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171.
Fanconi Anemia (FA) is a rare disorder with incidence of 1in 350,000 births. It is characterized by progressive bone marrow failure leading to death of many patients in their childhood while development of cancer at later stages of life in some. The treatment of FA is still a medical challenge. Current treatments of FA include androgen administration, hematopoietic growth factors administration and hematopoietic stem cell transplantation (HSCT). Clinical gene therapy trials are still ongoing. The partial success of current therapies has renewed interest in the search for new treatments. Generation of patient-specific induced pluripotent stem (iPS) has shown promising results for cell and gene based therapy. Small molecule interventions have been observed to delay tumor onset in FA. Tumors deficient in FA pathway can be treated by profiling of DNA repair pathway through synthetic lethality mechanism. Targeting toll-like receptor 8 (TLR8) dependent TNFα overexpression is yet another upcoming therapeutic approach to treat FA patients. In conclusion, in the present scenario of treatments available for FA, a proper algorithm of treatment decisions must be followed for better management of FA patients and to ensure their increased survival. Innovative therapeutic approaches that can prevent both anemia and cancer should be developed for more effective treatment of FA. 相似文献
172.
Babu R Prasad Gillian Mullins Natalia Nikolskaya David Connolly Terry J Smith Valérie A Gérard Stephen J Byrne Gemma-Louise Davies Yurii K Gun'ko Yury Rochev 《Journal of nanobiotechnology》2012,10(1):4
Background
The inherent toxicity of unmodified Quantum Dots (QDs) is a major hindrance to their use in biological applications. To make them more potent as neuroprosthetic and neurotherapeutic agents, thioglycolic acid (TGA) capped CdTe QDs, were coated with a gelatine layer and investigated in this study with differentiated pheochromocytoma 12 (PC12) cells. The QD - cell interactions were investigated after incubation periods of up to 17 days by MTT and APOTOX-Glo Triplex assays along with using confocal microscopy. 相似文献173.
Aminoacyl tRNA synthetases play a central role in protein synthesis by charging tRNAs with amino acids. Yeast mitochondrial lysyl tRNA synthetase (Msk1), in addition to the aminoacylation of mitochondrial tRNA, also functions as a chaperone to facilitate the import of cytosolic lysyl tRNA. In this report, we show that human mitochondrial Kars (lysyl tRNA synthetase) can complement the growth defect associated with the loss of yeast Msk1 and can additionally facilitate the in vitro import of tRNA into mitochondria. Surprisingly, the import of lysyl tRNA can occur independent of Msk1 in vivo. This suggests that an alternative mechanism is present for the import of lysyl tRNA in yeast. 相似文献
174.
Masuku SM Babu D Martin EM Koo OK O'Bryan CA Crandall PG Ricke SC 《Journal of applied microbiology》2012,113(1):89-95
Aims: To test the efficacy of four wipe cloth types (cotton bar towel, nonwoven, microfibre and blended cellulose/cotton) with either quaternary ammonia cleaning solution or silver dihydrogen citrate (SDC) in cleaning food contact surfaces. Methods: Swab samples collected from untreated, cloth‐treated and cloth disinfectant‐treated surfaces were subjected to hygiene monitoring using adenosine triphosphate (ATP) bioluminescence and aerobic total plate counting (TPC) assays. Results: Adenosine triphosphate measurements taken after wiping the surfaces showed poor cleaning by nonwoven cloths (2·89 RLU 100 cm?2) than the microfibre (2·30 RLU 100 cm?2), cotton terry bar (2·26 RLU 100 cm?2) and blended cellulose/cotton cloth types (2·20 RLU 100 cm?2). The cellulose/cotton cloth showed highest log reduction in ATP‐B RLU values (95%) and CFU values (98·03%) when used in combination with SDC disinfectant. Conclusions: Cleaning effect of wiping cloths on food contact surfaces can be enhanced by dipping them in SDC disinfectant. ATP‐B measurements can be used for real‐time hygiene monitoring in public sector, and testing microbial contamination provides more reliable measure of cleanliness. Significance and Impact of the Study: Contaminated food contact surfaces need regular hygiene monitoring. This study could help to estimate and establish contamination thresholds for surfaces at public sector facilities and to base the effectiveness of cleaning methods. 相似文献
175.
Kamalakannan V Kirthika S Haripriya K Babu S Narayanan RB 《Microbes and infection / Institut Pasteur》2012,14(7-8):610-618
Recombinant Wolbachia heat shock protein 60 (rWmhsp60) induces gene expression of pro-inflammatory cytokines IL-1β, IL-6 and TNF-α in human monocytic cell line THP-1. In addition, it inhibits the phagocytic activity and does not alter the nitric oxide production by differentiated THP-1 macrophages, which corroborates with no significant change in inducible nitric oxide synthase gene expression in rWmhsp60 treated THP-1 monocytes. Further, 24 h stimulation of peripheral blood mononuclear cells from normal individuals by rWmhsp60 reveals that monocytes enter the late apoptotic stage, while lymphocytes do not show apoptosis. Thus these findings suggest that rWmhsp60 may contribute to inflammation mediated monocyte dysfunction in filarial pathogenesis. 相似文献
176.
Recent advances in network theory have led to considerable progress in our understanding of complex real world systems and their behavior in response to external threats or fluctuations. Much of this research has been invigorated by demonstration of the 'robust, yet fragile' nature of cellular and large-scale systems transcending biology, sociology, and ecology, through application of the network theory to diverse interactions observed in nature such as plant-pollinator, seed-dispersal agent and host-parasite relationships. In this work, we report the development of NEXCADE, an automated and interactive program for inducing disturbances into complex systems defined by networks, focusing on the changes in global network topology and connectivity as a function of the perturbation. NEXCADE uses a graph theoretical approach to simulate perturbations in a user-defined manner, singly, in clusters, or sequentially. To demonstrate the promise it holds for broader adoption by the research community, we provide pre-simulated examples from diverse real-world networks including eukaryotic protein-protein interaction networks, fungal biochemical networks, a variety of ecological food webs in nature as well as social networks. NEXCADE not only enables network visualization at every step of the targeted attacks, but also allows risk assessment, i.e. identification of nodes critical for the robustness of the system of interest, in order to devise and implement context-based strategies for restructuring a network, or to achieve resilience against link or node failures. Source code and license for the software, designed to work on a Linux-based operating system (OS) can be downloaded at http://www.nipgr.res.in/nexcade_download.html. In addition, we have developed NEXCADE as an OS-independent online web server freely available to the scientific community without any login requirement at http://www.nipgr.res.in/nexcade.html. 相似文献
177.
Experimental conditions or the presence of interacting components can lead to variations in the structural models of macromolecules. However, the role of these factors in conformational selection is often omitted by in silico methods to extract dynamic information from protein structural models. Structures of small peptides, considered building blocks for larger macromolecular structural models, can substantially differ in the context of a larger protein. This limitation is more evident in the case of modeling large multi-subunit macromolecular complexes using structures of the individual protein components. Here we report an analysis of variations in structural models of proteins with high sequence similarity. These models were analyzed for sequence features of the protein, the role of scaffolding segments including interacting proteins or affinity tags and the chemical components in the experimental conditions. Conformational features in these structural models could be rationalized by conformational selection events, perhaps induced by experimental conditions. This analysis was performed on a non-redundant dataset of protein structures from different SCOP classes. The sequence-conformation correlations that we note here suggest additional features that could be incorporated by in silico methods to extract dynamic information from protein structural models. 相似文献
178.
179.
Nagulapalli M Parigi G Yuan J Gsponer J Deraos G Bamm VV Harauz G Matsoukas J de Planque MR Gerothanassis IP Babu MM Luchinat C Tzakos AG 《Structure (London, England : 1993)》2012,20(3):522-533
Protein interactions within regulatory networks should adapt in a spatiotemporal-dependent dynamic environment, in order to process and respond to diverse and versatile cellular signals. However, the principles governing recognition pliability in protein complexes are not well understood. We have investigated a region of the intrinsically disordered protein myelin basic protein (MBP(145-165)) that interacts with calmodulin, but that also promiscuously binds other biomolecules (membranes, modifying enzymes). To characterize this interaction, we implemented an NMR spectroscopic approach that calculates, for each conformation of the complex, the maximum occurrence based on recorded pseudocontact shifts and residual dipolar couplings. We found that the MBP(145-165)-calmodulin interaction is characterized by structural heterogeneity. Quantitative comparative analysis indicated that distinct conformational landscapes of structural heterogeneity are sampled for different calmodulin-target complexes. Such structural heterogeneity in protein complexes could potentially explain the way that transient and promiscuous protein interactions are optimized and tuned in complex regulatory networks. 相似文献
180.
Bupranolol is a promising candidate for transdermal drug delivery system (TDDS) development. The effect of permeation enhancers on the in vivo delivery and beta-blocking effect of reservoir type TDDS was studied in comparison with intravenous BPL in rabbits. The beta-blocking effect was quantified by measuring the inhibition of isoprenaline induced tachycardia in rabbits after BPL administration via transdermal and intravenous routes. The reservoir type TDDS containing a hydroxypropyl cellulose gel and polyethylene membrane was used as a control device. In comparison, the TDDS containing skin penetration enhancers, either 2-pyrrolidone or partially methylated beta cyclodextrin (PMbetaCD) were evaluated. The control device (no enhancer) produced about 52% inhibition of isoprenaline induced tachycardia at 2 h and the effect continued over 24 h application period, however, the devices with 2-pyrolidone or PMbetaCD produced about 85% inhibition of isoprenaline induced tachycardia at 3 h and the same effect continued over 24 h application period. Likewise, the AUC of these devices were significantly higher than that of control device. The intravenous bupranolol showed rapid decline in the pharmacodynamic effect with time indicating its rapid elimination. The in vivo delivery of bupranolol (as estimated by a mass balance study) from the devices made with pyrolidone or PMbetaCD was 3-fold higher than that of control. The results of this study strongly suggest that the penetration enhancers in the TDDS increased the in vivo delivery of BPL, thereby increased the beta-blocking activity of BPL by 50-60% higher than control, enabling the reduction of the TDDS patch size, accordingly. 相似文献