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981.
Dalton JP Demanga CG Reiling SJ Wunderlich J Eng JW Rohrbach P 《International journal for parasitology》2012,42(3):215-220
We describe methods for the large-scale in vitro culturing of synchronous and asynchronous blood-stage Plasmodium falciparum parasites in sterile disposable plastic bioreactors controlled by wave-induced motion (wave bioreactor). These cultures perform better than static flask cultures in terms of preserving parasite cell cycle synchronicity and reducing the number of multiple-infected erythrocytes. The straight-forward methods described here will facilitate the large scale production of malaria parasites for antigen and organelle isolation and characterisation, for the high throughput screening of compound libraries with whole cells or extracts, and the development of live- or whole-cell malaria vaccines under good manufacturing practice compliant standards. 相似文献
982.
983.
Weissgerber P Kriebs U Tsvilovskyy V Olausson J Kretz O Stoerger C Mannebach S Wissenbach U Vennekens R Middendorff R Flockerzi V Freichel M 《The Journal of biological chemistry》2012,287(22):17930-17941
Replacement of aspartate residue 541 by alanine (D541A) in the pore of TRPV6 channels in mice disrupts Ca(2+) absorption by the epididymal epithelium, resulting in abnormally high Ca(2+) concentrations in epididymal luminal fluid and in a dramatic but incomplete loss of sperm motility and fertilization capacity, raising the possibility of residual activity of channels formed by TRPV6(D541A) proteins (Weissgerber, P., Kriebs, U., Tsvilovskyy, V., Olausson, J., Kretz, O., Stoerger, C., Vennekens, R., Wissenbach, U., Middendorff, R., Flockerzi, V., and Freichel, M. (2011) Sci. Signal. 4, ra27). It is known from other cation channels that introducing pore mutations even if they largely affect their conductivity and permeability can evoke considerably different phenotypes compared with the deletion of the corresponding protein. Therefore, we generated TRPV6-deficient mice (Trpv6(-/-)) by deleting exons encoding transmembrane domains with the pore-forming region and the complete cytosolic C terminus harboring binding sites for TRPV6-associated proteins that regulate its activity and plasma membrane anchoring. Using this strategy, we aimed to determine whether the TRPV6(D541A) pore mutant still contributes to residual channel activity and/or channel-independent functions in vivo. Trpv6(-/-) males reveal severe defects in fertility and motility and viability of sperm and a significant increase in epididymal luminal Ca(2+) concentration that is mirrored by a lack of Ca(2+) uptake by the epididymal epithelium. Therewith, Trpv6 excision affects epididymal Ca(2+) handling and male fertility to the same extent as the introduction of the D541A pore mutation, arguing against residual functions of the TRPV6(D541A) pore mutant in epididymal epithelial cells. 相似文献
984.
K Richter L Burch F Chao D Henke C Jiang J Daly ML Zhao G Kissling M Diaz 《The Journal of biological chemistry》2012,287(38):31856-31865
We recently identified a novel germinal center GTPase, SLIP-GC, that localizes to replication factories in B cells and that, when reduced, induces DNA breaks in lymphoma B cell lines in an activation-induced deaminase (AID)-dependent manner. Herein, we generated mice deficient in SLIP-GC and examined the impact of SLIP-GC deficiency in immunoglobulin hypermutation and class switch recombination, both AID-dependent mechanisms. SLIP-GC-deficient mice experienced a substantial increase in mutations at G:C base pairs at the region downstream of JH4 in the immunoglobulin heavy chain locus. This change was reflected in the overall mutation frequency, and it was associated with an increase in transitions from G:C base pairs, a hallmark of AID-mediated deamination during replication. In addition, G:C transitions at non-immunoglobulin loci also increased in these mice. Given the intracellular localization of SLIP-GC to sites of replicating DNA, these results suggest that SLIP-GC protects replicating DNA from AID-mediated deamination of cytosines in both strands. 相似文献
985.
986.
When the urothelial barrier, i.e., the blood−urine barrier, is injured, rapid resealing of the injury is crucial for the normal
functioning of the organism. In order to investigate the mechanisms required for rapid resealing of the barrier, we established
in vitro models of hyperplastic and normoplastic urothelia. We found that hyperplastic urothelia achieve significantly higher
transepithelial resistance (TER) than normoplastic urothelia. However, the expression of cell junctional (claudin-8, occludin,
E-cadherin) and differentiation-related proteins (cytokeratin 20 and uroplakins) is weaker in hyperplastic urothelia. Further
investigation of cell differentiation status at the ultrastructural level confirmed that superficial urothelial cells (UCs)
in hyperplastic urothelial models achieve a lower differentiation stage than superficial UCs in normoplastic urothelial models.
With the establishment of such in vitro models and the aid of TER measurements, flow cytometry, molecular and ultrastructural
analysis, we here provide unequivocal evidence that the specific cell-cycle distribution and, consequently, the number of
cell layers have a significant influence on the barrier function of urothelia. We demonstrate the importance of hyperplasia
for the rapid restoration of the urothelial barrier and the maintenance of high TER until the UCs reach a highly differentiated
stage and restoration of the urothelial barrier after injury is complete. The information that this approach provides is unique
and we expect that further exploitation of hyperplastic and normoplastic urothelial models in future studies may advance our
understanding of blood−urine barrier development and functionality. 相似文献
987.
988.
Grimm MO Rothhaar TL Grösgen S Burg VK Hundsdörfer B Haupenthal VJ Friess P Kins S Grimm HS Hartmann T 《The Journal of nutritional biochemistry》2012,23(10):1214-1223
Hydrogenation of oils and diary products of ruminant animals leads to an increasing amount of trans fatty acids in the human diet. Trans fatty acids are incorporated in several lipids and accumulate in the membrane of cells. Here we systematically investigate whether the regulated intramembrane proteolysis of the amyloid precursor protein (APP) is affected by trans fatty acids compared to the cis conformation. Our experiments clearly show that trans fatty acids compared to cis fatty acids increase amyloidogenic and decrease nonamyloidogenic processing of APP, resulting in an increased production of amyloid beta (Aβ) peptides, main components of senile plaques, which are a characteristic neuropathological hallmark for Alzheimer's disease (AD). Moreover, our results show that oligomerization and aggregation of Aβ are increased by trans fatty acids. The mechanisms identified by this in vitro study suggest that the intake of trans fatty acids potentially increases the AD risk or causes an earlier onset of the disease. 相似文献
989.
Historical evidences suggest that the Himalayas have some strong biogeographical links to the Alps. In view of this fact,
the present study aims to understand the similarities in plant species distribution and their ethnobotanical uses in the Indian
Himalayas and the Slovenian Alps. The plant species common in both the mountain systems and used by local inhabitants were
compiled by extensive literature search and also by carrying out primary surveys. Ethnobotanical information was collected
through personal interviews of villagers with the help of local assistants and also through direct and indirect observations
made during the field surveys. A total of 59 ethnobotanical species representing 17 families common in both the Indian Himalayas
and the Slovenian Alps were documented, of these 78% obtained medicinal properties and traditionally used by local people
for curing diseases. Comparatively, people of the Indian Himalayas used plants for medicine in higher percentage (73%) than
the people of Slovenia (42%). Of the total medicinal plants, only 7 plant species such as Acorus
calamus, Capsella
bursa-partoris, Hypericum
perforatum, Origanum
vulgare, Prunella
vulgaris, Solanum
nigrum and Urtica
dioica had some common uses in both the Slovenian Alps and the Indian Himalayas. In the Slovenian Alps, the maximum ethnobotanical
species (61%) had wide distribution range whereas maximum ethnobotanical species in the Indian Himalayas (62%) had localized
distribution. Though, 27% of common ethnobotanical species belonged to different threat categories, only 2 species—Taxus
baccata and Hippophae
rhamnoides—are placed under similar threat category in these two different mountain areas. The study unfolds relationship in plant species
distribution and their ethnobotanical uses along with offering an opportunity to provide information on uses of plant species
though available but unknown to community. 相似文献
990.
Takács D Nagy I Bombicz P Egyed O Jemnitz K Riedl Z Molnár J Amaral L Hajós G 《Bioorganic & medicinal chemistry》2012,20(14):4258-4270
N-dienylphenothiazines synthesized from tetrazolo[1,5-a]pyridinium salts by treatment with phenothiazine were subjected to catalytic hydrogenation to yield N-butylphenothiazines, whereas transformation of these dienes with borane dimethyl sulfide (BH(3) × Me(2)S) resulted in selective hydroboration of one double bond and full reduction of the other double bond to give 2-hydroxybutylphenothiazines. Position of the hydroxyl group was supported by NMR spectroscopy and verified by X-ray analysis. Comparison of MDR modulatory activity of the new derivatives revealed that the hydroxybutyl compounds are promising candidates for development of novel MDR inhibitors. 相似文献