno-Histoquímica , Masculino , Pessoa de Meia-Idade , Músculo Esquelético/ultraestrutura , Pós-Menopausa , Fatores Sexuais
8.
J Fish Dis ; 31(10): 755-63, 2008 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-18681904

RESUMO

Bacterial kidney disease (BKD), caused by Renibacterium salmoninarum (Rs), is a serious threat to salmon in aquaculture as well as to wild populations. We have developed a real-time polymerase chain reaction (PCR) for detection of Rs in kidney samples. The PCR is based on detection of unique parts of the 16S rRNA gene of Rs and DNA equivalent to 1-10 Rs genomes was detected per reaction. No cross-reactivity with other fish pathogenic or related bacteria could be demonstrated. Analysis of individual kidney samples collected from BKD classified populations identified 39.9% of the fish as positive by real-time PCR compared with 28.0% by polyclonal enzyme-linked immunosorbent assay (ELISA). The real-time PCR assay was found to be well suited for complementary use with ELISA for diagnosis of BKD, with the ability to detect clinical as well as covert Rs infections. The infection level determined by the polyclonal ELISA and by real-time PCR was significantly correlated.


Assuntos
Infecções por Actinomycetales/veterinária , Doenças dos Peixes/diagnóstico , Nefropatias/veterinária , Micrococcaceae/fisiologia , Reação em Cadeia da Polimerase/veterinária , Infecções por Actinomycetales/diagnóstico , Animais , Anticorpos Antibacterianos/metabolismo , Ensaio de Imunoadsorção Enzimática , Rim/microbiologia , Nefropatias/diagnóstico , Oncorhynchus mykiss/microbiologia , Reação em Cadeia da Polimerase/métodos , Sensibilidade e Especificidade
9.
Sci Rep ; 8(1): 14767, 2018 10 03.
Artigo em Inglês | MEDLINE | ID: mdl-30283061

RESUMO

The aim was to investigate how physical capacity changes from adolescence through early adulthood to middle age with focus on early aging. The aim was also to study if physical capacity in middle age could be predicted by factors in adolescence or early adulthood. A cohort of men and women in Sweden (SPAF-1958, n = 425) have been followed for 36 years, at 16, 34, and 52 years of age. The study includes, among other variables, objective measures of physical capacity. At age 52, 50% of the original cohort participated in exercise testing. Physical capacity increased from 16 to 34 years. From 34 to 52 years, physical capacity decreased in both genders by 15-20% in all but one test. Physical capacity at 16 and 34 years of age were better predictors of physical capacity at age 52 than body dimensions, school grades and life style factors. In conclusion, present data confirm earlier cross-sectional studies regarding the decrease in aerobic capacity and muscular strength during the early ageing period in both genders. The study has also generated novel data that show a smaller decline in muscular endurance than previously reported. Finally, physical capacity is fairly stable from adolescence to middle age.


Assuntos
Envelhecimento/fisiologia , Teste de Esforço , Força Muscular/fisiologia , Aptidão Física/fisiologia , Adolescente , Adulto , Índice de Massa Corporal , Tolerância ao Exercício , Feminino , Humanos , Estilo de Vida , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Suécia , Adulto Jovem
10.
Sci Rep ; 8(1): 9124, 2018 06 14.
Artigo em Inglês | MEDLINE | ID: mdl-29904069

RESUMO

Amphibians are threatened on a global scale and pollutants may be contributing to population declines, but how chemicals impact on their reproduction is poorly understood. We conducted a life cycle analysis to investigate the impacts of early life exposure to two anti-androgens (exposure until completion of metamorphosis;stage 66): flutamide, (50 µg/L)/linuron (9 and 45 µg/L)) on sexual development and breeding competence in Xenopus tropicalis. Our analyses included: mRNA levels of dmrt1, cyp17, amh, cyp19, foxl2 and ar (tadpoles/metamorphs), gonadal histomorphology (metamorphs/adults), mRNA levels of ar/gr (adult male brain/gonad/forelimb), testosterone/corticosterone levels (adult males), secondary sexual characteristics (forelimb width/nuptial pad: adult males) and breeding competence (amplexus/fertility: adult males). Compared to controls, feminised sex ratios and increased number of spermatogonia (adults) were observed after exposure to flutamide and the lower linuron concentration. Exposure to the lower linuron concentration also resulted in demasculinisation of secondary sexual characteristics and reduced male fertility. Flutamide exposure resulted in masculinisation of the nuptial pad and elevated mRNA levels of dmrt1, cyp17, amh and foxl2 in brains (metamorphs). Testosterone levels were higher in all treatment groups, however, overall few effects were observed in response to the higher linuron concentration. Our findings advance understanding of reproductive biology of X. tropicalis and illustrate negative effects of linuron on reproductive processes at a concentration measured in freshwater environments.


Assuntos
Antagonistas de Androgênios , Herbicidas , Infertilidade Masculina , Proteínas de Xenopus/metabolismo , Antagonistas de Androgênios/efeitos adversos , Antagonistas de Androgênios/farmacologia , Animais , Fertilidade/efeitos dos fármacos , Herbicidas/efeitos adversos , Herbicidas/farmacologia , Infertilidade Masculina/induzido quimicamente , Infertilidade Masculina/metabolismo , Infertilidade Masculina/patologia , Masculino , Xenopus
11.
J Clin Invest ; 101(1): 79-85, 1998 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-9421469

RESUMO

We have demonstrated previously that dichloroacetate can attenuate skeletal muscle fatigue by up to 35% in a canine model of peripheral ischemia (Timmons, J.A., S.M. Poucher, D. Constantin-Teodosiu, V. Worrall, I.A. Macdonald, and P.L. Greenhaff. 1996. J. Clin. Invest. 97:879-883). This was thought to be a consequence of dichloroacetate increasing acetyl group availability early during contraction. In this study we characterized the metabolic effects of dichloroacetate in a human model of peripheral muscle ischemia. On two separate occasions (control-saline or dichloroacetate infusion), nine subjects performed 8 min of single-leg knee extension exercise at an intensity aimed at achieving volitional exhaustion in approximately 8 min. During exercise each subject's lower limbs were exposed to 50 mmHg of positive pressure, which reduces blood flow by approximately 20%. Dichloroacetate increased resting muscle pyruvate dehydrogenase complex activation status by threefold and elevated acetylcarnitine concentration by fivefold. After 3 min of exercise, phosphocreatine degradation and lactate accumulation were both reduced by approximately 50% after dichloroacetate pretreatment, when compared with control conditions. However, after 8 min of exercise no differences existed between treatments. Therefore, it would appear that dichloroacetate can delay the accumulation of metabolites which lead to the development of skeletal muscle fatigue during ischemia but does not alter the metabolic profile when a maximal effort is approached.


Assuntos
Ácido Dicloroacético/farmacologia , Exercício Físico/fisiologia , Músculo Esquelético/efeitos dos fármacos , Músculo Esquelético/metabolismo , Acetilcarnitina/metabolismo , Trifosfato de Adenosina/metabolismo , Adulto , Glicemia/metabolismo , Fenômenos Fisiológicos Cardiovasculares , Glicogênio/metabolismo , Humanos , Ácido Láctico/metabolismo , Masculino , Músculo Esquelético/irrigação sanguínea , Fosfocreatina/metabolismo , Complexo Piruvato Desidrogenase/metabolismo , Fatores de Tempo
12.
J Appl Physiol (1985) ; 103(3): 1012-20, 2007 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-17569764

RESUMO

Eleven subjects performed one-legged exercise four times per week for 5 wk. The subjects exercised one leg for 45 min with restricted blood flow (R leg), followed by exercise with the other leg at the same absolute workload with unrestricted blood flow (UR leg). mRNA and protein expression were measured in biopsies from the vastus lateralis muscle obtained at rest before the training period, after 10 days, and after 5 wk of training, as well as 120 min after the first and last exercise bouts. Basal Ang-2 and Tie-1 mRNA levels increased in both legs with training. The Ang-2-to-Ang-1 ratio increased to a greater extent in the R leg. The changes in Ang-2 mRNA were followed by similar changes at the protein level. In the R leg, VEGF-A mRNA expression responded transiently after acute exercise both before and after the 5-wk training program. Over the course of the exercise program, there was a concurrent increase in basal VEGF-A protein and VEGFR-2 mRNA in the R leg. Ki-67 mRNA showed a greater increase in the R leg and the protein was localized to the endothelial cells. In summary, the increased translation of VEGF-A is suggested to be caused by the short mRNA burst induced by each exercise bout. The concurrent increase in the Ang-2-to-Ang-1 ratio and the VEGF-expression combined with the higher level of Ki-67 mRNA in the R leg indicate that changes in these systems are of importance also in nonpathological angiogenic condition such as voluntary exercise in humans. It further establish that hypoxia/ischemia-related metabolic perturbation is likely to be involved as stimuli in this process in human skeletal muscle.


Assuntos
Angiopoietinas/metabolismo , Exercício Físico/fisiologia , Perna (Membro)/irrigação sanguínea , Músculo Quadríceps/metabolismo , Fator A de Crescimento do Endotélio Vascular/metabolismo , Adulto , Biópsia , Proliferação de Células , Humanos , Antígeno Ki-67/metabolismo , Masculino , RNA Mensageiro/metabolismo , Receptor de TIE-1/metabolismo , Receptor TIE-2/metabolismo , Fluxo Sanguíneo Regional/fisiologia , Receptor 1 de Fatores de Crescimento do Endotélio Vascular/metabolismo , Receptor 2 de Fatores de Crescimento do Endotélio Vascular/metabolismo
13.
J Appl Physiol (1985) ; 102(6): 2346-51, 2007 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-17255365

RESUMO

The aims of this study were 1) to characterize changes in matrix metalloproteinase (MMP), endostatin, and vascular endothelial growth factor (VEGF)-A expression in skeletal muscle in response to a single bout of exercise in humans; and 2) to determine if any exchange of endostatin and VEGF-A between circulation and the exercising leg is associated with a change in the tissue expression or plasma concentration of these factors. Ten healthy males performed 65 min of cycle exercise, and muscle biopsies were obtained from the vastus lateralis muscle at rest and immediately and 120 min after exercise. In the muscle biopsies, measurements of mRNA expression levels of MMP-2, MMP-9, MMP-14, and tissue inhibitor of metalloproteinase; VEGF and endostatin protein levels; and MMP activities were performed. Femoral arterial and venous concentrations of VEGF-A and endostatin were determined before, during, and 120 min after exercise. A single bout of exercise increased MMP-9 mRNA and activated MMP-9 protein in skeletal muscle. No measurable increase of endostatin was observed in the skeletal muscle or in plasma following exercise. A concurrent increase in skeletal muscle VEGF-A mRNA and protein levels was induced by exercise, with no signs of peripheral uptake from the circulation. However, a decrease in plasma VEGF-A concentration occurred following exercise. Thus 1) a single bout of exercise activated the MMP system without any resulting change in tissue endostatin protein levels, and 2) the increased VEGF-A protein levels are due to changes in the skeletal muscle tissue itself. Other mechanisms are responsible for the observed exercise-induced decrease in VEGF-A in plasma.


Assuntos
Envelhecimento/fisiologia , Metaloproteinases da Matriz/metabolismo , Contração Muscular/fisiologia , Músculo Esquelético/fisiologia , Esforço Físico/fisiologia , Fator A de Crescimento do Endotélio Vascular/metabolismo , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Endostatinas/metabolismo , Ativação Enzimática , Teste de Esforço , Humanos , Masculino , Pessoa de Meia-Idade
14.
Mol Cell Biol ; 19(5): 3395-402, 1999 May.
Artigo em Inglês | MEDLINE | ID: mdl-10207063

RESUMO

A synthetic 22-mer peptide (peptide 46) derived from the p53 C-terminal domain can restore the growth suppressor function of mutant p53 proteins in human tumor cells (G. Selivanova et al., Nat. Med. 3:632-638, 1997). Here we demonstrate that peptide 46 binds mutant p53. Peptide 46 binding sites were found within both the core and C-terminal domains of p53. Lys residues within the peptide were critical for both p53 activation and core domain binding. The sequence-specific DNA binding of isolated tumor-derived mutant p53 core domains was restored by a C-terminal polypeptide. Our results indicate that C-terminal peptide binding to the core domain activates p53 through displacement of the negative regulatory C-terminal domain. Furthermore, stabilization of the core domain structure and/or establishment of novel DNA contacts may contribute to the reactivation of mutant p53. These findings should facilitate the design of p53-reactivating drugs for cancer therapy.


Assuntos
Mutação/genética , Fragmentos de Peptídeos/metabolismo , Proteína Supressora de Tumor p53/genética , Sequência de Aminoácidos , Sítios de Ligação , Proteínas de Ligação a DNA/genética , Humanos , Dados de Sequência Molecular , Ligação Proteica , Supressão Genética , Células Tumorais Cultivadas
15.
Complement Ther Clin Pract ; 13(2): 78-84, 2007 May.
Artigo em Inglês | MEDLINE | ID: mdl-17400142

RESUMO

UNLABELLED: Chinese research indicates that the Qigong method reduces psychosomatic and physical symptoms through an effect on the sympathetic nervous system. OBJECTIVES: The aim was to investigate the effects of Qigong on stress among computer operators. DESIGN: Ten women were included in a Qigong group and an equal number in a control group. Heart rate, blood pressure, and finger temperature were measured at the beginning and at the end of the working day during 5 weeks. twenty four-hours urine samples were collected in the first and last weeks to measure catecholamine excretion in urine. Participants kept a daily record of psychological measures of strain and weekly measures of stress levels. RESULTS AND CONCLUSIONS: Qigong reduced noradrenaline excretion in urine (p<0.05), and influenced the heart rate and temperature, indicating reduced activity of the sympathetic nervous system. Moreover, Qigong reduced low-back symptoms (p<0.05). In conclusion, Qigong exercise may reduce stress at computerised work.


Assuntos
Ansiedade/prevenção & controle , Exercícios Respiratórios , Esgotamento Profissional/prevenção & controle , Comportamentos Relacionados com a Saúde , Adulto , Análise de Variância , Pressão Sanguínea , Temperatura Corporal , Esgotamento Profissional/psicologia , Catecolaminas/urina , Feminino , Frequência Cardíaca , Humanos , Masculino , Pessoa de Meia-Idade , Psicometria , Inquéritos e Questionários
16.
Nanoscale Res Lett ; 12(1): 117, 2017 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-28228002

RESUMO

Freedom of design that was introduced as organic photovoltaic (OPV) modules were fabricated by printing. As proof-of-concept, we show OPV leaf fabrication in A5 size using gravure and rotary screen printing processes for the main active layers of the OPV structure. These printing methods allow direct printing of any kind of arbitrary, two-dimensional shapes including patterning of the electric contacts thus post-patterning stages are not needed. Fabrication of custom-shaped OPV modules requires detailed information about the technical boundaries set by the manufacturing process and materials which in turn influence the layout design and R2R upscaling. In this paper, we show custom-shaped OPV modules, patterned directly in a shape of a tree leaf with an overall size of 110 cm2 and an active area of 50 cm2 providing a power conversion efficiency of 2.0% and maximum power of 98 mW.

17.
Life Sci ; 79(10): 999-1006, 2006 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-16828117

RESUMO

INTRODUCTION: Human embryonic stem cells (hES) have emerged as a potentially new therapeutic approach for treatment of heart and other diseases applying the concept of regenerative medicine. A method for in vivo visualization and tracking of transplanted hES would increase our understanding of in vivo hES behavior in both experimental and clinical settings. The aim of this study was to evaluate the feasibility of magnetic labeling and visualization of hES with magnetic resonance imaging (MRI). METHODS: hES were established and expanded according to standard procedures. After expansion, the cells were cultured under feeder free conditions and magnetically labeled by addition of dextran-coated Ferrum-oxide particles (Endorem) to the medium. Accumulation of small particles of iron-oxide (SPIO) in hES was assessed by Prussian blue staining and electron microscopy. For in vitro MRI, the labeled and unlabeled hES were examined in cell solution and after transplantation into explanted mouse heart ( approximately 100,000 cells) on a Bruker Avance DMX 500 vertical magnet at 11.75 T. A multi-slice, multi spin-echo T(2)-weighted images were obtained. For in vivo imaging, the experiments were performed on male Sprague-Dawley using Bruker Biospec 2.35 T magnet. The hES were directly injected ( approximately 500,000 cells) after surgical procedure (thoracotomy) into anterior left ventricular (LV) wall. Multi-slice T(2)-weighted gradient echo images were obtained using cardiac gating. RESULTS: hES appeared to be unaffected by magnetic labeling and maintained their ability to proliferate and differentiate. No additive agent for membrane permeabilisation was needed for facilitation of intracellular SPIO accumulation. Prussian blue and electron microscopy have revealed numerous iron particles in the cytoplasm of hES. On T(2)-weighted images, the labeled cells have shown well-defined hyopintense areas at the site of injection in anterior LV wall both in vitro and in vivo. CONCLUSIONS: It is feasible to magnetically label and visualize hES both in vitro and in vivo. MR visualization of magnetically labeled hES may be a valuable tool for in vivo tracking of hES.


Assuntos
Ferro/farmacocinética , Imageamento por Ressonância Magnética , Magnetismo , Óxidos/farmacocinética , Transplante de Células-Tronco , Células-Tronco/citologia , Células-Tronco/metabolismo , Animais , Diferenciação Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Dextranos , Estudos de Viabilidade , Óxido Ferroso-Férrico , Coração/anatomia & histologia , Humanos , Nanopartículas de Magnetita , Ratos , Coloração e Rotulagem , Transplante de Células-Tronco/métodos , Células-Tronco/efeitos dos fármacos , Transplante Heterólogo
18.
J Appl Physiol (1985) ; 98(6): 2137-46, 2005 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-15661835

RESUMO

VEGF-A contributes to muscle tissue angiogenesis following aerobic exercise training. The temporal response of the VEGF-A isoforms and their target receptors has not been comprehensively profiled in human skeletal muscle. We combined submaximal exercise with and without reduced leg blood flow to establish whether ischemia-induced metabolic stress was an important physiological stimuli responsible for regulating the VEGF-A system in humans. Nine healthy men performed two 45-min bouts of one-leg knee-extension exercise, with and without blood flow restriction. Muscle biopsies were obtained at rest and 2 and 6 h after exercise. Expression (mRNA) of the VEGF-A splice variants and related receptors [VEGF receptor (VEGFR)-1, VEGFR-2, and neuropilin-1] was determined by using qPCR. VEGF-A(total) expression increased more robustly after exercise with reduced blood flow, and initially this principally reflected an increase in VEGF-A(165). Six hours after exercise, there was a relatively greater increase in VEGF-A(189), and this response was not influenced by blood flow conditions. VEGFR-1 mRNA expression increased 2 h after exercise, and neuropilin-1 expression was transiently reduced, while all three receptors increased by 6 h. There was no evidence for the expression of the inhibitory VEGF-A(165B) variant in human skeletal muscle. Our study, reflecting both VEGF-A ligand and receptors, implicates metabolic perturbation as a regulator of human muscle angiogenesis and demonstrates that VEGF-A splice variants are distinctly regulated. Our findings also indicate that all three receptor genes exhibit different pretranslational regulation, in response to exercise in humans.


Assuntos
Músculo Esquelético/metabolismo , Esforço Físico , Receptores de Fatores de Crescimento do Endotélio Vascular/genética , Receptores de Fatores de Crescimento do Endotélio Vascular/metabolismo , Traumatismo por Reperfusão/fisiopatologia , Fator A de Crescimento do Endotélio Vascular/genética , Fator A de Crescimento do Endotélio Vascular/metabolismo , Adaptação Fisiológica/genética , Adolescente , Adulto , Velocidade do Fluxo Sanguíneo/genética , DNA Recombinante/genética , Teste de Esforço , Regulação da Expressão Gênica/genética , Variação Genética/genética , Humanos , Masculino , Contração Muscular/genética , Músculo Esquelético/irrigação sanguínea
19.
Cardiovasc Res ; 18(7): 443-6, 1984 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-6744365

RESUMO

Myoglobin, muscle fibre diameter, and citrate synthase activity were measured in leg muscle of untrained and trained men and in the myocardium from the apex of the left ventricle and from papillary muscle in patients subjected to open heart surgery. The citrate synthase (CS) activity was 60% higher in trained than in untrained skeletal muscle. In the myocardium it was around four times greater than in untrained skeletal muscle but there was no difference between the apex of the left ventricle and papillary muscle. The fibre diameter varied almost threefold between the different groups of muscles with the largest diameter in untrained skeletal muscle and the with the largest diameter in untrained skeletal muscle and the smallest in papillary muscle. The myoglobin content in trained skeletal muscle did not differ from that of untrained muscle. In the left ventricle it was only 40% of that found in untrained muscle while papillary muscle had almost twice as high a myoglobin content as did the left ventricle. The ratio between myoglobin and fibre diameter, however, was of similar magnitude in skeletal muscle and the left ventricle while it was twice as high in papillary muscle as in the other muscles. In conclusion, the diffusion distance in terms of fibre diameter decreased with increased oxidative capacity (CS activity), when comparing the statistical means of the four different groups. The capacity for oxygen diffusion in relation to oxygen demand measured as the ratio of myoglobin to fibre diameter appeared to be of similar magnitude in skeletal muscle and left ventricle but was higher in papillary muscle.


Assuntos
Músculos/metabolismo , Miocárdio/metabolismo , Mioglobina/metabolismo , Adulto , Antropometria , Citrato (si)-Sintase/metabolismo , Humanos , Masculino , Pessoa de Meia-Idade , Músculos/anatomia & histologia , Músculos/enzimologia , Miocárdio/enzimologia , Aptidão Física
20.
Cardiovasc Res ; 42(1): 99-103, 1999 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-10435000

RESUMO

UNLABELLED: This study hypothesized that female patients with chronic heart failure (CHF), similarly as previously reported for male patients, have a decreased proportion of type I (slow twitch) muscle fibers combined with fiber atrophy, and respond to exercise training with an increased muscular fiber area and performance, and with an unaltered fiber type distribution. METHODS: Sixteen women [age 62 +/- 10 years (mean +/- SD)] with stable, moderate CHF (left ventricular ejection fraction 28 +/- 8%) underwent percutaneous needle biopsies of the lateral vastus muscle, and assessments of isokinetic muscle strength and exercise tests with respiratory gas and blood lactate analyses, before and after 8 weeks of intensive knee extensor endurance training. RESULTS: When compared to healthy age-matched women, the women with CHF unexpectedly had a normal proportion of type I fibers (51 +/- 15%), but a decreased cross-sectional area in both type I and II fibers. Exercise training increased the cross-sectional area of muscle fibers up to the reference range (21%, p < 0.04), while the relative number of type I fibers decreased (12%, p < 0.03). Training also increased muscle strength (16%, p < 0.0001) and peak oxygen uptake (20%, p < 0.0001). The increase in peak oxygen uptake was directly related to the training-induced increase in fiber areas (r = 0.63; p < 0.03), and decrease in lactate accumulation was inversely related to the training-induced decrease in the relative number of type I fibers (r = -0.62; p < 0.02). CONCLUSIONS: As for men with CHF, a skeletal muscle atrophy was found in women, but contrary to the hypothesis, the proportion of type I muscle fibers was normal. Exercise training counteracted the atrophy suggesting skeletal muscle trainability in female CHF patients.


Assuntos
Insuficiência Cardíaca/patologia , Músculo Esquelético/patologia , Educação Física e Treinamento , Resistência Física , Adulto , Idoso , Biópsia por Agulha , Estudos de Casos e Controles , Doença Crônica , Teste de Esforço , Feminino , Insuficiência Cardíaca/fisiopatologia , Insuficiência Cardíaca/terapia , Humanos , Ácido Láctico/sangue , Modelos Lineares , Pessoa de Meia-Idade , Fibras Musculares de Contração Rápida/patologia , Fibras Musculares de Contração Lenta/patologia , Músculo Esquelético/fisiopatologia , Consumo de Oxigênio
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