The integrated analysis of metabolic and protein interaction networks reveals novel molecular organizing principles

Background: The study of biological interaction networks is a central theme of systems biology. Here, we investigate the relationships between two distinct types of interaction networks: the metabolic pathway map and the protein-protein interaction network (PIN). It has long been established that successive enzymatic steps are often catalyzed by physically interacting proteins forming permanent or transient multi-enzymes complexes. Inspecting high-throughput PIN data, it was shown recently that, indeed, enzymes involved in successive reactions are generally more likely to interact than other protein pairs. In our study, we expanded this line of research to include comparisons of the underlying respective network topologies as well as to investigate whether the spatial organization of enzyme interactions correlates with metabolic efficiency. Results: Analyzing yeast data, we detected long-range correlations between shortest paths between proteins in both network types suggesting a mutual correspondence of both network architectures. We discovered that the organizing principles of physical interactions between metabolic enzymes differ from the general PIN of all proteins. While physical interactions between proteins are generally dissortative, enzyme interactions were observed to be assortative. Thus, enzymes frequently interact with other enzymes of similar rather than different degree. Enzymes carrying high flux loads are more likely to physically interact than enzymes with lower metabolic throughput. In particular, enzymes associated with catabolic pathways as well as enzymes involved in the biosynthesis of complex molecules were found to exhibit high degrees of physical clustering. Single proteins were identified that connect major components of the cellular metabolism and may thus be essential for the structural integrity of several biosynthetic systems. Conclusion: Our results reveal topological equivalences between the protein interaction network and the metabolic pathway network. Evolved protein interactions may contribute significantly towards increasing the efficiency of metabolic processes by permitting higher metabolic fluxes. Thus, our results shed further light on the unifying principles shaping the evolution of both the functional (metabolic) as well as the physical interaction network

Inferring robust gene networks from expression data by a sensitivity-based incremental evolution method

<p>Abstract</p> <p>Background</p> <p>Reconstructing gene regulatory networks (GRNs) from expression data is one of the most important challenges in systems biology research. Many computational models and methods have been proposed to automate the process of network reconstruction. Inferring robust networks with desired behaviours remains challenging, however. This problem is related to network dynamics but has yet to be investigated using network modeling.</p> <p>Results</p> <p>We propose an incremental evolution approach for inferring GRNs that takes network robustness into consideration and can deal with a large number of network parameters. Our approach includes a sensitivity analysis procedure to iteratively select the most influential network parameters, and it uses a swarm intelligence procedure to perform parameter optimization. We have conducted a series of experiments to evaluate the external behaviors and internal robustness of the networks inferred by the proposed approach. The results and analyses have verified the effectiveness of our approach.</p> <p>Conclusions</p> <p>Sensitivity analysis is crucial to identifying the most sensitive parameters that govern the network dynamics. It can further be used to derive constraints for network parameters in the network reconstruction process. The experimental results show that the proposed approach can successfully infer robust GRNs with desired system behaviors.</p

Branch Retinal Vein Occlusion: Pathogenesis, Visual Prognosis, and Treatment Modalities

In branch retinal vein occlusion (BRVO), abnormal arteriovenous crossing with vein compression, degenerative changes of the vessel wall and abnormal hematological factors constitute the primary mechanism of vessel occlusion. In general, BRVO has a good prognosis: 50–60% of eyes are reported to have a final visual acuity (VA) of 20/40 or better even without treatment. One important prognostic factor for final VA appears to be the initial VA. Grid laser photocoagulation is an established treatment for macular edema in a particular group of patients with BRVO, while promising results for this condition are shown by intravitreal application of steroids or new vascular endothelial growth factor inhibitors. Vitrectomy with or without arteriovenous sheathotomy combined with removal of the internal limiting membrane may improve vision in eyes with macular edema which are unresponsive to or ineligible for laser treatment

Factors influencing visual acuity after intravitreal triamcinolone acetonide as treatment of exudative age related macular degeneration

Aim: To evaluate factors influencing change in visual acuity (VA) after intravitreal injection of triamcinolone acetonide as treatment of exudative age related macular degeneration (AMD). Methods: This prospective, interventional, comparative non-randomised clinical case series study included 94 patients (99 eyes) showing progressive exudative AMD with occult (n = 61 eyes), minimally classic (n = 18), predominantly classic (n = 1), or totally classic (n = 8) subfoveal neovascularisation. Mean follow up was 8.5 (SD 4.7) months (median, 7.3 months; range 3.1–24.5 months). All patients received an intravitreal injection of 20–25 mg of triamcinolone acetonide. Results: An increase in best VA of at least one line on the Snellen charts was found in 63 (63.1%) eyes. Correspondingly, mean VA increased significantly (p<0.001) from 0.17 (SD 0.13) to 0.22 (SD 0.17) after the injection. Postoperative increase in VA was significantly (p<0.001) and negatively correlated with preoperative VA (correlation coefficient, −0.49). Gain in visual acuity was significantly (p = 0.009) higher if preoperative visual acuity was less than 0.08 (gain: 3.2 (SD 2.9) Snellen lines) than if preoperative VA ranged between 0.08 and 0.20 (gain: 1.2 (SD 2.2) Snellen lines). Change in VA was significantly (p = 0.016) less if preoperative VA was higher than 0.20 (change: −0.8 (SD 3.4) Snellen lines). Maximal gain in VA was significantly (p = 0.035) larger in eyes with retinal pigment epithelium detachment than in eyes with minimally classic subfoveal neovascularisation. This was statistically independent of age (p = 0.99), refractive error (p = 0.88), sex (p = 0.92), and duration of follow up (p = 0.46). Conclusions: Gain in VA after intravitreal injection of 20–25 mg of triamcinolone acetonide is significantly and negatively correlated with preoperative VA. It is significantly larger in eyes with retinal pigment epithelium detachment than in eyes with minimally classic subfoveal neovascularisation

Potential of the 1 CU accommodative intraocular lens

Aim: To assess the accommodative power of a new foldable monofocal intraocular lens. Method: A prospective randomised non-masked clinical interventional study. The study included 40 patients attending the hospital for cataract surgery and who were randomly distributed into a study group receiving a new foldable monofocal intraocular lens with flexible haptics, and a control group receiving a standard foldable intraocular lens. Mean follow up period was 8.51 (SD 1.34) months (range 4–11 months) Standard cataract surgery consisted of clear cornea incision, capsulorrhexis, phacoemulsification, and intraocular lens implantation, with topical anaesthesia. The main outcome measures were preoperative and postoperative visual acuity for near and distance; range of accommodation; change in anterior chamber depth. Results: In the study group compared with the control group, range of accommodation was significantly (p = 0.01) higher (1.01 (SD 0.4) dioptres versus 0.50 (0.11) dioptres) and change in anterior chamber depth was significantly more pronounced (0.82 (0.30) versus 0.40 (0.32), p = 0.01). Both groups did not vary significantly in best corrected vision (0.94 (0.12) versus 0.93 (0.18); p = 0.74). Conclusion: During a mean follow up period of 8 months after implantation, the new foldable monofocal intraocular lens with flexible haptics showed an accommodative power of about 1 dioptre, which was significantly higher than the accommodative power of a conventional monofocal flexible intraocular lens. The difference in the accommodative power between the two intraocular lenses was paralleled by a difference in the change of the anterior chamber depth

Diffuse diabetic macular oedema treated by intravitreal triamcinolone acetonide: a comparative, non-randomised study

Aim: To report on visual outcome of patients receiving an intravitreal injection of triamcinolone acetonide for treatment of diffuse diabetic macular oedema. Methods: Prospective, comparative, non-randomised clinical interventional study included 136 patients with diffuse diabetic macular oedema. Patients of the study group (97 eyes) received an intravitreal injection of 20–25 mg of triamcinolone acetonide and no other retinal treatment. Patients of the control group (69 eyes) received focal or panretinal laser treatment if indicated. Mean (standard deviation) follow up was 8.4 (SD 6.0) months (range 1.03–25.2 months). Results: Visual acuity (VA) increased significantly (p<0.001) in the study group with 66 (68%) eyes gaining in VA by at least two Snellen lines. In the control group, VA did not change significantly during the first 4 months of follow up, and decreased significantly (p<0.001) towards the end of the follow up. Difference in change of best VA was significant (p<0.001) between both groups. Correspondingly, the number of patients with VA improvement of two or more Snellen lines and visual loss of two or more Snellen lines, respectively, was significantly (p<0.001) higher and lower, respectively, in the study group. Conclusions: Intravitreal triamcinolone acetonide can temporarily increase VA in some patients with diffuse diabetic macular oedema

Diffuse diabetic macular oedema treated by intravitreal triamcinolone acetonide: a comparative, non-randomised study

Aim: To report on visual outcome of patients receiving an intravitreal injection of triamcinolone acetonide for treatment of diffuse diabetic macular oedema. Methods: Prospective, comparative, non-randomised clinical interventional study included 136 patients with diffuse diabetic macular oedema. Patients of the study group (97 eyes) received an intravitreal injection of 20–25 mg of triamcinolone acetonide and no other retinal treatment. Patients of the control group (69 eyes) received focal or panretinal laser treatment if indicated. Mean (standard deviation) follow up was 8.4 (SD 6.0) months (range 1.03–25.2 months). Results: Visual acuity (VA) increased significantly (p<0.001) in the study group with 66 (68%) eyes gaining in VA by at least two Snellen lines. In the control group, VA did not change significantly during the first 4 months of follow up, and decreased significantly (p<0.001) towards the end of the follow up. Difference in change of best VA was significant (p<0.001) between both groups. Correspondingly, the number of patients with VA improvement of two or more Snellen lines and visual loss of two or more Snellen lines, respectively, was significantly (p<0.001) higher and lower, respectively, in the study group. Conclusions: Intravitreal triamcinolone acetonide can temporarily increase VA in some patients with diffuse diabetic macular oedema