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41.
The realization that microRNAs are intimately linked to cancer pathogenesis has spawned an explosion of research activity in recent years. Their presence is not merely predictive of tumor origin and behavior, they are causally linked to the emergence and development of cancer by acting as oncogenes or tumor suppressors. The understanding of the functional consequences of altered microRNA expression in cancer is progressing rapidly, even though the prediction of microRNA targets is still a hit and miss process. MicroRNAs may not act primarily by strongly reducing the expression of a few prominent cancer-regulatory genes, but by influencing the properties of the network of which these regulators are a central part. By coordinately regulating many genes, microRNAs are exquisitely suited to act as stabilizers of networks and to prevent extreme variations in phenotype due to intrinsic and extrinsic disturbances. Many advanced tumors show defects in microRNA expression and processing, which could increase phenotypic variability within tumors. This allows small subsets of cells with altered characteristics to emerge, which can have grave consequences as typically a small fraction of tumor cells is responsible for metastasis and treatment resistance, and ultimately treatment failure. Investigating microRNAs from the perspective of master regulators of network stability in cancer calls for new experimental approaches and may help to understand causes of cancer heterogeneity and disease progression. 相似文献
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Nathalie Jurisch-Yaksi Applonia J. Rose Huiqi Lu Tim Raemaekers Sebastian Munck Pieter Baatsen Veerle Baert Wendy Vermeire Suzie J. Scales Daphne Verleyen Roel Vandepoel Przemko Tylzanowski Emre Yaksi Thomy de Ravel H. Joseph Yost Guy Froyen Cammon B. Arrington Wim Annaert 《The Journal of cell biology》2013,200(6):709-720
Cilia project from the surface of most vertebrate cells and are important for several physiological and developmental processes. Ciliary defects are linked to a variety of human diseases, named ciliopathies, underscoring the importance of understanding signaling pathways involved in cilia formation and maintenance. In this paper, we identified Rer1p as the first endoplasmic reticulum/cis-Golgi–localized membrane protein involved in ciliogenesis. Rer1p, a protein quality control receptor, was highly expressed in zebrafish ciliated organs and regulated ciliary structure and function. Both in zebrafish and mammalian cells, loss of Rer1p resulted in the shortening of cilium and impairment of its motile or sensory function, which was reflected by hearing, vision, and left–right asymmetry defects as well as decreased Hedgehog signaling. We further demonstrate that Rer1p depletion reduced ciliary length and function by increasing γ-secretase complex assembly and activity and, consequently, enhancing Notch signaling as well as reducing Foxj1a expression. 相似文献
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Mathijs A. J. van de Put Lisette Hoeksema Wouter Wanders Ilja M. Nolte Johanna M. M. Hooymans Leonoor I. Los 《PloS one》2014,9(12)
Objective
To determine the vision-related quality of life (VR-QOL) after surgery for macula-off rhegmatogenous retinal detachment (RRD) in relation to visual acuity, contrast acuity, and color vision.Methods
In a prospective observational study, we included 55 patients with a macula-off RRD. Best corrected visual acuity (BCVA), color vision (saturated and desaturated color confusion indices (CCI)) and contrast acuity were measured at 12 months postoperatively in both the RRD eye and the fellow control eye, and the 25-item National Eye Institute Visual Function Questionnaire (NEI VFQ-25) was filled out.Results
Operated and fellow control eyes differed significantly in mean LogMAR BCVA (P<0.0001), median Log contrast acuity (P<0.0001), saturated CCI (P = 0.009), and desaturated CCI (P = 0.016). Significant correlations were observed between the NEI VFQ-25 overall composite score and postoperative LogMAR BCVA (R = −0.551, P<0.0001), contrast acuity (R = 0.472, P<0.0001), saturated CCI (R = −0.315, P = 0.023), and desaturated CCI (R = −0.283, P = 0.044).Conclusions
A lower VR-QOL was highly correlated to a worse postoperative BCVA and contrast acuity and to a lesser extent to color vision disturbances. 相似文献46.
Ferry N Raemaekers RJ Majerus ME Jouanin L Port G Gatehouse JA Gatehouse AM 《Molecular ecology》2003,12(2):493-504
Insect-resistant transgenic plants have been suggested to have deleterious effects on beneficial predators through transmission of the transgene product by the pest to the predator. To test this hypothesis, effects of oilseed rape expressing the cysteine protease inhibitor oryzacystatin-1 (OC-1) on the predatory ladybird Harmonia axyridis were investigated using diamondback moth Plutella xylostella as the pest species. As expected, oilseed rape expressing OC-1 had no effects on either development or survival of the pest, which utilizes serine digestive proteases. Immunoassays confirmed accumulation of the transgene product in pest larval tissues at levels of up to 3 ng per gut. Characterization of proteolytic digestive enzymes of H. axyridis demonstrated that larvae and adults utilize cysteine and aspartic proteases; the former activity was completely inhibited by oryzacystatin in vitro. However, when H. axyridis larvae consumed prey reared on OC-1 expressing plants over their entire life cycle, no significant effects upon survival or overall development were observed. The inhibitor initially stimulated development, with a shortening of the developmental period of the second instar by 27% (P < 0.0001) accompanied by a 36% increase in weight of second instar larvae (P = 0.007). OC-1 had no detrimental effects on reproductive fitness of adult H. axyridis. Interestingly there was a significant increase in consumption of OC-1 dosed prey. The results show that prey reared on transgenic plants expressing a protein which inhibited ladybird digestive enzymes in vitro had no effects in vivo; the ladybird was able to up-regulate digestive proteases in response to the inhibitor. 相似文献
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RNA-binding protein Dnd1 inhibits microRNA access to target mRNA 总被引:12,自引:0,他引:12
Kedde M Strasser MJ Boldajipour B Oude Vrielink JA Slanchev K le Sage C Nagel R Voorhoeve PM van Duijse J Ørom UA Lund AH Perrakis A Raz E Agami R 《Cell》2007,131(7):1273-1286
MicroRNAs (miRNAs) are inhibitors of gene expression capable of controlling processes in normal development and cancer. In mammals, miRNAs use a seed sequence of 6-8 nucleotides (nt) to associate with 3' untranslated regions (3'UTRs) of mRNAs and inhibit their expression. Intriguingly, occasionally not only the miRNA-targeting site but also sequences in its vicinity are highly conserved throughout evolution. We therefore hypothesized that conserved regions in mRNAs may serve as docking platforms for modulators of miRNA activity. Here we demonstrate that the expression of dead end 1 (Dnd1), an evolutionary conserved RNA-binding protein (RBP), counteracts the function of several miRNAs in human cells and in primordial germ cells of zebrafish by binding mRNAs and prohibiting miRNAs from associating with their target sites. These effects of Dnd1 are mediated through uridine-rich regions present in the miRNA-targeted mRNAs. Thus, our data unravel a novel role of Dnd1 in protecting certain mRNAs from miRNA-mediated repression. 相似文献
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Purpose
To evaluate postoperative metamorphopsia in macula-off rhegmatogenous retinal detachment (RRD) and its association with visual function, vision related quality of life, and optical coherence tomography (OCT) findings.Methods
45 patients with primary macula-off RRD were included. At 12 months postoperatively, data on metamorphopsia using sine amsler charts (SAC), best corrected visual acuity (BCVA), letter contrast sensitivity, color vision (saturated and desaturated color confusion indexes), critical print size, reading acuity, the 25-item National Eye Institute Visual Functioning Questionnaire (NEI-VFQ-25), and OCT, were obtained.Results
Metamorphopsia was present in 39 patients (88.6%), with most of them (n = 35, 77.8%) showing only mild metamorphopsia (SAC score = 1). Patients with metamorphopsia had significantly worse postoperative BCVA (p = 0.02), critical print size (p<0.0005), and reading acuity (p = 0.001) compared to patients without metamorphopsia. Other visual function outcomes and NEI-VFQ-25 overall composite score were all also somewhat lower in patients with metamorphopsia, but this did not reach statistical significance. No association with OCT findings was present.Conclusion
The prevalence of postoperative metamorphopsia in macula-off RRD patients is high, however, the degree of metamorphopsia is relatively low. When metamorphopsia is present, visual functions seem to be compromised, while vision related quality of life is only mildly affected. 相似文献49.
D J Chivers J J Raemaekers F P Aldrich-Blake 《Folia primatologica; international journal of primatology》1975,23(1-2):1-49
Long-term observations are presented on the behaviour of the siamang ape, Symphalangus syndactylus, in the lowland forest of central Malaya. The data were collected during two dry and three fruiting seasons between 1969 and 1973 inclusive on two groups with adjacent ranges; comparisons are made within and between sample periods, and between groups. The influence of weather on daily activities is considered. Food intake is analysed in terms of number of food trees, number of visits to these trees, and the cumulative time spent feeding on various food categories. Ranging behaviour is investigated in terms of distance travelled, area covered, and distribution of time and of food trees about the range. The occurrence of calling is described and compared with that of the white-handed gibbon in the same area. A discussion ensues on each of these aspects of behaviour in turn. Emphasis is laid on the similarity of behaviour of the two groups at any one time, and on the degree of their response to the fluctuations of environment variables. Finally, the application to siamang of ranging concepts currently used in animal behaviour is considered briefly. 相似文献
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