The Experts below are selected from a list of 360 Experts worldwide ranked by ideXlab platform
Christophe Dardonville - One of the best experts on this subject based on the ideXlab platform.
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Recent advances in antitrypanosomal chemotherapy: patent literature 2002–2005. Expert
2016Co-Authors: Christophe DardonvilleAbstract:Sleeping sickness and Chagas ’ disease (African and American trypanosomiases, respectively) are protozoan parasitic diseases threatening millions of people in sub-Saharan Africa and Latin America, respectively. Trypanosomiases are among the most neglected diseases in the world, lacking desperately from financial support for investigation. The current chemotherapy of both diseases is poor and suffers from intolerable side-effects and low efficacy in many cases. A review of the patent literature (2002-early 2005) claiming for molecules with antitrypanosomal activity afforded 36 entries, equally shared between industry and academia. Among the targets validated against trypanosomes, patents dealing with proteases inhibitors were the most represented (16 patents). Other targets claimed in the patent literature included Membrane Architecture (sterol biosynthesis inhibitors, protein farnesyltransferase inhibitors), DNA (DNA binders, tubulin inhibitors) and pyrimidine metabolism (CTP synthetase inhibitors). Natural products were also a great source of trypanocidal lead compounds (9 patents). A few patents claiming for compounds with antitrypanosoma
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recent advances in antitrypanosomal chemotherapy patent literature 2002 2004
Expert Opinion on Therapeutic Patents, 2005Co-Authors: Christophe DardonvilleAbstract:Sleeping sickness and Chagas disease (African and American trypanosomiases, respectively) are protozoan parasitic diseases threatening millions of people in sub-Saharan Africa and Latin America. Trypanosomiases are among the most neglected diseases in the world, desperately lacking financial support for investigation. The current chemotherapy of both diseases is poor and suffers from intolerable side effects and low efficacy in many cases. A review of the patent literature from 2002 to early 2005 claiming molecules with antitrypanosomal activity afforded 36 entries, equally shared between industry and acadaemia. Among the targets validated against trypanosomes, patents dealing with protease inhibitors were the most represented (16 patents). Other targets claimed in the patent literature included Membrane Architecture (sterol biosynthesis inhibitors, protein farnesyltransferase inhibitors), DNA (DNA binders, tubulin inhibitors) and pyrimidine metabolism (cytidine triphosphate [CTP] synthetase inhibitors). ...
Jake Baum - One of the best experts on this subject based on the ideXlab platform.
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quantitative phospho proteomics reveals the plasmodium merozoite triggers pre invasion host kinase modification of the red cell cytoskeleton
Scientific Reports, 2016Co-Authors: Elizabeth S Zuccala, Timothy J Satchwell, Fiona Angrisano, Yan Hong Tan, Marieangela C Wilson, Kate J Heesom, Jake BaumAbstract:The invasive blood-stage malaria parasite - the merozoite - induces rapid morphological changes to the target erythrocyte during entry. However, evidence for active molecular changes in the host cell that accompany merozoite invasion is lacking. Here, we use invasion inhibition assays, erythrocyte resealing and high-definition imaging to explore red cell responses during invasion. We show that although merozoite entry does not involve erythrocyte actin reorganisation, it does require ATP to complete the process. Towards dissecting the ATP requirement, we present an in depth quantitative phospho-proteomic analysis of the erythrocyte during each stage of invasion. Specifically, we demonstrate extensive increased phosphorylation of erythrocyte proteins on merozoite attachment, including modification of the cytoskeletal proteins beta-spectrin and PIEZO1. The association with merozoite contact but not active entry demonstrates that parasite-dependent phosphorylation is mediated by host-cell kinase activity. This provides the first evidence that the erythrocyte is stimulated to respond to early invasion events through molecular changes in its Membrane Architecture.
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cryo electron tomography reveals four Membrane Architecture of the plasmodium apicoplast
Malaria Journal, 2013Co-Authors: Leandro Lemgruber, Mikhail Kudryashev, Chaitali Dekiwadia, David T Riglar, Jake Baum, Henning Stahlberg, Stuart A Ralph, Friedrich FrischknechtAbstract:The apicoplast is a plastid organelle derived from a secondary endosymbiosis, containing biosynthetic pathways essential for the survival of apicomplexan parasites. The Toxoplasma apicoplast clearly possesses four Membranes but in related Plasmodium spp. the apicoplast has variably been reported to have either three or four Membranes. Cryo-electron tomography was employed to image merozoites of Plasmodium falciparum and Plasmodium berghei frozen in their near-native state. Three-dimensional reconstructions revealed the number of apicoplast Membranes and the association of the apicoplast with other organelles. Routine transmission electron microscopy of parasites preserved by high-pressure freezing followed by freeze substitution techniques was also used to analyse apicoplast morphology. Cryo-preserved parasites showed clearly four Membranes surrounding the apicoplast. A wider gap between the second and third apicoplast Membranes was frequently observed. The apicoplast was found in close proximity to the nucleus and to the rhoptries. The apicoplast matrix showed ribosome-sized particles and membranous whorls. The Plasmodium apicoplast possesses four Membranes, as do the apicoplasts of other apicomplexan parasites. This is consistent with a four-Membraned secondary endosymbiotic plastid ancestor.
Raimund Wagener - One of the best experts on this subject based on the ideXlab platform.
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Col6a1 Null Mice as a Model to Study Skin Phenotypes in Patients with Collagen VI Related Myopathies: Expression of Classical and Novel Collagen VI Variants during Wound Healing
2016Co-Authors: Ra Lettmann, Paolo Bonaldo, Wilhelm Bloch, Tobias Maaß, Anja Niehoff, Jan-niklas Schulz, Beate Eckes, Sabine A. Eming, Raimund WagenerAbstract:Patients suffering from collagen VI related myopathies caused by mutations in COL6A1, COL6A2 and COL6A3 often also display skin abnormalities, like formation of keloids or ‘‘cigarette paper’ ’ scars, dry skin, striae rubrae and keratosis pilaris (follicular keratosis). Here we evaluated if Col6a1 null mice, an established animal model for the muscle changes in collagen VI related myopathies, are also suitable for the study of mechanisms leading to the skin pathology. We performed a comprehensive study of the expression of all six collagen VI chains in unwounded and challenged skin of wild type and Col6a1 null mice. Expression of collagen VI chains is regulated in both skin wounds and bleomycin-induced fibrosis and the collagen VI a3 chain is proteolytically processed in both wild type and Col6a1 null mice. Interestingly, we detected a decreased tensile strength of the skin and an altered collagen fibril and basement Membrane Architecture in Col6a1 null mice, the latter being features that are also found in collagen VI myopathy patients. Although Col6a1 null mice do not display an overt wound healing defect, these mice are a relevant animal model to study the skin pathology in collagen V
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Col6a1 Null Mice as a Model to Study Skin Phenotypes in Patients with Collagen VI Related Myopathies: Expression of Classical and Novel Collagen VI Variants during Wound Healing
2014Co-Authors: Sandra Lettmann, Paolo Bonaldo, Wilhelm Bloch, Tobias Maaß, Anja Niehoff, Jan-niklas Schulz, Beate Eckes, Sabine A. Eming, Raimund WagenerAbstract:Patients suffering from collagen VI related myopathies caused by mutations in COL6A1, COL6A2 and COL6A3 often also display skin abnormalities, like formation of keloids or “cigarette paper” scars, dry skin, striae rubrae and keratosis pilaris (follicular keratosis). Here we evaluated if Col6a1 null mice, an established animal model for the muscle changes in collagen VI related myopathies, are also suitable for the study of mechanisms leading to the skin pathology. We performed a comprehensive study of the expression of all six collagen VI chains in unwounded and challenged skin of wild type and Col6a1 null mice. Expression of collagen VI chains is regulated in both skin wounds and bleomycin-induced fibrosis and the collagen VI α3 chain is proteolytically processed in both wild type and Col6a1 null mice. Interestingly, we detected a decreased tensile strength of the skin and an altered collagen fibril and basement Membrane Architecture in Col6a1 null mice, the latter being features that are also found in collagen VI myopathy patients. Although Col6a1 null mice do not display an overt wound healing defect, these mice are a relevant animal model to study the skin pathology in collagen VI related disease.
Friedrich Frischknecht - One of the best experts on this subject based on the ideXlab platform.
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cryo electron tomography reveals four Membrane Architecture of the plasmodium apicoplast
Malaria Journal, 2013Co-Authors: Leandro Lemgruber, Mikhail Kudryashev, Chaitali Dekiwadia, David T Riglar, Jake Baum, Henning Stahlberg, Stuart A Ralph, Friedrich FrischknechtAbstract:The apicoplast is a plastid organelle derived from a secondary endosymbiosis, containing biosynthetic pathways essential for the survival of apicomplexan parasites. The Toxoplasma apicoplast clearly possesses four Membranes but in related Plasmodium spp. the apicoplast has variably been reported to have either three or four Membranes. Cryo-electron tomography was employed to image merozoites of Plasmodium falciparum and Plasmodium berghei frozen in their near-native state. Three-dimensional reconstructions revealed the number of apicoplast Membranes and the association of the apicoplast with other organelles. Routine transmission electron microscopy of parasites preserved by high-pressure freezing followed by freeze substitution techniques was also used to analyse apicoplast morphology. Cryo-preserved parasites showed clearly four Membranes surrounding the apicoplast. A wider gap between the second and third apicoplast Membranes was frequently observed. The apicoplast was found in close proximity to the nucleus and to the rhoptries. The apicoplast matrix showed ribosome-sized particles and membranous whorls. The Plasmodium apicoplast possesses four Membranes, as do the apicoplasts of other apicomplexan parasites. This is consistent with a four-Membraned secondary endosymbiotic plastid ancestor.
Himadri B Pakrasi - One of the best experts on this subject based on the ideXlab platform.
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organization and flexibility of cyanobacterial thylakoid Membranes examined by neutron scattering
Journal of Biological Chemistry, 2013Co-Authors: Michelle Liberton, Lawrence E Page, William B Odell, Hugh Oneill, Eugene Mamontov, Volker S Urban, Himadri B PakrasiAbstract:Cyanobacteria are prokaryotes that can use photosynthesis to convert sunlight into cellular fuel. Knowledge of the organization of the Membrane systems in cyanobacteria is critical to understanding the metabolic processes in these organisms. We examined the wild-type strain of Synechocystis sp. PCC 6803 and a series of mutants with altered light-harvesting phycobilisome antenna systems for changes in thylakoid Membrane Architecture under different conditions. Using small-angle neutron scattering, it was possible to resolve correlation distances of subcellular structures in live cells on the nanometer scale and capture dynamic light-induced changes to these distances. Measurements made from samples with varied scattering contrasts confirmed that these distances could be attributed to the thylakoid lamellar system. We found that the changes to the thylakoid system were reversible between light- and dark-adapted states, demonstrating a robust structural flexibility in the Architecture of cyanobacterial cells. Chemical disruption of photosynthetic electron transfer diminished these changes, confirming the involvement of the photosynthetic apparatus. We have correlated these findings with electron microscopy data to understand the origin of the changes in the Membranes and found that light induces an expansion in the center-to-center distances between the thylakoid Membrane layers. These combined data lend a dynamic dimension to the intracellular organization in cyanobacterial cells.
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unique thylakoid Membrane Architecture of a unicellular n2 fixing cyanobacterium revealed by electron tomography
Plant Physiology, 2011Co-Authors: Michelle Liberton, Jotham R Austin, Howard R Berg, Himadri B PakrasiAbstract:Cyanobacteria, descendants of the endosymbiont that gave rise to modern-day chloroplasts, are vital contributors to global biological energy conversion processes. A thorough understanding of the physiology of cyanobacteria requires detailed knowledge of these organisms at the level of cellular Architecture and organization. In these prokaryotes, the large Membrane protein complexes of the photosynthetic and respiratory electron transport chains function in the intracellular thylakoid Membranes. Like plants, the Architecture of the thylakoid Membranes in cyanobacteria has direct impact on cellular bioenergetics, protein transport, and molecular trafficking. However, whole-cell thylakoid organization in cyanobacteria is not well understood. Here we present, by using electron tomography, an in-depth analysis of the Architecture of the thylakoid Membranes in a unicellular cyanobacterium, Cyanothece sp. ATCC 51142. Based on the results of three-dimensional tomographic reconstructions of near-entire cells, we determined that the thylakoids in Cyanothece 51142 form a dense and complex network that extends throughout the entire cell. This thylakoid Membrane network is formed from the branching and splitting of Membranes and encloses a single lumenal space. The entire thylakoid network spirals as a peripheral ring of Membranes around the cell, an organization that has not previously been described in a cyanobacterium. Within the thylakoid Membrane network are areas of quasi-helical arrangement with similarities to the thylakoid Membrane system in chloroplasts. This cyanobacterial thylakoid arrangement is an efficient means of packing a large volume of Membranes in the cell while optimizing intracellular transport and trafficking.