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121.
Pellinen T Tuomi S Arjonen A Wolf M Edgren H Meyer H Grosse R Kitzing T Rantala JK Kallioniemi O Fässler R Kallio M Ivaska J 《Developmental cell》2008,15(3):371-385
Adherent cells undergo remarkable changes in shape during cell division. However, the functional interplay between cell adhesion turnover and the mitotic machinery is poorly understood. The endo/exocytic trafficking of integrins is regulated by the small GTPase Rab21, which associates with several integrin alpha subunits. Here, we show that targeted trafficking of integrins to and from the cleavage furrow is required for successful cytokinesis, and that this is regulated by Rab21. Rab21 activity, integrin-Rab21 association, and integrin endocytosis are all necessary for normal cytokinesis, which becomes impaired when integrin-mediated adhesion at the cleavage furrow fails. We also describe a chromosomal deletion and loss of Rab21 gene expression in human cancer, which leads to the accumulation of multinucleate cells. Importantly, reintroduction of Rab21 rescued this phenotype. In conclusion, Rab21-regulated integrin trafficking is essential for normal cell division, and its defects may contribute to multinucleation and genomic instability, which are hallmarks of cancer. 相似文献
122.
The effects of timed ingestion of high-quality protein before and after resistance exercise are not well known. In this study,
young men were randomized to protein (n = 11), placebo (n = 10) and control (n = 10) groups. Muscle cross-sectional area by MRI and muscle forces were analyzed before and after 21 weeks of either heavy
resistance training (RT) or control period. Muscle biopsies were taken before, and 1 and 48 h after 5 × 10 repetition leg
press exercise (RE) as well as 21 weeks after RT. Protein (15 g of whey both before and after exercise) or non-energetic placebo
were provided to subjects in the context of both single RE bout (acute responses) as well as each RE workout twice a week
throughout the 21-week-RT. Protein intake increased (P ≤ 0.05) RT-induced muscle cross-sectional area enlargement and cell-cycle kinase cdk2 mRNA expression in the vastus lateralis
muscle suggesting higher proliferating cell activation response with protein supplementation. Moreover, protein intake seemed
to prevent 1 h post-RE decrease in myostatin and myogenin mRNA expression but did not affect activin receptor IIb, p21, FLRG,
MAFbx or MyoD expression. In conclusion, protein intake close to resistance exercise workout may alter mRNA expression in
a manner advantageous for muscle hypertrophy. 相似文献
123.
The formation of a carbon-carbon bond is an essential step in the biosynthetic pathways by which fatty acids and polyketides are made. The thiolase superfamily enzymes catalyse this carbon-carbon-bond formation via a thioester-dependent Claisen-condensation-reaction mechanism. In this way, fatty-acid chains and polyketides are made by sequentially adding simple building blocks, such as acetate units, to the growing molecule. A common feature of these enzymes is a reactive cysteine residue that is transiently acylated in the catalytic cycle. The wide catalytic diversity of the thiolase superfamily enzymes is of great interest. In particular, the type-III polyketide synthases make complicated compounds of great biological importance using multiple, subsequent condensation reactions, which are all catalysed in the same active-site cavity. The crucial metabolic importance of the bacterial fatty-acid-synthesizing enzymes stimulates in-depth studies that aim to develop efficient anti-bacterial drugs. 相似文献
124.
Veikko Salomaa Aki Havulinna Olli Saarela Tanja Zeller Pekka Jousilahti Antti Jula Thomas Muenzel Arpo Aromaa Alun Evans Kari Kuulasmaa Stefan Blankenberg 《PloS one》2010,5(4)
Background
The prevalence of diabetes is increasing in all industrialized countries and its prevention has become a public health priority. However, the predictors of diabetes risk are insufficiently understood. We evaluated, whether 31 novel biomarkers could help to predict the risk of incident diabetes.Methods and Findings
The biomarkers were evaluated primarily in the FINRISK97 cohort (n = 7,827; 417 cases of clinically incident diabetes during the follow-up). The findings were replicated in the Health 2000 cohort (n = 4,977; 179 cases of clinically incident diabetes during the follow-up). We used Cox proportional hazards models to calculate the relative risk of diabetes, after adjusting for the classic risk factors, separately for each biomarker. Next, we assessed the discriminatory ability of single biomarkers using receiver operating characteristic curves and C-statistics, integrated discrimination improvement (IDI) and net reclassification improvement (NRI). Finally, we derived a biomarker score in the FINRISK97 cohort and validated it in the Health 2000 cohort. A score consisting of adiponectin, apolipoprotein B, C-reactive protein and ferritin almost doubled the relative risk of diabetes in the validation cohort (HR per one standard deviation increase 1.88, p = 2.8 e-5). It also improved discrimination of the model (IDI = 0.0149, p<0.0001) and reclassification of diabetes risk (NRI = 11.8%, p = 0.006). Gender-specific analyses suggested that the best score differed between men and women. Among men, the best results were obtained with the score of four biomarkers: adiponectin, apolipoprotein B, ferritin and interleukin-1 receptor antagonist, which gave an NRI of 25.4% (p<0.0001). Among women, the best score included adiponectin, apolipoprotein B, C-reactive protein and insulin. It gave an NRI of 13.6% (p = 0.041).Conclusions
We identified novel biomarkers that were associated with the risk of clinically incident diabetes over and above the classic risk factors. This gives new insights into the pathogenesis of diabetes and may help with targeting prevention and treatment. 相似文献125.
Jarna C. Hannukainen Kari K. Kalliokoski Ronald J.M. Borra Antti P.M. Viljanen Tuula Janatuinen Urho M. Kujala Jaakko Kaprio Olli J. Heinonen Tapio Viljanen Merja Haaparanta Patricia Iozzo Riitta Parkkola Pirjo Nuutila 《Obesity (Silver Spring, Md.)》2010,18(2):261-265
Visceral adipose tissue has been shown to have high lipolytic activity. The aim of this study was to examine whether free fatty acid (FFA) uptake into visceral adipose tissue is enhanced compared to abdominal subcutaneous tissue in vivo. Abdominal adipose tissue FFA uptake was measured using positron emission tomography (PET) and [18F]‐labeled 6‐thia‐hepta‐decanoic acid ([18F]FTHA) and fat masses using magnetic resonance imaging (MRI) in 18 healthy young adult males. We found that FFA uptake was 30% higher in visceral compared to subcutaneous adipose tissue (0.0025 ± 0.0018 vs. 0.0020 ± 0.0016 µmol/g/min, P = 0.005). Visceral and subcutaneous adipose tissue FFA uptakes were strongly associated with each other (P < 0.001). When tissue FFA uptake per gram of fat was multiplied by the total tissue mass, total FFA uptake was almost 1.5 times higher in abdominal subcutaneous than in visceral adipose tissue. In conclusion, we observed enhanced FFA uptake in visceral compared to abdominal subcutaneous adipose tissue and, simultaneously, these metabolic rates were strongly associated with each other. The higher total tissue FFA uptake in subcutaneous than in visceral adipose tissue indicates that although visceral fat is active in extracting FFA, its overall contribution to systemic metabolism is limited in healthy lean males. Our results indicate that subcutaneous, rather than visceral fat storage plays a more direct role in systemic FFA availability. The recognized relationship between abdominal visceral fat mass and metabolic complications may be explained by direct effects of visceral fat on the liver. 相似文献
126.
Rose G Romeo G Dato S Crocco P Bruni AC Hervonen A Majamaa K Sevini F Franceschi C Passarino G;GEnetics of Healthy Ageing Project Consortium 《PloS one》2010,5(10):e13395
Tissue specific somatic mutations occurring in the mtDNA control region have been proposed to provide a survival advantage. Data on twins and on relatives of long-lived subjects suggested that the occurrence/accumulation of these mutations may be genetically influenced. To further investigate control region somatic heteroplasmy in the elderly, we analyzed the segment surrounding the nt 150 position (previously reported as specific of Leukocytes) in various types of leukocytes obtained from 195 ultra-nonagenarians sib-pairs of Italian or Finnish origin collected in the frame of the GEHA Project. We found a significant correlation of the mtDNA control region heteroplasmy between sibs, confirming a genetic influence on this phenomenon. Furthermore, many subjects showed heteroplasmy due to mutations different from the C150T transition. In these cases heteroplasmy was correlated within sibpairs in Finnish and northern Italian samples, but not in southern Italians. This suggested that the genetic contribution to control region mutations may be population specific. Finally, we observed a possible correlation between heteroplasmy and Hand Grip strength, one of the best markers of physical performance and of mortality risk in the elderly. Our study provides new evidence on the relevance of mtDNA somatic mutations in aging and longevity and confirms that the occurrence of specific point mutations in the mtDNA control region may represent a strategy for the age-related remodelling of organismal functions. 相似文献
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Mikko Taina Miika Korhonen Mika Haataja Antti Muuronen Otso Arponen Marja Hedman Pekka J?k?l? Petri Sipola Pirjo Mustonen Ritva Vanninen 《PloS one》2014,9(7)