| 5241. |
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| 5242. |
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| 5243. |
- Patra, Hirak
(författare)
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Cell selective response to gold nanoparticles : Cellular specificity of gold nanoparticles
- 2007
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Ingår i: Nanomedicine. - : Elsevier. - 1549-9634 .- 1549-9642. ; 3:2, s. 111-119
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Tidskriftsartikel (refereegranskat)abstract
- Gold nanoparticles (GNPs) are considered a potential probe to detect cancer. The present article investigates whether GNPs, even in the absence of any specific functionalization, induce any cell specific response. We report GNP-induced death response in human carcinoma lung cell line A549. In contrast, the two other cell lines tested, BHK21 (baby hamster kidney) and HepG2 (human hepatocellular liver carcinoma), remained unaffected by GNP treatment. The specificity of the induction of the death response in A549 cells implies that GNPs do not universally target all cell types. Flow-cytometric studies indicated that the response was dose dependent and had a threshold effect (in A549). Gradual increase in GNP concentration induces a proportional cleavage of poly(ADP-ribose) polymerase. The programmed nature of the death response is implied, because such cleavage follows activation of caspases. Notably, at higher GNP concentration there was an asymmetric accumulation of GNPs in the periphery outside the cell nucleus of the A549 cells. This was confirmed by confocal microscopy, a green scattering (possibly, surface-enhanced Raman effect) appearing on selective z-slices of the image.
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| 5244. |
- Patra, Hirak, 1981-, et al.
(författare)
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Gold Nanostructures and their Applications in Diagnosis and Therapy of Cancer
- 2012
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Ingår i: Nanotechnology. - New Delhi, India : Narosa Publishing House. - 9788184871593 ; , s. 27-35
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Bokkapitel (övrigt vetenskapligt/konstnärligt)abstract
- The molecular level scenario of cancer is recently rescaled from interactive molecular interaction maps to network representation and dynamic modeling (Stromback et al.**). The rescaling is primarily motivated by a systems biology approach (Gitenkunst et al 2007; Pribyl**). The future of nanoparticle based biological research perhaps lies in such systems based picture of interaction of nanoparticles with cells and their different compartments.At present there are two distinct directions in which one finds prospects of nanoparticle based research in biology. Development of novel nano-probes used either for imaging or for therapeutic purpose and each of these perspectives are intricately related to the signaling networks existing in cancerous or normal cells (Irish et al., 2006). The nanotechnology approach can enable controlled perturbation in cell and intercellular compartments. In addition this will enable, efficient extraction of image based information of the cellular and sub cellular function, and design of drugs particularly in cases in which the targeted delivery is intended (Hu et al., 2007).Thus, nanotechnology based approaches are fast emerging as efficient aids to in vitro diagnostic techniques and to therapeutic procedures. The focus of this chapter is to concentrate on approaches in nanotechnology based diagnosis. This would be followed up by some discussions on formulation of nano-therapeutic strategy where specialized issues like toxicity and their significance would be touched-upon (Yadav et al, 2009). The hypotheses with which the nanotechnology is applied in cancer research are (a) Early stage detection is very difficult due to less phenotypic expressions. (b) Most of the anticancer drugs cannot differentiate greatly between normal and cancerous cells. While the first point is pivotal in the diagnostic approaches, the second aspect is more relevant with respect to nano-based therapeutic procedures.Advanced technologies for tumor imaging, early detection, new methods for accurate diagnosis and prognosis are components of the former. The second issue, namely the targeted therapy has been subject of keen interest to a large section of researchers. Introduction of processes like laser or superficial X-ray irradiation in which nanoparticles may cause targeted and specific killing is an encouraging aspect of its use. Safety issues of nanoparticle-based drugs, their biodegradation or exclusion are the issues that have to develop side by side so as to make nano drugs acceptable in medicine. Other than this, special progresses in the treating aggressive and lethal cancers such as bone metastasis and development of nanomaterials that can be accessible to brain and other inaccessible tissues are some of the additional aspects that need a detailed consideration. A third equally important perspective exists for nanoparticle based sensing. This aspect is especially important for plasmonic nanoparticles like gold colloids.
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| 5245. |
- Perisic, Ljubica, et al.
(författare)
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Schip1 Is a Novel Podocyte Foot Process Protein that Mediates Actin Cytoskeleton Rearrangements and Forms a Complex with Nherf2 and Ezrin
- 2015
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Ingår i: PLOS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 10:3
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Tidskriftsartikel (refereegranskat)abstract
- Background Podocyte foot process effacement accompanied by actin cytoskeleton rearrangements is a cardinal feature of many progressive human proteinuric diseases. Results By microarray profiling of mouse glomerulus, SCHIP1 emerged as one of the most highly enriched transcripts. We detected Schip1 protein in the kidney glomerulus, specifically in podocytes foot processes. Functionally, Schip1 inactivation in zebrafish by morpholino knock-down results in foot process disorganization and podocyte loss leading to proteinuria. In cultured podocytes Schip1 localizes to cortical actin-rich regions of lamellipodia, where it forms a complex with Nherf2 and ezrin, proteins known to participate in actin remodeling stimulated by PDGF beta signaling. Mechanistically, overexpression of Schip1 in vitro causes accumulation of cortical F-actin with dissolution of transversal stress fibers and promotes cell migration in response to PDGF-BB stimulation. Upon actin disassembly by latrunculin A treatment, Schip1 remains associated with the residual F-actin-containing structures, suggesting a functional connection with actin cytoskeleton possibly via its interaction partners. A similar assay with cytochalasin D points to stabilization of cortical actin cytoskeleton in Schip1 overexpressing cells by attenuation of actin depolymerisation. Conclusions Schip1 is a novel glomerular protein predominantly expressed in podocytes, necessary for the zebrafish pronephros development and function. Schip1 associates with the cortical actin cytoskeleton network and modulates its dynamics in response to PDGF signaling via interaction with the Nherf2/ezrin complex. Its implication in proteinuric diseases remains to be further investigated.
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| 5246. |
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| 5247. |
- Petre, Daniela-Geta, et al.
(författare)
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Surface functionalization of polylactic acid fibers with alendronate groups does not improve the mechanical properties of fiber-reinforced calcium phosphate cements
- 2019
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Ingår i: Journal of The Mechanical Behavior of Biomedical Materials. - : ELSEVIER SCIENCE BV. - 1751-6161 .- 1878-0180. ; 90, s. 472-483
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Tidskriftsartikel (refereegranskat)abstract
- Calcium phosphate cements (CPCs) are frequently used as synthetic bone substitute, but their intrinsic low fracture toughness impedes their application in highly loaded skeletal sites. However, fibers can be used to reduce the brittleness of these CPCs provided that the affinity between the fibers and cement matrix facilitates the transfer of loads from the matrix to the fibers. The aim of the present work was to improve the interface between hydrophobic polylactic acid (PLA) microfibers and hydrophilic CPC. To this end, calcium-binding alendronate groups were conjugated onto the surface of PLA microfibers via different strategies to immobilize a tunable amount of alendronate onto the fiber surface. CPCs reinforced with PLA fibers revealed toughness values which were up to 50-fold higher than unreinforced CPCs. Nevertheless, surface functionalization of PLA microfibers with alendronate groups did not improve the mechanical properties of fiber-reinforced CPCs.
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| 5248. |
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| 5249. |
- Pietras, Zuzanna, 1993-
(författare)
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Small angle scattering as a tool to study protein structure and interactions
- 2022
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- This thesis uses small angle X-ray and neutron scattering (SAXS/SANS) to gain structural and functional insight into the molecular regulation of critical life processes in prokaryotic and eukaryotic species. The presented studies highlight the strength of combining low-resolution structure determination with biophysical and in silico modelling methods to extensively characterize proteins and their interactions. DNA-binding: MexR protein belongs to the family of bacterial transcription regulators and control the expression of multidrug efflux pumps in Pseudomonas Aeruginosa by binding to a DNA region of the operator. SAXS/SANS data supported by MD (Molecular Dynamics) simulations demonstrated that the MexR dimer in solution undergoes a DNA-binding conformational selection mechanism. To gain a better understanding about the system, a low-resolution structural model was resolved in order to assess protein binding to the entire operator region comprising of two closely located DNA recognition sites. The study demonstrates that the use of scattering techniques to investigate similar systems is straightforward and provides knowledge of relevance for clinical understanding and future drug design. Viral host factors: Picornaviruses represent a large family of small RNA viruses that are responsible for a range of diseases in humans and animals. Recently a non-essential human phospholipase PLAAT3 was identified as a key host factor for some picornaviruses. Several picornaviruses representing different branches of the picornaviral phylogenetic tree contain a type of 2A protein in their genome that share a conserved H-box/NC motif with PLAAT3. To understand the role of these 2A proteins in the viral life cycle and to map their plasticity, high resolution techniques were complemented with SAXS to evaluate the structural rearrangements and flexibility. Ubiquitination: In eukaryotes, ubiquitination is a fundamental posttranslational modification, where a small protein ubiquitin is covalently attached to a target protein via sophisticated multienzyme process. SANS can be used to study this mechanism in solution by modular deuteration of ubiquitin complexes. To explore this possibility further, an E2 conjugating enzyme was attached to a deuterated ubiquitin via an isopeptide bond, and a neutron contrast variation experiment was performed. To investigate the flexibility of the E2~Ub conjugate, a multi-state modelling approach was employed to sample its conformational landscape. SANS methods in protein science: A final methods paper outlines and details the experimental requirements, procedures and pre-studies that need to be considered to optimise a successful experimental approach for SANS with contrast variation on biomolecular complexes and assemblies in solution.
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| 5250. |
- Porcel, Betina, et al.
(författare)
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Trypanosoma rangeli and Trypanosoma cruzi : molecular characterization of genes encoding putative calcium-binding proteins, highly conserved in typanosomatids
- 1996
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Ingår i: Experimental parasitology. - : Elsevier BV. - 0014-4894 .- 1090-2449. ; 84:3, s. 387-399
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Tidskriftsartikel (refereegranskat)abstract
- Genes encoding a 29-kDa flagellar calcium-binding protein (F29) in Trypanosoma cruzi, strongly homologous to EF-hand calcium-binding protein-encoding genes previously reported in this parasite, were isolated by immunoscreening. F29 is encoded by a number of very similar genes, highly conserved among different T. cruzi isolates. The genes are located on a pair of homologous chromosomes, arranged in one or two clusters of tandem repeats. PCR amplification of Trypanosoma rangeli genomic DNA, using primers derived from the T. cruzi F29 sequence made it possible to isolate the homologous gene in T. rangeli, encoding a 23-kDa protein called TrCaBP. Gene sequence comparisons showed homology to EF-hand calcium-binding proteins from T. cruzi (82.8%), Trypanosoma brucei brucei (60.2%), and Entamoeba histolytica (28.4%). Northern blot analysis revealed that the TrCaBP gene is expressed in T. rangeli as a polyadenylated transcript. The TrCaBP-encoding genes are present in at least 20 copies per cell, organized in tandem arrays, on large T. rangeli chromosomes in some isolates and on two smaller ones in others. This gene, however, seems to be absent from Leishmania.
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