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71.
Safeguarding the welfare of animals is an important aim when defining housing and management standards in animal based, experimental research. While such standards are usually defined per animal species, it is known that considerable differences between laboratory mouse strains exist, for example with regard to their emotional traits. Following earlier experiments, in which we found that 129P3 mice show a lack of habituation of anxiety related behaviour after repeated exposure to an initially novel environment (non-adaptive profile), we here investigated four other 129 inbred mouse substrains (129S2/SvPas, 129S2/SvHsd (exp 1); 129P2 and 129X1 (exp 2)) on habituation of anxiety related behaviour. Male mice of each strain were repeatedly placed in the modified hole board test, measuring anxiety-related behaviour, exploratory and locomotor behaviour. The results reveal that all four substrains show a lack of habituation behaviour throughout the period of testing. Although not in all of the substrains a possible confounding effect of general activity can be excluded, our findings suggest that the genetic background of the 129 substrains may increase their vulnerability to cope with environmental challenges, such as exposure to novelty. This vulnerability might negatively affect the welfare of these mice under standard laboratory conditions when compared with other strains. Based on our findings we suggest to consider (sub)strain-specific guidelines and protocols, taking the (subs)train-specific adaptive capabilities into account. 相似文献
72.
Diana Marklein Ulrike Graab Ivonne Naumann Tiandong Yan Rosalie Ridzewski Frauke Nitzki Albert Rosenberger Kai Dittmann Jürgen Wienands Leszek Wojnowski Simone Fulda Heidi Hahn 《PloS one》2012,7(12)
We searched for a drug capable of sensitization of sarcoma cells to doxorubicin (DOX). We report that the dual PI3K/mTOR inhibitor PI103 enhances the efficacy of DOX in several sarcoma cell lines and interacts with DOX in the induction of apoptosis. PI103 decreased the expression of MDR1 and MRP1, which resulted in DOX accumulation. However, the enhancement of DOX-induced apoptosis was unrelated to DOX accumulation. Neither did it involve inhibition of mTOR. Instead, the combination treatment of DOX plus PI103 activated Bax, the mitochondrial apoptosis pathway, and caspase 3. Caspase 3 activation was also observed in xenografts of sarcoma cells in nude mice upon combination of DOX with the specific PI3K inhibitor GDC-0941. Although the increase in apoptosis did not further impact on tumor growth when compared to the efficient growth inhibition by GDC-0941 alone, these findings suggest that inhibition of PI3K may improve DOX-induced proapoptotic effects in sarcoma. Taken together with similar recent studies of neuroblastoma- and glioblastoma-derived cells, PI3K inhibition seems to be a more general option to sensitize tumor cells to anthracyclines. 相似文献
73.
Deschermeier C Hecht LS Bach F Rützel K Stanway RR Nagel A Seeber F Heussler VT 《Cellular microbiology》2012,14(3):416-430
Lipoic acid is an essential cofactor for enzymes that participate in key metabolic pathways in most organisms. While in mammalian cells lipoylated proteins reside exclusively in the mitochondria, apicomplexan parasites of the genus Plasmodium harbour two independent lipoylation pathways in the mitochondrion and the apicoplast, a second organelle of endosymbiotic origin. Protein lipoylation in the apicoplast relies on de novo lipoic acid synthesis while lipoylation of proteins in the mitochondrion depends on scavenging of lipoic acid from the host cell. Here, we analyse the impact of lipoic acid scavenging on the development of Plasmodium berghei liver stage parasites. Treatment of P. berghei-infected HepG2 cells with the lipoic acid analogue 8-bromo-octanoic acid (8-BOA) abolished lipoylation of mitochondrial enzyme complexes in the parasite while lipoylation of apicoplast proteins was not affected. Parasite growth as well as the ability of the parasites to successfully complete liver stage development by merosome formation were severely impaired but not completely blocked by 8-BOA. Liver stage parasites were most sensitive to 8-BOA treatment during schizogony, the phase of development when the parasite grows and undergoes extensive nuclear division to form a multinucleated syncytium. Live cell imaging as well as immunofluorescence analysis and electronmicroscopy studies revealed a close association of both host cell and parasite mitochondria with the parasitophorous vacuole membrane suggesting that host cell mitochondria might be involved in lipoic acid uptake by the parasite from the host cell. 相似文献
74.
Hennigs JK Burhenne N Stähler F Winnig M Walter B Meyerhof W Schmale H 《Journal of neurochemistry》2008,106(5):2249-2262
In a search for sweet taste receptor interacting proteins, we have identified the calcium- and integrin-binding protein 1 (CIB1) as specific binding partner of the intracellular carboxyterminal domain of the rat sweet taste receptor subunit Tas1r2. In heterologous human embryonic kidney 293 (HEK293) cells, the G protein chimeras Gα16gust44 and Gα15i3 link the sweet taste receptor dimer TAS1R2/TAS1R3 to an inositol 1,4,5-trisphosphate (InsP3 )-dependent Ca2+ release pathway. To demonstrate the influence of CIB1 on the cytosolic Ca2+ concentration, we used sweet and umami compounds as well as other InsP3 -generating ligands in FURA-2-based Ca2+ assays in wild-type HEK293 cells and HEK293 cells expressing functional human sweet and umami taste receptor dimers. Stable and transient depletion of CIB1 by short-hairpin RNA increased the Ca2+ response of HEK293 cells to the InsP3 -generating ligands ATP, UTP and carbachol. Over-expression of CIB1 had the opposite effect as shown for the sweet ligand saccharin, the umami receptor ligand monosodium glutamate and UTP. The CIB1 effect was dependent on the thapsigargin-sensitive Ca2+ store of the endoplasmic reticulum (ER) and independent of extracellular Ca2+ . The function of CIB1 on InsP3 -evoked Ca2+ release from the ER is most likely mediated by its interaction with the InsP3 receptor. Thus, CIB1 seems to be an inhibitor of InsP3 -dependent Ca2+ release in vivo . 相似文献
75.
Korf U Derdak S Tresch A Henjes F Schumacher S Schmidt C Hahn B Lehmann WD Poustka A Beissbarth T Klingmüller U 《Proteomics》2008,8(21):4603-4612
The quantitative analysis of signaling networks requires highly sensitive methods for the time-resolved determination of protein phosphorylation. For this reason, we developed a quantitative protein microarray that monitors the activation of multiple signaling pathways in parallel, and at high temporal resolution. A label-free sandwich approach was combined with near infrared detection, thus permitting the accurate quantification of low-level phosphoproteins in limited biological samples corresponding to less than 50,000 cells, and with a very low standard deviation of approximately 5%. The identification of suitable antibody pairs was facilitated by determining their accuracy and dynamic range using our customized software package Quantpro. Thus, we are providing an important tool to generate quantitative data for systems biology approaches, and to drive innovative diagnostic applications. 相似文献
76.
Ackermann F Zitranski N Heydecke D Wilhelm B Gudermann T Boekhoff I 《Journal of cellular physiology》2008,214(3):757-768
The success of acrosomal exocytosis, a complex process with a variety of interrelated steps, relies on the coordinated interaction of participating signaling molecules. Since scaffolding proteins are known to spatially organize sequential signaling pathways, we examined whether the Multi-PDZ domain protein MUPP1, recently identified in mammalian spermatozoa, is functionally active in controlling acrosomal secretion in mammalian sperm cells. To address this question, permeabilized mouse sperm were loaded with inhibitory antibodies against MUPP1 as well as with a photosensitive Ca(2+) chelator which allows a controlled release of acrosomal Ca(2+). The results revealed that MUPP1 controls initial tethering and docking of the acrosomal vesicle, whereas syntaxin 2, a t-SNARE protein also expressed in the acrosomal cap of mammalian spermatozoa, appears to take part in the final process of acrosomal fusion. Interestingly, using immunogold electron microscopy, it was found that MUPP1 is detectable in the region of the periacrosomal membrane. Furthermore, in isolated detergent-insoluble glycolipid-enriched membrane domains from epididymal spermatozoa, MUPP1 was found to show a striking association with the Triton X-100 insoluble membrane fraction, which did not change significantly upon sperm capacitation or partial chemical extraction of cholesterol. This evidence points to a role of MUPP1 as a membrane raft-associated molecular organizer, and suggests that mammalian spermatozoa may use a scaffolding protein and distinct membrane subdomains to spatially organize components involved in the process of acrosomal exocytosis. 相似文献
77.
Ena/VASP: proteins at the tip of the nervous system 总被引:3,自引:0,他引:3
The emergence of neurites from a symmetrical cell body is an essential feature of nervous system development. Neurites are the precursors of axons and dendrites and are tipped by growth cones, motile structures that guide elongating axons in the developing nervous system. Growth cones steer the axon along a defined path to its appropriate target in response to guidance cues. This navigation involves the dynamic extension and withdrawal of actin-filled finger-like protrusions called filopodia that continuously sample their environment. Ena/VASP proteins, a conserved family of actin-regulatory proteins, are crucial for filopodia formation and function downstream of several guidance cues. Here we review recent findings into Ena/VASP function in neurite initiation, axon outgrowth and guidance. 相似文献
78.
79.
Objective: The aim of the study was to assess the uptake of dental services by the old and very old population within the scope of the Berlin Aging Study (Berliner Altersstudie BASE ). Design: A multi‐disciplinary structured interview was performed on 928 subjects, aged from 70 to 103 years of whom 516 persons volunteered to take part in a 14‐session intensive protocol. Six representative study groups were matched for age and gender. Subjects were asked to recall the timing of their most recent dental visit. Data were validated by sending for dental records and compared with all study participants from the multi‐disciplinary intake assessment. Data were related to age group, dental state, dementia and education. Results: Reported last contact with dental services ranged from 2 weeks to 52 years (median 18 months) with a higher time lapse in the study groups aged 85 and older. Dentate subjects had seen their dentist more recently than edentate subjects. Higher education correlated with an increased dental utilisation. Subjective memory on the time lapse since the last dental appointment coincided in 13% of the subjects with available dental records (n=84), was misjudged between one and six months in 55%, and by more than six months in the remainder. Moderately or severely demented subjects who remembered their last dental appointment (n=48 of 70) showed no consistently different utilisation to healthy or mildly demented studs participants. Conclusion: Edentate old and very old subjects show the least frequent utilisation of dental services. Data on motivation and barriers to care are needed to develop strategies to improve the use of dental services and thus promote oral health in late life. 相似文献
80.
Mónica M. Solórzano Kraemer Atahualpa S. Kraemer Frauke Stebner Daniel J. Bickel Jes Rust 《PloS one》2015,10(3)
All entomological traps have a capturing bias, and amber, viewed as a trap, is no exception. Thus the fauna trapped in amber does not represent the total existing fauna of the former amber forest, rather the fauna living in and around the resin producing tree. In this paper we compare arthropods from a forest very similar to the reconstruction of the Miocene Mexican amber forest, and determine the bias of different trapping methods, including amber. We also show, using cluster analyses, measurements of the trapped arthropods, and guild distribution, that the amber trap is a complex entomological trap not comparable with a single artificial trap. At the order level, the most similar trap to amber is the sticky trap. However, in the case of Diptera, at the family level, the Malaise trap is also very similar to amber. Amber captured a higher diversity of arthropods than each of the artificial traps, based on our study of Mexican amber from the Middle Miocene, a time of climate optimum, where temperature and humidity were probably higher than in modern Central America. We conclude that the size bias is qualitatively independent of the kind of trap for non–extreme values. We suggest that frequent specimens in amber were not necessarily the most frequent arthropods in the former amber forest. Selected taxa with higher numbers of specimens appear in amber because of their ecology and behavior, usually closely related with a tree–inhabiting life. Finally, changes of diversity from the Middle Miocene to Recent time in Central and South America can be analyzed by comparing the rich amber faunas from Mexico and the Dominican Republic with the fauna trapped using sticky and Malaise traps in Central America. 相似文献