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Savage DB Agostini M Barroso I Gurnell M Luan J Meirhaeghe A Harding AH Ihrke G Rajanayagam O Soos MA George S Berger D Thomas EL Bell JD Meeran K Ross RJ Vidal-Puig A Wareham NJ O'Rahilly S Chatterjee VK Schafer AJ 《Nature genetics》2002,31(4):379-384
Impaired insulin action is a key feature of type 2 diabetes and is also found, to a more extreme degree, in familial syndromes of insulin resistance. Although inherited susceptibility to insulin resistance may involve the interplay of several genetic loci, no clear examples of interactions among genes have yet been reported. Here we describe a family in which five individuals with severe insulin resistance, but no unaffected family members, were doubly [corrected] heterozygous with respect to frameshift/premature stop mutations in two unlinked genes, PPARG and PPP1R3A these encode peroxisome proliferator activated receptor gamma, which is highly expressed in adipocytes, and protein phosphatase 1, regulatory subunit 3, the muscle-specific regulatory subunit of protein phosphatase 1, which are centrally involved in the regulation of carbohydrate and lipid metabolism, respectively. That mutant molecules primarily involved in either carbohydrate or lipid metabolism can combine to produce a phenotype of extreme insulin resistance provides a model of interactions among genes that may underlie common human metabolic disorders such as type 2 diabetes. 相似文献
74.
McGregor L Makela V Darling SM Vrontou S Chalepakis G Roberts C Smart N Rutland P Prescott N Hopkins J Bentley E Shaw A Roberts E Mueller R Jadeja S Philip N Nelson J Francannet C Perez-Aytes A Megarbane A Kerr B Wainwright B Woolf AS Winter RM Scambler PJ 《Nature genetics》2003,34(2):203-208
Fraser syndrome (OMIM 219000) is a multisystem malformation usually comprising cryptophthalmos, syndactyly and renal defects. Here we report autozygosity mapping and show that the locus FS1 at chromosome 4q21 is associated with Fraser syndrome, although the condition is genetically heterogeneous. Mutation analysis identified five frameshift mutations in FRAS1, which encodes one member of a family of novel proteins related to an extracellular matrix (ECM) blastocoelar protein found in sea urchin. The FRAS1 protein contains a series of N-terminal cysteine-rich repeat motifs previously implicated in BMP metabolism, suggesting that it has a role in both structure and signal propagation in the ECM. It has been speculated that Fraser syndrome is a human equivalent of the blebbed phenotype in the mouse, which has been associated with mutations in at least five loci including bl. As mapping data were consistent with homology of FRAS1 and bl, we screened DNA from bl/bl mice and identified a premature termination of mouse Fras1. Thus, the bl mouse is a model for Fraser syndrome in humans, a disorder caused by disrupted epithelial integrity in utero. 相似文献
75.
Female multiple mating and alternative mating systems can decrease the opportunity for sexual selection. Sperm competition is often the outcome of females mating with multiple males and has been observed in many animals, and alternative reproductive systems are widespread among species with external fertilization and parental care. Multiple paternity without associated complex behaviour related to mating or parental care is also seen in simultaneously spawning amphibians and fishes that release gametes into water. Here we report 'clutch piracy' in a montane population of the common frog Rana temporaria, a reproductive behaviour previously unknown in vertebrates with external fertilization. Males of this species clasp the females and the pair deposits one spherical clutch of eggs. No parental care is provided. 'Pirate' males search for freshly laid clutches, clasp them as they would do a female and fertilize the eggs that were left unfertilized by the 'parental' male. This behaviour does not seem to be size-dependent, and some males mate with a female and perform clutch piracy in the same season. Piracy affected 84% of the clutches and in some cases increased the proportion of eggs fertilized, providing direct fitness benefits both for the pirate males and the females. Sexual selection--probably caused by a strong male-biased sex ratio--occurs in this population, as indicated by size-assortative mating; however, clutch piracy may reduce its impact. This provides a good model to explore how alternative mating strategies can affect the intensity of sexual selection. 相似文献
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In this paper we will propose an empirical analysis of spatial and temporal boundaries. Unlike other proposals, which deal mainly with the commonsense level of the subject, we will ground our explication on well-established scientific practice and language. In this way we show how to reconsider in an innovative way questions such as the distinction between the bona fide boundaries and the fiat boundaries, the thickness and the ownership of the boundaries. At the same time we propose a division between ex mensura boundaries and qui vulgo dicuntur boundaries. What is it, therefore, that divides the atmosphere from the water? [Leonardo da Vinci, Notebooks] 相似文献
78.
Silvia Ravera Marina Podestà Federica Sabatini Chiara Fresia Marta Columbaro Silvia Bruno Ezio Fulcheri Luca Antonio Ramenghi Francesco Frassoni 《Cellular and molecular life sciences : CMLS》2018,75(5):889-903
We evaluated the energy metabolism of human mesenchymal stem cells (MSC) isolated from umbilical cord (UC) of preterm (< 37 weeks of gestational age) and term (≥ 37 weeks of gestational age) newborns, using MSC from adult bone marrow as control. A metabolic switch has been observed around the 34th week of gestational age from a prevalently anaerobic glycolysis to the oxidative phosphorylation. This metabolic change is associated with the organization of mitochondria reticulum: preterm MSCs presented a scarcely organized mitochondrial reticulum and low expression of proteins involved in the mitochondrial fission/fusion, compared to term MSCs. These changes seem governed by the expression of CLUH, a cytosolic messenger RNA-binding protein involved in the mitochondria biogenesis and distribution inside the cell; in fact, CLUH silencing in term MSC determined a metabolic fingerprint similar to that of preterm MSC. Our study discloses novel information on the production of energy and mitochondrial organization and function, during the passage from fetal to adult life, providing useful information for the management of preterm birth. 相似文献
79.
German Antonio Villanueva-Bonilla Suyen Safuan-Naide João Vasconcellos-Neto 《Journal of Natural History》2018,52(5-6):361-376
Numerous phenological studies on spiders belonging to the families Oxyopidae, Thomisidae, Lycosidae, Selenopidae (e.g. Selenops cocheleti) and Salticidae (e.g. Psecas chapoda and Psecas viridipurpureus) have been conducted in the neotropical region. However, studies that simultaneously compare population dynamics and age structure in populations of sympatric species are limited, especially in Oxyopidae. The population dynamics and phenology of two congeneric lynx spider (Peucetia rubrolineata and Peucetia flava) were examined in southeastern Brazil. Several characteristics of the age structure were compared between the two spider species. The variation in the total abundance of individuals and age structure and their relationship with climatic variables were similar between the two spiders. Adults of these spiders were present mainly in spring, indicating an annual reproductive cycle and a ‘stenochronous spring’ phenological pattern. The recruitment of spiders occurred in summer for P. rubrolineata and P. flava, followed by successive phenological peaks at all stages of development. Rainfall and temperature had a positive correlation to population flux in the two spider species studied. Despite the significant climatic effects observed in the Serra do Japi, the phenological pattern of the population in this study was not always repeated in other species of spiders (e.g. Selenops cocheleti). 相似文献
80.
Yesica R. Nievas Veronica M. Coceres Victor Midlej Wanderley de Souza Marlene Benchimol Antonio Pereira-Neves Ajay A. Vashisht James A. Wohlschlegel Patricia J. Johnson Natalia de Miguel 《Cellular and molecular life sciences : CMLS》2018,75(12):2211-2226
Trichomonas vaginalis is a common sexually transmitted parasite that colonizes the human urogenital tract, where it remains extracellular and adheres to epithelial cells. Infections range from asymptomatic to highly inflammatory, depending on the host and the parasite strain. Despite the serious consequences associated with trichomoniasis disease, little is known about parasite or host factors involved in attachment of the parasite-to-host epithelial cells. Here, we report the identification of microvesicle-like structures (MVs) released by T. vaginalis. MVs are considered universal transport vehicles for intercellular communication as they can incorporate peptides, proteins, lipids, miRNA, and mRNA, all of which can be transferred to target cells through receptor–ligand interactions, fusion with the cell membrane, and delivery of a functional cargo to the cytoplasm of the target cell. In the present study, we demonstrated that T. vaginalis release MVs from the plasma and the flagellar membranes of the parasite. We performed proteomic profiling of these structures demonstrating that they possess physical characteristics similar to mammalian extracellular vesicles and might be selectively charged with specific protein content. In addition, we demonstrated that viable T. vaginalis parasites release large vesicles (LVs), membrane structures larger than 1 µm that are able to interact with other parasites and with the host cell. Finally, we show that both populations of vesicles present on the surface of T vaginalis are induced in the presence of host cells, consistent with a role in modulating cell interactions. 相似文献