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Rainer Schobert - One of the best experts on this subject based on the ideXlab platform.
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Modification of uptake and subcellular distribution of doxorubicin by N-acylhydrazone residues as visualised by intrinsic fluorescence
Cancer Chemotherapy and Pharmacology, 2012Co-Authors: Katharina Effenberger-neidnicht, Sandra Breyer, Katharina Mahal, Florenz Sasse, Rainer SchobertAbstract:Purpose Doxorubicin ( 1 ) is commonly used in the treatment of a wide range of cancers. Some N -acylhydrazones of 1 were previously found to have an improved tumour and organ selectivity. In order to clarify the molecular basis for this effect, the cellular uptake into various cancer cells and the localisation in PtK_2 Potoroo kidney cells of 1 and its N -acylhydrazones derived from heptadecanoic acid ( 2 ) and 11-(menthoxycarbonyl)undecanoic acid ( 3 ) were studied drawing on their intrinsic fluorescence. Methods The uptake of compounds 1 – 3 into human cells of HL-60 leukaemia, 518A2 melanoma, HT-29 colon, and resistant KB-V1/Vbl and MCF-7/Topo breast carcinomas was determined fluorometrically from their residual amounts in the supernatant. Their time-dependent accumulation in PtK_2 Potoroo kidney cells was visualised by fluorescence microscopy. Results The uptake, though not the cytotoxicity, of 2 in multi-drug resistant MCF-7/Topo breast cancer cells was conspicuously greater than that of 1 and 3 , probably due to an attractive lipophilic interaction with the lipid-rich membranes of these cells. In non-malignant PtK_2 cells, both 1 and 3 accumulated initially in the nuclei. Upon prolonged incubation, their fluorescent metabolites were visualised in lysosomes neighbouring the nuclei. In contrast, conjugate 2 was not observed in the nuclei at any time. After 2 h, it had accumulated in vesicles scattered all over the cells, and upon prolonged incubation, its fluorescent metabolites were concentrated in the cellular membrane. Conclusions Long unbranched fatty acyl residues when attached to doxorubicin via a hydrazone can act as lipophilic membrane anchors. This allows an increased uptake of such derivatives into lipid-rich membranes especially of multi-drug resistant cancer cells, a retarded release from there into the cytosol and the eventual storage of their metabolites again in the cell membrane rather than in lysosomes.
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Modification of uptake and subcellular distribution of doxorubicin by N-acylhydrazone residues as visualised by intrinsic fluorescence.
Cancer Chemotherapy and Pharmacology, 2011Co-Authors: Katharina Effenberger-neidnicht, Sandra Breyer, Katharina Mahal, Florenz Sasse, Rainer SchobertAbstract:Purpose Doxorubicin (1) is commonly used in the treatment of a wide range of cancers. Some N-acylhydrazones of 1 were previously found to have an improved tumour and organ selectivity. In order to clarify the molecular basis for this effect, the cellular uptake into various cancer cells and the localisation in PtK2 Potoroo kidney cells of 1 and its N-acylhydrazones derived from heptadecanoic acid (2) and 11-(menthoxycarbonyl)undecanoic acid (3) were studied drawing on their intrinsic fluorescence.
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Cellular Localisation of Antitumoral 6‐Alkyl Thymoquinones Revealed by an Alkyne–Azide Click Reaction and the Streptavidin–Biotin System
Chembiochem : a European journal of chemical biology, 2011Co-Authors: Katharina Effenberger-neidnicht, Sandra Breyer, Katharina Mahal, Florenz Sasse, Randi Diestel, Rainer SchobertAbstract:The subcellular distribution and accumulation of thymoquinone 1, a natural anticancer agent, has hitherto been unknown. We prepared 6-(dec-9-ynyl)thymoquinone 3, an alkyne-labelled derivative with anticancer activity similar to that of its parent compound 1. Alkyne 3 was seen, after a Huisgen-type click reaction with 3-azido-7-hydroxycoumarin, to accumulate in distinct compartments of the nuclei of PtK(2) Potoroo kidney cells, and in adjoining regions that were stained with an antibody specific for the Golgi apparatus. In contrast, a biotinlabelled thymoquinone 4 seemed to accumulate across the entire cell nucleus upon visualisation with streptavidin; but this was less easily traceable because of co-staining of other structures such as mitochondria. In conclusion, for small drug-like molecules, visualisation by alkyne-azide cycloaddition seems to be superior to conventional visualisation by the biotin-streptavidin system.
Katharina Effenberger-neidnicht - One of the best experts on this subject based on the ideXlab platform.
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Modification of uptake and subcellular distribution of doxorubicin by N-acylhydrazone residues as visualised by intrinsic fluorescence
Cancer Chemotherapy and Pharmacology, 2012Co-Authors: Katharina Effenberger-neidnicht, Sandra Breyer, Katharina Mahal, Florenz Sasse, Rainer SchobertAbstract:Purpose Doxorubicin ( 1 ) is commonly used in the treatment of a wide range of cancers. Some N -acylhydrazones of 1 were previously found to have an improved tumour and organ selectivity. In order to clarify the molecular basis for this effect, the cellular uptake into various cancer cells and the localisation in PtK_2 Potoroo kidney cells of 1 and its N -acylhydrazones derived from heptadecanoic acid ( 2 ) and 11-(menthoxycarbonyl)undecanoic acid ( 3 ) were studied drawing on their intrinsic fluorescence. Methods The uptake of compounds 1 – 3 into human cells of HL-60 leukaemia, 518A2 melanoma, HT-29 colon, and resistant KB-V1/Vbl and MCF-7/Topo breast carcinomas was determined fluorometrically from their residual amounts in the supernatant. Their time-dependent accumulation in PtK_2 Potoroo kidney cells was visualised by fluorescence microscopy. Results The uptake, though not the cytotoxicity, of 2 in multi-drug resistant MCF-7/Topo breast cancer cells was conspicuously greater than that of 1 and 3 , probably due to an attractive lipophilic interaction with the lipid-rich membranes of these cells. In non-malignant PtK_2 cells, both 1 and 3 accumulated initially in the nuclei. Upon prolonged incubation, their fluorescent metabolites were visualised in lysosomes neighbouring the nuclei. In contrast, conjugate 2 was not observed in the nuclei at any time. After 2 h, it had accumulated in vesicles scattered all over the cells, and upon prolonged incubation, its fluorescent metabolites were concentrated in the cellular membrane. Conclusions Long unbranched fatty acyl residues when attached to doxorubicin via a hydrazone can act as lipophilic membrane anchors. This allows an increased uptake of such derivatives into lipid-rich membranes especially of multi-drug resistant cancer cells, a retarded release from there into the cytosol and the eventual storage of their metabolites again in the cell membrane rather than in lysosomes.
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Modification of uptake and subcellular distribution of doxorubicin by N-acylhydrazone residues as visualised by intrinsic fluorescence.
Cancer Chemotherapy and Pharmacology, 2011Co-Authors: Katharina Effenberger-neidnicht, Sandra Breyer, Katharina Mahal, Florenz Sasse, Rainer SchobertAbstract:Purpose Doxorubicin (1) is commonly used in the treatment of a wide range of cancers. Some N-acylhydrazones of 1 were previously found to have an improved tumour and organ selectivity. In order to clarify the molecular basis for this effect, the cellular uptake into various cancer cells and the localisation in PtK2 Potoroo kidney cells of 1 and its N-acylhydrazones derived from heptadecanoic acid (2) and 11-(menthoxycarbonyl)undecanoic acid (3) were studied drawing on their intrinsic fluorescence.
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Cellular Localisation of Antitumoral 6‐Alkyl Thymoquinones Revealed by an Alkyne–Azide Click Reaction and the Streptavidin–Biotin System
Chembiochem : a European journal of chemical biology, 2011Co-Authors: Katharina Effenberger-neidnicht, Sandra Breyer, Katharina Mahal, Florenz Sasse, Randi Diestel, Rainer SchobertAbstract:The subcellular distribution and accumulation of thymoquinone 1, a natural anticancer agent, has hitherto been unknown. We prepared 6-(dec-9-ynyl)thymoquinone 3, an alkyne-labelled derivative with anticancer activity similar to that of its parent compound 1. Alkyne 3 was seen, after a Huisgen-type click reaction with 3-azido-7-hydroxycoumarin, to accumulate in distinct compartments of the nuclei of PtK(2) Potoroo kidney cells, and in adjoining regions that were stained with an antibody specific for the Golgi apparatus. In contrast, a biotinlabelled thymoquinone 4 seemed to accumulate across the entire cell nucleus upon visualisation with streptavidin; but this was less easily traceable because of co-staining of other structures such as mitochondria. In conclusion, for small drug-like molecules, visualisation by alkyne-azide cycloaddition seems to be superior to conventional visualisation by the biotin-streptavidin system.
Andrew W. Claridge - One of the best experts on this subject based on the ideXlab platform.
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Population characteristics and management of the long-nosed Potoroo (Potorous tridactylus) in high-quality habitat in the Southern Highlands of New South Wales
Australian Mammalogy, 2015Co-Authors: Melinda Norton, Alison Prentice, Juliet Dingle, Kris French, Andrew W. ClaridgeAbstract:Since European settlement in Australia the long-nosed Potoroo (Potorous tridactylus) has suffered greatly from fox predation and habitat loss, fragmentation and degradation. To better understand the threats it faces we examined the population dynamics of the Potoroo at two study sites in the Southern Highlands of New South Wales over five years, using live-trapping. As neither site had experienced inappropriate habitat change for over 25 years, fox predation was considered the major threat to this population. An assessment of fox activity and diet was undertaken at both sites for comparison with Potoroo abundance. Potoroos increased at both sites over time, although at one site this increase was only in density and not range. The density increase would not have been detected using camera surveys, a monitoring technique recommended for this species. The relative abundance of foxes fluctuated over the study despite fox control in one of the two sites. Analysis of fox scats at the same sites indicated high levels of predation on Potoroos. Future management should aim to provide effective fox control (particularly following any fire due to the associated loss of ground cover) and improved fox monitoring to ensure an accurate understanding of what is happening to the fox population.
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Habitat associations of the long-nosed Potoroo (Potorous tridactylus) at multiple spatial scales
Australian Journal of Zoology, 2010Co-Authors: Melinda Norton, Kristine French, Andrew W. ClaridgeAbstract:This study examined the coarse- and fine-scale habitat preferences of the long-nosed Potoroo (Potorous tridactylus) in the Southern Highlands of New South Wales, in order to inform the management of this threatened species. Live-trapping was conducted in autumn and spring, from 2005 to 2008, at two sites. Macrohabitat preferences were examined by comparing trap success with numerous habitat attributes at each trap site. In spring 2007 and autumn 2008, microhabitat use was also examined, using the spool-and-line technique and forage digging assessments. While Potoroos were trapped in a wide range of macrohabitats, they displayed some preference for greater canopy and shrub cover, and ground cover with lower floristic diversity. While most individuals also displayed preferences for various microhabitat attributes, no clear trends were evident across all individuals. Potoroos displayed some foraging preference for microhabitats with higher shrub cover densities and more open ground cover. Despite extensive fox predation risks, individual Potoroos did not all preferentially utilise dense ground cover. Future management of known and potential Potoroo habitat should aim to provide effective introduced predator control and enhance the diversity of vegetation attributes while avoiding practices that simplify the habitat.
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Detection of medium-sized ground-dwelling mammals using infrared digital cameras: an alternative way forward?
Australian Mammalogy, 2010Co-Authors: Andrew W. Claridge, David Paull, Simon C. BarryAbstract:Infrared digital cameras were used to examine temporal detection rates of medium-sized ground-dwelling mammals in a coastal woodland landscape. From three successive deployments at fixed stations, a range of mammals was detected, including three target species: the long-nosed bandicoot, the long-nosed Potoroo and the southern brown bandicoot. Reporting rates of target species were largely consistent and in some cases high. The swamp wallaby was the most commonly detected species, ranging from 47–67% of cameras on any given deployment. Long-nosed bandicoots were detected at 37–53% of cameras, long-nosed Potoroos 13–23% and southern brown bandicoots 10–17%. In total, bandicoots and Potoroos were detected at 23 of 30 sites (77%) while forage-diggings of these mammals were universally present. There were differences in the detection rate of bandicoots and Potoroos in relation to 24-hourly cycles: all three species were less likely to be detected between dawn and dusk than dusk and dawn. Otherwise, with few exceptions, the rate at which bandicoots and Potoroos were detected over time within a deployment did not vary markedly. Infrared digital cameras offer great potential as sampling devices for bandicoots and Potoroos because of their greater detection efficiency relative to other techniques.
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Population biology of the long-nosed Potoroo (Potorous tridactylus) in the Southern Highlands of New South Wales
Australian Journal of Zoology, 2010Co-Authors: Melinda Norton, Andrew W. Claridge, Kris French, Alison PrenticeAbstract:The population biology of the long-nosed Potoroo (Potorous tridactylus) was investigated at Barren Grounds Nature Reserve and Budderoo National Park in the Southern Highlands of New South Wales (NSW). Both study areas are important conservation reserves for this threatened species, with a large gap north (~300 km) to the next known viable population on the mid-north coast of NSW at Mount Royal. Potoroos were live-trapped using bandicoot-sized cage traps, each set ~100 m apart along walking tracks and fire trails. Trapping was conducted each autumn and spring over five years to enumerate the local population of Potoroos and to describe their morphometrics. The local long-nosed Potoroos were larger in size than those recorded to the south on mainland Australia, but smaller than those in north-eastern NSW, supporting the concept of a latitudinal cline in body size. Sexual dimorphism was observed, with adult males having larger body weights, head lengths and pes lengths. Between one-third and two-thirds of all males and females were captured in only a single trapping session, indicative of low levels of survivorship and/or high levels of dispersal or transience. Males regularly overlapped at trap sites with females, more so than with other males, while females rarely overlapped at trap sites. Barren Grounds Nature Reserve supported a larger number of Potoroos and a greater degree of home range overlap between individuals.
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Bettongs, Potoroos and the Musky Rat-kangaroo
2007Co-Authors: Andrew W. Claridge, John H. Seebeck, Rw RoseAbstract:Rat-kangaroos have not coped well with the impact of European settlement in Australia. Of the 11 species present in 1788, two are extinct, two are either mostly or totally restricted to offshore islands and the range of all other species has been much reduced. Habitat alienation, altered fire regimes, grazing, predation by introduced carnivores, competition from rabbits and timber harvesting have variously taken their toll on these little-seen animals. The rat-kangaroo was one of the first Australian marsupials to be seen alive in Europe. Collected close to the settlement at Sydney Cove, a pair of them were exhibited in London in 1789. These animals were called by the local Aboriginal people 'Pot-o-roo', and by the European settlers, 'Kangooroo rat'. They were the Long-nosed Potoroo, Potorous tridactylus, the first of what we now call 'Rat-kangaroos' to be discovered. Bettongs, Potoroos and the Musky Rat-kangaroo provides an extraordinary glimpse into the secretive lives of these unusual marsupials. It also reveals little-known facts about the critical functional role these creatures play in maintaining the forest and woodland habitats in which they live.
Russell P. Hobbs - One of the best experts on this subject based on the ideXlab platform.
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Identification of a novel species of Eimeria Schneider, 1875 from the woylie, Bettongia penicillata Gray (Diprotodontia: Potoroidae) and the genetic characterisation of three Eimeria spp. from other potoroid marsupials
Systematic Parasitology, 2019Co-Authors: Amy S. Northover, Sarah Keatley, Aileen D. Elliot, Russell P. Hobbs, Rongchang Yang, Alan J. Lymbery, Stephanie S. Godfrey, Adrian F. Wayne, R. C. Andrew ThompsonAbstract:Faecal samples (n = 1,093) collected from the woylie Bettongia penicillata Gray, in south-western Australia were examined for the presence of coccidian parasites. Eimeria sp. oöcysts were detected in 15.2% of samples. Faecal samples obtained from the eastern bettong Bettongia gaimardi (Desmarest) (n = 4) and long-nosed Potoroo Potorous tridactylus (Kerr) (n = 12) in Tasmania, were also screened for the presence of Eimeria spp. (prevalence 50% and 41.7%, respectively). Morphological and genetic comparison with other known species of Eimeria indicates that the material identified in woylies is novel. This study aimed to (i) morphologically describe and genetically characterise Eimeria woyliei n. sp. found in woylies; and (ii) genetically characterise Eimeria gaimardi Barker, O’Callaghan & Beveridge, 1988, Eimeria potoroi Barker, O’Callaghan & Beveridge, 1988, and Eimeria mundayi Barker, O’Callaghan & Beveridge, 1988, from other potoroid marsupials. Molecular phylogenetic analyses conducted at the 18S rDNA and mitochondrial cytochrome c oxidase subunit 1 ( cox 1) loci revealed that E. woyliei n. sp. was most closely related to Eimeria setonicis Barker, O’Callaghan & Beveridge, 1988, at the 18S rDNA locus, and Eimeria trichosuri O’Callaghan & O’Donoghue, 2001, at the cox 1 locus. Eimeria woyliei n. sp. is the sixth species of Eimeria to be formally described from potoroid marsupials.
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A new species of Potoroxyuris (Nematoda: Oxyuridae) from the woylie Bettongia penicillata (Marsupialia: Potoroidae) from southwestern Australia.
International journal for parasitology. Parasites and wildlife, 2016Co-Authors: Russell P. Hobbs, Aileen ElliotAbstract:Potoroxyuris keninupensis n.sp. (Nematoda: Oxyuridae) is described based on specimens recovered from the caecum and colon of two woylies, Bettongia penicillata (Marsupialia: Potoroidae) from Western Australia. Only one other species of Potoroxyuris has been described previously, Potoroxyuris Potoroo (Johnston and Mawson, 1939) Mawson, 1964, from Potorous tridactylus. The new species is most easily differentiated from P. Potoroo by the shape of the pharyngeal lobes. The pharyngeal lobes of P. keninupensis n. sp. are widest at the base while those of P. Potoroo are widest at the tip. The genus Potoroxyuris most closely resembles Macropoxyuris based especially on structures of the caudal end of males. The other three genera of oxyurids known to infect Australian marsupials have longer caudal alae, and more caudal papillae than these two genera. The genus Potoroxyuris has previously been defined by the characteristic that the pharyngeal lobes protrude through the oral opening. However, the pharyngeal lobes of P. keninupensis n. sp. do not quite protrude, so the definition of the genus should be modified as follows. The genus Potoroxyuris can be easily differentiated from Macropoxyuris by the following differences in the morphology of the buccal cavity. The pharyngeal lobes of Potoroxyuris almost reach the oral opening, or protrude beyond it, whereas those of Macropoxyuris only reach to about the anterior third of the buccal cavity. The buccal cavity of Potoroxyuris is poorly cuticularized compared to Macropoxyuris and other genera of oxyurids known from Australian marsupials, and does not contain inter-radial lamellae.
Aileen Elliot - One of the best experts on this subject based on the ideXlab platform.
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A new species of Potoroxyuris (Nematoda: Oxyuridae) from the woylie Bettongia penicillata (Marsupialia: Potoroidae) from southwestern Australia.
International journal for parasitology. Parasites and wildlife, 2016Co-Authors: Russell P. Hobbs, Aileen ElliotAbstract:Potoroxyuris keninupensis n.sp. (Nematoda: Oxyuridae) is described based on specimens recovered from the caecum and colon of two woylies, Bettongia penicillata (Marsupialia: Potoroidae) from Western Australia. Only one other species of Potoroxyuris has been described previously, Potoroxyuris Potoroo (Johnston and Mawson, 1939) Mawson, 1964, from Potorous tridactylus. The new species is most easily differentiated from P. Potoroo by the shape of the pharyngeal lobes. The pharyngeal lobes of P. keninupensis n. sp. are widest at the base while those of P. Potoroo are widest at the tip. The genus Potoroxyuris most closely resembles Macropoxyuris based especially on structures of the caudal end of males. The other three genera of oxyurids known to infect Australian marsupials have longer caudal alae, and more caudal papillae than these two genera. The genus Potoroxyuris has previously been defined by the characteristic that the pharyngeal lobes protrude through the oral opening. However, the pharyngeal lobes of P. keninupensis n. sp. do not quite protrude, so the definition of the genus should be modified as follows. The genus Potoroxyuris can be easily differentiated from Macropoxyuris by the following differences in the morphology of the buccal cavity. The pharyngeal lobes of Potoroxyuris almost reach the oral opening, or protrude beyond it, whereas those of Macropoxyuris only reach to about the anterior third of the buccal cavity. The buccal cavity of Potoroxyuris is poorly cuticularized compared to Macropoxyuris and other genera of oxyurids known from Australian marsupials, and does not contain inter-radial lamellae.