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81.
Background
Mucolipidosis Type IV is currently characterized as a lysosomal storage disorder with defects that include corneal clouding, achlorhydria and psychomotor retardation. MCOLN1, the gene responsible for this disease, encodes the protein mucolipin-1 that belongs to the "Transient Receptor Potential" family of proteins and has been shown to function as a non-selective cation channel whose activity is modulated by pH. Two cell biological defects that have been described in MLIV fibroblasts are a hyperacidification of lysosomes and a delay in the exit of lipids from lysosomes. 相似文献82.
Background
Paulinella chromatophora is a freshwater filose amoeba with photosynthetic endosymbionts (chromatophores) of cyanobacterial origin that are closely related to free-living Prochlorococcus and Synechococcus species (PS-clade). Members of the PS-clade of cyanobacteria contain a proteobacterial form 1A RubisCO (ribulose-1,5-bisphosphate carboxylase/oxygenase) that was acquired by horizontal gene transfer (HGT) of a carboxysomal operon. In rDNA-phylogenies, the Paulinella chromatophore diverged basal to the PS-clade, raising the question whether the HGT occurred before or after the split of the chromatophore ancestor. 相似文献83.
Karen CM Moraes Lívia F Diniz Maria Terezinha Bahia 《Memórias do Instituto Oswaldo Cruz》2015,110(2):181-191
Chagas disease, caused by the intracellular protozoan Trypanosoma
cruzi, is a serious health problem in Latin America. During this
parasitic infection, the heart is one of the major organs affected. The pathogenesis
of tissue remodelling, particularly regarding cardiomyocyte behaviour after parasite
infection and the molecular mechanisms that occur immediately following parasite
entry into host cells are not yet completely understood. When cells are infected with
T. cruzi, they develop an inflammatory response, in which
cyclooxygenase-2 (COX-2) catalyses rate-limiting steps in the arachidonic acid
pathway. However, how the parasite interaction modulates COX-2 activity is poorly
understood. In this study, the H9c2 cell line was used as our model and we
investigated cellular and biochemical aspects during the initial 48 h of parasitic
infection. Oscillatory activity of COX-2 was observed, which correlated with the
control of the pro-inflammatory environment in infected cells. Interestingly,
subcellular trafficking was also verified, correlated with the control of Cox-2 mRNA
or the activated COX-2 protein in cells, which is directly connected with the
assemble of stress granules structures. Our collective findings suggest that in the
very early stage of the T. cruzi-host cell interaction, the parasite
is able to modulate the cellular metabolism in order to survives. 相似文献
84.
Cíntia Júnia Monteiro Suianne Letícia Antunes Mota Lívia de Figueiredo Diniz Maria Terezinha Bahia Karen CM Moraes 《Memórias do Instituto Oswaldo Cruz》2015,110(8):996-1002
Chagas disease, which is caused by the intracellular protozoanTrypanosoma
cruzi, is a serious health problem in Latin America. The heart is one of
the major organs affected by this parasitic infection. The pathogenesis of tissue
remodelling, particularly regarding cardiomyocyte behaviour after parasite infection,
and the molecular mechanisms that occur immediately following parasite entry into
host cells are not yet completely understood. Previous studies have reported that the
establishment of parasitism is connected to the activation of the
phosphatidylinositol-3 kinase (PI3K), which controls important steps in cellular
metabolism by regulating the production of the second messenger
phosphatidylinositol-3,4,5-trisphosphate. Particularly, the tumour suppressor PTEN is
a negative regulator of PI3K signalling. However, mechanistic details of the
modulatory activity of PTEN on Chagas disease have not been elucidated. To address
this question, H9c2 cells were infected with T. cruzi Berenice 62
strain and the expression of a specific set of microRNAs (miRNAs) were investigated.
Our cellular model demonstrated that miRNA-190b is correlated to the decrease of
cellular viability rates by negatively modulating PTEN protein expression in
T. cruzi-infected cells. 相似文献
85.
Tulika Sarma Athanasia Koutsouris Jiang Zhu Yu Aleksandar Krbanjevic Thomas J. Hope Mark M. Rasenick 《The Journal of biological chemistry》2015,290(16):10045-10056
Signals that activate the G protein Gαs and promote neuronal differentiation evoke Gαs internalization in rat pheochromocytoma (PC12) cells. These agents also significantly increase Gαs association with microtubules, resulting in an increase in microtubule dynamics because of the activation of tubulin GTPase by Gαs. To determine the function of Gαs/microtubule association in neuronal development, we used real-time trafficking of a GFP-Gαs fusion protein. GFP-Gαs concentrates at the distal end of the neurites in differentiated living PC12 cells as well as in cultured hippocampal neurons. Gαs translocates to specialized membrane compartments at tips of growing neurites. A dominant-negative Gα chimera that interferes with Gαs binding to tubulin and activation of tubulin GTPase attenuates neurite elongation and neurite number both in PC12 cells and primary hippocampal neurons. This effect is greatest on differentiation induced by activated Gαs. Together, these data suggest that activated Gαs translocates from the plasma membrane and, through interaction with tubulin/microtubules in the cytosol, is important for neurite formation, development, and outgrowth. Characterization of neuronal G protein dynamics and their contribution to microtubule dynamics is important for understanding the molecular mechanisms by which G protein-coupled receptor signaling orchestrates neuronal growth and differentiation. 相似文献
86.
87.
Zhao J Del Bigio MR Weiler HA 《Prostaglandins, leukotrienes, and essential fatty acids》2011,84(1-2):63-70
Maternal diabetes may compromise infant arachidonic acid (AA) status and development. This study tested if maternal AA supplementation improves neurodevelopment in adult offspring. Rat dams were randomized into 6 groups: Saline-Placebo, streptozotocin-induced diabetes with glucose controlled at <13mmol/L, or poorly controlled at 13-20mmol/L using insulin; and fed either a Control or AA (0.5% fat) diet throughout reproduction. Weaned-offspring were fed regular chow to 12 weeks of age. Testing included exploratory behavior, rota rod and water maze (WM). Poorly controlled offspring showed longer (p≤0.018) escape-latency on testing-day 1 WM but not thereafter (p>0.05). Maternal glucose concentration positively correlated with (p=0.006) male offspring testing-day 1 WM latency. The AA-diet offspring performed better in WM and rota rod (p≤0.032) and showed higher exploratory behavior (p=0.008) than Control-diet offspring. These data suggest maternal hyperglycemia has longstanding consequences to initial stages of learning in the offspring. Maternal AA supplementation and training positively influence learning outcomes. 相似文献
88.
Anna Wolc Jesus Arango Petek Settar Janet E Fulton Neil P O'Sullivan Rudolf Preisinger David Habier Rohan Fernando Dorian J Garrick Jack CM Dekkers 《遗传、选种与进化》2011,43(1):23
Background
The predictive ability of genomic estimated breeding values (GEBV) originates both from associations between high-density markers and QTL (Quantitative Trait Loci) and from pedigree information. Thus, GEBV are expected to provide more persistent accuracy over successive generations than breeding values estimated using pedigree-based methods. The objective of this study was to evaluate the accuracy of GEBV in a closed population of layer chickens and to quantify their persistence over five successive generations using marker or pedigree information.Methods
The training data consisted of 16 traits and 777 genotyped animals from two generations of a brown-egg layer breeding line, 295 of which had individual phenotype records, while others had phenotypes on 2,738 non-genotyped relatives, or similar data accumulated over up to five generations. Validation data included phenotyped and genotyped birds from five subsequent generations (on average 306 birds/generation). Birds were genotyped for 23,356 segregating SNP. Animal models using genomic or pedigree relationship matrices and Bayesian model averaging methods were used for training analyses. Accuracy was evaluated as the correlation between EBV and phenotype in validation divided by the square root of trait heritability.Results
Pedigree relationships in outbred populations are reduced by 50% at each meiosis, therefore accuracy is expected to decrease by the square root of 0.5 every generation, as observed for pedigree-based EBV (Estimated Breeding Values). In contrast the GEBV accuracy was more persistent, although the drop in accuracy was substantial in the first generation. Traits that were considered to be influenced by fewer QTL and to have a higher heritability maintained a higher GEBV accuracy over generations. In conclusion, GEBV capture information beyond pedigree relationships, but retraining every generation is recommended for genomic selection in closed breeding populations. 相似文献89.
Background
A recent epidemiological study demonstrated a reduced risk of lung cancer mortality in breast cancer patients using antiestrogens. These and other data implicate a role for estrogens in lung cancer, particularly nonsmall cell lung cancer (NSCLC). Approximately 61% of human NSCLC tumors express nuclear estrogen receptor β (ERβ); however, the role of ERβ and estrogens in NSCLC is likely to be multifactorial. Here we tested the hypothesis that proteins interacting with ERβ in human lung adenocarcinoma cells that respond proliferatively to estradiol (E2) are distinct from those in non-E2-responsive cells.Methods
FLAG affinity purification of FLAG-ERβ-interacting proteins was used to isolate ERβ-interacting proteins in whole cell extracts from E2 proliferative H1793 and non-E2-proliferative A549 lung adenocarcinoma cell lines. Following trypsin digestion, proteins were identified using liquid chromatography electrospray ionization tandem mass spectrometry (LC-MS/MS). Proteomic data were analyzed using Ingenuity Pathway Analysis. Select results were confirmed by coimmunoprecipitation.Results
LC-MS/MS identified 27 non-redundant ERβ-interacting proteins. ERβ-interacting proteins included hsp70, hsp60, vimentin, histones and calmodulin. Ingenuity Pathway Analysis of the ERβ-interacting proteins revealed differences in molecular and functional networks between H1793 and A549 lung adenocarcinoma cells. Coimmunoprecipitation experiments in these and other lung adenocarcinoma cells confirmed that ERβ and EGFR interact in a gender-dependent manner and in response to E2 or EGF. BRCA1 interacted with ERβ in A549 cell lines and in human lung adenocarcinoma tumors, but not normal lung tissue.Conclusion
Our results identify specific differences in ERβ-interacting proteins in lung adenocarcinoma cells corresponding to ligand-dependent differences in estrogenic responses.90.