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71.
Paula Clemente Susana Peralta Alberto Cruz-Bermudez Lucía Echevarría Flavia Fontanesi Antoni Barrientos Miguel A. Fernandez-Moreno Rafael Garesse 《The Journal of biological chemistry》2013,288(12):8321-8331
Cytochrome c oxidase (COX) or complex IV of the mitochondrial respiratory chain plays a fundamental role in energy production of aerobic cells. In humans, COX deficiency is the most frequent cause of mitochondrial encephalomyopathies. Human COX is composed of 13 subunits of dual genetic origin, whose assembly requires an increasing number of nuclear-encoded accessory proteins known as assembly factors. Here, we have identified and characterized human CCDC56, an 11.7-kDa mitochondrial transmembrane protein, as a new factor essential for COX biogenesis. CCDC56 shares sequence similarity with the yeast COX assembly factor Coa3 and was termed hCOA3. hCOA3-silenced cells display a severe COX functional alteration owing to a decreased stability of newly synthesized COX1 and an impairment in the holoenzyme assembly process. We show that hCOA3 physically interacts with both the mitochondrial translation machinery and COX structural subunits. We conclude that hCOA3 stabilizes COX1 co-translationally and promotes its assembly with COX partner subunits. Finally, our results identify hCOA3 as a new candidate when screening for genes responsible for mitochondrial diseases associated with COX deficiency. 相似文献
72.
The mating call of Isoperla bipartita is described. The male call is composed of 3–10 groups, each of 1–4 rubs. The times between rubs average 89.52 msec (between first and second), 43.52 msec (between second and third) and 35.28 msec (between third and fourth). The time between two groups averages 180.75 msec and varies from 142 to 290 msec. The female answer is composed of a beat and rub repeated at 479.09 msec intervals on average and interspersed between the male call groups between 94 and 184 msec (mean = 118.11 msec) after the last rub of the male group. The I. bipartita call can be considered as a ‘complex and modified pattern’ because the male produces calls of 1–4 rubs by group and the female answers overlapping the male call by percussion-rubbing-produced signals. Moreover, it is different from other studied Iberian Isoperla calls, being probably a species-specific behavioural pattern. 相似文献
73.
Roselló-Lletí E Rivera M Cortés R Azorín I Sirera R Martínez-Dolz L Hove L Cinca J Lago F González-Juanatey JR Salvador A Portolés M 《Biochemical and biophysical research communications》2012,418(2):222-228
We investigate for the first time the influence of heart failure (HF) on nucleolar organization and proteins in patients with ischemic (ICM) or dilated cardiomyopathy (DCM). A total of 71 human hearts from ICM (n=38) and DCM (n=27) patients, undergoing heart transplantation and control donors (n=6), were analysed by western-blotting, RT-PCR and cell biology methods. When we compared protein levels according to HF etiology, nucleolin was increased in both ICM (117%, p<0.05) and DCM (141%, p<0.01). Moreover, mRNA expression were also upregulated in ICM (1.46-fold, p<0.05) and DCM (1.70-fold, p<0.05. Immunofluorescence studies showed that the highest intensity of nucleolin was into nucleolus (p<0.0001), and it was increased in pathological hearts (p<0.0001). Ultrastructure analysis by electron microscopy showed an increase in the nucleus and nucleolus size in ICM (17%, p<0.05 and 131%, p<0.001) and DCM (56%, p<0.01 and 69%, p<0.01). Nucleolar organization was influenced by HF irrespective of etiology, increasing fibrillar centers (p<0.001), perinucleolar chromatin (p<0.01) and dense fibrillar components (p<0.01). Finally, left ventricular function parameters were related with nucleolin levels in ischemic hearts (p<0.0001). The present study demonstrates that HF influences on morphology and organization of nucleolar components, revealing changes in the expression and in the levels of nucleolin protein. 相似文献
74.
José A. G. Agúndez Pedro Ayuso José A. Cornejo-García Miguel Blanca María J. Torres Inmaculada Do?a María Salas Natalia Blanca-López Gabriela Canto Carmen Rondon Paloma Campo José J. Laguna Javier Fernández Carmen Martínez Elena García-Martín 《PloS one》2012,7(11)
Non-steroidal anti-inflammatory drugs (NSAIDs) are the drugs most frequently involved in hypersensitivity drug reactions. Histamine is released in the allergic response to NSAIDs and is responsible for some of the clinical symptoms. The aim of this study is to analyze clinical association of functional polymorphisms in the genes coding for enzymes involved in histamine homeostasis with hypersensitivity response to NSAIDs. We studied a cohort of 442 unrelated Caucasian patients with hypersensitivity to NSAIDs. Patients who experienced three or more episodes with two or more different NSAIDs were included. If this requirement was not met diagnosis was established by challenge. A total of 414 healthy unrelated controls ethnically matched with patients and from the same geographic area were recruited. Analyses of the SNPs rs17740607, rs2073440, rs1801105, rs2052129, rs10156191, rs1049742 and rs1049793 in the HDC, HNMT and DAO genes were carried out by means of TaqMan assays. The detrimental DAO 16 Met allele (rs10156191), which causes decreased metabolic capacity, is overrepresented among patients with crossed-hypersensitivity to NSAIDs with an OR = 1.7 (95% CI = 1.3–2.1; Pc = 0.0003) with a gene-dose effect (P = 0.0001). The association was replicated in two populations from different geographic areas (Pc = 0.008 and Pc = 0.004, respectively).
Conclusions and implications
The DAO polymorphism rs10156191 which causes impaired metabolism of circulating histamine is associated with the clinical response in crossed-hypersensitivity to NSAIDs and could be used as a biomarker of response. 相似文献75.
Ramírez-Salinas Gema L. García-Machorro J. Quiliano Miguel Zimic Mirko Briz Verónica Rojas-Hernández Saul Correa-Basurto J. 《Journal of molecular modeling》2015,21(11):1-14
Journal of Molecular Modeling - There is a wide variety of ion channel types with various types of blockers, making research in this field very complicated. To reduce this complexity, it is... 相似文献
76.
Miguel ángel Mu?oz-Ruiz P?ivi Hartikainen Juha Koikkalainen Robin Wolz Valtteri Julkunen Eini Niskanen Sanna-Kaisa Herukka Miia Kivipelto Ritva Vanninen Daniel Rueckert Yawu Liu Jyrki L?tj?nen Hilkka Soininen 《PloS one》2012,7(12)
Background
MRI is an important clinical tool for diagnosing dementia-like diseases such as Frontemporal Dementia (FTD). However there is a need to develop more accurate and standardized MRI analysis methods.Objective
To compare FTD with Alzheimer’s Disease (AD) and Mild Cognitive Impairment (MCI) with three automatic MRI analysis methods - Hippocampal Volumetry (HV), Tensor-based Morphometry (TBM) and Voxel-based Morphometry (VBM), in specific regions of interest in order to determine the highest classification accuracy.Methods
Thirty-seven patients with FTD, 46 patients with AD, 26 control subjects, 16 patients with progressive MCI (PMCI) and 48 patients with stable MCI (SMCI) were examined with HV, TBM for shape change, and VBM for gray matter density. We calculated the Correct Classification Rate (CCR), sensitivity (SS) and specificity (SP) between the study groups.Results
We found unequivocal results differentiating controls from FTD with HV (hippocampus left side) (CCR = 0.83; SS = 0.84; SP = 0.80), with TBM (hippocampus and amygdala (CCR = 0.80/SS = 0.71/SP = 0.94), and with VBM (all the regions studied, especially in lateral ventricle frontal horn, central part and occipital horn) (CCR = 0.87/SS = 0.81/SP = 0.96). VBM achieved the highest accuracy in differentiating AD and FTD (CCR = 0.72/SS = 0.67/SP = 0.76), particularly in lateral ventricle (frontal horn, central part and occipital horn) (CCR = 0.73), whereas TBM in superior frontal gyrus also achieved a high accuracy (CCR = 0.71/SS = 0.68/SP = 0.73). TBM resulted in low accuracy (CCR = 0.62) in the differentiation of AD from FTD using all regions of interest, with similar results for HV (CCR = 0.55).Conclusion
Hippocampal atrophy is present not only in AD but also in FTD. Of the methods used, VBM achieved the highest accuracy in its ability to differentiate between FTD and AD. 相似文献77.
Luis‐Miguel Chevin 《Evolution; international journal of organic evolution》2016,70(3):513-525
Species selection resulting from trait‐dependent speciation and extinction is increasingly recognized as an important mechanism of phenotypic macroevolution. However, the recent bloom in statistical methods quantifying this process faces a scarcity of dynamical theory for their interpretation, notably regarding the relative contributions of deterministic versus stochastic evolutionary forces. I use simple diffusion approximations of birth‐death processes to investigate how the expected and random components of macroevolutionary change depend on phenotype‐dependent speciation and extinction rates, as can be estimated empirically. I show that the species selection coefficient for a binary trait, and selection differential for a quantitative trait, depend not only on differences in net diversification rates (speciation minus extinction), but also on differences in species turnover rates (speciation plus extinction), especially in small clades. The randomness in speciation and extinction events also produces a species‐level equivalent to random genetic drift, which is stronger for higher turnover rates. I then show how microevolutionary processes including mutation, organismic selection, and random genetic drift cause state transitions at the species level, allowing comparison of evolutionary forces across levels. A key parameter that would be needed to apply this theory is the distribution and rate of origination of new optimum phenotypes along a phylogeny. 相似文献
78.
José Miguel Gasulla Fernando Escaso Iván Narváez Francisco Ortega José Luis Sanz 《PloS one》2015,10(12)
A new styracosternan ornithopod genus and species is here described based on a partial postcranial skeleton and an associated dentary tooth of a single specimen from the Arcillas de Morella Formation (Early Cretaceous, late Barremian) at the Morella locality, (Castellón, Spain). Morelladon beltrani gen. et sp. nov. is diagnosed by eight autapomorphic features. The set of autapomorphies includes: very elongated and vertical neural spines of the dorsal vertebrae, midline keel on ventral surface of the second to fourth sacral vertebrae restricted to the anterior half of the centrum, a posterodorsally inclined medial ridge on the postacetabular process of the ilium that meets its dorsal margin and distal end of the straight ischial shaft laterally expanded, among others. Phylogenetic analyses reveal that the new Iberian form is more closely related to its synchronic and sympatric contemporary European taxa Iguanodon bernissartensis and Mantellisaurus atherfieldensis, known from Western Europe, than to other Early Cretaceous Iberian styracosternans (Delapparentia turolensis and Proa valdearinnoensis). The recognition of Morelladon beltrani gen. et sp. nov. indicates that the Iberian Peninsula was home to a highly diverse medium to large bodied styracosternan assemblage during the Early Cretaceous. 相似文献
79.
Miguel Arredondo María José Mendiburo Sebastián Flores Steven T. Singleton Michael D. Garrick 《Biometals》2014,27(1):115-123
Divalent Metal Transporter 1 (DMT1) is an apical Fe transporter in the duodenum and is involved in endosomal Fe export. Four protein isoforms have been described for DMT1, two from mRNA with an iron responsive element (IRE) and two from mRNA without it. The sets of two begin in exon 1A or 2. We have characterized copper transport using mouse 2/?IRE DMT1 during regulated ectopic expression. HEK293 cells carrying a TetR:Hyg element were stably transfected with pDEST31 containing a 2/?IRE construct. 64Cu1+ incorporation in doxycycline treated cells exhibited 18.6 and 30.0-fold increases in Cu content, respectively when were exposed to 10 and 100 μM of extracellular Cu. Cu content was ~4-fold above that of parent cells or cells carrying just the vector. 64Cu uptake in transfected cells pre-incubated with 5 μM of Cu-His revealed a Vmax and Km of 11.98 ± 0.52 pmol mg protein?1 min?1 and 2.03 ± 0.03 μM, respectively. Doxycycline-stimulated Cu uptake was linear with time. The rates of apical Cu uptake decreased and transepithelial transport increased when intracellular Cu increased. The optimal pH for Cu transport was 6.5; uptake of Cu was temperature dependent. Silver does not inhibit Cu uptake in cells carrying the vector. In conclusion, Cu uptake in HEK293 cells that over-expressed the 2/?IRE isoform of DMT1 transporter supports our earlier contention that DMT1 transports Cu as Cu1+. 相似文献
80.
Cecília Dur?es Carla S. Moreira Inês Alvelos Adélia Mendes Liliana R. Santos José Carlos Machado Miguel Melo César Esteves Celestino Neves Manuel Sobrinho-Sim?es Paula Soares 《PloS one》2014,9(8)