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Pan R.K.,Chennai Mathematical Institute | Chatterjee N.,Vision Research Foundation | Sinha S.,Chennai Mathematical Institute

One of the biggest challenges in biology is to understand how activity at the cellular level of neurons, as a result of their mutual interactions, leads to the observed behavior of an organism responding to a variety of environmental stimuli. Investigating the intermediate or mesoscopic level of organization in the nervous system is a vital step towards understanding how the integration of micro-level dynamics results in macro-level functioning. The coordination of many different co-occurring processes at this level underlies the command and control of overall network activity. In this paper, we have considered the somatic nervous system of the nematode Caenorhabditis elegans, for which the entire neuronal connectivity diagram is known. We focus on the organization of the system into modules, i.e., neuronal groups having relatively higher connection density compared to that of the overall network. We show that this mesoscopic feature cannot be explained exclusively in terms of considerations such as, optimizing for resource constraints (viz., total wiring cost) and communication efficiency (i.e., network path length). Even including information about the genetic relatedness of the cells cannot account for the observed modular structure. Comparison with other complex networks designed for efficient transport (of signals or resources) implies that neuronal networks form a distinct class. This suggests that the principal function of the network, viz., processing of sensory information resulting in appropriate motor response, may be playing a vital role in determining the connection topology. Using modular spectral analysis we make explicit the intimate relation between function and structure in the nervous system. This is further brought out by identifying functionally critical neurons purely on the basis of patterns of intra- and inter-modular connections. Our study reveals how the design of the nervous system reflects several constraints, including its key functional role as a processor of information. © 2010 Pan et al. Source

Bhavsar D.,SASTRA University | Subramanian K.,Vision Research Foundation | Sethuraman S.,SASTRA University | Krishnan U.M.,SASTRA University
Current Gene Therapy

Gene silencing has emerged as a promising strategy for molecular therapy of various malignant, viral, hereditary and inflammatory disorders. However, its translation from lab to clinic is yet to gain momentum due to the numerous problems that plague its development. A multi-functional siRNA delivery system with desired properties such as enhanced immune compatibility, target specificity, high cell uptake and excellent silencing efficiency is required to understand the challenges involved in the selection and modification of small interfering RNA (siRNA), factors influencing the complexation process and the response of the biological system to the formulation. Liposomes have been used as delivery systems due to its versatility in handling different types of drugs, tunable size, charge and surface functionalities that improve its effectiveness in vivo. This review highlights the challenges involved in gene silencing and describes the progression of liposomal systems used in gene silencing. The rationale in introducing chemical modifications in siRNA, synthesizing designer cationic lipids and evolution of hybrid liposomal systems has been elaborated, emphasizing their merits and short-comings. Finally, a description of the current state of clinical trials involving liposomal formulations has been included to provide an unbiased perspective of the future of liposomal systems and gene silencing tools as therapeutic tools. © 2012 Bentham Science Publishers. Source

Roy R.,Vitreo Retina Services | Das D.,Vitreo Retina Services | Biswas J.,Vision Research Foundation
Ocular Immunology and Inflammation

Purpose: To determine the viral diagnosis and clinical outcome of eyes with acute retinal necrosis (ARN). Method: A retrospective analysis was done of 62 eyes of 53 patients presenting to a tertiary care ophthalmic institute between 1997 and 2007 with features of ARN. All patients with active disease were started immediately on intravenous acyclovir followed by oral antivirals along with systemic steroids. A prophylactic laser retinopexy was performed in patients with a clear media to areas posterior to the necrotic retina. Results: The aqueous and the vitreous sample revealed herpes simplex virus in 19 (30.60%) and varicella zoster virus in 28 patients (45.16%). Forty-one (66.12%) eyes had retinal detachment. Prophylactic laser photocoagulation was given in 19 (30.64%) eyes. Surgical intervention was required in 32 (51.61%) eyes. Favorable functional outcome was seen in 28 (45.1%) eyes. Conclusion: ARN is a fulminant disorder, which if treated early and aggressively gives good results. © 2014 Informa Healthcare USA, Inc. All rights reserved: reproduction in whole or part not permitted. Source

Singh N.,Deakin University | Krishnakumar S.,Vision Research Foundation | Kanwar R.K.,Deakin University | Cheung C.H.A.,National Cheng Kung University | Kanwar J.R.,Deakin University
Drug Discovery Today

Drug resistance is frequently found in cancer patients who have prolonged chemotherapeutic treatments. Overcoming this phenomenon to make therapy available to these patients is one of the most important features in developing effective cancer therapeutic strategies. Identification of drug resistance causative molecules is one of the most focused areas of cancer research today. Many molecules have been identified in conferring cancer cells the property of drug resistance, and various small molecule inhibitors have been developed to target these molecules to restore the sensitivity of different traditional chemotherapeutic agents, which are frequently found to exhibit reduced potency during prolonged treatment, in cancer patients. Survivin, a member of the inhibitor of apoptosis proteins (IAP) family, has been identified as one of the most crucial biomarkers in the recognition of drug resistance. Survivin is overexpressed in tumor cells, helping in its proliferation and survival, and its overexpression is positively correlated with poor prognosis for cancer patients. Targeted therapeutic measures to inhibit survivin in cancers, particularly drug-resistant tumors, are the recent focus of research for cancer treatment. © 2014 Elsevier Ltd. All rights reserved. Source

Sreenivasan S.,Vision Research Foundation | Sreenivasan S.,Birla Institute of Technology and Science | Krishnakumar S.,Vision Research Foundation
Current Eye Research

Purpose: Curcumin (diferuloylmethane), a phenolic compound obtained from the rhizome of the herb Curcuma longa, is known to have anti-proliferative and anti-tumor properties. In this study, we evaluated the cytotoxic effect of curcumin alone and in combination with individual drugs like carboplatin, etoposide, or vincristine in a human retinoblastoma (RB) cancer cell line.Materials and methods: A drug-drug interaction was analyzed using the median effect/isobologram method and combination index values were used to characterize the interaction as synergistic or additive. We also performed the apoptosis and cell-cycle kinetics study with single drugs in combination with curcumin in a human RB cell lines (Y79 and Weri-Rb1).Results: Curcumin caused concentration-dependent decrease in cell proliferation, cell kinetics, and also induced apoptosis in both the RB cell lines. When combination of curcumin with individual drugs like carboplatin or etoposide or vincristine was treated on to RB cells, both cell viability and cell cycling were reduced and increased apoptosis was noted, in comparison with single drug treatment. These effects were significant in both the cell lines, indicating the ability of curcumin to increase the sensitivity of RB cells to chemotherapy drugs.Conclusion: Our in vitro findings showed that the combination of curcumin with single drug treatment showed marked synergistic inhibitory effect against RB cell lines. These results suggest that curcumin can be used as a modulator which may have a potential therapeutic value for the treatment of RB cancer patients. © 2015 Taylor & Francis Group, LLC. Source

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